Nephrology

Tumor necrosis factor receptor 1 is an effective marker for all-cause mortality in type 2 diabetes with kidney disease, according to results of a French study.

Additionally, TNFR1 was found to add clinical utility to the U.K. Prospective Diabetes Study (UKPDS) outcome equation for mortality.

"Our data showed a clear and graded relationship between concentrations of serum TNFR1 and risk of all-cause mortality," Pierre Jean Saulnier, Ph.D., of the University of Poitiers (France) and his colleagues wrote.

In a follow-up analysis of the SURDIAGENE study, designed to identify genetic and environmental causes of micro- and macrovascular complications in type 2 diabetes, investigators followed 522 patients with baseline urinary albumin to creatinine ratios (uACR) greater than 30 mg/mmol, an estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2, or both. Patients with a history of myocardial infarction and/or stroke were considered to have cardiovascular disease at baseline (Diabetes Care 2014 March 12 [doi:10.2337/dc13-2580]).

The primary endpoint was all-cause mortality. The secondary endpoint was the occurrence of a composite renal outcome in patients who did not have end-stage renal disease at baseline. The median duration of the study was 48 months. In that time, 196 deaths occurred.

The increased rate of death correlated with increased levels of TNFR1 across quartiles: 4.7% patient years in the first quartile, 7.7% in the second, 9.3% in the third, and 15.9% in the fourth.

Of note, when the investigators ran a multivariate analysis using age, diabetes duration, hemoglobin A_1c, uACR, and eGFR, they found that the risk of death tripled in patients in the fourth quartile (adjusted hazard ratio, 2.98), compared with patients in the first quartile.

When TNFR1 was combined with the UKDPS equation, which uses age, diabetes duration, sex, ethnicity, current smoking status, systolic blood pressure, HbA_1c, body mass index, eGFR, heart rate, atrial fibrillation, albuminuria, and peripheral vascular disease, the predictive value for mortality improved significantly (P = .03).

TNFR1 is a proinflammatory marker that a growing body of literature indicates has prognostic value for cardiovascular disease in patients with diabetes. "Our current findings add to this literature," the researchers wrote, adding that while it was not the focus of their study, the data may contribute to understanding the role of TNFR1 in vasculopathy and diabetes-related events such as amputation.

None of the authors of this study reported any relevant disclosures. Funding was provided by the French Ministry of Health, among others.

[email protected]

Tumor necrosis factor receptor 1 is an effective marker for all-cause mortality in type 2 diabetes with kidney disease, according to results of a French study.

Additionally, TNFR1 was found to add clinical utility to the U.K. Prospective Diabetes Study (UKPDS) outcome equation for mortality.

"Our data showed a clear and graded relationship between concentrations of serum TNFR1 and risk of all-cause mortality," Pierre Jean Saulnier, Ph.D., of the University of Poitiers (France) and his colleagues wrote.

In a follow-up analysis of the SURDIAGENE study, designed to identify genetic and environmental causes of micro- and macrovascular complications in type 2 diabetes, investigators followed 522 patients with baseline urinary albumin to creatinine ratios (uACR) greater than 30 mg/mmol, an estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2, or both. Patients with a history of myocardial infarction and/or stroke were considered to have cardiovascular disease at baseline (Diabetes Care 2014 March 12 [doi:10.2337/dc13-2580]).

The primary endpoint was all-cause mortality. The secondary endpoint was the occurrence of a composite renal outcome in patients who did not have end-stage renal disease at baseline. The median duration of the study was 48 months. In that time, 196 deaths occurred.

The increased rate of death correlated with increased levels of TNFR1 across quartiles: 4.7% patient years in the first quartile, 7.7% in the second, 9.3% in the third, and 15.9% in the fourth.

Of note, when the investigators ran a multivariate analysis using age, diabetes duration, hemoglobin A_1c, uACR, and eGFR, they found that the risk of death tripled in patients in the fourth quartile (adjusted hazard ratio, 2.98), compared with patients in the first quartile.

When TNFR1 was combined with the UKDPS equation, which uses age, diabetes duration, sex, ethnicity, current smoking status, systolic blood pressure, HbA_1c, body mass index, eGFR, heart rate, atrial fibrillation, albuminuria, and peripheral vascular disease, the predictive value for mortality improved significantly (P = .03).

TNFR1 is a proinflammatory marker that a growing body of literature indicates has prognostic value for cardiovascular disease in patients with diabetes. "Our current findings add to this literature," the researchers wrote, adding that while it was not the focus of their study, the data may contribute to understanding the role of TNFR1 in vasculopathy and diabetes-related events such as amputation.

None of the authors of this study reported any relevant disclosures. Funding was provided by the French Ministry of Health, among others.

[email protected]

Tumor necrosis factor receptor 1 is an effective marker for all-cause mortality in type 2 diabetes with kidney disease, according to results of a French study.

Additionally, TNFR1 was found to add clinical utility to the U.K. Prospective Diabetes Study (UKPDS) outcome equation for mortality.

"Our data showed a clear and graded relationship between concentrations of serum TNFR1 and risk of all-cause mortality," Pierre Jean Saulnier, Ph.D., of the University of Poitiers (France) and his colleagues wrote.

In a follow-up analysis of the SURDIAGENE study, designed to identify genetic and environmental causes of micro- and macrovascular complications in type 2 diabetes, investigators followed 522 patients with baseline urinary albumin to creatinine ratios (uACR) greater than 30 mg/mmol, an estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2, or both. Patients with a history of myocardial infarction and/or stroke were considered to have cardiovascular disease at baseline (Diabetes Care 2014 March 12 [doi:10.2337/dc13-2580]).

The primary endpoint was all-cause mortality. The secondary endpoint was the occurrence of a composite renal outcome in patients who did not have end-stage renal disease at baseline. The median duration of the study was 48 months. In that time, 196 deaths occurred.

The increased rate of death correlated with increased levels of TNFR1 across quartiles: 4.7% patient years in the first quartile, 7.7% in the second, 9.3% in the third, and 15.9% in the fourth.

Of note, when the investigators ran a multivariate analysis using age, diabetes duration, hemoglobin A_1c, uACR, and eGFR, they found that the risk of death tripled in patients in the fourth quartile (adjusted hazard ratio, 2.98), compared with patients in the first quartile.

When TNFR1 was combined with the UKDPS equation, which uses age, diabetes duration, sex, ethnicity, current smoking status, systolic blood pressure, HbA_1c, body mass index, eGFR, heart rate, atrial fibrillation, albuminuria, and peripheral vascular disease, the predictive value for mortality improved significantly (P = .03).

TNFR1 is a proinflammatory marker that a growing body of literature indicates has prognostic value for cardiovascular disease in patients with diabetes. "Our current findings add to this literature," the researchers wrote, adding that while it was not the focus of their study, the data may contribute to understanding the role of TNFR1 in vasculopathy and diabetes-related events such as amputation.

None of the authors of this study reported any relevant disclosures. Funding was provided by the French Ministry of Health, among others.

[email protected]

Acute pyelonephritis is a serious and common medical complication of pregnancy. It is estimated to occur in up to 1%-2% of pregnancies and is a common nonobstetrical indication for antepartum hospital admissions. Its prevalence is probably even higher in obstetrical clinics serving underserved inner-city populations such as ours in Newark, N.J.

The diagnosis of acute pyelonephritis is based on clinical signs and symptoms. Patients usually feel ill and have fever, chills, flank pain (usually right-sided), dysuria, and urgency and frequency. Nausea and vomiting also may be present. Laboratory abnormalities may include pyuria and bacteriuria, with white blood cell counts often predictive of pyelonephritis. A urine culture and sensitivity will often reveal Escherichia coli, but other less commonly found causative organisms may be detected as well.

It is the prevailing view that most pregnant women with acute pyelonephritis should be hospitalized for careful monitoring, evaluated for possible sepsis, and treated with parenteral antibiotics. Recently published retrospective cohort studies, as well as our own experience, have emphasized that the risks of preterm labor and delivery in these patients can be significant, as can the risks of septic shock and other complications. Treatment, therefore, should be aggressive, with careful monitoring and charting of vital signs, including urinary output; and fetal monitoring and monitoring of uterine contractions. That way one can identify patients who are not responding to treatment or who may be developing septic shock or preterm labor.

Studies have shown that 10%-12% of all pregnant women have asymptomatic bacteriuria. Because physiologic changes associated with pregnancy encourage urinary stasis, there is an increased risk of progression to acute pyelonephritis with the potential for serious infectious complications, even in pregnant women who are otherwise healthy. By and large, however, pyelonephritis is usually a preventable problem given access to prenatal care. Screening for asymptomatic bacteriuria during the first prenatal visit is important, and repeat screening in each trimester in women who are at high risk for recurrent infection is critical for preventing symptomatic and possibly severe infection.

Our screening preference is to perform a urine culture and sensitivity test at the first prenatal visit. Other providers may utilize a urinalysis and leukocyte esterase test initially, but as this approach is not as sensitive or specific, it must be followed by a urine culture and sensitivity testing if the urinalysis results are positive. Obstetricians and others providing prenatal care should utilize whatever approach works best for their patients and environment. Most importantly, screening for asymptomatic bacteriuria must occur early in the pregnancy.

Additional urine culture and sensitivity testing are advisable for patients who are at high risk for urinary tract infections, such as those who have had frequent UTIs before pregnancy and those who have anemia, sickle cell trait, a history of renal stones, diabetes mellitus, obesity, or neurologic disorders (such as neurogenic bladder and multiple sclerosis). Considering the increase in prevalence of obesity and diabetes, these high-risk patients represent a growing proportion of the obstetric population and appear to be at increased risk of UTIs as well. Women of increasing age and increasing parity also may be at higher risk of developing UTIs during pregnancy.

Cranberry juice has been touted for years as an effective remedy for the prevention and treatment of UTIs in women, and I advise my patients who have a UTI during pregnancy, who have diabetes, or who have other risk factors, to drink a glass of unsweetened cranberry juice each day. No definitive mechanism of action has been established, but it appears that cranberry juice prevents or interferes with the adherence of bacteria (particularly E. coli) to uroepithelial cells. It is important to emphasize to patients to consume unsweetened cranberry juice and not cranberry juice cocktail because of the high sugar content in the latter.

Recent research has emphasized that pregnancies of women who develop pyelonephritis are more likely to be complicated by spontaneous preterm birth, septicemia, and other adverse outcomes. In a retrospective cohort study of more than 546,000 singleton pregnancies delivered in all Kaiser Permanente of Southern California hospitals from 1993 to 2010, women with pyelonephritis were almost 57 times more likely than those without pyelonephritis to develop septicemia and 1.3 times more likely to have spontaneous preterm birth.

In addition, pregnancies of women with pyelonephritis were 2.6 times more likely than those of the baseline obstetric population to be complicated by anemia and 16.5 times more likely to be complicated by acute renal failure (Am. J. Obstet. Gynecol. 2014;210:219.e1-6). The overall incidence of acute antepartum pyelonephritis in this cohort study was relatively low compared with the incidence in other populations – 0.5% – which is not surprising given that patients in Kaiser’s integrated health care system routinely receive prenatal screening for asymptomatic bacteriuria.

Another retrospective population-based study comparing almost 220,000 singleton pregnancies of patients with and without acute pyelonephritis concluded that the infection is an independent risk factor for preterm delivery (Eur. J. Obstet. Gynecol. Reprod. Biol 2012;162:24-7).

After admission to the hospital, patients must be carefully monitored for uterine contractions and changes in vital signs and fetal heart rate. Several years ago, in an effort to empirically and synergistically target E. coli, the most common cause of UTIs and pyelonephritis, we began administering both an extended-spectrum cephalosporin (intravenous ceftriaxone) and an antimicrobial that will target gram-negative organisms, such as an aminoglycoside (gentamicin) or aztreonam.

We established this protocol because reviews of the outcomes at our institution indicated that intravenous ceftriaxone alone had not prevented some of our patients from developing septic shock in the first 8-20 hours post admission, despite the fact that culture and sensitivity results later indicated that the organism was E. coli and sensitive to the antimicrobial.

While we have not yet done any formal data analysis since changing our protocol, the combination parenteral antimicrobial regimen prescribed on admission appears to be effective in preventing the development of septic shock. We prescribe ceftriaxone 2 g intravenously once a day and gentamicin 5 mg/kg per day. Both drugs are continued until the patient improves clinically and has been afebrile for 48 hours.

At discharge, patients are prescribed a 10- to 14-day oral antimicrobial regimen dependent upon the culture and sensitivity report. Because at least 50% of E. coli are resistant to penicillin-like antimicrobials, the initial treatment no longer involves the use of ampicillin or amoxicillin. A repeat urine culture test at the end of treatment to confirm clearance of the infection is essential.

The possibility of anatomical obstructions in the urinary system should be investigated in pregnant patients who have multiple UTIs or who are unresponsive to appropriate antibiotic therapy for pyelonephritis. In this group we have performed ultrasound of the urinary tract system and have diagnosed renal stones as the risk factor for recurrent UTI. These patients are prescribed antimicrobial prophylaxis for the duration of the pregnancy. After delivery, they are referred to a urologist for follow-up care and treatment.

Dr. Apuzzio reported that he has no disclosures relevant to this Master Class.

Dr. Apuzzio is a professor in the department of obstetrics, gynecology, and women’s health, director of prenatal diagnosis and infectious diseases, professor of radiology, and director of maternal-fetal medicine at Rutgers New Jersey Medical School, Newark.

Acute pyelonephritis is a serious and common medical complication of pregnancy. It is estimated to occur in up to 1%-2% of pregnancies and is a common nonobstetrical indication for antepartum hospital admissions. Its prevalence is probably even higher in obstetrical clinics serving underserved inner-city populations such as ours in Newark, N.J.

The diagnosis of acute pyelonephritis is based on clinical signs and symptoms. Patients usually feel ill and have fever, chills, flank pain (usually right-sided), dysuria, and urgency and frequency. Nausea and vomiting also may be present. Laboratory abnormalities may include pyuria and bacteriuria, with white blood cell counts often predictive of pyelonephritis. A urine culture and sensitivity will often reveal Escherichia coli, but other less commonly found causative organisms may be detected as well.

It is the prevailing view that most pregnant women with acute pyelonephritis should be hospitalized for careful monitoring, evaluated for possible sepsis, and treated with parenteral antibiotics. Recently published retrospective cohort studies, as well as our own experience, have emphasized that the risks of preterm labor and delivery in these patients can be significant, as can the risks of septic shock and other complications. Treatment, therefore, should be aggressive, with careful monitoring and charting of vital signs, including urinary output; and fetal monitoring and monitoring of uterine contractions. That way one can identify patients who are not responding to treatment or who may be developing septic shock or preterm labor.

Studies have shown that 10%-12% of all pregnant women have asymptomatic bacteriuria. Because physiologic changes associated with pregnancy encourage urinary stasis, there is an increased risk of progression to acute pyelonephritis with the potential for serious infectious complications, even in pregnant women who are otherwise healthy. By and large, however, pyelonephritis is usually a preventable problem given access to prenatal care. Screening for asymptomatic bacteriuria during the first prenatal visit is important, and repeat screening in each trimester in women who are at high risk for recurrent infection is critical for preventing symptomatic and possibly severe infection.

Our screening preference is to perform a urine culture and sensitivity test at the first prenatal visit. Other providers may utilize a urinalysis and leukocyte esterase test initially, but as this approach is not as sensitive or specific, it must be followed by a urine culture and sensitivity testing if the urinalysis results are positive. Obstetricians and others providing prenatal care should utilize whatever approach works best for their patients and environment. Most importantly, screening for asymptomatic bacteriuria must occur early in the pregnancy.

Additional urine culture and sensitivity testing are advisable for patients who are at high risk for urinary tract infections, such as those who have had frequent UTIs before pregnancy and those who have anemia, sickle cell trait, a history of renal stones, diabetes mellitus, obesity, or neurologic disorders (such as neurogenic bladder and multiple sclerosis). Considering the increase in prevalence of obesity and diabetes, these high-risk patients represent a growing proportion of the obstetric population and appear to be at increased risk of UTIs as well. Women of increasing age and increasing parity also may be at higher risk of developing UTIs during pregnancy.

Cranberry juice has been touted for years as an effective remedy for the prevention and treatment of UTIs in women, and I advise my patients who have a UTI during pregnancy, who have diabetes, or who have other risk factors, to drink a glass of unsweetened cranberry juice each day. No definitive mechanism of action has been established, but it appears that cranberry juice prevents or interferes with the adherence of bacteria (particularly E. coli) to uroepithelial cells. It is important to emphasize to patients to consume unsweetened cranberry juice and not cranberry juice cocktail because of the high sugar content in the latter.

Recent research has emphasized that pregnancies of women who develop pyelonephritis are more likely to be complicated by spontaneous preterm birth, septicemia, and other adverse outcomes. In a retrospective cohort study of more than 546,000 singleton pregnancies delivered in all Kaiser Permanente of Southern California hospitals from 1993 to 2010, women with pyelonephritis were almost 57 times more likely than those without pyelonephritis to develop septicemia and 1.3 times more likely to have spontaneous preterm birth.

In addition, pregnancies of women with pyelonephritis were 2.6 times more likely than those of the baseline obstetric population to be complicated by anemia and 16.5 times more likely to be complicated by acute renal failure (Am. J. Obstet. Gynecol. 2014;210:219.e1-6). The overall incidence of acute antepartum pyelonephritis in this cohort study was relatively low compared with the incidence in other populations – 0.5% – which is not surprising given that patients in Kaiser’s integrated health care system routinely receive prenatal screening for asymptomatic bacteriuria.

Another retrospective population-based study comparing almost 220,000 singleton pregnancies of patients with and without acute pyelonephritis concluded that the infection is an independent risk factor for preterm delivery (Eur. J. Obstet. Gynecol. Reprod. Biol 2012;162:24-7).

After admission to the hospital, patients must be carefully monitored for uterine contractions and changes in vital signs and fetal heart rate. Several years ago, in an effort to empirically and synergistically target E. coli, the most common cause of UTIs and pyelonephritis, we began administering both an extended-spectrum cephalosporin (intravenous ceftriaxone) and an antimicrobial that will target gram-negative organisms, such as an aminoglycoside (gentamicin) or aztreonam.

We established this protocol because reviews of the outcomes at our institution indicated that intravenous ceftriaxone alone had not prevented some of our patients from developing septic shock in the first 8-20 hours post admission, despite the fact that culture and sensitivity results later indicated that the organism was E. coli and sensitive to the antimicrobial.

While we have not yet done any formal data analysis since changing our protocol, the combination parenteral antimicrobial regimen prescribed on admission appears to be effective in preventing the development of septic shock. We prescribe ceftriaxone 2 g intravenously once a day and gentamicin 5 mg/kg per day. Both drugs are continued until the patient improves clinically and has been afebrile for 48 hours.

At discharge, patients are prescribed a 10- to 14-day oral antimicrobial regimen dependent upon the culture and sensitivity report. Because at least 50% of E. coli are resistant to penicillin-like antimicrobials, the initial treatment no longer involves the use of ampicillin or amoxicillin. A repeat urine culture test at the end of treatment to confirm clearance of the infection is essential.

The possibility of anatomical obstructions in the urinary system should be investigated in pregnant patients who have multiple UTIs or who are unresponsive to appropriate antibiotic therapy for pyelonephritis. In this group we have performed ultrasound of the urinary tract system and have diagnosed renal stones as the risk factor for recurrent UTI. These patients are prescribed antimicrobial prophylaxis for the duration of the pregnancy. After delivery, they are referred to a urologist for follow-up care and treatment.

Dr. Apuzzio reported that he has no disclosures relevant to this Master Class.

Dr. Apuzzio is a professor in the department of obstetrics, gynecology, and women’s health, director of prenatal diagnosis and infectious diseases, professor of radiology, and director of maternal-fetal medicine at Rutgers New Jersey Medical School, Newark.

Acute pyelonephritis is a serious and common medical complication of pregnancy. It is estimated to occur in up to 1%-2% of pregnancies and is a common nonobstetrical indication for antepartum hospital admissions. Its prevalence is probably even higher in obstetrical clinics serving underserved inner-city populations such as ours in Newark, N.J.

The diagnosis of acute pyelonephritis is based on clinical signs and symptoms. Patients usually feel ill and have fever, chills, flank pain (usually right-sided), dysuria, and urgency and frequency. Nausea and vomiting also may be present. Laboratory abnormalities may include pyuria and bacteriuria, with white blood cell counts often predictive of pyelonephritis. A urine culture and sensitivity will often reveal Escherichia coli, but other less commonly found causative organisms may be detected as well.

It is the prevailing view that most pregnant women with acute pyelonephritis should be hospitalized for careful monitoring, evaluated for possible sepsis, and treated with parenteral antibiotics. Recently published retrospective cohort studies, as well as our own experience, have emphasized that the risks of preterm labor and delivery in these patients can be significant, as can the risks of septic shock and other complications. Treatment, therefore, should be aggressive, with careful monitoring and charting of vital signs, including urinary output; and fetal monitoring and monitoring of uterine contractions. That way one can identify patients who are not responding to treatment or who may be developing septic shock or preterm labor.

Studies have shown that 10%-12% of all pregnant women have asymptomatic bacteriuria. Because physiologic changes associated with pregnancy encourage urinary stasis, there is an increased risk of progression to acute pyelonephritis with the potential for serious infectious complications, even in pregnant women who are otherwise healthy. By and large, however, pyelonephritis is usually a preventable problem given access to prenatal care. Screening for asymptomatic bacteriuria during the first prenatal visit is important, and repeat screening in each trimester in women who are at high risk for recurrent infection is critical for preventing symptomatic and possibly severe infection.

Our screening preference is to perform a urine culture and sensitivity test at the first prenatal visit. Other providers may utilize a urinalysis and leukocyte esterase test initially, but as this approach is not as sensitive or specific, it must be followed by a urine culture and sensitivity testing if the urinalysis results are positive. Obstetricians and others providing prenatal care should utilize whatever approach works best for their patients and environment. Most importantly, screening for asymptomatic bacteriuria must occur early in the pregnancy.

Additional urine culture and sensitivity testing are advisable for patients who are at high risk for urinary tract infections, such as those who have had frequent UTIs before pregnancy and those who have anemia, sickle cell trait, a history of renal stones, diabetes mellitus, obesity, or neurologic disorders (such as neurogenic bladder and multiple sclerosis). Considering the increase in prevalence of obesity and diabetes, these high-risk patients represent a growing proportion of the obstetric population and appear to be at increased risk of UTIs as well. Women of increasing age and increasing parity also may be at higher risk of developing UTIs during pregnancy.

Cranberry juice has been touted for years as an effective remedy for the prevention and treatment of UTIs in women, and I advise my patients who have a UTI during pregnancy, who have diabetes, or who have other risk factors, to drink a glass of unsweetened cranberry juice each day. No definitive mechanism of action has been established, but it appears that cranberry juice prevents or interferes with the adherence of bacteria (particularly E. coli) to uroepithelial cells. It is important to emphasize to patients to consume unsweetened cranberry juice and not cranberry juice cocktail because of the high sugar content in the latter.

Recent research has emphasized that pregnancies of women who develop pyelonephritis are more likely to be complicated by spontaneous preterm birth, septicemia, and other adverse outcomes. In a retrospective cohort study of more than 546,000 singleton pregnancies delivered in all Kaiser Permanente of Southern California hospitals from 1993 to 2010, women with pyelonephritis were almost 57 times more likely than those without pyelonephritis to develop septicemia and 1.3 times more likely to have spontaneous preterm birth.

In addition, pregnancies of women with pyelonephritis were 2.6 times more likely than those of the baseline obstetric population to be complicated by anemia and 16.5 times more likely to be complicated by acute renal failure (Am. J. Obstet. Gynecol. 2014;210:219.e1-6). The overall incidence of acute antepartum pyelonephritis in this cohort study was relatively low compared with the incidence in other populations – 0.5% – which is not surprising given that patients in Kaiser’s integrated health care system routinely receive prenatal screening for asymptomatic bacteriuria.

Another retrospective population-based study comparing almost 220,000 singleton pregnancies of patients with and without acute pyelonephritis concluded that the infection is an independent risk factor for preterm delivery (Eur. J. Obstet. Gynecol. Reprod. Biol 2012;162:24-7).

After admission to the hospital, patients must be carefully monitored for uterine contractions and changes in vital signs and fetal heart rate. Several years ago, in an effort to empirically and synergistically target E. coli, the most common cause of UTIs and pyelonephritis, we began administering both an extended-spectrum cephalosporin (intravenous ceftriaxone) and an antimicrobial that will target gram-negative organisms, such as an aminoglycoside (gentamicin) or aztreonam.

We established this protocol because reviews of the outcomes at our institution indicated that intravenous ceftriaxone alone had not prevented some of our patients from developing septic shock in the first 8-20 hours post admission, despite the fact that culture and sensitivity results later indicated that the organism was E. coli and sensitive to the antimicrobial.

While we have not yet done any formal data analysis since changing our protocol, the combination parenteral antimicrobial regimen prescribed on admission appears to be effective in preventing the development of septic shock. We prescribe ceftriaxone 2 g intravenously once a day and gentamicin 5 mg/kg per day. Both drugs are continued until the patient improves clinically and has been afebrile for 48 hours.

At discharge, patients are prescribed a 10- to 14-day oral antimicrobial regimen dependent upon the culture and sensitivity report. Because at least 50% of E. coli are resistant to penicillin-like antimicrobials, the initial treatment no longer involves the use of ampicillin or amoxicillin. A repeat urine culture test at the end of treatment to confirm clearance of the infection is essential.

The possibility of anatomical obstructions in the urinary system should be investigated in pregnant patients who have multiple UTIs or who are unresponsive to appropriate antibiotic therapy for pyelonephritis. In this group we have performed ultrasound of the urinary tract system and have diagnosed renal stones as the risk factor for recurrent UTI. These patients are prescribed antimicrobial prophylaxis for the duration of the pregnancy. After delivery, they are referred to a urologist for follow-up care and treatment.

Dr. Apuzzio reported that he has no disclosures relevant to this Master Class.

Dr. Apuzzio is a professor in the department of obstetrics, gynecology, and women’s health, director of prenatal diagnosis and infectious diseases, professor of radiology, and director of maternal-fetal medicine at Rutgers New Jersey Medical School, Newark.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

More than 50% of patients taking an anticholinergic drug for symptoms of overactive bladder (OAB) stop taking their medicine—and at least half of those stop within the first 6 months. Two-thirds of patients never start again. That’s according to a study by researchers from Beaumont Hospital in Royal Oak, Michigan; Xcenda, LLC in Palm Harbor, Florida; and Allergan, Inc. in Irvine, California, who analyzed medical, pharmacy, and other data from the IMS LifeLink Health Plan Claims Database of 103,250 patients with OAB.

Anticholinergic drugs included oxybutynin, tolterodine, trospium, fesoterodine, and solifenacin, but 42% of patients received tolterodine extended release (ER) as their index prescription. To be considered a discontinuation, the patient had to have a gap of at least 45 days in therapy, based on fill dates and days’ supply. The corresponding time to treatment failure (TTF) was estimated as the number of days between the index date and the date of the first medication switch or estimated discontinuation date. Treatment reinitiation was defined as the documentation of a filled prescription for any anticholinergic agent after a discontinuation period of at least 45 days. The researchers in this study used claims data to avoid the problem of self-reported adherence, since patients often overstate their adherence to medications.

Initial treatment with the index drug failed in nearly all (92%) patients. Of those, only 6% were associated with switching drugs. More than half had permanently stopped all anticholinergic drugs at 24 months. Moreover, 33% of patients filled only 1 prescription, suggesting early failure (within the first 30 days).

The proportion of treatment failures was high across all primary diagnoses, ranging from 89% to 97%. Failure was also high regardless of the therapy. For instance, 90% of 43,902 patients on tolterodine ER and 96% of 2,246 patients on oxybutynin transdermal did not meet treatment goals. The researchers then took those numbers and pooled outcomes across all drugs to estimate the overall impact of anticholinergic treatment for patients with OAB and found that the mean TTF was 159 days.

Many patients (81%) who switched treatment during the 24-month study period also had no luck with the second drug. Treatment also failed for 29% who tried a third drug. Treatment failure didn’t always stop them from trying, though: About one-third started treatment again after a gap of at least 45 days, and about one-fifth restarted after 1 year.

Empirical studies of medications to treat chronic conditions have found persistence to OAB medications to be very low, the researchers say. When compared with oral antidiabetic drugs, angiotensin receptor blockers, statins, bisphosphonates, and prostaglandins, OAB medications had the lowest persistence rates at 6 months: 32% compared with 72% for oral antidiabetes drugs.

In research of patients with OAB, achievement of treatment goals is a strong predictor of treatment satisfaction, and dissatisfaction with treatment outcomes is the most common reason for patients stopping their treatment. Poor adherence to OAB drugs can have a negative impact on quality of life and increase the risk of medical sequelae, such as urinary tract infections. Thus, when anticholinergics fail, the researchers say, it’s important to give patients options, such as botulinum toxin A, sacral neuromodulation, and percutaneous tibial nerve stimulation.

Despite the “potential for better adherence” with some anticholinergic drugs, their findings suggest that the benefits of anticholinergic use in OAB are not being realized, and many patients may end up without any drug therapy at all.

Source
Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D. Clin Ther. 2013;35(11):1744-1751.
doi: 10.1016/j.clinthera.2013.08.017.

More than 50% of patients taking an anticholinergic drug for symptoms of overactive bladder (OAB) stop taking their medicine—and at least half of those stop within the first 6 months. Two-thirds of patients never start again. That’s according to a study by researchers from Beaumont Hospital in Royal Oak, Michigan; Xcenda, LLC in Palm Harbor, Florida; and Allergan, Inc. in Irvine, California, who analyzed medical, pharmacy, and other data from the IMS LifeLink Health Plan Claims Database of 103,250 patients with OAB.

Anticholinergic drugs included oxybutynin, tolterodine, trospium, fesoterodine, and solifenacin, but 42% of patients received tolterodine extended release (ER) as their index prescription. To be considered a discontinuation, the patient had to have a gap of at least 45 days in therapy, based on fill dates and days’ supply. The corresponding time to treatment failure (TTF) was estimated as the number of days between the index date and the date of the first medication switch or estimated discontinuation date. Treatment reinitiation was defined as the documentation of a filled prescription for any anticholinergic agent after a discontinuation period of at least 45 days. The researchers in this study used claims data to avoid the problem of self-reported adherence, since patients often overstate their adherence to medications.

Initial treatment with the index drug failed in nearly all (92%) patients. Of those, only 6% were associated with switching drugs. More than half had permanently stopped all anticholinergic drugs at 24 months. Moreover, 33% of patients filled only 1 prescription, suggesting early failure (within the first 30 days).

The proportion of treatment failures was high across all primary diagnoses, ranging from 89% to 97%. Failure was also high regardless of the therapy. For instance, 90% of 43,902 patients on tolterodine ER and 96% of 2,246 patients on oxybutynin transdermal did not meet treatment goals. The researchers then took those numbers and pooled outcomes across all drugs to estimate the overall impact of anticholinergic treatment for patients with OAB and found that the mean TTF was 159 days.

Many patients (81%) who switched treatment during the 24-month study period also had no luck with the second drug. Treatment also failed for 29% who tried a third drug. Treatment failure didn’t always stop them from trying, though: About one-third started treatment again after a gap of at least 45 days, and about one-fifth restarted after 1 year.

Empirical studies of medications to treat chronic conditions have found persistence to OAB medications to be very low, the researchers say. When compared with oral antidiabetic drugs, angiotensin receptor blockers, statins, bisphosphonates, and prostaglandins, OAB medications had the lowest persistence rates at 6 months: 32% compared with 72% for oral antidiabetes drugs.

In research of patients with OAB, achievement of treatment goals is a strong predictor of treatment satisfaction, and dissatisfaction with treatment outcomes is the most common reason for patients stopping their treatment. Poor adherence to OAB drugs can have a negative impact on quality of life and increase the risk of medical sequelae, such as urinary tract infections. Thus, when anticholinergics fail, the researchers say, it’s important to give patients options, such as botulinum toxin A, sacral neuromodulation, and percutaneous tibial nerve stimulation.

Despite the “potential for better adherence” with some anticholinergic drugs, their findings suggest that the benefits of anticholinergic use in OAB are not being realized, and many patients may end up without any drug therapy at all.

Source
Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D. Clin Ther. 2013;35(11):1744-1751.
doi: 10.1016/j.clinthera.2013.08.017.

More than 50% of patients taking an anticholinergic drug for symptoms of overactive bladder (OAB) stop taking their medicine—and at least half of those stop within the first 6 months. Two-thirds of patients never start again. That’s according to a study by researchers from Beaumont Hospital in Royal Oak, Michigan; Xcenda, LLC in Palm Harbor, Florida; and Allergan, Inc. in Irvine, California, who analyzed medical, pharmacy, and other data from the IMS LifeLink Health Plan Claims Database of 103,250 patients with OAB.

Anticholinergic drugs included oxybutynin, tolterodine, trospium, fesoterodine, and solifenacin, but 42% of patients received tolterodine extended release (ER) as their index prescription. To be considered a discontinuation, the patient had to have a gap of at least 45 days in therapy, based on fill dates and days’ supply. The corresponding time to treatment failure (TTF) was estimated as the number of days between the index date and the date of the first medication switch or estimated discontinuation date. Treatment reinitiation was defined as the documentation of a filled prescription for any anticholinergic agent after a discontinuation period of at least 45 days. The researchers in this study used claims data to avoid the problem of self-reported adherence, since patients often overstate their adherence to medications.

Initial treatment with the index drug failed in nearly all (92%) patients. Of those, only 6% were associated with switching drugs. More than half had permanently stopped all anticholinergic drugs at 24 months. Moreover, 33% of patients filled only 1 prescription, suggesting early failure (within the first 30 days).

The proportion of treatment failures was high across all primary diagnoses, ranging from 89% to 97%. Failure was also high regardless of the therapy. For instance, 90% of 43,902 patients on tolterodine ER and 96% of 2,246 patients on oxybutynin transdermal did not meet treatment goals. The researchers then took those numbers and pooled outcomes across all drugs to estimate the overall impact of anticholinergic treatment for patients with OAB and found that the mean TTF was 159 days.

Many patients (81%) who switched treatment during the 24-month study period also had no luck with the second drug. Treatment also failed for 29% who tried a third drug. Treatment failure didn’t always stop them from trying, though: About one-third started treatment again after a gap of at least 45 days, and about one-fifth restarted after 1 year.

Empirical studies of medications to treat chronic conditions have found persistence to OAB medications to be very low, the researchers say. When compared with oral antidiabetic drugs, angiotensin receptor blockers, statins, bisphosphonates, and prostaglandins, OAB medications had the lowest persistence rates at 6 months: 32% compared with 72% for oral antidiabetes drugs.

In research of patients with OAB, achievement of treatment goals is a strong predictor of treatment satisfaction, and dissatisfaction with treatment outcomes is the most common reason for patients stopping their treatment. Poor adherence to OAB drugs can have a negative impact on quality of life and increase the risk of medical sequelae, such as urinary tract infections. Thus, when anticholinergics fail, the researchers say, it’s important to give patients options, such as botulinum toxin A, sacral neuromodulation, and percutaneous tibial nerve stimulation.

Despite the “potential for better adherence” with some anticholinergic drugs, their findings suggest that the benefits of anticholinergic use in OAB are not being realized, and many patients may end up without any drug therapy at all.

Source
Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D. Clin Ther. 2013;35(11):1744-1751.
doi: 10.1016/j.clinthera.2013.08.017.

Maintenance percutaneous tibial nerve stimulation in patients with multiple sclerosis led to sustained improvements in medically refractory lower urinary tract symptoms in a prospective, multicenter open-label trial.

All initial responders continued to respond after an average of 2 years of maintenance therapy, reported Dr. Claudio Gobbi of the Neurocentre of Southern Switzerland, Lugano, and his associates.

The prospective, multicenter open-label study recruited patients with multiple sclerosis who had lower urinary tract symptoms that had not responded to medical therapy. Symptom criteria included overactive bladder, incomplete voiding, hesitancy, poor or slow flow, prolonged and interrupted flow, and straining to void (J. Urol. 2014;191:697-702).

A total of 83 patients (mean age, 49 years; 62 women) completed 12 initial weekly sessions of percutaneous tibial nerve stimulation (PTNS). In all, 74 (89%) reported at least 50% improvement in lower urinary tract symptoms on the Patient Perception of Bladder Condition questionnaire.

These responders then underwent 30-minute PTNS maintenance sessions every 2, 3, or 4 weeks as needed. Most patients (60%) required treatment every 2 weeks, the researchers said.

After the 12 weekly PTNS treatments, most responders reported their bladder symptoms as moderately improved (based on a global response assessment), and mean treatment satisfaction was 70% (based on a visual analog scale). At 24 months’ follow-up, most patients described their symptoms as markedly improved, and mean treatment satisfaction was 82% (P less than .05).

The investigators also reported significant improvements over a 24-month period in measures of voiding and bladder diary parameters (including frequency of daytime urination, nocturia, and voided volume). Patients reported no relevant adverse effects of treatment.

Dr. Gobbi and his associates noted several caveats to their findings. The study probably lacked sufficient power to detect differences between subgroups, they said. The investigators also did not collect data on drinking habits or lifestyle modifications, each of which could have independently affected treatment outcomes. And the study included only patients who responded to and completed the initial treatment, which created a selection bias for patients willing to adhere to maintenance PTNS.

"Although the efficacy of PTNS was sustained for 2 years, the progressive neurologic course of MS with deteriorating bladder function may affect longer positive treatment outcomes," they added.

One author disclosed having financial interests or other relationships with Medtronic, Allergan, and Astellas. Dr. Gobbi and his other coauthors reported no conflicts of interest.

Maintenance percutaneous tibial nerve stimulation in patients with multiple sclerosis led to sustained improvements in medically refractory lower urinary tract symptoms in a prospective, multicenter open-label trial.

All initial responders continued to respond after an average of 2 years of maintenance therapy, reported Dr. Claudio Gobbi of the Neurocentre of Southern Switzerland, Lugano, and his associates.

The prospective, multicenter open-label study recruited patients with multiple sclerosis who had lower urinary tract symptoms that had not responded to medical therapy. Symptom criteria included overactive bladder, incomplete voiding, hesitancy, poor or slow flow, prolonged and interrupted flow, and straining to void (J. Urol. 2014;191:697-702).

A total of 83 patients (mean age, 49 years; 62 women) completed 12 initial weekly sessions of percutaneous tibial nerve stimulation (PTNS). In all, 74 (89%) reported at least 50% improvement in lower urinary tract symptoms on the Patient Perception of Bladder Condition questionnaire.

These responders then underwent 30-minute PTNS maintenance sessions every 2, 3, or 4 weeks as needed. Most patients (60%) required treatment every 2 weeks, the researchers said.

After the 12 weekly PTNS treatments, most responders reported their bladder symptoms as moderately improved (based on a global response assessment), and mean treatment satisfaction was 70% (based on a visual analog scale). At 24 months’ follow-up, most patients described their symptoms as markedly improved, and mean treatment satisfaction was 82% (P less than .05).

The investigators also reported significant improvements over a 24-month period in measures of voiding and bladder diary parameters (including frequency of daytime urination, nocturia, and voided volume). Patients reported no relevant adverse effects of treatment.

Dr. Gobbi and his associates noted several caveats to their findings. The study probably lacked sufficient power to detect differences between subgroups, they said. The investigators also did not collect data on drinking habits or lifestyle modifications, each of which could have independently affected treatment outcomes. And the study included only patients who responded to and completed the initial treatment, which created a selection bias for patients willing to adhere to maintenance PTNS.

"Although the efficacy of PTNS was sustained for 2 years, the progressive neurologic course of MS with deteriorating bladder function may affect longer positive treatment outcomes," they added.

One author disclosed having financial interests or other relationships with Medtronic, Allergan, and Astellas. Dr. Gobbi and his other coauthors reported no conflicts of interest.

Maintenance percutaneous tibial nerve stimulation in patients with multiple sclerosis led to sustained improvements in medically refractory lower urinary tract symptoms in a prospective, multicenter open-label trial.

All initial responders continued to respond after an average of 2 years of maintenance therapy, reported Dr. Claudio Gobbi of the Neurocentre of Southern Switzerland, Lugano, and his associates.

The prospective, multicenter open-label study recruited patients with multiple sclerosis who had lower urinary tract symptoms that had not responded to medical therapy. Symptom criteria included overactive bladder, incomplete voiding, hesitancy, poor or slow flow, prolonged and interrupted flow, and straining to void (J. Urol. 2014;191:697-702).

A total of 83 patients (mean age, 49 years; 62 women) completed 12 initial weekly sessions of percutaneous tibial nerve stimulation (PTNS). In all, 74 (89%) reported at least 50% improvement in lower urinary tract symptoms on the Patient Perception of Bladder Condition questionnaire.

These responders then underwent 30-minute PTNS maintenance sessions every 2, 3, or 4 weeks as needed. Most patients (60%) required treatment every 2 weeks, the researchers said.

After the 12 weekly PTNS treatments, most responders reported their bladder symptoms as moderately improved (based on a global response assessment), and mean treatment satisfaction was 70% (based on a visual analog scale). At 24 months’ follow-up, most patients described their symptoms as markedly improved, and mean treatment satisfaction was 82% (P less than .05).

The investigators also reported significant improvements over a 24-month period in measures of voiding and bladder diary parameters (including frequency of daytime urination, nocturia, and voided volume). Patients reported no relevant adverse effects of treatment.

Dr. Gobbi and his associates noted several caveats to their findings. The study probably lacked sufficient power to detect differences between subgroups, they said. The investigators also did not collect data on drinking habits or lifestyle modifications, each of which could have independently affected treatment outcomes. And the study included only patients who responded to and completed the initial treatment, which created a selection bias for patients willing to adhere to maintenance PTNS.

"Although the efficacy of PTNS was sustained for 2 years, the progressive neurologic course of MS with deteriorating bladder function may affect longer positive treatment outcomes," they added.

One author disclosed having financial interests or other relationships with Medtronic, Allergan, and Astellas. Dr. Gobbi and his other coauthors reported no conflicts of interest.

The prevalence of bladder incontinence rose from 21.1% in 1992 to 30.2% in 2010 for Medicare beneficiaries aged 65 years and older – an increase of 43%, according to data from the Medicare Current Beneficiary Survey.

Among white non-Hispanic patients, prevalence of bladder incontinence rose by 48% – going from 20.7% in 1992 to 30.6% in 2010. Prevalence in Hispanics rose from 22.7% in 1992 to 28.5% in 2010, for an increase of almost 26%. Black non-Hispanics saw their prevalence of bladder incontinence rise from 23.2% in 1992 to 27.7% in 2010 – an increase of more than 19%.

In the overall Medicare population for the same time period, bladder incontinence was reported almost twice as often among women – going from 25.8% in 1992 to 38.3% in 2010 – as in men – 13.4% in 1992 and 19.5% in 2010, according to MCBS data on the CDC Health Data Interactive.

[email protected]

The prevalence of bladder incontinence rose from 21.1% in 1992 to 30.2% in 2010 for Medicare beneficiaries aged 65 years and older – an increase of 43%, according to data from the Medicare Current Beneficiary Survey.

Among white non-Hispanic patients, prevalence of bladder incontinence rose by 48% – going from 20.7% in 1992 to 30.6% in 2010. Prevalence in Hispanics rose from 22.7% in 1992 to 28.5% in 2010, for an increase of almost 26%. Black non-Hispanics saw their prevalence of bladder incontinence rise from 23.2% in 1992 to 27.7% in 2010 – an increase of more than 19%.

In the overall Medicare population for the same time period, bladder incontinence was reported almost twice as often among women – going from 25.8% in 1992 to 38.3% in 2010 – as in men – 13.4% in 1992 and 19.5% in 2010, according to MCBS data on the CDC Health Data Interactive.

[email protected]

The prevalence of bladder incontinence rose from 21.1% in 1992 to 30.2% in 2010 for Medicare beneficiaries aged 65 years and older – an increase of 43%, according to data from the Medicare Current Beneficiary Survey.

Among white non-Hispanic patients, prevalence of bladder incontinence rose by 48% – going from 20.7% in 1992 to 30.6% in 2010. Prevalence in Hispanics rose from 22.7% in 1992 to 28.5% in 2010, for an increase of almost 26%. Black non-Hispanics saw their prevalence of bladder incontinence rise from 23.2% in 1992 to 27.7% in 2010 – an increase of more than 19%.

In the overall Medicare population for the same time period, bladder incontinence was reported almost twice as often among women – going from 25.8% in 1992 to 38.3% in 2010 – as in men – 13.4% in 1992 and 19.5% in 2010, according to MCBS data on the CDC Health Data Interactive.

[email protected]

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

When used to treat ventilator-associated pneumonia, the antibacterial drug doripenem is linked to a greater risk of mortality and lower clinical cure rates compared with imipenem and cilastatin for injection, according to a drug safety communication issued by the Food and Drug Administration.

Doripenem, an intravenous penem antibacterial drug marketed as Doribax, is not approved to treat any type of pneumonia. A warning about increased mortality in patients with ventilator-associated pneumonia (VAP), for which the use of doripenem is unapproved, has been added to the drug’s label. In a statement posted on March 6, the FDA recommended that health care professionals "consider whether the benefits of Doribax treatment are likely to exceed its potential risks in patients who develop pneumonia while on ventilators."

The safety communication is based on an FDA analysis of a 3-year study comparing 7 days of treatment with doripenem to 10 days of treatment with imipenem and cilastatin in patients with VAP. All-cause mortality over 28 days was 23% among those treated with doripenem, compared with 16.7% among those treated with imipenem and cilastatin. Clinical cure rates also were lower in the doripenem-treated patients in the study, which was stopped prematurely in 2011.

The statement adds that doripenem, approved in 2007, "is still considered safe and effective" for treating adults with complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis, which are FDA-approved indications.

In January 2012, the FDA issued a statement about the prematurely terminated study.

The revised doripenem label is available on the FDA website. The label change was made in January. Doripenem is manufactured by Shionogi.

Imipenem and cilastatin for injection is marketed as Primaxin in the United States.

Serious adverse events associated with doripenem should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

[email protected]

When used to treat ventilator-associated pneumonia, the antibacterial drug doripenem is linked to a greater risk of mortality and lower clinical cure rates compared with imipenem and cilastatin for injection, according to a drug safety communication issued by the Food and Drug Administration.

Doripenem, an intravenous penem antibacterial drug marketed as Doribax, is not approved to treat any type of pneumonia. A warning about increased mortality in patients with ventilator-associated pneumonia (VAP), for which the use of doripenem is unapproved, has been added to the drug’s label. In a statement posted on March 6, the FDA recommended that health care professionals "consider whether the benefits of Doribax treatment are likely to exceed its potential risks in patients who develop pneumonia while on ventilators."

The safety communication is based on an FDA analysis of a 3-year study comparing 7 days of treatment with doripenem to 10 days of treatment with imipenem and cilastatin in patients with VAP. All-cause mortality over 28 days was 23% among those treated with doripenem, compared with 16.7% among those treated with imipenem and cilastatin. Clinical cure rates also were lower in the doripenem-treated patients in the study, which was stopped prematurely in 2011.

The statement adds that doripenem, approved in 2007, "is still considered safe and effective" for treating adults with complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis, which are FDA-approved indications.

In January 2012, the FDA issued a statement about the prematurely terminated study.

The revised doripenem label is available on the FDA website. The label change was made in January. Doripenem is manufactured by Shionogi.

Imipenem and cilastatin for injection is marketed as Primaxin in the United States.

Serious adverse events associated with doripenem should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

[email protected]

When used to treat ventilator-associated pneumonia, the antibacterial drug doripenem is linked to a greater risk of mortality and lower clinical cure rates compared with imipenem and cilastatin for injection, according to a drug safety communication issued by the Food and Drug Administration.

Doripenem, an intravenous penem antibacterial drug marketed as Doribax, is not approved to treat any type of pneumonia. A warning about increased mortality in patients with ventilator-associated pneumonia (VAP), for which the use of doripenem is unapproved, has been added to the drug’s label. In a statement posted on March 6, the FDA recommended that health care professionals "consider whether the benefits of Doribax treatment are likely to exceed its potential risks in patients who develop pneumonia while on ventilators."

The safety communication is based on an FDA analysis of a 3-year study comparing 7 days of treatment with doripenem to 10 days of treatment with imipenem and cilastatin in patients with VAP. All-cause mortality over 28 days was 23% among those treated with doripenem, compared with 16.7% among those treated with imipenem and cilastatin. Clinical cure rates also were lower in the doripenem-treated patients in the study, which was stopped prematurely in 2011.

The statement adds that doripenem, approved in 2007, "is still considered safe and effective" for treating adults with complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis, which are FDA-approved indications.

In January 2012, the FDA issued a statement about the prematurely terminated study.

The revised doripenem label is available on the FDA website. The label change was made in January. Doripenem is manufactured by Shionogi.

Imipenem and cilastatin for injection is marketed as Primaxin in the United States.

Serious adverse events associated with doripenem should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

[email protected]

A long-acting intramuscular formulation of testosterone has been approved by the Food and Drug Administration for treating hypogonadism, with a label that includes a boxed warning about the risks of pulmonary oil microembolism and anaphylaxis associated with treatment.

The depot formulation of testosterone undecanoate (TU), in castor oil and benzoyl benzoate, has been approved for treating adult men with primary hypogonadism or hypogonadotropic hypogonadism, congenital or acquired. The indications section includes the statement that it "should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis."

The drug will be available, with restrictions, through the Aveed Risk Evaluation and Mitigation Strategy (REMS), according to the manufacturer, Endo Pharmaceuticals, which is marketing the product as Aveed. Under the REMS, prescriber education and certification will be required and distribution of the product will be restricted, according to the company.

The product is available in single-use vials; the recommended dosing is 3 mL (750 mg) at the start of treatment, at 4 weeks, and then at 10-week intervals. After each injection, patients are observed for symptoms of pulmonary oil microembolism (POME) or anaphylaxis for 30 minutes in the physician’s office, clinic, or hospital, the only places where the drug can be administered. Symptoms of serious POME reactions include an urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope.

Since Endo filed for approval in 2007, approval of TU has been held up for safety reasons, namely reports of anaphylaxis and POME during or shortly after injections were administered, in clinical and postmarketing studies in countries where the product was approved. At a meeting in April 2013, the FDA’s Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee split on the safety issue, voting 9-9 on whether they believed the drug had an acceptable safety profile for the proposed use.

Approval was based on the results of a phase III, 84-week, single-arm study of 130 hypogonadal men (mean age, 54 years), which determined that TU was an effective testosterone replacement therapy, based on serum testosterone levels. There was one case of a patient who had mild coughing after the third injection, which was later attributed to POME, according to the prescribing information.

But more cases have been reported after approval in countries outside the United States and in a review of 18 clinical studies; where possible cases of POME were adjudicated, of about 3,500 patients there were 9 cases of POME in 8 patients and 2 cases of anaphylaxis.

The product has been available since 2003 outside the United States, where it is marketed by Bayer Pharma and its subsidiaries.

The company is providing information about the REMS at www.AveedREMS.com and 855-755-0494.

Serious adverse events associated with testosterone undecanoate should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

[email protected]

A long-acting intramuscular formulation of testosterone has been approved by the Food and Drug Administration for treating hypogonadism, with a label that includes a boxed warning about the risks of pulmonary oil microembolism and anaphylaxis associated with treatment.

The depot formulation of testosterone undecanoate (TU), in castor oil and benzoyl benzoate, has been approved for treating adult men with primary hypogonadism or hypogonadotropic hypogonadism, congenital or acquired. The indications section includes the statement that it "should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis."

The drug will be available, with restrictions, through the Aveed Risk Evaluation and Mitigation Strategy (REMS), according to the manufacturer, Endo Pharmaceuticals, which is marketing the product as Aveed. Under the REMS, prescriber education and certification will be required and distribution of the product will be restricted, according to the company.

The product is available in single-use vials; the recommended dosing is 3 mL (750 mg) at the start of treatment, at 4 weeks, and then at 10-week intervals. After each injection, patients are observed for symptoms of pulmonary oil microembolism (POME) or anaphylaxis for 30 minutes in the physician’s office, clinic, or hospital, the only places where the drug can be administered. Symptoms of serious POME reactions include an urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope.

Since Endo filed for approval in 2007, approval of TU has been held up for safety reasons, namely reports of anaphylaxis and POME during or shortly after injections were administered, in clinical and postmarketing studies in countries where the product was approved. At a meeting in April 2013, the FDA’s Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee split on the safety issue, voting 9-9 on whether they believed the drug had an acceptable safety profile for the proposed use.

Approval was based on the results of a phase III, 84-week, single-arm study of 130 hypogonadal men (mean age, 54 years), which determined that TU was an effective testosterone replacement therapy, based on serum testosterone levels. There was one case of a patient who had mild coughing after the third injection, which was later attributed to POME, according to the prescribing information.

But more cases have been reported after approval in countries outside the United States and in a review of 18 clinical studies; where possible cases of POME were adjudicated, of about 3,500 patients there were 9 cases of POME in 8 patients and 2 cases of anaphylaxis.

The product has been available since 2003 outside the United States, where it is marketed by Bayer Pharma and its subsidiaries.

The company is providing information about the REMS at www.AveedREMS.com and 855-755-0494.

Serious adverse events associated with testosterone undecanoate should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

[email protected]

A long-acting intramuscular formulation of testosterone has been approved by the Food and Drug Administration for treating hypogonadism, with a label that includes a boxed warning about the risks of pulmonary oil microembolism and anaphylaxis associated with treatment.

The depot formulation of testosterone undecanoate (TU), in castor oil and benzoyl benzoate, has been approved for treating adult men with primary hypogonadism or hypogonadotropic hypogonadism, congenital or acquired. The indications section includes the statement that it "should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis."

The drug will be available, with restrictions, through the Aveed Risk Evaluation and Mitigation Strategy (REMS), according to the manufacturer, Endo Pharmaceuticals, which is marketing the product as Aveed. Under the REMS, prescriber education and certification will be required and distribution of the product will be restricted, according to the company.

The product is available in single-use vials; the recommended dosing is 3 mL (750 mg) at the start of treatment, at 4 weeks, and then at 10-week intervals. After each injection, patients are observed for symptoms of pulmonary oil microembolism (POME) or anaphylaxis for 30 minutes in the physician’s office, clinic, or hospital, the only places where the drug can be administered. Symptoms of serious POME reactions include an urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope.

Since Endo filed for approval in 2007, approval of TU has been held up for safety reasons, namely reports of anaphylaxis and POME during or shortly after injections were administered, in clinical and postmarketing studies in countries where the product was approved. At a meeting in April 2013, the FDA’s Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee split on the safety issue, voting 9-9 on whether they believed the drug had an acceptable safety profile for the proposed use.

Approval was based on the results of a phase III, 84-week, single-arm study of 130 hypogonadal men (mean age, 54 years), which determined that TU was an effective testosterone replacement therapy, based on serum testosterone levels. There was one case of a patient who had mild coughing after the third injection, which was later attributed to POME, according to the prescribing information.

But more cases have been reported after approval in countries outside the United States and in a review of 18 clinical studies; where possible cases of POME were adjudicated, of about 3,500 patients there were 9 cases of POME in 8 patients and 2 cases of anaphylaxis.

The product has been available since 2003 outside the United States, where it is marketed by Bayer Pharma and its subsidiaries.

The company is providing information about the REMS at www.AveedREMS.com and 855-755-0494.

Serious adverse events associated with testosterone undecanoate should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

[email protected]

Preimplant biopsy of donor kidneys doesn’t accurately predict the organs’ viability and leads to many acceptable kidneys being discarded, according to two separate reports published online in the Clinical Journal of the American Society of Nephrology.

Biopsies are obtained routinely from donor kidneys in the United States, and unfavorable biopsy findings are the most frequently cited reason for discarding donor kidneys as unacceptable. Ideally, such samples would be obtained by core needle biopsy, would not be frozen, would be thoroughly examined by a pathologist with special training in reading kidney biopsies, and would be assessed meticulously for chronic tubular atrophy, arteriolar hyalinosis, interstitial inflammation, interstitial fibrosis, and the presence and severity of acute tubular necrosis.

In actual practice, however, these samples are almost always obtained by wedge biopsy, are frozen, and are rushed through a perfunctory examination by whatever pathologist is available so that the organ can be transplanted as quickly as possible if it is found to be acceptable. So many clinicians have questioned whether the results of such biopsies actually assess the organs’ viability and predict graft failure, both groups of researchers noted.

In what they described as the largest cohort study to date on this issue, one team analyzed data regarding 651 consecutive kidney transplants performed during a 2-year period, for which four organ procurement organizations obtained the kidneys from 369 deceased donors. The four organizations performed wedge biopsies immediately after procurement, and different pathology services evaluated frozen sections from these organs and reported their findings to potential transplant centers.

Patient outcomes were tracked using information in the United Network for Organ Sharing (UNOS) database, said Dr. Isaac E. Hall of the section of nephrology and the program of applied translational research, Yale University, New Haven, Conn., and his associates.

They assessed whether a biopsy finding of acute tubular necrosis correlated with the graft’s performance after transplantation. Acute tubular necrosis was reported in 110 biopsies (17%) overall. The four procurement organizations varied widely in their reported rates of the abnormality, from a low of zero cases to a high of 25% of cases. This variation suggests that the process of obtaining and interpreting these biopsies is, at best, not uniform among procurement groups, according to the investigators.

During a median follow-up of 1 year, the primary outcome of interest – delayed graft function – occurred in 45% of kidneys that were reported to have tubular necrosis and in 39% of those reportedly free of such necrosis. This is a nonsignificant difference. There also was no significant difference in the secondary outcome of graft failure between recipients of organs with acute tubular necrosis, compared with recipients of organs without it.

In summary, there was no significant association between biopsy reports of acute tubular necrosis and graft viability. "It is reasonable to question whether acute tubular necrosis, or acute kidney injury in general for that matter, truly causes important allograft outcomes," Dr. Hall and his colleagues wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.08270813]).

In the second study, Dr. Bertram L. Kasiske of the Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, and his associates assessed the records for 83 kidneys that were discarded because of unfavorable biopsy findings (cases) and 83 contralateral kidneys from the same donors that were transplanted (contralateral controls). They compared these findings with those for 151 transplanted kidneys from 83 deceased donors who were matched for the index cases’ donor profiles.

"Ours is the first controlled study to compare biopsy findings between discarded kidneys and matched transplanted kidneys," Dr. Kasiske and his colleagues noted.

They found that most of the biopsy reports were of low quality, and very few indicated the amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, or acute tubular necrosis. The percentage of glomerulosclerosis was often the only finding upon which to base the decision of whether to use or discard the allograft.

But the percentage of glomerulosclerosis overlapped substantially between cases (discarded kidneys) and controls (transplanted kidneys). This suggests that "information obtained from procurement biopsies is of low quality and may lead to unnecessary discard of transplantable kidneys," Dr. Kasiske and his associates wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.07610713]).

"A reasonable conclusion from this and other studies is that the widespread practice of routinely obtaining procurement biopsies should be abandoned, as has been successfully done in Europe," they noted.

Dr. Hall’s study was supported by the American Heart Association, the Roche Organ Transplantation Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Health Resources and Services Administration. Dr. Kasiske’s study was supported by the Minneapolis Medical Research Foundation, the Organ Procurement and Transplantation Network, the Scientific Registry of Transplant Recipients, and the United Network for Organ Sharing. Both research groups reported no potential financial conflicts of interest.

Preimplant biopsy of donor kidneys doesn’t accurately predict the organs’ viability and leads to many acceptable kidneys being discarded, according to two separate reports published online in the Clinical Journal of the American Society of Nephrology.

Biopsies are obtained routinely from donor kidneys in the United States, and unfavorable biopsy findings are the most frequently cited reason for discarding donor kidneys as unacceptable. Ideally, such samples would be obtained by core needle biopsy, would not be frozen, would be thoroughly examined by a pathologist with special training in reading kidney biopsies, and would be assessed meticulously for chronic tubular atrophy, arteriolar hyalinosis, interstitial inflammation, interstitial fibrosis, and the presence and severity of acute tubular necrosis.

In actual practice, however, these samples are almost always obtained by wedge biopsy, are frozen, and are rushed through a perfunctory examination by whatever pathologist is available so that the organ can be transplanted as quickly as possible if it is found to be acceptable. So many clinicians have questioned whether the results of such biopsies actually assess the organs’ viability and predict graft failure, both groups of researchers noted.

In what they described as the largest cohort study to date on this issue, one team analyzed data regarding 651 consecutive kidney transplants performed during a 2-year period, for which four organ procurement organizations obtained the kidneys from 369 deceased donors. The four organizations performed wedge biopsies immediately after procurement, and different pathology services evaluated frozen sections from these organs and reported their findings to potential transplant centers.

Patient outcomes were tracked using information in the United Network for Organ Sharing (UNOS) database, said Dr. Isaac E. Hall of the section of nephrology and the program of applied translational research, Yale University, New Haven, Conn., and his associates.

They assessed whether a biopsy finding of acute tubular necrosis correlated with the graft’s performance after transplantation. Acute tubular necrosis was reported in 110 biopsies (17%) overall. The four procurement organizations varied widely in their reported rates of the abnormality, from a low of zero cases to a high of 25% of cases. This variation suggests that the process of obtaining and interpreting these biopsies is, at best, not uniform among procurement groups, according to the investigators.

During a median follow-up of 1 year, the primary outcome of interest – delayed graft function – occurred in 45% of kidneys that were reported to have tubular necrosis and in 39% of those reportedly free of such necrosis. This is a nonsignificant difference. There also was no significant difference in the secondary outcome of graft failure between recipients of organs with acute tubular necrosis, compared with recipients of organs without it.

In summary, there was no significant association between biopsy reports of acute tubular necrosis and graft viability. "It is reasonable to question whether acute tubular necrosis, or acute kidney injury in general for that matter, truly causes important allograft outcomes," Dr. Hall and his colleagues wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.08270813]).

In the second study, Dr. Bertram L. Kasiske of the Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, and his associates assessed the records for 83 kidneys that were discarded because of unfavorable biopsy findings (cases) and 83 contralateral kidneys from the same donors that were transplanted (contralateral controls). They compared these findings with those for 151 transplanted kidneys from 83 deceased donors who were matched for the index cases’ donor profiles.

"Ours is the first controlled study to compare biopsy findings between discarded kidneys and matched transplanted kidneys," Dr. Kasiske and his colleagues noted.

They found that most of the biopsy reports were of low quality, and very few indicated the amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, or acute tubular necrosis. The percentage of glomerulosclerosis was often the only finding upon which to base the decision of whether to use or discard the allograft.

But the percentage of glomerulosclerosis overlapped substantially between cases (discarded kidneys) and controls (transplanted kidneys). This suggests that "information obtained from procurement biopsies is of low quality and may lead to unnecessary discard of transplantable kidneys," Dr. Kasiske and his associates wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.07610713]).

"A reasonable conclusion from this and other studies is that the widespread practice of routinely obtaining procurement biopsies should be abandoned, as has been successfully done in Europe," they noted.

Dr. Hall’s study was supported by the American Heart Association, the Roche Organ Transplantation Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Health Resources and Services Administration. Dr. Kasiske’s study was supported by the Minneapolis Medical Research Foundation, the Organ Procurement and Transplantation Network, the Scientific Registry of Transplant Recipients, and the United Network for Organ Sharing. Both research groups reported no potential financial conflicts of interest.

Preimplant biopsy of donor kidneys doesn’t accurately predict the organs’ viability and leads to many acceptable kidneys being discarded, according to two separate reports published online in the Clinical Journal of the American Society of Nephrology.

Biopsies are obtained routinely from donor kidneys in the United States, and unfavorable biopsy findings are the most frequently cited reason for discarding donor kidneys as unacceptable. Ideally, such samples would be obtained by core needle biopsy, would not be frozen, would be thoroughly examined by a pathologist with special training in reading kidney biopsies, and would be assessed meticulously for chronic tubular atrophy, arteriolar hyalinosis, interstitial inflammation, interstitial fibrosis, and the presence and severity of acute tubular necrosis.

In actual practice, however, these samples are almost always obtained by wedge biopsy, are frozen, and are rushed through a perfunctory examination by whatever pathologist is available so that the organ can be transplanted as quickly as possible if it is found to be acceptable. So many clinicians have questioned whether the results of such biopsies actually assess the organs’ viability and predict graft failure, both groups of researchers noted.

In what they described as the largest cohort study to date on this issue, one team analyzed data regarding 651 consecutive kidney transplants performed during a 2-year period, for which four organ procurement organizations obtained the kidneys from 369 deceased donors. The four organizations performed wedge biopsies immediately after procurement, and different pathology services evaluated frozen sections from these organs and reported their findings to potential transplant centers.

Patient outcomes were tracked using information in the United Network for Organ Sharing (UNOS) database, said Dr. Isaac E. Hall of the section of nephrology and the program of applied translational research, Yale University, New Haven, Conn., and his associates.

They assessed whether a biopsy finding of acute tubular necrosis correlated with the graft’s performance after transplantation. Acute tubular necrosis was reported in 110 biopsies (17%) overall. The four procurement organizations varied widely in their reported rates of the abnormality, from a low of zero cases to a high of 25% of cases. This variation suggests that the process of obtaining and interpreting these biopsies is, at best, not uniform among procurement groups, according to the investigators.

During a median follow-up of 1 year, the primary outcome of interest – delayed graft function – occurred in 45% of kidneys that were reported to have tubular necrosis and in 39% of those reportedly free of such necrosis. This is a nonsignificant difference. There also was no significant difference in the secondary outcome of graft failure between recipients of organs with acute tubular necrosis, compared with recipients of organs without it.

In summary, there was no significant association between biopsy reports of acute tubular necrosis and graft viability. "It is reasonable to question whether acute tubular necrosis, or acute kidney injury in general for that matter, truly causes important allograft outcomes," Dr. Hall and his colleagues wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.08270813]).

In the second study, Dr. Bertram L. Kasiske of the Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, and his associates assessed the records for 83 kidneys that were discarded because of unfavorable biopsy findings (cases) and 83 contralateral kidneys from the same donors that were transplanted (contralateral controls). They compared these findings with those for 151 transplanted kidneys from 83 deceased donors who were matched for the index cases’ donor profiles.

"Ours is the first controlled study to compare biopsy findings between discarded kidneys and matched transplanted kidneys," Dr. Kasiske and his colleagues noted.

They found that most of the biopsy reports were of low quality, and very few indicated the amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, or acute tubular necrosis. The percentage of glomerulosclerosis was often the only finding upon which to base the decision of whether to use or discard the allograft.

But the percentage of glomerulosclerosis overlapped substantially between cases (discarded kidneys) and controls (transplanted kidneys). This suggests that "information obtained from procurement biopsies is of low quality and may lead to unnecessary discard of transplantable kidneys," Dr. Kasiske and his associates wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.07610713]).

"A reasonable conclusion from this and other studies is that the widespread practice of routinely obtaining procurement biopsies should be abandoned, as has been successfully done in Europe," they noted.

Dr. Hall’s study was supported by the American Heart Association, the Roche Organ Transplantation Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Health Resources and Services Administration. Dr. Kasiske’s study was supported by the Minneapolis Medical Research Foundation, the Organ Procurement and Transplantation Network, the Scientific Registry of Transplant Recipients, and the United Network for Organ Sharing. Both research groups reported no potential financial conflicts of interest.