Nephrology

SAN DIEGO – Cirrhotics with spontaneous bacterial peritonitis probably need albumin only if their total bilirubin is above 4 mg/dL and/or their blood urea nitrogen (BUN) is above 30 mg/dL, according to transplant hepatologist Dr. James Burton.

Supplementation expands plasma volume to attenuate the splanchnic and systemic vasodilation associated with spontaneous bacterial peritonitis (SBP), increasing blood flow to the kidneys and preserving renal function, said Dr. Burton, medical director of liver transplantation at the University of Colorado Hospital, Aurora.

But it seems to be needed only when SBP patients are at high risk for renal failure, according to two studies.

The first randomized 63 cirrhotic SBP patients to cefotaxime alone and 63 to cefotaxime plus albumin, 1.5 g/kg on day 1 and 1.0 g/kg on day 3. The regimen wiped out the infection in most patients. Renal impairment and mortality were significantly lower in the albumin group, but only patients with total baseline bilirubins above 4 mg/dL and/or BUNs greater than 30 mg/dL benefited from albumin, Dr. Burton said (N. Engl. J. Med. 1999;341:403-9).

A follow-up 28-subject study limited albumin supplementation, again 1.5 g/kg on day 1 and 1.0 g/kg on day 3, to SBP patients with similar parameters or creatinines above 1 mg/dL. It was the right choice; none of the 15 patients with lower baseline values developed renal impairment, Dr. Burton said (Gut 2007;56:597-9).

He noted that it’s possible for patients to have SBP without obvious symptoms, so "if you’re sick enough to have cirrhosis and be in the hospital, you need a needle in your abdomen to rule out" the condition.

In general, cirrhotics have low levels of albumin, which is responsible for about 80% of plasma’s oncotic pressure. Also, what they have "may not work as well" to transport fatty acids, hormones, and enzymes, and drugs.

Outpatient supplementation for cirrhotics not only seems to reduce the need for paracentesis, but also makes patients feel better. "I am a believer because my patients tell me it works. Some of my patients refer to it as ‘nectar of the gods.’ This is more than just the oncotic things. I also think they are transporting hormones, carrying drugs, and other stuff better. So I am a big believer," Dr. Burton said.

He opts for 25% albumin instead of 5%, to reduce fluid load and also because "there is a lot of sodium in 5% albumin. Obviously, these patients need to have their sodium restricted," he said.

When paracentesis is needed, "studies suggest you can probably [remove] 4-6 liters without giving albumin." Even so, "we often give albumin during paracentesis," he said.

Dr. Burton said he has no relevant financial disclosures.

SAN DIEGO – Cirrhotics with spontaneous bacterial peritonitis probably need albumin only if their total bilirubin is above 4 mg/dL and/or their blood urea nitrogen (BUN) is above 30 mg/dL, according to transplant hepatologist Dr. James Burton.

Supplementation expands plasma volume to attenuate the splanchnic and systemic vasodilation associated with spontaneous bacterial peritonitis (SBP), increasing blood flow to the kidneys and preserving renal function, said Dr. Burton, medical director of liver transplantation at the University of Colorado Hospital, Aurora.

But it seems to be needed only when SBP patients are at high risk for renal failure, according to two studies.

The first randomized 63 cirrhotic SBP patients to cefotaxime alone and 63 to cefotaxime plus albumin, 1.5 g/kg on day 1 and 1.0 g/kg on day 3. The regimen wiped out the infection in most patients. Renal impairment and mortality were significantly lower in the albumin group, but only patients with total baseline bilirubins above 4 mg/dL and/or BUNs greater than 30 mg/dL benefited from albumin, Dr. Burton said (N. Engl. J. Med. 1999;341:403-9).

A follow-up 28-subject study limited albumin supplementation, again 1.5 g/kg on day 1 and 1.0 g/kg on day 3, to SBP patients with similar parameters or creatinines above 1 mg/dL. It was the right choice; none of the 15 patients with lower baseline values developed renal impairment, Dr. Burton said (Gut 2007;56:597-9).

He noted that it’s possible for patients to have SBP without obvious symptoms, so "if you’re sick enough to have cirrhosis and be in the hospital, you need a needle in your abdomen to rule out" the condition.

In general, cirrhotics have low levels of albumin, which is responsible for about 80% of plasma’s oncotic pressure. Also, what they have "may not work as well" to transport fatty acids, hormones, and enzymes, and drugs.

Outpatient supplementation for cirrhotics not only seems to reduce the need for paracentesis, but also makes patients feel better. "I am a believer because my patients tell me it works. Some of my patients refer to it as ‘nectar of the gods.’ This is more than just the oncotic things. I also think they are transporting hormones, carrying drugs, and other stuff better. So I am a big believer," Dr. Burton said.

He opts for 25% albumin instead of 5%, to reduce fluid load and also because "there is a lot of sodium in 5% albumin. Obviously, these patients need to have their sodium restricted," he said.

When paracentesis is needed, "studies suggest you can probably [remove] 4-6 liters without giving albumin." Even so, "we often give albumin during paracentesis," he said.

Dr. Burton said he has no relevant financial disclosures.

SAN DIEGO – Cirrhotics with spontaneous bacterial peritonitis probably need albumin only if their total bilirubin is above 4 mg/dL and/or their blood urea nitrogen (BUN) is above 30 mg/dL, according to transplant hepatologist Dr. James Burton.

Supplementation expands plasma volume to attenuate the splanchnic and systemic vasodilation associated with spontaneous bacterial peritonitis (SBP), increasing blood flow to the kidneys and preserving renal function, said Dr. Burton, medical director of liver transplantation at the University of Colorado Hospital, Aurora.

But it seems to be needed only when SBP patients are at high risk for renal failure, according to two studies.

The first randomized 63 cirrhotic SBP patients to cefotaxime alone and 63 to cefotaxime plus albumin, 1.5 g/kg on day 1 and 1.0 g/kg on day 3. The regimen wiped out the infection in most patients. Renal impairment and mortality were significantly lower in the albumin group, but only patients with total baseline bilirubins above 4 mg/dL and/or BUNs greater than 30 mg/dL benefited from albumin, Dr. Burton said (N. Engl. J. Med. 1999;341:403-9).

A follow-up 28-subject study limited albumin supplementation, again 1.5 g/kg on day 1 and 1.0 g/kg on day 3, to SBP patients with similar parameters or creatinines above 1 mg/dL. It was the right choice; none of the 15 patients with lower baseline values developed renal impairment, Dr. Burton said (Gut 2007;56:597-9).

He noted that it’s possible for patients to have SBP without obvious symptoms, so "if you’re sick enough to have cirrhosis and be in the hospital, you need a needle in your abdomen to rule out" the condition.

In general, cirrhotics have low levels of albumin, which is responsible for about 80% of plasma’s oncotic pressure. Also, what they have "may not work as well" to transport fatty acids, hormones, and enzymes, and drugs.

Outpatient supplementation for cirrhotics not only seems to reduce the need for paracentesis, but also makes patients feel better. "I am a believer because my patients tell me it works. Some of my patients refer to it as ‘nectar of the gods.’ This is more than just the oncotic things. I also think they are transporting hormones, carrying drugs, and other stuff better. So I am a big believer," Dr. Burton said.

He opts for 25% albumin instead of 5%, to reduce fluid load and also because "there is a lot of sodium in 5% albumin. Obviously, these patients need to have their sodium restricted," he said.

When paracentesis is needed, "studies suggest you can probably [remove] 4-6 liters without giving albumin." Even so, "we often give albumin during paracentesis," he said.

Dr. Burton said he has no relevant financial disclosures.

NATIONAL HARBOR, MD.  – De novo dipstick proteinuria accurately predicted acute kidney injury among 328 critically ill septic patients, a retrospective chart study has shown.

With sepsis, inflammation results in increased capillary permeability to plasma proteins, manifesting in an increased excretion of albumin into the urine. Because the production of creatinine from the muscle is reduced in septic patients, relying on changes in serum creatinine could delay the diagnosis of this acute kidney injury (AKI), according to Dr. Javier Neyra.

Photo courtesy Dr. Javier Neyra

"It is highly important to identify biomarkers that are sensitive, specific, and provide timely and early diagnosis of acute kidney injury before substantial damage has already been done. ... De novo dipstick proteinuria represents a simple, inexpensive biomarker in sepsis with predictive power for AKI," said Dr. Neyra of the Henry Ford Hospital, Detroit.

Charts from a total of 2,252 patients admitted to the intensive care unit for severe sepsis between January 2004 and July 2011 were analyzed retrospectively. Patients with a baseline serum creatinine level greater than 1.5 mg/dL, the presence of dipstick proteinuria within 3 months of the admission date, or common causes of false-positive dipstick tests such as urinary tract infection or gross hematuria were excluded. Of the remaining 470 patients, 328 had undergone dipstick testing on admission. Of those, 46% (152) had dipstick proteinuria.

Serum creatinine increased by at least 0.3 mg/dL in 210 (64%) patients within the first 72 hours of admission, signifying the first stage of acute kidney injury. In this group, new-onset dipstick proteinuria was found in 114 (54%) patients, for a positive predictive value of 75%. Dipstick proteinuria was found in 91 (55%) of 166 patients who met the Acute Kidney Injury Network criteria for AKI, for a positive predictive value of 60%.

After adjustment for age, sex, race, comorbidities, hemodynamic status, and other variables, de novo dipstick proteinuria at the time of admission independently predicted AKI with an odds ratio of 2.3 (95% confidence interval, 1.4-3.8), Dr. Neyra reported in a poster at a meeting sponsored by the National Kidney Foundation.

In an interview, Dr. Neyra explained that such information identifies septic patients who would benefit from more careful monitoring of kidney function and hemodynamic stability. In addition, in those patients it would be important to avoid nephrotoxic agents such as aminoglycoside antibiotics and nonsteroidal anti-inflammatory agents, as well as exposure to contrast material unless it was absolutely necessary.

"The dipstick is a test that you already have in your hospital that you can utilize. It’s simple, inexpensive, and it’s already there," he said.

Dr. Neyra stated that he had no relevant financial disclosures.

NATIONAL HARBOR, MD.  – De novo dipstick proteinuria accurately predicted acute kidney injury among 328 critically ill septic patients, a retrospective chart study has shown.

With sepsis, inflammation results in increased capillary permeability to plasma proteins, manifesting in an increased excretion of albumin into the urine. Because the production of creatinine from the muscle is reduced in septic patients, relying on changes in serum creatinine could delay the diagnosis of this acute kidney injury (AKI), according to Dr. Javier Neyra.

Photo courtesy Dr. Javier Neyra

"It is highly important to identify biomarkers that are sensitive, specific, and provide timely and early diagnosis of acute kidney injury before substantial damage has already been done. ... De novo dipstick proteinuria represents a simple, inexpensive biomarker in sepsis with predictive power for AKI," said Dr. Neyra of the Henry Ford Hospital, Detroit.

Charts from a total of 2,252 patients admitted to the intensive care unit for severe sepsis between January 2004 and July 2011 were analyzed retrospectively. Patients with a baseline serum creatinine level greater than 1.5 mg/dL, the presence of dipstick proteinuria within 3 months of the admission date, or common causes of false-positive dipstick tests such as urinary tract infection or gross hematuria were excluded. Of the remaining 470 patients, 328 had undergone dipstick testing on admission. Of those, 46% (152) had dipstick proteinuria.

Serum creatinine increased by at least 0.3 mg/dL in 210 (64%) patients within the first 72 hours of admission, signifying the first stage of acute kidney injury. In this group, new-onset dipstick proteinuria was found in 114 (54%) patients, for a positive predictive value of 75%. Dipstick proteinuria was found in 91 (55%) of 166 patients who met the Acute Kidney Injury Network criteria for AKI, for a positive predictive value of 60%.

After adjustment for age, sex, race, comorbidities, hemodynamic status, and other variables, de novo dipstick proteinuria at the time of admission independently predicted AKI with an odds ratio of 2.3 (95% confidence interval, 1.4-3.8), Dr. Neyra reported in a poster at a meeting sponsored by the National Kidney Foundation.

In an interview, Dr. Neyra explained that such information identifies septic patients who would benefit from more careful monitoring of kidney function and hemodynamic stability. In addition, in those patients it would be important to avoid nephrotoxic agents such as aminoglycoside antibiotics and nonsteroidal anti-inflammatory agents, as well as exposure to contrast material unless it was absolutely necessary.

"The dipstick is a test that you already have in your hospital that you can utilize. It’s simple, inexpensive, and it’s already there," he said.

Dr. Neyra stated that he had no relevant financial disclosures.

NATIONAL HARBOR, MD.  – De novo dipstick proteinuria accurately predicted acute kidney injury among 328 critically ill septic patients, a retrospective chart study has shown.

With sepsis, inflammation results in increased capillary permeability to plasma proteins, manifesting in an increased excretion of albumin into the urine. Because the production of creatinine from the muscle is reduced in septic patients, relying on changes in serum creatinine could delay the diagnosis of this acute kidney injury (AKI), according to Dr. Javier Neyra.

Photo courtesy Dr. Javier Neyra

"It is highly important to identify biomarkers that are sensitive, specific, and provide timely and early diagnosis of acute kidney injury before substantial damage has already been done. ... De novo dipstick proteinuria represents a simple, inexpensive biomarker in sepsis with predictive power for AKI," said Dr. Neyra of the Henry Ford Hospital, Detroit.

Charts from a total of 2,252 patients admitted to the intensive care unit for severe sepsis between January 2004 and July 2011 were analyzed retrospectively. Patients with a baseline serum creatinine level greater than 1.5 mg/dL, the presence of dipstick proteinuria within 3 months of the admission date, or common causes of false-positive dipstick tests such as urinary tract infection or gross hematuria were excluded. Of the remaining 470 patients, 328 had undergone dipstick testing on admission. Of those, 46% (152) had dipstick proteinuria.

Serum creatinine increased by at least 0.3 mg/dL in 210 (64%) patients within the first 72 hours of admission, signifying the first stage of acute kidney injury. In this group, new-onset dipstick proteinuria was found in 114 (54%) patients, for a positive predictive value of 75%. Dipstick proteinuria was found in 91 (55%) of 166 patients who met the Acute Kidney Injury Network criteria for AKI, for a positive predictive value of 60%.

After adjustment for age, sex, race, comorbidities, hemodynamic status, and other variables, de novo dipstick proteinuria at the time of admission independently predicted AKI with an odds ratio of 2.3 (95% confidence interval, 1.4-3.8), Dr. Neyra reported in a poster at a meeting sponsored by the National Kidney Foundation.

In an interview, Dr. Neyra explained that such information identifies septic patients who would benefit from more careful monitoring of kidney function and hemodynamic stability. In addition, in those patients it would be important to avoid nephrotoxic agents such as aminoglycoside antibiotics and nonsteroidal anti-inflammatory agents, as well as exposure to contrast material unless it was absolutely necessary.

"The dipstick is a test that you already have in your hospital that you can utilize. It’s simple, inexpensive, and it’s already there," he said.

Dr. Neyra stated that he had no relevant financial disclosures.

ATLANTA – Men in their 40s with a low prostate specific antigen can probably safely delay additional testing for 10-15 years.

Young men with a higher baseline level, however, are twice as likely to develop prostate cancer over the same time period and should probably have their PSA tested at regular intervals, Dr. Christopher Weight said at the annual meeting of the American Urologic Association.

His prospective study of 268 men in their 40s showed that none of the men with a baseline PSA of 1.0 ng/mL or less developed high-risk disease by 10 years and only 3% developed it by 15 years. The findings could provide an effective way to risk-stratify young populations, reducing unnecessary testing and the consequences that sometimes follow it, he said.

"We have to admit that we overdiagnose and overtreat men," Dr. Weight said at a press briefing. "But there is danger in completely throwing out the PSA test. Testing men early can help us identify those who can safely delay additional testing and those who will benefit from more frequent tests."

Dr. Weight, a urology oncology fellow at the Mayo Clinic, Rochester, Minn., turned to the Olmsted County cohort for the study data. Since 1990, most of the residents in the county have received their medical care through the Mayo Clinic and its affiliate centers. A linked health records database provides information for long-term population-based studies.

His analysis included 268 men, all of whom had a baseline PSA drawn sometime during their 40s (median age 45 years). The men also had a transrectal ultrasound and digital rectal exam. They have been followed now for up to 20 years, with a median time of 16 years.

Among the cohort, 192 had a baseline PSA of 1.0 ng/mL or lower and 76 had a level of more than 1.0 ng/mL. There were no significant between-group differences in either family history or the results of the rectal exam.

Over the full follow-up period, men with the lower PSA level had a significantly lower risk of exceeding the age-specific cut points for PSA than did men with the higher levels (10% vs. 50%).

By the end of the follow-up period, there were six incident cases of prostate cancer in the low-PSA group, all of which were low-risk disease. This translated to an incidence rate of 1.6 per 1,000 patient/ years, with a mean of 15 years until diagnosis.

Twice as many men in the high-PSA group developed prostate cancer (12). Of these cases, 10 were low-risk disease and 2 high-risk. This translated into a rate of 8/1,000 patient-years, with a mean of 10 years to diagnosis.

The baseline measurement was fairly predictive of 15-year outcomes, Dr. Weight said. A cutoff of 1.0 ng/mL at the initial test had a sensitivity of 67% and a specificity of 74% for predicting the occurrence of prostate cancer. Changing the cutoff to 0.7 ng/mL on the initial test resulted in a sensitivity of 83% and a specificity of 46%

The results show that this single, early PSA level may be helpful in counseling patients about follow-up, said Dr. Scott Eggener, who moderated the briefing.

"The goals of any test are to identify the cohort of people most likely to benefit, and those people in whom screening can be limited to minimize the potential harms of the test," said Dr. Eggener, director of urology outcomes and translational research at the University of Chicago Medical Center. "If a young man has a very low PSA, we can feel comfortable in recommending that he have another test in several years, somewhat like what’s done with a screening colonoscopy. If the level is higher, this patient probably needs to be followed more frequently."

Neither Dr. Weight nor Dr. Eggener had any financial disclosures.

ATLANTA – Men in their 40s with a low prostate specific antigen can probably safely delay additional testing for 10-15 years.

Young men with a higher baseline level, however, are twice as likely to develop prostate cancer over the same time period and should probably have their PSA tested at regular intervals, Dr. Christopher Weight said at the annual meeting of the American Urologic Association.

His prospective study of 268 men in their 40s showed that none of the men with a baseline PSA of 1.0 ng/mL or less developed high-risk disease by 10 years and only 3% developed it by 15 years. The findings could provide an effective way to risk-stratify young populations, reducing unnecessary testing and the consequences that sometimes follow it, he said.

"We have to admit that we overdiagnose and overtreat men," Dr. Weight said at a press briefing. "But there is danger in completely throwing out the PSA test. Testing men early can help us identify those who can safely delay additional testing and those who will benefit from more frequent tests."

Dr. Weight, a urology oncology fellow at the Mayo Clinic, Rochester, Minn., turned to the Olmsted County cohort for the study data. Since 1990, most of the residents in the county have received their medical care through the Mayo Clinic and its affiliate centers. A linked health records database provides information for long-term population-based studies.

His analysis included 268 men, all of whom had a baseline PSA drawn sometime during their 40s (median age 45 years). The men also had a transrectal ultrasound and digital rectal exam. They have been followed now for up to 20 years, with a median time of 16 years.

Among the cohort, 192 had a baseline PSA of 1.0 ng/mL or lower and 76 had a level of more than 1.0 ng/mL. There were no significant between-group differences in either family history or the results of the rectal exam.

Over the full follow-up period, men with the lower PSA level had a significantly lower risk of exceeding the age-specific cut points for PSA than did men with the higher levels (10% vs. 50%).

By the end of the follow-up period, there were six incident cases of prostate cancer in the low-PSA group, all of which were low-risk disease. This translated to an incidence rate of 1.6 per 1,000 patient/ years, with a mean of 15 years until diagnosis.

Twice as many men in the high-PSA group developed prostate cancer (12). Of these cases, 10 were low-risk disease and 2 high-risk. This translated into a rate of 8/1,000 patient-years, with a mean of 10 years to diagnosis.

The baseline measurement was fairly predictive of 15-year outcomes, Dr. Weight said. A cutoff of 1.0 ng/mL at the initial test had a sensitivity of 67% and a specificity of 74% for predicting the occurrence of prostate cancer. Changing the cutoff to 0.7 ng/mL on the initial test resulted in a sensitivity of 83% and a specificity of 46%

The results show that this single, early PSA level may be helpful in counseling patients about follow-up, said Dr. Scott Eggener, who moderated the briefing.

"The goals of any test are to identify the cohort of people most likely to benefit, and those people in whom screening can be limited to minimize the potential harms of the test," said Dr. Eggener, director of urology outcomes and translational research at the University of Chicago Medical Center. "If a young man has a very low PSA, we can feel comfortable in recommending that he have another test in several years, somewhat like what’s done with a screening colonoscopy. If the level is higher, this patient probably needs to be followed more frequently."

Neither Dr. Weight nor Dr. Eggener had any financial disclosures.

ATLANTA – Men in their 40s with a low prostate specific antigen can probably safely delay additional testing for 10-15 years.

Young men with a higher baseline level, however, are twice as likely to develop prostate cancer over the same time period and should probably have their PSA tested at regular intervals, Dr. Christopher Weight said at the annual meeting of the American Urologic Association.

His prospective study of 268 men in their 40s showed that none of the men with a baseline PSA of 1.0 ng/mL or less developed high-risk disease by 10 years and only 3% developed it by 15 years. The findings could provide an effective way to risk-stratify young populations, reducing unnecessary testing and the consequences that sometimes follow it, he said.

"We have to admit that we overdiagnose and overtreat men," Dr. Weight said at a press briefing. "But there is danger in completely throwing out the PSA test. Testing men early can help us identify those who can safely delay additional testing and those who will benefit from more frequent tests."

Dr. Weight, a urology oncology fellow at the Mayo Clinic, Rochester, Minn., turned to the Olmsted County cohort for the study data. Since 1990, most of the residents in the county have received their medical care through the Mayo Clinic and its affiliate centers. A linked health records database provides information for long-term population-based studies.

His analysis included 268 men, all of whom had a baseline PSA drawn sometime during their 40s (median age 45 years). The men also had a transrectal ultrasound and digital rectal exam. They have been followed now for up to 20 years, with a median time of 16 years.

Among the cohort, 192 had a baseline PSA of 1.0 ng/mL or lower and 76 had a level of more than 1.0 ng/mL. There were no significant between-group differences in either family history or the results of the rectal exam.

Over the full follow-up period, men with the lower PSA level had a significantly lower risk of exceeding the age-specific cut points for PSA than did men with the higher levels (10% vs. 50%).

By the end of the follow-up period, there were six incident cases of prostate cancer in the low-PSA group, all of which were low-risk disease. This translated to an incidence rate of 1.6 per 1,000 patient/ years, with a mean of 15 years until diagnosis.

Twice as many men in the high-PSA group developed prostate cancer (12). Of these cases, 10 were low-risk disease and 2 high-risk. This translated into a rate of 8/1,000 patient-years, with a mean of 10 years to diagnosis.

The baseline measurement was fairly predictive of 15-year outcomes, Dr. Weight said. A cutoff of 1.0 ng/mL at the initial test had a sensitivity of 67% and a specificity of 74% for predicting the occurrence of prostate cancer. Changing the cutoff to 0.7 ng/mL on the initial test resulted in a sensitivity of 83% and a specificity of 46%

The results show that this single, early PSA level may be helpful in counseling patients about follow-up, said Dr. Scott Eggener, who moderated the briefing.

"The goals of any test are to identify the cohort of people most likely to benefit, and those people in whom screening can be limited to minimize the potential harms of the test," said Dr. Eggener, director of urology outcomes and translational research at the University of Chicago Medical Center. "If a young man has a very low PSA, we can feel comfortable in recommending that he have another test in several years, somewhat like what’s done with a screening colonoscopy. If the level is higher, this patient probably needs to be followed more frequently."

Neither Dr. Weight nor Dr. Eggener had any financial disclosures.

"Do not use prostate-specific antigen (PSA)–based screening for prostate cancer."

With these words, the U.S. Preventive Services Task Force (USPSTF) finalized its stance against using this blood test to screen men universally in the United States for prostate cancer.

This firm position is unlikely to end the controversy that ensued after the task force released its draft recommendations in October 2011 ("U.S. Task Force: No PSA Testing for Healthy Men.") Editorials opposing and supporting universal prostate specific antigen (PSA) screening accompany publication early online of the final recommendations in the May 22 issue of Annals of Internal Medicine.

The 16-member task force gave population-based PSA screening a grade D recommendation, after a public comment period yielded no new, overwhelming evidence countering the draft recommendations against universal testing. This means the members believe there is moderate or high certainty that the harms of the intervention are equal to or outweigh the benefits.

"Science shows us the benefit is small and the harms significant," Dr. Virginia A. Moyer, the task force chair, said in an interview.

Fever, blood in the urine, transient urinary difficulties, and moderate-to-severe pain associated with biopsy are potential harms associated with screening cited in the recommendations. Risk for perioperative death, cardiovascular events, urinary incontinence, erectile dysfunction, and bowel dysfunction are some of the harms associated with treatment of prostate cancer.

The recommendation applies to "men in the general U.S. population, regardless of age." The new position replaces the 2008 recommendations, which cited insufficient evidence to support improved health outcomes associated with prostate cancer screening for men younger than 75 years and more conclusive evidence pointing to more harm than benefit for men aged 75 years or older.

The new literature-based recommendations leave room for physicians and patients particularly concerned about risk of prostate cancer to consider individual PSA testing. The USPSTF learned during the public comment period that it needed to emphasize that the recommendations do not preclude such discussions, said Dr. Moyer, professor of pediatrics at Baylor College of Medicine, Houston.

"One of the main things we clarified was ... that this is not a recommendation not to talk to patients about it or not to address the patient’s concerns," she said.

Opponents Step Forward

Coming out against the new recommendations is an ad hoc group of nine oncologists, primary care physicians, and preventive medicine specialists. In an accompanying editorial they argue against curtailment of PSA screening, criticize a lack of specialty physician involvement on the task force, and question the quality of evidence in two large trials heavily weighted in the task force’s decision making: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (N. Engl. J. Med. 2009;360:1310-9) and the European Randomized Study for Prostate Cancer (ERSCP) (N. Engl. J. Med. 2012;366:981-90).

"The most important flaws of the PLCO are the greater than 50% ‘contamination’ rate by nonprotocol PSA measurements in the control group, prescreening of 40% of study participants before enrollment in the trial, and the fact that two thirds of patients with abnormal screening tests did not have prompt biopsy," the ad hoc group wrote.

"The study has a known flaw – that a fair number in the control group got screened – which would tend to make the intervention and control groups look more alike," Dr. Moyer acknowledged.

The task force, however, offset this potential bias with inclusion of the European study, she said. The different methodologies used in the two studies provided balance.

The task force does not include urologists or cancer specialists, the ad hoc group also pointed out.

Dr. Moyer said that these specialty physicians were involved in the evidence report initially developed for review by the task force. The members of the task force have "precisely the expertise needed" to advise these doctors on management of asymptomatic men in the primary care setting, she added.

"We are experts in primary care and prevention, and we advise primary care physicians," Dr. Moyer said.

Dr. Otis Brawley Backs Task Force

Backing the task force’s recommendations is Dr. Otis Brawley, chief medical officer of the American Cancer Society. "What many people, doctors as well as lay people, have not truly appreciated is that there are significant harms associated with prostate cancer screening," he said in an interview. "Those harms are seen consistently in every clinical trial that has been done to assess screening."

Dr. Brawley supports individual PSA screening as long as it follows a thorough and balanced informed consent process. "I and the American Cancer Society hold out that there are some people at high risk and some people who are so concerned about prostate cancer that, if they understand the considerable harms and understand that the possibility of benefit is a possibility and not proven, and they want to be screened ... they should be allowed to get screened."

"Part of the reason the task force came down so hard is because this [informed consent] has not been happening," said Dr. Brawley, professor of hematology and oncology at the Emory Clinic in Atlanta.

Another reason, he said, is that "we have all these mass screening events going on. Not only is there no informed decision-making done and not only is there no information regarding harms, but men are being told screening can only benefit them."

Dr. Brawley outlined these and other considerations in a second editorial that accompanies the recommendations.

Going forward, Dr. Brawley recommends that physicians provide patients with a brief, written handout on prostate cancer that summarizes the task force recommendations, including potential benefits and harms of PSA screening. Patients could review the information prior to seeing their physician and then opt in or opt out of this screening, he said.

The American Cancer Society provides a patient handout on "Testing for Prostate Cancer" online. The USPSTF also is posting guidance for physicians on counseling patients in light of its new recommendations.

Dr. Moyer acknowledged that the issues surrounding PSA screening are emotionally charged. "Change is stunningly hard," she said. Our understanding of cancer dates back to the 1950s or earlier. Our thinking has been that you get one cancer cell in your body and then it’s a march to imminent death. We now recognize that cancer is not a monolithic thing."

Regarding prostate cancer, she added, "For the vast majority of men, it will not affect them in their lifetime."

"Unfortunately, at the moment, the PSA is the only test we have," Dr. Moyer said. "The test itself is not very good. The PSA test is too sensitive – it picks up almost anything that happens to the prostate." She added. "The dream is that a better test is developed."

Dr. Moyer and Dr. Brawley had no relevant financial disclosures.

"Do not use prostate-specific antigen (PSA)–based screening for prostate cancer."

With these words, the U.S. Preventive Services Task Force (USPSTF) finalized its stance against using this blood test to screen men universally in the United States for prostate cancer.

This firm position is unlikely to end the controversy that ensued after the task force released its draft recommendations in October 2011 ("U.S. Task Force: No PSA Testing for Healthy Men.") Editorials opposing and supporting universal prostate specific antigen (PSA) screening accompany publication early online of the final recommendations in the May 22 issue of Annals of Internal Medicine.

The 16-member task force gave population-based PSA screening a grade D recommendation, after a public comment period yielded no new, overwhelming evidence countering the draft recommendations against universal testing. This means the members believe there is moderate or high certainty that the harms of the intervention are equal to or outweigh the benefits.

"Science shows us the benefit is small and the harms significant," Dr. Virginia A. Moyer, the task force chair, said in an interview.

Fever, blood in the urine, transient urinary difficulties, and moderate-to-severe pain associated with biopsy are potential harms associated with screening cited in the recommendations. Risk for perioperative death, cardiovascular events, urinary incontinence, erectile dysfunction, and bowel dysfunction are some of the harms associated with treatment of prostate cancer.

The recommendation applies to "men in the general U.S. population, regardless of age." The new position replaces the 2008 recommendations, which cited insufficient evidence to support improved health outcomes associated with prostate cancer screening for men younger than 75 years and more conclusive evidence pointing to more harm than benefit for men aged 75 years or older.

The new literature-based recommendations leave room for physicians and patients particularly concerned about risk of prostate cancer to consider individual PSA testing. The USPSTF learned during the public comment period that it needed to emphasize that the recommendations do not preclude such discussions, said Dr. Moyer, professor of pediatrics at Baylor College of Medicine, Houston.

"One of the main things we clarified was ... that this is not a recommendation not to talk to patients about it or not to address the patient’s concerns," she said.

Opponents Step Forward

Coming out against the new recommendations is an ad hoc group of nine oncologists, primary care physicians, and preventive medicine specialists. In an accompanying editorial they argue against curtailment of PSA screening, criticize a lack of specialty physician involvement on the task force, and question the quality of evidence in two large trials heavily weighted in the task force’s decision making: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (N. Engl. J. Med. 2009;360:1310-9) and the European Randomized Study for Prostate Cancer (ERSCP) (N. Engl. J. Med. 2012;366:981-90).

"The most important flaws of the PLCO are the greater than 50% ‘contamination’ rate by nonprotocol PSA measurements in the control group, prescreening of 40% of study participants before enrollment in the trial, and the fact that two thirds of patients with abnormal screening tests did not have prompt biopsy," the ad hoc group wrote.

"The study has a known flaw – that a fair number in the control group got screened – which would tend to make the intervention and control groups look more alike," Dr. Moyer acknowledged.

The task force, however, offset this potential bias with inclusion of the European study, she said. The different methodologies used in the two studies provided balance.

The task force does not include urologists or cancer specialists, the ad hoc group also pointed out.

Dr. Moyer said that these specialty physicians were involved in the evidence report initially developed for review by the task force. The members of the task force have "precisely the expertise needed" to advise these doctors on management of asymptomatic men in the primary care setting, she added.

"We are experts in primary care and prevention, and we advise primary care physicians," Dr. Moyer said.

Dr. Otis Brawley Backs Task Force

Backing the task force’s recommendations is Dr. Otis Brawley, chief medical officer of the American Cancer Society. "What many people, doctors as well as lay people, have not truly appreciated is that there are significant harms associated with prostate cancer screening," he said in an interview. "Those harms are seen consistently in every clinical trial that has been done to assess screening."

Dr. Brawley supports individual PSA screening as long as it follows a thorough and balanced informed consent process. "I and the American Cancer Society hold out that there are some people at high risk and some people who are so concerned about prostate cancer that, if they understand the considerable harms and understand that the possibility of benefit is a possibility and not proven, and they want to be screened ... they should be allowed to get screened."

"Part of the reason the task force came down so hard is because this [informed consent] has not been happening," said Dr. Brawley, professor of hematology and oncology at the Emory Clinic in Atlanta.

Another reason, he said, is that "we have all these mass screening events going on. Not only is there no informed decision-making done and not only is there no information regarding harms, but men are being told screening can only benefit them."

Dr. Brawley outlined these and other considerations in a second editorial that accompanies the recommendations.

Going forward, Dr. Brawley recommends that physicians provide patients with a brief, written handout on prostate cancer that summarizes the task force recommendations, including potential benefits and harms of PSA screening. Patients could review the information prior to seeing their physician and then opt in or opt out of this screening, he said.

The American Cancer Society provides a patient handout on "Testing for Prostate Cancer" online. The USPSTF also is posting guidance for physicians on counseling patients in light of its new recommendations.

Dr. Moyer acknowledged that the issues surrounding PSA screening are emotionally charged. "Change is stunningly hard," she said. Our understanding of cancer dates back to the 1950s or earlier. Our thinking has been that you get one cancer cell in your body and then it’s a march to imminent death. We now recognize that cancer is not a monolithic thing."

Regarding prostate cancer, she added, "For the vast majority of men, it will not affect them in their lifetime."

"Unfortunately, at the moment, the PSA is the only test we have," Dr. Moyer said. "The test itself is not very good. The PSA test is too sensitive – it picks up almost anything that happens to the prostate." She added. "The dream is that a better test is developed."

Dr. Moyer and Dr. Brawley had no relevant financial disclosures.

"Do not use prostate-specific antigen (PSA)–based screening for prostate cancer."

With these words, the U.S. Preventive Services Task Force (USPSTF) finalized its stance against using this blood test to screen men universally in the United States for prostate cancer.

This firm position is unlikely to end the controversy that ensued after the task force released its draft recommendations in October 2011 ("U.S. Task Force: No PSA Testing for Healthy Men.") Editorials opposing and supporting universal prostate specific antigen (PSA) screening accompany publication early online of the final recommendations in the May 22 issue of Annals of Internal Medicine.

The 16-member task force gave population-based PSA screening a grade D recommendation, after a public comment period yielded no new, overwhelming evidence countering the draft recommendations against universal testing. This means the members believe there is moderate or high certainty that the harms of the intervention are equal to or outweigh the benefits.

"Science shows us the benefit is small and the harms significant," Dr. Virginia A. Moyer, the task force chair, said in an interview.

Fever, blood in the urine, transient urinary difficulties, and moderate-to-severe pain associated with biopsy are potential harms associated with screening cited in the recommendations. Risk for perioperative death, cardiovascular events, urinary incontinence, erectile dysfunction, and bowel dysfunction are some of the harms associated with treatment of prostate cancer.

The recommendation applies to "men in the general U.S. population, regardless of age." The new position replaces the 2008 recommendations, which cited insufficient evidence to support improved health outcomes associated with prostate cancer screening for men younger than 75 years and more conclusive evidence pointing to more harm than benefit for men aged 75 years or older.

The new literature-based recommendations leave room for physicians and patients particularly concerned about risk of prostate cancer to consider individual PSA testing. The USPSTF learned during the public comment period that it needed to emphasize that the recommendations do not preclude such discussions, said Dr. Moyer, professor of pediatrics at Baylor College of Medicine, Houston.

"One of the main things we clarified was ... that this is not a recommendation not to talk to patients about it or not to address the patient’s concerns," she said.

Opponents Step Forward

Coming out against the new recommendations is an ad hoc group of nine oncologists, primary care physicians, and preventive medicine specialists. In an accompanying editorial they argue against curtailment of PSA screening, criticize a lack of specialty physician involvement on the task force, and question the quality of evidence in two large trials heavily weighted in the task force’s decision making: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (N. Engl. J. Med. 2009;360:1310-9) and the European Randomized Study for Prostate Cancer (ERSCP) (N. Engl. J. Med. 2012;366:981-90).

"The most important flaws of the PLCO are the greater than 50% ‘contamination’ rate by nonprotocol PSA measurements in the control group, prescreening of 40% of study participants before enrollment in the trial, and the fact that two thirds of patients with abnormal screening tests did not have prompt biopsy," the ad hoc group wrote.

"The study has a known flaw – that a fair number in the control group got screened – which would tend to make the intervention and control groups look more alike," Dr. Moyer acknowledged.

The task force, however, offset this potential bias with inclusion of the European study, she said. The different methodologies used in the two studies provided balance.

The task force does not include urologists or cancer specialists, the ad hoc group also pointed out.

Dr. Moyer said that these specialty physicians were involved in the evidence report initially developed for review by the task force. The members of the task force have "precisely the expertise needed" to advise these doctors on management of asymptomatic men in the primary care setting, she added.

"We are experts in primary care and prevention, and we advise primary care physicians," Dr. Moyer said.

Dr. Otis Brawley Backs Task Force

Backing the task force’s recommendations is Dr. Otis Brawley, chief medical officer of the American Cancer Society. "What many people, doctors as well as lay people, have not truly appreciated is that there are significant harms associated with prostate cancer screening," he said in an interview. "Those harms are seen consistently in every clinical trial that has been done to assess screening."

Dr. Brawley supports individual PSA screening as long as it follows a thorough and balanced informed consent process. "I and the American Cancer Society hold out that there are some people at high risk and some people who are so concerned about prostate cancer that, if they understand the considerable harms and understand that the possibility of benefit is a possibility and not proven, and they want to be screened ... they should be allowed to get screened."

"Part of the reason the task force came down so hard is because this [informed consent] has not been happening," said Dr. Brawley, professor of hematology and oncology at the Emory Clinic in Atlanta.

Another reason, he said, is that "we have all these mass screening events going on. Not only is there no informed decision-making done and not only is there no information regarding harms, but men are being told screening can only benefit them."

Dr. Brawley outlined these and other considerations in a second editorial that accompanies the recommendations.

Going forward, Dr. Brawley recommends that physicians provide patients with a brief, written handout on prostate cancer that summarizes the task force recommendations, including potential benefits and harms of PSA screening. Patients could review the information prior to seeing their physician and then opt in or opt out of this screening, he said.

The American Cancer Society provides a patient handout on "Testing for Prostate Cancer" online. The USPSTF also is posting guidance for physicians on counseling patients in light of its new recommendations.

Dr. Moyer acknowledged that the issues surrounding PSA screening are emotionally charged. "Change is stunningly hard," she said. Our understanding of cancer dates back to the 1950s or earlier. Our thinking has been that you get one cancer cell in your body and then it’s a march to imminent death. We now recognize that cancer is not a monolithic thing."

Regarding prostate cancer, she added, "For the vast majority of men, it will not affect them in their lifetime."

"Unfortunately, at the moment, the PSA is the only test we have," Dr. Moyer said. "The test itself is not very good. The PSA test is too sensitive – it picks up almost anything that happens to the prostate." She added. "The dream is that a better test is developed."

Dr. Moyer and Dr. Brawley had no relevant financial disclosures.

After initially turning it down – and being pressured to reevaluate by the U.K. Department of Health – the clinical effectiveness agency for England and Wales has decided to recommend abiraterone, in combination with glucocorticoids, as a second-line treatment for metastatic prostate cancer.

The National Institute for Health and Clinical Excellence announced on May 16 that its new draft guidance recommending abiraterone (Zytiga, Janssen) for castration-resistant prostate cancer came in response to both a new manufacturer pricing agreement and additional information on how many patients were likely to be eligible for treatment.

In February, NICE had deemed abiraterone, which has been shown to prolong survival by a median 4.6 months, not cost-effective at an estimated £63,200 per quality-adjusted life year.

The following month, the U.K. Department of Health asked NICE to reevaluate its decision with regard to its estimates of the number of men eligible to be treated with abiraterone. NICE evaluates differently end-of-life treatments for patients with a life expectancy of less than 2 years, depending on the size of the population affected.

A revised pricing scheme in addition to revised estimates of the population eligible for abiraterone treatment lowered NICE’s estimates to £46,800 per QALY, just under its threshold for an end-of-life treatment in a small population.

Abiraterone works by blocking androgen synthesis in the adrenal glands, prostate tissue, and prostate tumors. It is indicated for men whose disease has progressed following docetaxel-containing chemotherapy regimens, and who have been deemed "castration resistant" because their tumors do not respond to androgen-deprivation treatments that may or may not include surgical castration.

The list price of abiraterone is £2,930 for a 30-day supply of 120 tablets; NICE did not disclose the new discounted price. It is taken as a single dose of 1,000 mg daily, in four tablets. In a manufacturer-sponsored randomized controlled trial (n = 1,195), subjects receiving abiraterone plus prednisone or prednisolone saw a median overall survival gain of 14.8 months compared with 10.9 months for those taking placebo plus either prednisone or prednisolone after 1 year follow-up (HR 0.65; 95% confidence interval, 0.54-0.77; P less than .001).

The trial (N. Engl. J. Med. 2011;364:1995-2005) was stopped due to significant evidence of benefit, but follow-up continued, and an updated analysis after 20.2 months showed that median survival continued to be significantly longer in the abiraterone group than the prednisolone group (15.8 months compared with 11.2 months; HR 0.74; 95% CI 0.64 to 0.86).

In its earlier draft guidance NICE had estimated the number of men eligible for second-line treatment with abiraterone to be at least 3,500 in 2011. The revised estimate suggests that only 2,500 would have been eligible – a small population, by NICE’s calculations, and therefore meeting its cost-effectiveness criteria for an end-of-life treatment.

After initially turning it down – and being pressured to reevaluate by the U.K. Department of Health – the clinical effectiveness agency for England and Wales has decided to recommend abiraterone, in combination with glucocorticoids, as a second-line treatment for metastatic prostate cancer.

The National Institute for Health and Clinical Excellence announced on May 16 that its new draft guidance recommending abiraterone (Zytiga, Janssen) for castration-resistant prostate cancer came in response to both a new manufacturer pricing agreement and additional information on how many patients were likely to be eligible for treatment.

In February, NICE had deemed abiraterone, which has been shown to prolong survival by a median 4.6 months, not cost-effective at an estimated £63,200 per quality-adjusted life year.

The following month, the U.K. Department of Health asked NICE to reevaluate its decision with regard to its estimates of the number of men eligible to be treated with abiraterone. NICE evaluates differently end-of-life treatments for patients with a life expectancy of less than 2 years, depending on the size of the population affected.

A revised pricing scheme in addition to revised estimates of the population eligible for abiraterone treatment lowered NICE’s estimates to £46,800 per QALY, just under its threshold for an end-of-life treatment in a small population.

Abiraterone works by blocking androgen synthesis in the adrenal glands, prostate tissue, and prostate tumors. It is indicated for men whose disease has progressed following docetaxel-containing chemotherapy regimens, and who have been deemed "castration resistant" because their tumors do not respond to androgen-deprivation treatments that may or may not include surgical castration.

The list price of abiraterone is £2,930 for a 30-day supply of 120 tablets; NICE did not disclose the new discounted price. It is taken as a single dose of 1,000 mg daily, in four tablets. In a manufacturer-sponsored randomized controlled trial (n = 1,195), subjects receiving abiraterone plus prednisone or prednisolone saw a median overall survival gain of 14.8 months compared with 10.9 months for those taking placebo plus either prednisone or prednisolone after 1 year follow-up (HR 0.65; 95% confidence interval, 0.54-0.77; P less than .001).

The trial (N. Engl. J. Med. 2011;364:1995-2005) was stopped due to significant evidence of benefit, but follow-up continued, and an updated analysis after 20.2 months showed that median survival continued to be significantly longer in the abiraterone group than the prednisolone group (15.8 months compared with 11.2 months; HR 0.74; 95% CI 0.64 to 0.86).

In its earlier draft guidance NICE had estimated the number of men eligible for second-line treatment with abiraterone to be at least 3,500 in 2011. The revised estimate suggests that only 2,500 would have been eligible – a small population, by NICE’s calculations, and therefore meeting its cost-effectiveness criteria for an end-of-life treatment.

After initially turning it down – and being pressured to reevaluate by the U.K. Department of Health – the clinical effectiveness agency for England and Wales has decided to recommend abiraterone, in combination with glucocorticoids, as a second-line treatment for metastatic prostate cancer.

The National Institute for Health and Clinical Excellence announced on May 16 that its new draft guidance recommending abiraterone (Zytiga, Janssen) for castration-resistant prostate cancer came in response to both a new manufacturer pricing agreement and additional information on how many patients were likely to be eligible for treatment.

In February, NICE had deemed abiraterone, which has been shown to prolong survival by a median 4.6 months, not cost-effective at an estimated £63,200 per quality-adjusted life year.

The following month, the U.K. Department of Health asked NICE to reevaluate its decision with regard to its estimates of the number of men eligible to be treated with abiraterone. NICE evaluates differently end-of-life treatments for patients with a life expectancy of less than 2 years, depending on the size of the population affected.

A revised pricing scheme in addition to revised estimates of the population eligible for abiraterone treatment lowered NICE’s estimates to £46,800 per QALY, just under its threshold for an end-of-life treatment in a small population.

Abiraterone works by blocking androgen synthesis in the adrenal glands, prostate tissue, and prostate tumors. It is indicated for men whose disease has progressed following docetaxel-containing chemotherapy regimens, and who have been deemed "castration resistant" because their tumors do not respond to androgen-deprivation treatments that may or may not include surgical castration.

The list price of abiraterone is £2,930 for a 30-day supply of 120 tablets; NICE did not disclose the new discounted price. It is taken as a single dose of 1,000 mg daily, in four tablets. In a manufacturer-sponsored randomized controlled trial (n = 1,195), subjects receiving abiraterone plus prednisone or prednisolone saw a median overall survival gain of 14.8 months compared with 10.9 months for those taking placebo plus either prednisone or prednisolone after 1 year follow-up (HR 0.65; 95% confidence interval, 0.54-0.77; P less than .001).

The trial (N. Engl. J. Med. 2011;364:1995-2005) was stopped due to significant evidence of benefit, but follow-up continued, and an updated analysis after 20.2 months showed that median survival continued to be significantly longer in the abiraterone group than the prednisolone group (15.8 months compared with 11.2 months; HR 0.74; 95% CI 0.64 to 0.86).

In its earlier draft guidance NICE had estimated the number of men eligible for second-line treatment with abiraterone to be at least 3,500 in 2011. The revised estimate suggests that only 2,500 would have been eligible – a small population, by NICE’s calculations, and therefore meeting its cost-effectiveness criteria for an end-of-life treatment.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

SAN DIEGO – Terlipressin, widely used in Europe for hepatorenal syndrome but not yet approved in the United States, would be a useful option for this difficult-to-treat condition, said transplant hepatologist Dr. James Burton at the annual meeting of the Society of Hospital Medicine.

Currently, U.S. clinicians do their best with albumin and vasoconstrictors such as octreotide and midodrine to counteract the intense splanchnic vasodilatation that causes the condition (J. Clin. Gastroenterol. 2009;43:680-5).

Hepatorenal syndrome is a complication of advanced cirrhosis that can lead to renal failure. Liver transplantation is "the only treatment we currently have available to us that is very effective," especially for rapidly progressing type 1 HRS [hepatorenal syndrome]," said Dr. Burton, associate professor of medicine and the medical director of liver transplantation at the University of Colorado Hospital, Aurora.

The European vasopressin analogue terlipressin (Lucassin) has a long half-life that allows for bolus dosing every 4-6 hours. Several studies found evidence that the drug might be beneficial.

In one study, 56 patients with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) plus albumin. Another 56 patients received placebo plus albumin.

Serum creatinine level decreased to 1.5 mg/dL or less in 14 (25%) terlipressin patients, but in only 7 (12.5%) placebo patients by day 14. This difference was not statistically significant, however. The two groups had similar adverse event rates (Gastroenterology 2008;134:1360-8).

A significant benefit was found in a randomized study of 46 patients. Serum creatinine fell below 1.5 mg/dL or decreased 50% from baseline in 10 (43.5%) patients treated with albumin and terlipressin (1-2 mg/4 hours), vs. 2 (8.7%) patients treated with albumin alone (P = .017). Ten terlipressin patients and four albumin-only patients had cardiovascular complications (Gastroenterology 2008;134:1352-9).

In a third study, which was also randomized, 24 HRS patients received albumin and terlipressin (3 mg/24 hours with escalation based on response) and 17 received standard U.S. treatment – albumin plus midodrine and octreotide, also escalated according to response.

Serum creatinine in that study fell below 1.5 mg/dL in 13 (54%) terlipressin patients and renal function improved in three-quarters. Creatinine fell below 1.5 mg/dL in just 2 (12%) of the standard-treatment patients, and renal function improved in about a third (Angeli et al. The Liver Meeting 2011, American Association for the Study of Liver Diseases).

However, in all three studies, people didn’t live any longer when they were given terlipressin, and this is what is holding up FDA approval, said Dr. Burton, who noted that he and his colleagues are working on a new study "to try to show a survival benefit" for the drug.

He said he hopes the FDA approves terlipressin "because it will be a very effective treatment for hepatorenal syndrome. It would be amazing and wonderful if I could prevent people from going on dialysis" as they wait for a new liver.

Dr. Burton said he has no relevant financial disclosures.

SAN DIEGO – Terlipressin, widely used in Europe for hepatorenal syndrome but not yet approved in the United States, would be a useful option for this difficult-to-treat condition, said transplant hepatologist Dr. James Burton at the annual meeting of the Society of Hospital Medicine.

Currently, U.S. clinicians do their best with albumin and vasoconstrictors such as octreotide and midodrine to counteract the intense splanchnic vasodilatation that causes the condition (J. Clin. Gastroenterol. 2009;43:680-5).

Hepatorenal syndrome is a complication of advanced cirrhosis that can lead to renal failure. Liver transplantation is "the only treatment we currently have available to us that is very effective," especially for rapidly progressing type 1 HRS [hepatorenal syndrome]," said Dr. Burton, associate professor of medicine and the medical director of liver transplantation at the University of Colorado Hospital, Aurora.

The European vasopressin analogue terlipressin (Lucassin) has a long half-life that allows for bolus dosing every 4-6 hours. Several studies found evidence that the drug might be beneficial.

In one study, 56 patients with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) plus albumin. Another 56 patients received placebo plus albumin.

Serum creatinine level decreased to 1.5 mg/dL or less in 14 (25%) terlipressin patients, but in only 7 (12.5%) placebo patients by day 14. This difference was not statistically significant, however. The two groups had similar adverse event rates (Gastroenterology 2008;134:1360-8).

A significant benefit was found in a randomized study of 46 patients. Serum creatinine fell below 1.5 mg/dL or decreased 50% from baseline in 10 (43.5%) patients treated with albumin and terlipressin (1-2 mg/4 hours), vs. 2 (8.7%) patients treated with albumin alone (P = .017). Ten terlipressin patients and four albumin-only patients had cardiovascular complications (Gastroenterology 2008;134:1352-9).

In a third study, which was also randomized, 24 HRS patients received albumin and terlipressin (3 mg/24 hours with escalation based on response) and 17 received standard U.S. treatment – albumin plus midodrine and octreotide, also escalated according to response.

Serum creatinine in that study fell below 1.5 mg/dL in 13 (54%) terlipressin patients and renal function improved in three-quarters. Creatinine fell below 1.5 mg/dL in just 2 (12%) of the standard-treatment patients, and renal function improved in about a third (Angeli et al. The Liver Meeting 2011, American Association for the Study of Liver Diseases).

However, in all three studies, people didn’t live any longer when they were given terlipressin, and this is what is holding up FDA approval, said Dr. Burton, who noted that he and his colleagues are working on a new study "to try to show a survival benefit" for the drug.

He said he hopes the FDA approves terlipressin "because it will be a very effective treatment for hepatorenal syndrome. It would be amazing and wonderful if I could prevent people from going on dialysis" as they wait for a new liver.

Dr. Burton said he has no relevant financial disclosures.

SAN DIEGO – Terlipressin, widely used in Europe for hepatorenal syndrome but not yet approved in the United States, would be a useful option for this difficult-to-treat condition, said transplant hepatologist Dr. James Burton at the annual meeting of the Society of Hospital Medicine.

Currently, U.S. clinicians do their best with albumin and vasoconstrictors such as octreotide and midodrine to counteract the intense splanchnic vasodilatation that causes the condition (J. Clin. Gastroenterol. 2009;43:680-5).

Hepatorenal syndrome is a complication of advanced cirrhosis that can lead to renal failure. Liver transplantation is "the only treatment we currently have available to us that is very effective," especially for rapidly progressing type 1 HRS [hepatorenal syndrome]," said Dr. Burton, associate professor of medicine and the medical director of liver transplantation at the University of Colorado Hospital, Aurora.

The European vasopressin analogue terlipressin (Lucassin) has a long half-life that allows for bolus dosing every 4-6 hours. Several studies found evidence that the drug might be beneficial.

In one study, 56 patients with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) plus albumin. Another 56 patients received placebo plus albumin.

Serum creatinine level decreased to 1.5 mg/dL or less in 14 (25%) terlipressin patients, but in only 7 (12.5%) placebo patients by day 14. This difference was not statistically significant, however. The two groups had similar adverse event rates (Gastroenterology 2008;134:1360-8).

A significant benefit was found in a randomized study of 46 patients. Serum creatinine fell below 1.5 mg/dL or decreased 50% from baseline in 10 (43.5%) patients treated with albumin and terlipressin (1-2 mg/4 hours), vs. 2 (8.7%) patients treated with albumin alone (P = .017). Ten terlipressin patients and four albumin-only patients had cardiovascular complications (Gastroenterology 2008;134:1352-9).

In a third study, which was also randomized, 24 HRS patients received albumin and terlipressin (3 mg/24 hours with escalation based on response) and 17 received standard U.S. treatment – albumin plus midodrine and octreotide, also escalated according to response.

Serum creatinine in that study fell below 1.5 mg/dL in 13 (54%) terlipressin patients and renal function improved in three-quarters. Creatinine fell below 1.5 mg/dL in just 2 (12%) of the standard-treatment patients, and renal function improved in about a third (Angeli et al. The Liver Meeting 2011, American Association for the Study of Liver Diseases).

However, in all three studies, people didn’t live any longer when they were given terlipressin, and this is what is holding up FDA approval, said Dr. Burton, who noted that he and his colleagues are working on a new study "to try to show a survival benefit" for the drug.

He said he hopes the FDA approves terlipressin "because it will be a very effective treatment for hepatorenal syndrome. It would be amazing and wonderful if I could prevent people from going on dialysis" as they wait for a new liver.

Dr. Burton said he has no relevant financial disclosures.

Q: I work as a hospitalist PA in a large teaching hospital. In our ICU we had a patient diagnosed with acute kidney injury after a coronary artery bypass graft. We consulted nephrology and they decided to start dialysis. There was quite a discussion about whether to use hemodialysis every other day or continuous renal replacement therapy. What is the basis for this question? Is there science behind the answer, or is it determined by nephrologist preference? 

The development of intermittent hemodialysis (IHD) revolutionized the care of patients with acute renal failure and allowed the medical establishment means to give these patients a chance to recover from their illness. However, IHD had (and continues to have) many downsides, and mortality in acute renal failure remains high. Thus, there is an ongoing search for the best renal replacement therapy; this search led to modern continuous therapies. Three main questions have arisen from this:

• Which Modality is Best?
• What is the optimal dose for dialysis?
• When should we initiate therapy? 

Continue reading for the answers... 

Which Modality is Best? IHD is a shorter treatment (2 to 4 hours), typically performed three times per week but as often as daily. Fluid and electrolyte clearance is rapid, making IHD very efficient but increasing the risk for complications, such as hemodynamic instability. Furthermore, the abrupt fluid and electrolyte shifts associated with IHD do not mimic native kidney function. Providing slower treatments delivered continuously over 24 hours has many benefits.

Continuous renal replacement therapy (CRRT) provides clearance of large amounts of fluid and electrolytes over 24 hours, with minimal hemodynamic disturbances. This allows for more gradual shifts in volume and electrolyte levels, reducing the potential for ischemic damage to the kidney and other organs. Also, CRRT more closely replicates normal renal function than IHD.

CRRT is now extremely safe and efficient, although it has been difficult to prove its superiority to IHD in regard to mortality. While there may be no actual benefit to CRRT, it is also likely that its benefit is observed only in certain subsets of patients with renal failure. For example, we do have compelling evidence of increased intracranial pressure during IHD; CRRT is much safer for patients at risk for this development.¹ It is also possible that we need to further improve CRRT systems and delivery in order to see a benefit.

Because current data favor neither CRRT nor IHD, most experts recommend choosing a therapy based on patient characteristics. For instance, hemodynamically unstable patients commonly receive generous amounts of fluid daily (antibiotics, nutrition, etc), and thus are often better suited for CRRT because it is more likely to remove higher volumes of fluid successfully, and less likely to contribute to hemodynamic instability than IHD. Conversely, patients with acute electrolyte deviations may benefit more from the rapid electrolyte removal IHD provides.

Additionally, stable patients may be more suitable candidates for IHD because of location (CRRT requires intensive care monitoring) and other variables.^2,3 Results from multiple studies have suggested that CRRT may also provide renal protection and consequently improve renal recovery. However, this evidence is not conclusive; the possibility needs further evaluation.¹

Continue reading for the optimal dose for dialysis...

What is the optimal dose for dialysis? This question, too, is plagued by inconclusive research findings. Paganini was the first to raise it formally in patients with acute renal failure; his research team found improved survival with higher doses, but had excluded the sickest and healthiest patients (according to probability of survival) from the study.⁴ This was followed by two additional studies with results that also seemed to support higher doses.^1,5

Then in 2008, in a a similar randomized controlled trial, Tolwani et al⁶ found no survival benefit with higher versus lower dosing; participants in this study were not excluded based on severity of illness. Also, Tolwani’s research team identified failure to achieve prescribed doses as one factor complicating dose comparison.⁶

Finally, two large randomized controlled trials were performed to evaluate dosage, one in the US⁷ and one in Australia and New Zealand.⁸ Neither research team was able to confirm survival benefits with higher-dose renal replacement therapy, and there were inconsistencies between doses used in the study and standard practice in the US. In fact, the low-dose group received dialysis exceeding what is current practice by more than 30%.

The current prevailing opinion is that we should reach a minimum dose: a Kt/V of 1.2, three times a week, for IHD; or a CRRT dose of 20 mL/kg/h. At this time, higher doses do not confer a clear survival benefit. It remains unknown whether certain patients may benefit from a higher dose. Further research is needed.

Continue reading to find out when to initiate therapy...

When should we initiate therapy? While some study results suggest that early initiation is better, this remains unconfirmed.¹ In theory, renal replacement therapy should be initiated early because it improves metabolic control and corrects fluid overload, facilitating management of hemodynamics and ventilation, and reducing the potential for complications caused by uremia-induced physiologic dysfunction. However, it is still unknown which patients would benefit most from early initiation, and the appropriate triggers for when to initiate therapy remain unclear.

So, how do you choose a renal replacement therapy? This is often a matter of opinion, based on evaluation of risks and benefits specific to the patient and clinical expertise with the renal replacement therapies available.

Patient safety must be a primary consideration. IHD and CRRT have dramatically improved in safety and efficacy, but it must yet be proven beyond a doubt which is superior. Outcomes may depend on how the chosen therapy is used to treat specific patient needs—not which therapy is chosen. Further research is needed to identify the best and safest way to provide renal replacement therapy.
Catherine Wells, DNP, ACNP-BC, CNN-NP, Division of Nephrology, University of Mississippi, Jackson

Continue for references...

REFERENCES
1. Prowle JR, Bellomo R. Continuous renal replacement therapy: recent advances and future research. Nat Rev Nephrol. 2010;6(9):521-529.

2. Abi Antoun T, Palevsky PM. Selection of modality of renal replacement therapy. Semin Dial. 2009; 22(2):108-113.

3. Vanholder R, Van Biesen W, Lameire N. What is the renal replacement method of choice for intensive care patients? J Am Soc Nephrol. 2001;12 suppl 17:S40-S43.

4. Augustine JJ, Sandy D, Seifert TH, Paganini EP. A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kidney Dis. 2004;44(6):1000-1007.

5. Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356(9223):26-30.

6. Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008;19(6):1233-1238.

7. Palevsky PM, Zhang JH, O’Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7-20.

8. Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1683.

Q: I work as a hospitalist PA in a large teaching hospital. In our ICU we had a patient diagnosed with acute kidney injury after a coronary artery bypass graft. We consulted nephrology and they decided to start dialysis. There was quite a discussion about whether to use hemodialysis every other day or continuous renal replacement therapy. What is the basis for this question? Is there science behind the answer, or is it determined by nephrologist preference? 

The development of intermittent hemodialysis (IHD) revolutionized the care of patients with acute renal failure and allowed the medical establishment means to give these patients a chance to recover from their illness. However, IHD had (and continues to have) many downsides, and mortality in acute renal failure remains high. Thus, there is an ongoing search for the best renal replacement therapy; this search led to modern continuous therapies. Three main questions have arisen from this:

• Which Modality is Best?
• What is the optimal dose for dialysis?
• When should we initiate therapy? 

Continue reading for the answers... 

Which Modality is Best? IHD is a shorter treatment (2 to 4 hours), typically performed three times per week but as often as daily. Fluid and electrolyte clearance is rapid, making IHD very efficient but increasing the risk for complications, such as hemodynamic instability. Furthermore, the abrupt fluid and electrolyte shifts associated with IHD do not mimic native kidney function. Providing slower treatments delivered continuously over 24 hours has many benefits.

Continuous renal replacement therapy (CRRT) provides clearance of large amounts of fluid and electrolytes over 24 hours, with minimal hemodynamic disturbances. This allows for more gradual shifts in volume and electrolyte levels, reducing the potential for ischemic damage to the kidney and other organs. Also, CRRT more closely replicates normal renal function than IHD.

CRRT is now extremely safe and efficient, although it has been difficult to prove its superiority to IHD in regard to mortality. While there may be no actual benefit to CRRT, it is also likely that its benefit is observed only in certain subsets of patients with renal failure. For example, we do have compelling evidence of increased intracranial pressure during IHD; CRRT is much safer for patients at risk for this development.¹ It is also possible that we need to further improve CRRT systems and delivery in order to see a benefit.

Because current data favor neither CRRT nor IHD, most experts recommend choosing a therapy based on patient characteristics. For instance, hemodynamically unstable patients commonly receive generous amounts of fluid daily (antibiotics, nutrition, etc), and thus are often better suited for CRRT because it is more likely to remove higher volumes of fluid successfully, and less likely to contribute to hemodynamic instability than IHD. Conversely, patients with acute electrolyte deviations may benefit more from the rapid electrolyte removal IHD provides.

Additionally, stable patients may be more suitable candidates for IHD because of location (CRRT requires intensive care monitoring) and other variables.^2,3 Results from multiple studies have suggested that CRRT may also provide renal protection and consequently improve renal recovery. However, this evidence is not conclusive; the possibility needs further evaluation.¹

Continue reading for the optimal dose for dialysis...

What is the optimal dose for dialysis? This question, too, is plagued by inconclusive research findings. Paganini was the first to raise it formally in patients with acute renal failure; his research team found improved survival with higher doses, but had excluded the sickest and healthiest patients (according to probability of survival) from the study.⁴ This was followed by two additional studies with results that also seemed to support higher doses.^1,5

Then in 2008, in a a similar randomized controlled trial, Tolwani et al⁶ found no survival benefit with higher versus lower dosing; participants in this study were not excluded based on severity of illness. Also, Tolwani’s research team identified failure to achieve prescribed doses as one factor complicating dose comparison.⁶

Finally, two large randomized controlled trials were performed to evaluate dosage, one in the US⁷ and one in Australia and New Zealand.⁸ Neither research team was able to confirm survival benefits with higher-dose renal replacement therapy, and there were inconsistencies between doses used in the study and standard practice in the US. In fact, the low-dose group received dialysis exceeding what is current practice by more than 30%.

The current prevailing opinion is that we should reach a minimum dose: a Kt/V of 1.2, three times a week, for IHD; or a CRRT dose of 20 mL/kg/h. At this time, higher doses do not confer a clear survival benefit. It remains unknown whether certain patients may benefit from a higher dose. Further research is needed.

Continue reading to find out when to initiate therapy...

When should we initiate therapy? While some study results suggest that early initiation is better, this remains unconfirmed.¹ In theory, renal replacement therapy should be initiated early because it improves metabolic control and corrects fluid overload, facilitating management of hemodynamics and ventilation, and reducing the potential for complications caused by uremia-induced physiologic dysfunction. However, it is still unknown which patients would benefit most from early initiation, and the appropriate triggers for when to initiate therapy remain unclear.

So, how do you choose a renal replacement therapy? This is often a matter of opinion, based on evaluation of risks and benefits specific to the patient and clinical expertise with the renal replacement therapies available.

Patient safety must be a primary consideration. IHD and CRRT have dramatically improved in safety and efficacy, but it must yet be proven beyond a doubt which is superior. Outcomes may depend on how the chosen therapy is used to treat specific patient needs—not which therapy is chosen. Further research is needed to identify the best and safest way to provide renal replacement therapy.
Catherine Wells, DNP, ACNP-BC, CNN-NP, Division of Nephrology, University of Mississippi, Jackson

Continue for references...

REFERENCES
1. Prowle JR, Bellomo R. Continuous renal replacement therapy: recent advances and future research. Nat Rev Nephrol. 2010;6(9):521-529.

2. Abi Antoun T, Palevsky PM. Selection of modality of renal replacement therapy. Semin Dial. 2009; 22(2):108-113.

3. Vanholder R, Van Biesen W, Lameire N. What is the renal replacement method of choice for intensive care patients? J Am Soc Nephrol. 2001;12 suppl 17:S40-S43.

4. Augustine JJ, Sandy D, Seifert TH, Paganini EP. A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kidney Dis. 2004;44(6):1000-1007.

5. Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356(9223):26-30.

6. Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008;19(6):1233-1238.

7. Palevsky PM, Zhang JH, O’Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7-20.

8. Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1683.

Q: I work as a hospitalist PA in a large teaching hospital. In our ICU we had a patient diagnosed with acute kidney injury after a coronary artery bypass graft. We consulted nephrology and they decided to start dialysis. There was quite a discussion about whether to use hemodialysis every other day or continuous renal replacement therapy. What is the basis for this question? Is there science behind the answer, or is it determined by nephrologist preference? 

The development of intermittent hemodialysis (IHD) revolutionized the care of patients with acute renal failure and allowed the medical establishment means to give these patients a chance to recover from their illness. However, IHD had (and continues to have) many downsides, and mortality in acute renal failure remains high. Thus, there is an ongoing search for the best renal replacement therapy; this search led to modern continuous therapies. Three main questions have arisen from this:

• Which Modality is Best?
• What is the optimal dose for dialysis?
• When should we initiate therapy? 

Continue reading for the answers... 

Which Modality is Best? IHD is a shorter treatment (2 to 4 hours), typically performed three times per week but as often as daily. Fluid and electrolyte clearance is rapid, making IHD very efficient but increasing the risk for complications, such as hemodynamic instability. Furthermore, the abrupt fluid and electrolyte shifts associated with IHD do not mimic native kidney function. Providing slower treatments delivered continuously over 24 hours has many benefits.

Continuous renal replacement therapy (CRRT) provides clearance of large amounts of fluid and electrolytes over 24 hours, with minimal hemodynamic disturbances. This allows for more gradual shifts in volume and electrolyte levels, reducing the potential for ischemic damage to the kidney and other organs. Also, CRRT more closely replicates normal renal function than IHD.

CRRT is now extremely safe and efficient, although it has been difficult to prove its superiority to IHD in regard to mortality. While there may be no actual benefit to CRRT, it is also likely that its benefit is observed only in certain subsets of patients with renal failure. For example, we do have compelling evidence of increased intracranial pressure during IHD; CRRT is much safer for patients at risk for this development.¹ It is also possible that we need to further improve CRRT systems and delivery in order to see a benefit.

Because current data favor neither CRRT nor IHD, most experts recommend choosing a therapy based on patient characteristics. For instance, hemodynamically unstable patients commonly receive generous amounts of fluid daily (antibiotics, nutrition, etc), and thus are often better suited for CRRT because it is more likely to remove higher volumes of fluid successfully, and less likely to contribute to hemodynamic instability than IHD. Conversely, patients with acute electrolyte deviations may benefit more from the rapid electrolyte removal IHD provides.

Additionally, stable patients may be more suitable candidates for IHD because of location (CRRT requires intensive care monitoring) and other variables.^2,3 Results from multiple studies have suggested that CRRT may also provide renal protection and consequently improve renal recovery. However, this evidence is not conclusive; the possibility needs further evaluation.¹

Continue reading for the optimal dose for dialysis...

What is the optimal dose for dialysis? This question, too, is plagued by inconclusive research findings. Paganini was the first to raise it formally in patients with acute renal failure; his research team found improved survival with higher doses, but had excluded the sickest and healthiest patients (according to probability of survival) from the study.⁴ This was followed by two additional studies with results that also seemed to support higher doses.^1,5

Then in 2008, in a a similar randomized controlled trial, Tolwani et al⁶ found no survival benefit with higher versus lower dosing; participants in this study were not excluded based on severity of illness. Also, Tolwani’s research team identified failure to achieve prescribed doses as one factor complicating dose comparison.⁶

Finally, two large randomized controlled trials were performed to evaluate dosage, one in the US⁷ and one in Australia and New Zealand.⁸ Neither research team was able to confirm survival benefits with higher-dose renal replacement therapy, and there were inconsistencies between doses used in the study and standard practice in the US. In fact, the low-dose group received dialysis exceeding what is current practice by more than 30%.

The current prevailing opinion is that we should reach a minimum dose: a Kt/V of 1.2, three times a week, for IHD; or a CRRT dose of 20 mL/kg/h. At this time, higher doses do not confer a clear survival benefit. It remains unknown whether certain patients may benefit from a higher dose. Further research is needed.

Continue reading to find out when to initiate therapy...

When should we initiate therapy? While some study results suggest that early initiation is better, this remains unconfirmed.¹ In theory, renal replacement therapy should be initiated early because it improves metabolic control and corrects fluid overload, facilitating management of hemodynamics and ventilation, and reducing the potential for complications caused by uremia-induced physiologic dysfunction. However, it is still unknown which patients would benefit most from early initiation, and the appropriate triggers for when to initiate therapy remain unclear.

So, how do you choose a renal replacement therapy? This is often a matter of opinion, based on evaluation of risks and benefits specific to the patient and clinical expertise with the renal replacement therapies available.

Patient safety must be a primary consideration. IHD and CRRT have dramatically improved in safety and efficacy, but it must yet be proven beyond a doubt which is superior. Outcomes may depend on how the chosen therapy is used to treat specific patient needs—not which therapy is chosen. Further research is needed to identify the best and safest way to provide renal replacement therapy.
Catherine Wells, DNP, ACNP-BC, CNN-NP, Division of Nephrology, University of Mississippi, Jackson

Continue for references...

REFERENCES
1. Prowle JR, Bellomo R. Continuous renal replacement therapy: recent advances and future research. Nat Rev Nephrol. 2010;6(9):521-529.

2. Abi Antoun T, Palevsky PM. Selection of modality of renal replacement therapy. Semin Dial. 2009; 22(2):108-113.

3. Vanholder R, Van Biesen W, Lameire N. What is the renal replacement method of choice for intensive care patients? J Am Soc Nephrol. 2001;12 suppl 17:S40-S43.

4. Augustine JJ, Sandy D, Seifert TH, Paganini EP. A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kidney Dis. 2004;44(6):1000-1007.

5. Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356(9223):26-30.

6. Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008;19(6):1233-1238.

7. Palevsky PM, Zhang JH, O’Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7-20.

8. Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1683.