Nephrology

After 13 years of follow-up, men who underwent annual screening for prostate cancer were no less likely to die of prostate cancer than were men who received usual care and opportunistic screening.

Cumulative mortality rates from prostate cancer differed by a statistically insignificant rate of 0.3 deaths per 10,000 person years in the intervention and usual-care arms of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, published online Jan. 6 in the Journal of the National Cancer Institute. Further, age, comorbidity status, and pretrial prostate-specific antigen (PSA) testing did not influence the results, wrote Dr. Gerald L. Andriole of Washington University, St. Louis, and his colleagues.

The PLCO trial randomly assigned 76,693 men, aged 55-74 years, to either 6 years of annual PSA screening in combination with 4 years of annual digital rectal examination (38,343) or to usual care (38,350), which included screening tests as recommended by physicians.

The goal was to evaluate the effect of adding annual screening and compare outcomes to the opportunistic screening already in place, the researchers said. It was expected that the impacts of earlier diagnosis and a persistent excess of cases because of annual screening in the intervention arm would exceed the impacts of opportunistic screening.

Prior to the study, 44% of all participants had undergone PSA screening. During the trial, 52% of the usual-care group, compared with the entire intervention group, underwent PSA testing.

The researchers had previously reported 7- and 10-year follow-up results. At 7 years of follow-up, yearly screening was associated with an increased incidence of prostate cancer diagnosis as compared with usual care. The rates of prostate cancer mortality and of all-cause mortality, however, were the same for both groups. Similarly, after 10 years of follow-up, no mortality benefit was observed for the intervention, the investigators reported previously (N. Engl. J. Med. 2009;360:1320-1328).

For the current study, Dr. Andriole and his associates ascertained all incident prostate cancer diagnoses and deaths through 13 years of follow-up or through December 31, 2009, and estimated relative risks as the ratio of observed rates of diagnoses and deaths in the intervention and control arms. They examined the interactions between prostate cancer mortality by trial arm and age, comorbidities, and pretrial PSA testing using Poisson regression modeling (J. Natl. Cancer Inst. 6 Jan. 2012 [doi: 10.1093/jnci/djr500]).

At 13 years, 4,250 of the 38,340 participants in the intervention arm had been diagnosed with prostate cancer, compared with 3,815 of the 38,345 control participants. "The cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10,000 person-years, respectively, resulting in a statistically significant 12% relative increase in the intervention arm," the authors wrote. Of the prostate cancer diagnoses, 401 in the intervention arm and 454 in the usual care arm were high-grade prostate cancers with Gleason scores of 8-10.

At 13 years of follow-up, there were 158 deaths in the intervention arm and 145 deaths in the usual-care arm. "The cumulative mortality rates from prostate cancer were 3.7 and 3.4 deaths per 10,000 person-years, respectively, resulting in a non-statistically significant difference between the two arms," according to the authors. The examination of mortality rates per 10,000 person-years and relative risks of prostate cancer mortality by age, comorbidity, and pretrial PSA testing produced no statistically significant interactions.

Deaths from all causes other than prostate, lung, and colorectal cancers differed by a factor of "borderline" statistical significance, with 5,783 deaths in the intervention arm and 5,982 in the usual-care arm, Dr. Andriole and his associates wrote. "Intervention and control arms showed 23% and 22% deaths, respectively, from non-PLCO cancers, and 21% and 19% deaths, respectively, from ischemic heart disease."

The authors acknowledged limitations of the study, including the possibility that a reduction in prostate cancer mortality in the analysis has somehow been masked by "the sticking diagnosis effect." In other words, more deaths were attributed to prostate cancer in the intervention arm. This possibility is supported by the statistically significant lower all-cause mortality in the intervention group as compared with the usual-care group. The percentage of deaths from other causes was higher in the intervention arm, so an error in cause of death attribution likely does not account for the excess prostate cancer deaths in the intervention group, they concluded.

The investigators plan to update the mortality findings through 15 years of follow-up, when those data become available.

Some of the study authors report relationships with Amgen, Augmenix, Bayer, Cambridge Endo, Caris, Envisioneering Medical, France Foundation, GenProbe, GlaxoSmithKline, Human Genome Sciences, Myriad Genetics, Steba Biotech, Ortho Clinical Diagnostics, and Viking Medical.

After 13 years of follow-up, men who underwent annual screening for prostate cancer were no less likely to die of prostate cancer than were men who received usual care and opportunistic screening.

Cumulative mortality rates from prostate cancer differed by a statistically insignificant rate of 0.3 deaths per 10,000 person years in the intervention and usual-care arms of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, published online Jan. 6 in the Journal of the National Cancer Institute. Further, age, comorbidity status, and pretrial prostate-specific antigen (PSA) testing did not influence the results, wrote Dr. Gerald L. Andriole of Washington University, St. Louis, and his colleagues.

The PLCO trial randomly assigned 76,693 men, aged 55-74 years, to either 6 years of annual PSA screening in combination with 4 years of annual digital rectal examination (38,343) or to usual care (38,350), which included screening tests as recommended by physicians.

The goal was to evaluate the effect of adding annual screening and compare outcomes to the opportunistic screening already in place, the researchers said. It was expected that the impacts of earlier diagnosis and a persistent excess of cases because of annual screening in the intervention arm would exceed the impacts of opportunistic screening.

Prior to the study, 44% of all participants had undergone PSA screening. During the trial, 52% of the usual-care group, compared with the entire intervention group, underwent PSA testing.

The researchers had previously reported 7- and 10-year follow-up results. At 7 years of follow-up, yearly screening was associated with an increased incidence of prostate cancer diagnosis as compared with usual care. The rates of prostate cancer mortality and of all-cause mortality, however, were the same for both groups. Similarly, after 10 years of follow-up, no mortality benefit was observed for the intervention, the investigators reported previously (N. Engl. J. Med. 2009;360:1320-1328).

For the current study, Dr. Andriole and his associates ascertained all incident prostate cancer diagnoses and deaths through 13 years of follow-up or through December 31, 2009, and estimated relative risks as the ratio of observed rates of diagnoses and deaths in the intervention and control arms. They examined the interactions between prostate cancer mortality by trial arm and age, comorbidities, and pretrial PSA testing using Poisson regression modeling (J. Natl. Cancer Inst. 6 Jan. 2012 [doi: 10.1093/jnci/djr500]).

At 13 years, 4,250 of the 38,340 participants in the intervention arm had been diagnosed with prostate cancer, compared with 3,815 of the 38,345 control participants. "The cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10,000 person-years, respectively, resulting in a statistically significant 12% relative increase in the intervention arm," the authors wrote. Of the prostate cancer diagnoses, 401 in the intervention arm and 454 in the usual care arm were high-grade prostate cancers with Gleason scores of 8-10.

At 13 years of follow-up, there were 158 deaths in the intervention arm and 145 deaths in the usual-care arm. "The cumulative mortality rates from prostate cancer were 3.7 and 3.4 deaths per 10,000 person-years, respectively, resulting in a non-statistically significant difference between the two arms," according to the authors. The examination of mortality rates per 10,000 person-years and relative risks of prostate cancer mortality by age, comorbidity, and pretrial PSA testing produced no statistically significant interactions.

Deaths from all causes other than prostate, lung, and colorectal cancers differed by a factor of "borderline" statistical significance, with 5,783 deaths in the intervention arm and 5,982 in the usual-care arm, Dr. Andriole and his associates wrote. "Intervention and control arms showed 23% and 22% deaths, respectively, from non-PLCO cancers, and 21% and 19% deaths, respectively, from ischemic heart disease."

The authors acknowledged limitations of the study, including the possibility that a reduction in prostate cancer mortality in the analysis has somehow been masked by "the sticking diagnosis effect." In other words, more deaths were attributed to prostate cancer in the intervention arm. This possibility is supported by the statistically significant lower all-cause mortality in the intervention group as compared with the usual-care group. The percentage of deaths from other causes was higher in the intervention arm, so an error in cause of death attribution likely does not account for the excess prostate cancer deaths in the intervention group, they concluded.

The investigators plan to update the mortality findings through 15 years of follow-up, when those data become available.

Some of the study authors report relationships with Amgen, Augmenix, Bayer, Cambridge Endo, Caris, Envisioneering Medical, France Foundation, GenProbe, GlaxoSmithKline, Human Genome Sciences, Myriad Genetics, Steba Biotech, Ortho Clinical Diagnostics, and Viking Medical.

After 13 years of follow-up, men who underwent annual screening for prostate cancer were no less likely to die of prostate cancer than were men who received usual care and opportunistic screening.

Cumulative mortality rates from prostate cancer differed by a statistically insignificant rate of 0.3 deaths per 10,000 person years in the intervention and usual-care arms of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, published online Jan. 6 in the Journal of the National Cancer Institute. Further, age, comorbidity status, and pretrial prostate-specific antigen (PSA) testing did not influence the results, wrote Dr. Gerald L. Andriole of Washington University, St. Louis, and his colleagues.

The PLCO trial randomly assigned 76,693 men, aged 55-74 years, to either 6 years of annual PSA screening in combination with 4 years of annual digital rectal examination (38,343) or to usual care (38,350), which included screening tests as recommended by physicians.

The goal was to evaluate the effect of adding annual screening and compare outcomes to the opportunistic screening already in place, the researchers said. It was expected that the impacts of earlier diagnosis and a persistent excess of cases because of annual screening in the intervention arm would exceed the impacts of opportunistic screening.

Prior to the study, 44% of all participants had undergone PSA screening. During the trial, 52% of the usual-care group, compared with the entire intervention group, underwent PSA testing.

The researchers had previously reported 7- and 10-year follow-up results. At 7 years of follow-up, yearly screening was associated with an increased incidence of prostate cancer diagnosis as compared with usual care. The rates of prostate cancer mortality and of all-cause mortality, however, were the same for both groups. Similarly, after 10 years of follow-up, no mortality benefit was observed for the intervention, the investigators reported previously (N. Engl. J. Med. 2009;360:1320-1328).

For the current study, Dr. Andriole and his associates ascertained all incident prostate cancer diagnoses and deaths through 13 years of follow-up or through December 31, 2009, and estimated relative risks as the ratio of observed rates of diagnoses and deaths in the intervention and control arms. They examined the interactions between prostate cancer mortality by trial arm and age, comorbidities, and pretrial PSA testing using Poisson regression modeling (J. Natl. Cancer Inst. 6 Jan. 2012 [doi: 10.1093/jnci/djr500]).

At 13 years, 4,250 of the 38,340 participants in the intervention arm had been diagnosed with prostate cancer, compared with 3,815 of the 38,345 control participants. "The cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10,000 person-years, respectively, resulting in a statistically significant 12% relative increase in the intervention arm," the authors wrote. Of the prostate cancer diagnoses, 401 in the intervention arm and 454 in the usual care arm were high-grade prostate cancers with Gleason scores of 8-10.

At 13 years of follow-up, there were 158 deaths in the intervention arm and 145 deaths in the usual-care arm. "The cumulative mortality rates from prostate cancer were 3.7 and 3.4 deaths per 10,000 person-years, respectively, resulting in a non-statistically significant difference between the two arms," according to the authors. The examination of mortality rates per 10,000 person-years and relative risks of prostate cancer mortality by age, comorbidity, and pretrial PSA testing produced no statistically significant interactions.

Deaths from all causes other than prostate, lung, and colorectal cancers differed by a factor of "borderline" statistical significance, with 5,783 deaths in the intervention arm and 5,982 in the usual-care arm, Dr. Andriole and his associates wrote. "Intervention and control arms showed 23% and 22% deaths, respectively, from non-PLCO cancers, and 21% and 19% deaths, respectively, from ischemic heart disease."

The authors acknowledged limitations of the study, including the possibility that a reduction in prostate cancer mortality in the analysis has somehow been masked by "the sticking diagnosis effect." In other words, more deaths were attributed to prostate cancer in the intervention arm. This possibility is supported by the statistically significant lower all-cause mortality in the intervention group as compared with the usual-care group. The percentage of deaths from other causes was higher in the intervention arm, so an error in cause of death attribution likely does not account for the excess prostate cancer deaths in the intervention group, they concluded.

The investigators plan to update the mortality findings through 15 years of follow-up, when those data become available.

Some of the study authors report relationships with Amgen, Augmenix, Bayer, Cambridge Endo, Caris, Envisioneering Medical, France Foundation, GenProbe, GlaxoSmithKline, Human Genome Sciences, Myriad Genetics, Steba Biotech, Ortho Clinical Diagnostics, and Viking Medical.

BALTIMORE – The safety profile for retigabine is generally consistent with that of other antiepileptic drugs, but data from studies in its evaluation process show that it also carries a novel, small increased risk of urinary voiding dysfunction.

At the annual meeting of the American Epilepsy Society Dr. Neil Brickel of GlaxoSmithKline’s clinical safety and pharmacovigilance group in Middlesex, England, reported on the safety of the novel drug in three phase III, randomized, double-blind, placebo-controlled trials, four phase II studies, and six long-term open-label extension studies, totalling 1,365 patients.

Retigabine is the international nonproprietary name of the drug, but it was approved in the United States in June 2011 under the adopted name ezogabine as an adjunctive therapy in adults with partial-onset seizures. It is a first-in-class potassium channel opener manufactured by GlaxoSmithKline and Valeant Pharmaceuticals International, and sold under the brand name Trobalt in Europe and Potiga in the United States.

In all of the studies that Dr. Brickel analyzed, retigabine was evaluated as a second, add-on agent. As of Oct. 2, 2009, 1,217 of the 1,365 patients had been on treatment at least 1 month, 801 for at least 6 months, and 586 for 1 year or longer.

As expected with any antiepileptic drug (AED), the most frequent adverse events involved the central nervous system. The most common in the three pivotal controlled trials were dizziness (23% of retigabine-treated patients vs. 9% of placebo-treated patients) and somnolence (reported by 22% vs. 12%, respectively). The only CNS adverse events that were not dose related were headache (reported by 15% of the retigabine group vs. 16% of the placebo group) and fatigue (by 15% and 6%, respectively). Other adverse events occurring in more than 10% of subjects were confusional state, tremor, and abnormal coordination. For the most part, patients reported these adverse events early on, during the titration phases of the trials, Dr. Brickel said.

Adverse events led to discontinuation in 437 patients (32%) of the total phase II/III study population. Again, these were primarily CNS and dose related. Discontinuations for any event occurred in 11% of the placebo group. Among those taking retigabine, discontinuations occurred in 17% of those assigned to 600 mg, 25% of those assigned to 900 mg, and 31% of those assigned to 1,200 mg. The most common reason for discontinuation was dizziness.

"Two-thirds of patients were able to continue in the study, even with the fixed titration regimen and at the 1,200-mg dose," Dr. Brickel noted.

Serious adverse events (SAEs) were infrequent, and also typically CNS related. In the three pivotal controlled trials, SAEs occurred in 6% of the placebo group and 9% of the retigabine patients. Six of the patients taking retigabine developed a psychotic disorder (five with 1,200 mg, one with 900 mg), compared with none of the placebo patients. Convulsions occurred in 1.2% of the placebo group and in 1.5% of the retigabine patients, across all doses. This finding was not unexpected, considering the underlying epilepsy, he said.

No other SAE was reported in more than two patients in any group. Deaths occurred in three placebo patients and two patients in the retigabine group. One in each group was a sudden death.

In the three pivotal trials, urinary and renal-related adverse events occurred in 17% of retigabine patients, compared with 13% of the placebo-treated patients. In the entire phase II/III study population, 26% of the 1,365 patients reported a urinary adverse event.

However, events related to urinary voiding dysfunction, which have a plausible biological relation to retigabine’s pharmacology, occurred in less than 4% of retigabine-treated patients in the phase III trials alone and in all phase II and III trial populations combined. Urinary hesitation was the most common of these in the entire phase II and III study group, occurring in 3.1%, followed by urinary retention in 1.9%. Catheterization was required in four patients taking retigabine and in one patient on placebo.

"These all occurred in a smaller number of patients and provide a better guide as to how many patents are potentially at risk. It is also important to note that these events were for the most part ‘mild’ in intensity and the patients were able to continue treatment," Dr. Brickel said in an interview.

Dr. Brickel also said that GSK is "communicating these risks to potential prescribers and encouraging them to advise patients of the symptoms relating to difficulty in passing urine that could range from discomfort on bladder emptying, hesitancy, poor flow through to a complete inability to void (acute urinary retention). GSK is keen to proactively manage this."

The study was funded by GSK and Valeant Pharmaceuticals International, and all of the investigators are employees of either company.

BALTIMORE – The safety profile for retigabine is generally consistent with that of other antiepileptic drugs, but data from studies in its evaluation process show that it also carries a novel, small increased risk of urinary voiding dysfunction.

At the annual meeting of the American Epilepsy Society Dr. Neil Brickel of GlaxoSmithKline’s clinical safety and pharmacovigilance group in Middlesex, England, reported on the safety of the novel drug in three phase III, randomized, double-blind, placebo-controlled trials, four phase II studies, and six long-term open-label extension studies, totalling 1,365 patients.

Retigabine is the international nonproprietary name of the drug, but it was approved in the United States in June 2011 under the adopted name ezogabine as an adjunctive therapy in adults with partial-onset seizures. It is a first-in-class potassium channel opener manufactured by GlaxoSmithKline and Valeant Pharmaceuticals International, and sold under the brand name Trobalt in Europe and Potiga in the United States.

In all of the studies that Dr. Brickel analyzed, retigabine was evaluated as a second, add-on agent. As of Oct. 2, 2009, 1,217 of the 1,365 patients had been on treatment at least 1 month, 801 for at least 6 months, and 586 for 1 year or longer.

As expected with any antiepileptic drug (AED), the most frequent adverse events involved the central nervous system. The most common in the three pivotal controlled trials were dizziness (23% of retigabine-treated patients vs. 9% of placebo-treated patients) and somnolence (reported by 22% vs. 12%, respectively). The only CNS adverse events that were not dose related were headache (reported by 15% of the retigabine group vs. 16% of the placebo group) and fatigue (by 15% and 6%, respectively). Other adverse events occurring in more than 10% of subjects were confusional state, tremor, and abnormal coordination. For the most part, patients reported these adverse events early on, during the titration phases of the trials, Dr. Brickel said.

Adverse events led to discontinuation in 437 patients (32%) of the total phase II/III study population. Again, these were primarily CNS and dose related. Discontinuations for any event occurred in 11% of the placebo group. Among those taking retigabine, discontinuations occurred in 17% of those assigned to 600 mg, 25% of those assigned to 900 mg, and 31% of those assigned to 1,200 mg. The most common reason for discontinuation was dizziness.

"Two-thirds of patients were able to continue in the study, even with the fixed titration regimen and at the 1,200-mg dose," Dr. Brickel noted.

Serious adverse events (SAEs) were infrequent, and also typically CNS related. In the three pivotal controlled trials, SAEs occurred in 6% of the placebo group and 9% of the retigabine patients. Six of the patients taking retigabine developed a psychotic disorder (five with 1,200 mg, one with 900 mg), compared with none of the placebo patients. Convulsions occurred in 1.2% of the placebo group and in 1.5% of the retigabine patients, across all doses. This finding was not unexpected, considering the underlying epilepsy, he said.

No other SAE was reported in more than two patients in any group. Deaths occurred in three placebo patients and two patients in the retigabine group. One in each group was a sudden death.

In the three pivotal trials, urinary and renal-related adverse events occurred in 17% of retigabine patients, compared with 13% of the placebo-treated patients. In the entire phase II/III study population, 26% of the 1,365 patients reported a urinary adverse event.

However, events related to urinary voiding dysfunction, which have a plausible biological relation to retigabine’s pharmacology, occurred in less than 4% of retigabine-treated patients in the phase III trials alone and in all phase II and III trial populations combined. Urinary hesitation was the most common of these in the entire phase II and III study group, occurring in 3.1%, followed by urinary retention in 1.9%. Catheterization was required in four patients taking retigabine and in one patient on placebo.

"These all occurred in a smaller number of patients and provide a better guide as to how many patents are potentially at risk. It is also important to note that these events were for the most part ‘mild’ in intensity and the patients were able to continue treatment," Dr. Brickel said in an interview.

Dr. Brickel also said that GSK is "communicating these risks to potential prescribers and encouraging them to advise patients of the symptoms relating to difficulty in passing urine that could range from discomfort on bladder emptying, hesitancy, poor flow through to a complete inability to void (acute urinary retention). GSK is keen to proactively manage this."

The study was funded by GSK and Valeant Pharmaceuticals International, and all of the investigators are employees of either company.

BALTIMORE – The safety profile for retigabine is generally consistent with that of other antiepileptic drugs, but data from studies in its evaluation process show that it also carries a novel, small increased risk of urinary voiding dysfunction.

At the annual meeting of the American Epilepsy Society Dr. Neil Brickel of GlaxoSmithKline’s clinical safety and pharmacovigilance group in Middlesex, England, reported on the safety of the novel drug in three phase III, randomized, double-blind, placebo-controlled trials, four phase II studies, and six long-term open-label extension studies, totalling 1,365 patients.

Retigabine is the international nonproprietary name of the drug, but it was approved in the United States in June 2011 under the adopted name ezogabine as an adjunctive therapy in adults with partial-onset seizures. It is a first-in-class potassium channel opener manufactured by GlaxoSmithKline and Valeant Pharmaceuticals International, and sold under the brand name Trobalt in Europe and Potiga in the United States.

In all of the studies that Dr. Brickel analyzed, retigabine was evaluated as a second, add-on agent. As of Oct. 2, 2009, 1,217 of the 1,365 patients had been on treatment at least 1 month, 801 for at least 6 months, and 586 for 1 year or longer.

As expected with any antiepileptic drug (AED), the most frequent adverse events involved the central nervous system. The most common in the three pivotal controlled trials were dizziness (23% of retigabine-treated patients vs. 9% of placebo-treated patients) and somnolence (reported by 22% vs. 12%, respectively). The only CNS adverse events that were not dose related were headache (reported by 15% of the retigabine group vs. 16% of the placebo group) and fatigue (by 15% and 6%, respectively). Other adverse events occurring in more than 10% of subjects were confusional state, tremor, and abnormal coordination. For the most part, patients reported these adverse events early on, during the titration phases of the trials, Dr. Brickel said.

Adverse events led to discontinuation in 437 patients (32%) of the total phase II/III study population. Again, these were primarily CNS and dose related. Discontinuations for any event occurred in 11% of the placebo group. Among those taking retigabine, discontinuations occurred in 17% of those assigned to 600 mg, 25% of those assigned to 900 mg, and 31% of those assigned to 1,200 mg. The most common reason for discontinuation was dizziness.

"Two-thirds of patients were able to continue in the study, even with the fixed titration regimen and at the 1,200-mg dose," Dr. Brickel noted.

Serious adverse events (SAEs) were infrequent, and also typically CNS related. In the three pivotal controlled trials, SAEs occurred in 6% of the placebo group and 9% of the retigabine patients. Six of the patients taking retigabine developed a psychotic disorder (five with 1,200 mg, one with 900 mg), compared with none of the placebo patients. Convulsions occurred in 1.2% of the placebo group and in 1.5% of the retigabine patients, across all doses. This finding was not unexpected, considering the underlying epilepsy, he said.

No other SAE was reported in more than two patients in any group. Deaths occurred in three placebo patients and two patients in the retigabine group. One in each group was a sudden death.

In the three pivotal trials, urinary and renal-related adverse events occurred in 17% of retigabine patients, compared with 13% of the placebo-treated patients. In the entire phase II/III study population, 26% of the 1,365 patients reported a urinary adverse event.

However, events related to urinary voiding dysfunction, which have a plausible biological relation to retigabine’s pharmacology, occurred in less than 4% of retigabine-treated patients in the phase III trials alone and in all phase II and III trial populations combined. Urinary hesitation was the most common of these in the entire phase II and III study group, occurring in 3.1%, followed by urinary retention in 1.9%. Catheterization was required in four patients taking retigabine and in one patient on placebo.

"These all occurred in a smaller number of patients and provide a better guide as to how many patents are potentially at risk. It is also important to note that these events were for the most part ‘mild’ in intensity and the patients were able to continue treatment," Dr. Brickel said in an interview.

Dr. Brickel also said that GSK is "communicating these risks to potential prescribers and encouraging them to advise patients of the symptoms relating to difficulty in passing urine that could range from discomfort on bladder emptying, hesitancy, poor flow through to a complete inability to void (acute urinary retention). GSK is keen to proactively manage this."

The study was funded by GSK and Valeant Pharmaceuticals International, and all of the investigators are employees of either company.

CHICAGO – Fusing MRI with real-time, three-dimensional ultrasound allows for more targeted prostate biopsies and finds additional cancers, compared with standard systematic biopsies.

"This may lead to fewer total biopsies, improved yield and improved confidence for active surveillance," Dr. Daniel J.A. Margolis said at the annual meeting of the Radiological Society of North America.

Direct MRI-guided biopsy is not universally available, leaving most centers to use two-dimensional ultrasound to systematically biopsy 12 areas of the prostate, whether they are all suspicious or not. Not surprising, roughly 30% of systematic core biopsies are false negative, explained radiologist Dr. Margolis of the University of California, Los Angeles.

Researchers at UCLA departments and the medical device company Eigen have been using external-array 3 Tesla MRI scans, including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced images to identify suspicious areas in the prostate. The areas are scored on a 5-point scale by a radiologist based on cancer risk, and the data are used to create a 3-D contoured reconstruction that is fused with real-time, transrectal ultrasound during biopsy.

Early results were promising in the two groups of men most likely to benefit from the new imaging technology – those with a prior negative biopsy and elevated prostate-specific antigen (PSA) levels and those with low-risk prostate cancer under active surveillance. In 47 such men, the biopsy-positivity rate was 33% with MRI-fusion ultrasound vs. 7% for systematic, nontargeted biopsy (Urol. Oncol. 2011;29:334-42).

At the meeting, Dr. Margolis presented data from 57 consecutive men with a previous biopsy, in whom MRI-fusion ultrasound identified 101 suspicious areas. In all, 22 men had 28 positive MRI targets.

Positive biopsies were found in 12 patients on targets only. Nine patients had positive lesions on both MRI-fusion ultrasound and systematic biopsy. In one additional patient, the positive systematic core was changed from Gleason 3+3 to 3+4 disease with the targeted biopsy.

Seven patients had positive biopsies found on systematic biopsy only, although all were Gleason score 3+3, less than 4 mm in size and less than 25% of the core, Dr. Margolis said.

A separate study presented in the same session suggests that fusing MRI with transrectal ultrasound biopsy may also be useful in identifying aggressive tumors in men with no prior prostate biopsy or suspicious digital rectal exam and a PSA of 3-10 ng/mL (mean 8 ng/mL).

The overall cancer detection rate was 52% among 323 (168/323) such men, 73% within MRI targets (144/197) and 19% with sextant biopsy (24/126), reported Dr. François Cornud, a consultant radiologist at René Descartes University, Paris.

In 98 patients with both MRI targeted- and sextant-positive biopsies, targeted biopsies identified significantly more cancers with a Gleason score greater than 6 (44% vs. 25%), with a length in any core of more than 7 mm (50% vs. 25.5%) and with a longer mean length (5.3 mm vs. 0.8 mm).

Interestingly, performance was similar whether the multiparametric MRI data were fused with the real-time ultrasound images visually or by a computerized electromagnetic navigator system.

"Targeted biopsies definitely provide better evaluation of tumor burden and Gleason score," Dr. Cornud said, adding that "a negative MRI prior to biopsy may mean no cancer or indolent cancer and may suggest that in these patients biopsy may be deferred."

Both studies were well received, although one attendee questioned whether the researchers have been able to convince frequently reluctant urologists that targeted biopsies are worth it. Dr. Margolis said his project was actually instigated by an urologist. Dr. Cornud said the majority of his urologists are now requesting an MRI and its findings.

Dr. Margolis reported a research grant from Siemens AG and a coauthor reported conflicts with several pharmaceutical and device firms. Dr. Cornud and his coauthors reported no relevant disclosures.

CHICAGO – Fusing MRI with real-time, three-dimensional ultrasound allows for more targeted prostate biopsies and finds additional cancers, compared with standard systematic biopsies.

"This may lead to fewer total biopsies, improved yield and improved confidence for active surveillance," Dr. Daniel J.A. Margolis said at the annual meeting of the Radiological Society of North America.

Direct MRI-guided biopsy is not universally available, leaving most centers to use two-dimensional ultrasound to systematically biopsy 12 areas of the prostate, whether they are all suspicious or not. Not surprising, roughly 30% of systematic core biopsies are false negative, explained radiologist Dr. Margolis of the University of California, Los Angeles.

Researchers at UCLA departments and the medical device company Eigen have been using external-array 3 Tesla MRI scans, including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced images to identify suspicious areas in the prostate. The areas are scored on a 5-point scale by a radiologist based on cancer risk, and the data are used to create a 3-D contoured reconstruction that is fused with real-time, transrectal ultrasound during biopsy.

Early results were promising in the two groups of men most likely to benefit from the new imaging technology – those with a prior negative biopsy and elevated prostate-specific antigen (PSA) levels and those with low-risk prostate cancer under active surveillance. In 47 such men, the biopsy-positivity rate was 33% with MRI-fusion ultrasound vs. 7% for systematic, nontargeted biopsy (Urol. Oncol. 2011;29:334-42).

At the meeting, Dr. Margolis presented data from 57 consecutive men with a previous biopsy, in whom MRI-fusion ultrasound identified 101 suspicious areas. In all, 22 men had 28 positive MRI targets.

Positive biopsies were found in 12 patients on targets only. Nine patients had positive lesions on both MRI-fusion ultrasound and systematic biopsy. In one additional patient, the positive systematic core was changed from Gleason 3+3 to 3+4 disease with the targeted biopsy.

Seven patients had positive biopsies found on systematic biopsy only, although all were Gleason score 3+3, less than 4 mm in size and less than 25% of the core, Dr. Margolis said.

A separate study presented in the same session suggests that fusing MRI with transrectal ultrasound biopsy may also be useful in identifying aggressive tumors in men with no prior prostate biopsy or suspicious digital rectal exam and a PSA of 3-10 ng/mL (mean 8 ng/mL).

The overall cancer detection rate was 52% among 323 (168/323) such men, 73% within MRI targets (144/197) and 19% with sextant biopsy (24/126), reported Dr. François Cornud, a consultant radiologist at René Descartes University, Paris.

In 98 patients with both MRI targeted- and sextant-positive biopsies, targeted biopsies identified significantly more cancers with a Gleason score greater than 6 (44% vs. 25%), with a length in any core of more than 7 mm (50% vs. 25.5%) and with a longer mean length (5.3 mm vs. 0.8 mm).

Interestingly, performance was similar whether the multiparametric MRI data were fused with the real-time ultrasound images visually or by a computerized electromagnetic navigator system.

"Targeted biopsies definitely provide better evaluation of tumor burden and Gleason score," Dr. Cornud said, adding that "a negative MRI prior to biopsy may mean no cancer or indolent cancer and may suggest that in these patients biopsy may be deferred."

Both studies were well received, although one attendee questioned whether the researchers have been able to convince frequently reluctant urologists that targeted biopsies are worth it. Dr. Margolis said his project was actually instigated by an urologist. Dr. Cornud said the majority of his urologists are now requesting an MRI and its findings.

Dr. Margolis reported a research grant from Siemens AG and a coauthor reported conflicts with several pharmaceutical and device firms. Dr. Cornud and his coauthors reported no relevant disclosures.

CHICAGO – Fusing MRI with real-time, three-dimensional ultrasound allows for more targeted prostate biopsies and finds additional cancers, compared with standard systematic biopsies.

"This may lead to fewer total biopsies, improved yield and improved confidence for active surveillance," Dr. Daniel J.A. Margolis said at the annual meeting of the Radiological Society of North America.

Direct MRI-guided biopsy is not universally available, leaving most centers to use two-dimensional ultrasound to systematically biopsy 12 areas of the prostate, whether they are all suspicious or not. Not surprising, roughly 30% of systematic core biopsies are false negative, explained radiologist Dr. Margolis of the University of California, Los Angeles.

Researchers at UCLA departments and the medical device company Eigen have been using external-array 3 Tesla MRI scans, including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced images to identify suspicious areas in the prostate. The areas are scored on a 5-point scale by a radiologist based on cancer risk, and the data are used to create a 3-D contoured reconstruction that is fused with real-time, transrectal ultrasound during biopsy.

Early results were promising in the two groups of men most likely to benefit from the new imaging technology – those with a prior negative biopsy and elevated prostate-specific antigen (PSA) levels and those with low-risk prostate cancer under active surveillance. In 47 such men, the biopsy-positivity rate was 33% with MRI-fusion ultrasound vs. 7% for systematic, nontargeted biopsy (Urol. Oncol. 2011;29:334-42).

At the meeting, Dr. Margolis presented data from 57 consecutive men with a previous biopsy, in whom MRI-fusion ultrasound identified 101 suspicious areas. In all, 22 men had 28 positive MRI targets.

Positive biopsies were found in 12 patients on targets only. Nine patients had positive lesions on both MRI-fusion ultrasound and systematic biopsy. In one additional patient, the positive systematic core was changed from Gleason 3+3 to 3+4 disease with the targeted biopsy.

Seven patients had positive biopsies found on systematic biopsy only, although all were Gleason score 3+3, less than 4 mm in size and less than 25% of the core, Dr. Margolis said.

A separate study presented in the same session suggests that fusing MRI with transrectal ultrasound biopsy may also be useful in identifying aggressive tumors in men with no prior prostate biopsy or suspicious digital rectal exam and a PSA of 3-10 ng/mL (mean 8 ng/mL).

The overall cancer detection rate was 52% among 323 (168/323) such men, 73% within MRI targets (144/197) and 19% with sextant biopsy (24/126), reported Dr. François Cornud, a consultant radiologist at René Descartes University, Paris.

In 98 patients with both MRI targeted- and sextant-positive biopsies, targeted biopsies identified significantly more cancers with a Gleason score greater than 6 (44% vs. 25%), with a length in any core of more than 7 mm (50% vs. 25.5%) and with a longer mean length (5.3 mm vs. 0.8 mm).

Interestingly, performance was similar whether the multiparametric MRI data were fused with the real-time ultrasound images visually or by a computerized electromagnetic navigator system.

"Targeted biopsies definitely provide better evaluation of tumor burden and Gleason score," Dr. Cornud said, adding that "a negative MRI prior to biopsy may mean no cancer or indolent cancer and may suggest that in these patients biopsy may be deferred."

Both studies were well received, although one attendee questioned whether the researchers have been able to convince frequently reluctant urologists that targeted biopsies are worth it. Dr. Margolis said his project was actually instigated by an urologist. Dr. Cornud said the majority of his urologists are now requesting an MRI and its findings.

Dr. Margolis reported a research grant from Siemens AG and a coauthor reported conflicts with several pharmaceutical and device firms. Dr. Cornud and his coauthors reported no relevant disclosures.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Dec. 7 voted that peginesatide, a new erythropoiesis-stimulating agent, has a favorable risk-benefit profile when used to treat anemia associated with chronic renal failure in patients who are on dialysis.

At a meeting of the FDA’s Oncologic Drugs Advisory Committee, it voted 15-1 with one abstention on the risk-benefit question. One of the two cardiologists on the panel voted no; the other abstained. The panel did not vote specifically on whether to recommend approval.

Affymax Inc., the manufacturer of peginesatide – a long-acting erythropoiesis-stimulating agent (ESA) administered intravenously or subcutaneously – has proposed that it be approved for the treatment of anemia associated with chronic kidney disease (CKD) in adults who are on dialysis, but not in CKD patients who are not on dialysis or in cancer patients. Peginesatide is administered once a month, which is less frequently than the two ESAs approved in the United States: epoetin alfa, marketed as Epogen and Procrit, and darbepoetin alfa, marketed as Aranesp. A pegylated epoetin beta (Mircera) is not available in the United States.

In two phase III studies of patients with anemia due to CKD who were on dialysis, 1,066 subjects were treated with peginesatide once a month and 542 were treated with epoetin administered one to three times a week. The effectiveness of peginesatide in maintaining hemoglobin levels at 10-12 g/dL through weeks 29-36 of treatment was similar to that of epoetin, with similar low transfusion rates in both groups. The safety profiles, including serious adverse events, deaths during the study, and adverse events resulting in permanent discontinuation of treatment, were similar in both treatment groups.

But in two phase III studies of patients with anemia due to CKD who were not on dialysis, peginesatide appeared to be less safe than darbepoetin. In these two studies, the rates of adverse events, serious adverse events, deaths during the study, adverse events leading to discontinuation as well as adverse cardiovascular outcomes were higher among those on peginesatide than among those on darbepoetin.

Panelists expressed concerned about this safety signal in the patients not on dialysis, but those who voted in favor of peginesatide for the proposed indication agreed that the safety and efficacy of peginesatide were comparable with epoetin in two large randomized studies and cited the convenience of once-a-month dosing for patients. They recommended postmarketing follow-up of these patients to provide longer-term data, since the average length of ESA treatment in patients with CKD is about 5 years and patients in the studies were followed for a little more than 1 year.

The two cardiologists on the panel cited concerns about the studies not being blinded and the possibility that the differences in toxicity in the two patient groups might not be explained pathophysiologically but instead might be the result of stricter entry criteria in the study of patients on dialysis. They also cited the potential for misuse of these drugs in patients.

Targeting higher hemoglobin levels with ESA treatment has been associated with an increased risk of MI and other adverse cardiovascular outcomes in several large clinical trials, which led to changes in treatment recommendations.

In 2007, a boxed warning about the increased risk of deaths and serious cardiovascular events when higher hemoglobin levels are targeted was added to the labels of ESAs, with the recommendation to individualize dosing to target and maintain hemoglobin levels within the 10-12 g/dL range. In 2009, a warning about the increased risk of stroke based on the results of a study of patients with diabetes and CKD who were not on dialysis was added to ESA labels.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Dec. 7 voted that peginesatide, a new erythropoiesis-stimulating agent, has a favorable risk-benefit profile when used to treat anemia associated with chronic renal failure in patients who are on dialysis.

At a meeting of the FDA’s Oncologic Drugs Advisory Committee, it voted 15-1 with one abstention on the risk-benefit question. One of the two cardiologists on the panel voted no; the other abstained. The panel did not vote specifically on whether to recommend approval.

Affymax Inc., the manufacturer of peginesatide – a long-acting erythropoiesis-stimulating agent (ESA) administered intravenously or subcutaneously – has proposed that it be approved for the treatment of anemia associated with chronic kidney disease (CKD) in adults who are on dialysis, but not in CKD patients who are not on dialysis or in cancer patients. Peginesatide is administered once a month, which is less frequently than the two ESAs approved in the United States: epoetin alfa, marketed as Epogen and Procrit, and darbepoetin alfa, marketed as Aranesp. A pegylated epoetin beta (Mircera) is not available in the United States.

In two phase III studies of patients with anemia due to CKD who were on dialysis, 1,066 subjects were treated with peginesatide once a month and 542 were treated with epoetin administered one to three times a week. The effectiveness of peginesatide in maintaining hemoglobin levels at 10-12 g/dL through weeks 29-36 of treatment was similar to that of epoetin, with similar low transfusion rates in both groups. The safety profiles, including serious adverse events, deaths during the study, and adverse events resulting in permanent discontinuation of treatment, were similar in both treatment groups.

But in two phase III studies of patients with anemia due to CKD who were not on dialysis, peginesatide appeared to be less safe than darbepoetin. In these two studies, the rates of adverse events, serious adverse events, deaths during the study, adverse events leading to discontinuation as well as adverse cardiovascular outcomes were higher among those on peginesatide than among those on darbepoetin.

Panelists expressed concerned about this safety signal in the patients not on dialysis, but those who voted in favor of peginesatide for the proposed indication agreed that the safety and efficacy of peginesatide were comparable with epoetin in two large randomized studies and cited the convenience of once-a-month dosing for patients. They recommended postmarketing follow-up of these patients to provide longer-term data, since the average length of ESA treatment in patients with CKD is about 5 years and patients in the studies were followed for a little more than 1 year.

The two cardiologists on the panel cited concerns about the studies not being blinded and the possibility that the differences in toxicity in the two patient groups might not be explained pathophysiologically but instead might be the result of stricter entry criteria in the study of patients on dialysis. They also cited the potential for misuse of these drugs in patients.

Targeting higher hemoglobin levels with ESA treatment has been associated with an increased risk of MI and other adverse cardiovascular outcomes in several large clinical trials, which led to changes in treatment recommendations.

In 2007, a boxed warning about the increased risk of deaths and serious cardiovascular events when higher hemoglobin levels are targeted was added to the labels of ESAs, with the recommendation to individualize dosing to target and maintain hemoglobin levels within the 10-12 g/dL range. In 2009, a warning about the increased risk of stroke based on the results of a study of patients with diabetes and CKD who were not on dialysis was added to ESA labels.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on Dec. 7 voted that peginesatide, a new erythropoiesis-stimulating agent, has a favorable risk-benefit profile when used to treat anemia associated with chronic renal failure in patients who are on dialysis.

At a meeting of the FDA’s Oncologic Drugs Advisory Committee, it voted 15-1 with one abstention on the risk-benefit question. One of the two cardiologists on the panel voted no; the other abstained. The panel did not vote specifically on whether to recommend approval.

Affymax Inc., the manufacturer of peginesatide – a long-acting erythropoiesis-stimulating agent (ESA) administered intravenously or subcutaneously – has proposed that it be approved for the treatment of anemia associated with chronic kidney disease (CKD) in adults who are on dialysis, but not in CKD patients who are not on dialysis or in cancer patients. Peginesatide is administered once a month, which is less frequently than the two ESAs approved in the United States: epoetin alfa, marketed as Epogen and Procrit, and darbepoetin alfa, marketed as Aranesp. A pegylated epoetin beta (Mircera) is not available in the United States.

In two phase III studies of patients with anemia due to CKD who were on dialysis, 1,066 subjects were treated with peginesatide once a month and 542 were treated with epoetin administered one to three times a week. The effectiveness of peginesatide in maintaining hemoglobin levels at 10-12 g/dL through weeks 29-36 of treatment was similar to that of epoetin, with similar low transfusion rates in both groups. The safety profiles, including serious adverse events, deaths during the study, and adverse events resulting in permanent discontinuation of treatment, were similar in both treatment groups.

But in two phase III studies of patients with anemia due to CKD who were not on dialysis, peginesatide appeared to be less safe than darbepoetin. In these two studies, the rates of adverse events, serious adverse events, deaths during the study, adverse events leading to discontinuation as well as adverse cardiovascular outcomes were higher among those on peginesatide than among those on darbepoetin.

Panelists expressed concerned about this safety signal in the patients not on dialysis, but those who voted in favor of peginesatide for the proposed indication agreed that the safety and efficacy of peginesatide were comparable with epoetin in two large randomized studies and cited the convenience of once-a-month dosing for patients. They recommended postmarketing follow-up of these patients to provide longer-term data, since the average length of ESA treatment in patients with CKD is about 5 years and patients in the studies were followed for a little more than 1 year.

The two cardiologists on the panel cited concerns about the studies not being blinded and the possibility that the differences in toxicity in the two patient groups might not be explained pathophysiologically but instead might be the result of stricter entry criteria in the study of patients on dialysis. They also cited the potential for misuse of these drugs in patients.

Targeting higher hemoglobin levels with ESA treatment has been associated with an increased risk of MI and other adverse cardiovascular outcomes in several large clinical trials, which led to changes in treatment recommendations.

In 2007, a boxed warning about the increased risk of deaths and serious cardiovascular events when higher hemoglobin levels are targeted was added to the labels of ESAs, with the recommendation to individualize dosing to target and maintain hemoglobin levels within the 10-12 g/dL range. In 2009, a warning about the increased risk of stroke based on the results of a study of patients with diabetes and CKD who were not on dialysis was added to ESA labels.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

An independent panel convened by the U.S. National Institutes of Health has endorsed the use of active surveillance and delay of treatment for men with localized, low-risk prostate cancer.

"Our panel found that many men with localized, low-risk prostate cancer should be closely monitored, permitting their treatment to be delayed until disease progression warrants it. Some of the men affected by prostate cancer will benefit from immediate treatment and others will benefit from observation," panel and conference chairperson Dr. Patricia A. Ganz said in a telebriefing.

However, monitoring or observational strategies, sometimes referred to as "watchful waiting" or "active surveillance," have not been uniformly studied, and available data do not yet point to clear follow-up protocols, said Dr. Ganz, director of the division of cancer prevention and control research at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles.

The panel identified the combination of a prostate-specific antigen (PSA) level less than 10 ng/dL and a Gleason score of 6 or lower as the emerging consensus definition of "low-risk" disease. "Using this definition, we estimate that more than 100,000 men diagnosed with prostate cancer each year in the United States would be candidates for active monitoring rather than immediate treatment," she said.

Additional research will be needed to determine the point at which treatment might ultimately be needed for men who are being closely monitored. The panel recommended that such studies receiving federal funding should not be done at a single site, but rather should be multicenter studies with large patient populations.

The consensus about active surveillance came from increasing evidence that outcomes for men with low-risk disease are not better for those who undergo surgery or radiation therapy. Among the evidence considered was the newly reported findings of the Prostate Cancer Intervention Versus Observation Trial (PIVOT), the only randomized controlled trial conducted on men identified via PSA screening that compared watchful waiting with radical prostatectomy.

With a median follow-up of 10 years, there were no statistically significant differences in prostate cancer mortality or all-cause mortality. "Supporting data from additional cohort studies give us confidence that the risk of death is minimal in a low risk population," the panel wrote.

According to the document, only about 10% of men eligible for observational strategies choose this approach. The reasons for this are probably due both to physician communication that favors treatment and to patient expectations. "When men are given a diagnosis of cancer, it’s very difficult to decline the standard therapy for this disease, which is either surgery or radiation therapy," Dr. Ganz noted.

For this reason, the panel also endorsed consideration of a name change to remove the anxiety-provoking term cancer to describe this low-risk condition, much as was done with cervical intraepithelial neoplasia for early-stage cervical neoplasms and ductal carcinoma in situ for lower-risk breast lesions.

"Some of the men affected by prostate cancer will benefit from immediate treatment and others will benefit from observation."

They also discussed ways in which urologists and primary care physicians ordering PSA tests could be educated to counsel patients about the potential benefits of active surveillance and delaying treatment, Dr. Ganz said.

"Anything we can do to bring this into the consultation room so that the patient feels comfortable raising this issue with his physician ... [Stakeholders] now have an NIH-vetted document that describes this as a reasonable approach to the management of prostate cancer and for those reasons it can be very powerful," she said.

The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement.

Panel members were compensated for travel to the conference, but were not otherwise paid and have no additional conflicts of interest. The statement does not constitute federal policy.

The draft statement is posted online, and the final version will be posted by mid to late January 2012.

An independent panel convened by the U.S. National Institutes of Health has endorsed the use of active surveillance and delay of treatment for men with localized, low-risk prostate cancer.

"Our panel found that many men with localized, low-risk prostate cancer should be closely monitored, permitting their treatment to be delayed until disease progression warrants it. Some of the men affected by prostate cancer will benefit from immediate treatment and others will benefit from observation," panel and conference chairperson Dr. Patricia A. Ganz said in a telebriefing.

However, monitoring or observational strategies, sometimes referred to as "watchful waiting" or "active surveillance," have not been uniformly studied, and available data do not yet point to clear follow-up protocols, said Dr. Ganz, director of the division of cancer prevention and control research at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles.

The panel identified the combination of a prostate-specific antigen (PSA) level less than 10 ng/dL and a Gleason score of 6 or lower as the emerging consensus definition of "low-risk" disease. "Using this definition, we estimate that more than 100,000 men diagnosed with prostate cancer each year in the United States would be candidates for active monitoring rather than immediate treatment," she said.

Additional research will be needed to determine the point at which treatment might ultimately be needed for men who are being closely monitored. The panel recommended that such studies receiving federal funding should not be done at a single site, but rather should be multicenter studies with large patient populations.

The consensus about active surveillance came from increasing evidence that outcomes for men with low-risk disease are not better for those who undergo surgery or radiation therapy. Among the evidence considered was the newly reported findings of the Prostate Cancer Intervention Versus Observation Trial (PIVOT), the only randomized controlled trial conducted on men identified via PSA screening that compared watchful waiting with radical prostatectomy.

With a median follow-up of 10 years, there were no statistically significant differences in prostate cancer mortality or all-cause mortality. "Supporting data from additional cohort studies give us confidence that the risk of death is minimal in a low risk population," the panel wrote.

According to the document, only about 10% of men eligible for observational strategies choose this approach. The reasons for this are probably due both to physician communication that favors treatment and to patient expectations. "When men are given a diagnosis of cancer, it’s very difficult to decline the standard therapy for this disease, which is either surgery or radiation therapy," Dr. Ganz noted.

For this reason, the panel also endorsed consideration of a name change to remove the anxiety-provoking term cancer to describe this low-risk condition, much as was done with cervical intraepithelial neoplasia for early-stage cervical neoplasms and ductal carcinoma in situ for lower-risk breast lesions.

"Some of the men affected by prostate cancer will benefit from immediate treatment and others will benefit from observation."

They also discussed ways in which urologists and primary care physicians ordering PSA tests could be educated to counsel patients about the potential benefits of active surveillance and delaying treatment, Dr. Ganz said.

"Anything we can do to bring this into the consultation room so that the patient feels comfortable raising this issue with his physician ... [Stakeholders] now have an NIH-vetted document that describes this as a reasonable approach to the management of prostate cancer and for those reasons it can be very powerful," she said.

The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement.

Panel members were compensated for travel to the conference, but were not otherwise paid and have no additional conflicts of interest. The statement does not constitute federal policy.

The draft statement is posted online, and the final version will be posted by mid to late January 2012.

An independent panel convened by the U.S. National Institutes of Health has endorsed the use of active surveillance and delay of treatment for men with localized, low-risk prostate cancer.

"Our panel found that many men with localized, low-risk prostate cancer should be closely monitored, permitting their treatment to be delayed until disease progression warrants it. Some of the men affected by prostate cancer will benefit from immediate treatment and others will benefit from observation," panel and conference chairperson Dr. Patricia A. Ganz said in a telebriefing.

However, monitoring or observational strategies, sometimes referred to as "watchful waiting" or "active surveillance," have not been uniformly studied, and available data do not yet point to clear follow-up protocols, said Dr. Ganz, director of the division of cancer prevention and control research at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles.

The panel identified the combination of a prostate-specific antigen (PSA) level less than 10 ng/dL and a Gleason score of 6 or lower as the emerging consensus definition of "low-risk" disease. "Using this definition, we estimate that more than 100,000 men diagnosed with prostate cancer each year in the United States would be candidates for active monitoring rather than immediate treatment," she said.

Additional research will be needed to determine the point at which treatment might ultimately be needed for men who are being closely monitored. The panel recommended that such studies receiving federal funding should not be done at a single site, but rather should be multicenter studies with large patient populations.

The consensus about active surveillance came from increasing evidence that outcomes for men with low-risk disease are not better for those who undergo surgery or radiation therapy. Among the evidence considered was the newly reported findings of the Prostate Cancer Intervention Versus Observation Trial (PIVOT), the only randomized controlled trial conducted on men identified via PSA screening that compared watchful waiting with radical prostatectomy.

With a median follow-up of 10 years, there were no statistically significant differences in prostate cancer mortality or all-cause mortality. "Supporting data from additional cohort studies give us confidence that the risk of death is minimal in a low risk population," the panel wrote.

According to the document, only about 10% of men eligible for observational strategies choose this approach. The reasons for this are probably due both to physician communication that favors treatment and to patient expectations. "When men are given a diagnosis of cancer, it’s very difficult to decline the standard therapy for this disease, which is either surgery or radiation therapy," Dr. Ganz noted.

For this reason, the panel also endorsed consideration of a name change to remove the anxiety-provoking term cancer to describe this low-risk condition, much as was done with cervical intraepithelial neoplasia for early-stage cervical neoplasms and ductal carcinoma in situ for lower-risk breast lesions.

"Some of the men affected by prostate cancer will benefit from immediate treatment and others will benefit from observation."

They also discussed ways in which urologists and primary care physicians ordering PSA tests could be educated to counsel patients about the potential benefits of active surveillance and delaying treatment, Dr. Ganz said.

"Anything we can do to bring this into the consultation room so that the patient feels comfortable raising this issue with his physician ... [Stakeholders] now have an NIH-vetted document that describes this as a reasonable approach to the management of prostate cancer and for those reasons it can be very powerful," she said.

The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement.

Panel members were compensated for travel to the conference, but were not otherwise paid and have no additional conflicts of interest. The statement does not constitute federal policy.

The draft statement is posted online, and the final version will be posted by mid to late January 2012.

Chronic kidney disease (CKD) is the silent epidemic. It often follows hypertension, diabetes, and obesity. Patients with CKD are not seen exclusively in a nephrology practice. Often, they are not referred to a nephrologist until their glomerular filtration rate (GFR) is less than 60 mL/min/1.73m².

CKD affects 11.5% of the US population ages 20 and older,¹ which translates to some 23 million people. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 382,000 people were receiving dialysis in 2008,¹ and this number is expected to more than double by 2020. It is essential for the practitioner in any specialty to be aware of their patients’ renal status and any adjustments that may entail.

Q: In diabetic patients with incipient nephropathy (microalbuminuria, but GFR > 90 mL/min, more specifically), do evidence-based recommendations exist that suggest renal dosing parameters be followed in order to protect against progressive nephropathy? This, of course, would constitute a secondary prevention strategy, since (as most clinicians know) glycemic and blood pressure control are the most important primary steps toward prevention.

A patient with microalbuminuria and preserved renal function, according to the estimated GFR (eGFR), would be classified as having CKD stage 2. Currently, no medication dosing guidelines are available for patients at this stage of CKD; however, as providers, we should be aware that the presence of microalbuminuria has important clinical implications.

Microalbuminuria is associated with increased risk for cardiovascular disease and progression of CKD.⁴ Accordingly, medication selection should be targeted at avoiding renal insult, limiting progression of nephropathy through the use of ACE inhibitors or angiotensin receptor blockers (ARBs), and promptly addressing and modifying the risk factors for cardiovascular disease.

Blood pressure (BP), glycemic control, and lipids should all be managed aggressively. The JNC7 (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure)⁵ and the K/DOQI (Kidney Disease Outcomes Quality Initiative) guidelines⁶ recommend a target BP below 130/80 mm Hg for CKD patients with proteinuria of less than 1 g/24 h; and below 120/80 mm Hg for patients with proteinuria greater than 1 g/24 h. Unpublished guidelines from “Kidney Disease: Improving Global Outcomes” (see www.kdigo.org) are encouraging practitioners to give nonhypertensive diabetic patients with proteinuria an ACE inhibitor or an ARB.

Nephrotoxins, such as NSAIDs and aminoglycosides, should be avoided. Contrast dye and nephrotoxic chemotherapeutic agents should be used with caution and only if clinically justified. If they are used, renal precautions should be taken, including preprocedure and postprocedure hydration.⁷

Whenever possible, an ACE inhibitor or an ARB should be initiated early, as the greatest benefit in slowing the progression of nephrosclerosis is realized when these medications are initiated before irreversible scarring has occurred.^5,6 Initiating one of these agents is preferable while the serum creatinine level is below 1.2 mg/dL.⁸ Creatinine and potassium should be checked within two weeks of initiating or increasing ACE inhibitor or ARB dosing.

As CKD progresses, patients are at risk for acidemia and hyperkalemia. Typically, these concerns are greater in CKD stages 4 to 5 but can be seen as early as CKD stage 3. Metformin should be prescribed with caution in patients with CKD stage 2 and changed to an alternate antihyperglycemic agent for men whose serum creatinine exceeds 1.5 mg/dL and for women with serum creatinine greater than 1.4 mg/dL.⁸

Clinically, it is recommended that metformin be avoided in patients whose eGFR is below 60 to 70 mL/min.⁹ The eGFR is a better indicator of CKD stage than serum creatinine; using serum creatinine alone to calculate the CKD stage could lead to a very wrong result. For example, a thin, elderly white woman can have a very low eGFR but a serum creatinine of 1.4 mg/dL or less (which is essentially normal).

Diabetic patients in particular are susceptible to hyperkalemia, so spironolactone, potassium, and sulfamethoxazole should be prescribed with caution. Potassium levels should be monitored in patients receiving b-blockers, ACE inhibitors, or ARBs.

Renal medication dosing guidelines, as noted in the FDA information in each drug’s package insert, generally offer recommendations for adjustment in CKD stage 4 or 5, which correspond to an eGFR of < 30 mL/min or < 15 mL/min, respectively. FDA renal dosing guidelines are often based on serum creatinine, but eGFR can vary widely for a particular serum creatinine level, depending upon patient variables such as age, weight, race, and gender (as in the example above).

In summary, although no specific published guidelines exist for patients with CKD stage 2, the presence of microalbuminuria is an important clinical indicator that should inform the provider’s approach to patient management.
Alexis Chettiar, ACNP, East Bay Nephrology Medical Group, Oakland, CA

References
1. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov. Accessed November 18, 2011.

2. Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis. 2001;38(1):104-108.

3. Blommel ML, Blommel AL. Pregabalin: an antiepileptic agent useful for neuropathic pain. Am J Health-System Pharm. 2007;64(14):1475-1482.

4. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421-426.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

6. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 suppl 1):S1-290.

7. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI™). www.kidney.org/professionals/kdoqi. Accessed November 18, 2011.

8. Post TW, Rose BD. Overview of management of chronic kidney disease in adults. www.uptodate.com/contents/overview-of-the-management-of-chronic-kidney-disease-in-adults/contributors. Accessed November 18, 2011.

9. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303.

Chronic kidney disease (CKD) is the silent epidemic. It often follows hypertension, diabetes, and obesity. Patients with CKD are not seen exclusively in a nephrology practice. Often, they are not referred to a nephrologist until their glomerular filtration rate (GFR) is less than 60 mL/min/1.73m².

CKD affects 11.5% of the US population ages 20 and older,¹ which translates to some 23 million people. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 382,000 people were receiving dialysis in 2008,¹ and this number is expected to more than double by 2020. It is essential for the practitioner in any specialty to be aware of their patients’ renal status and any adjustments that may entail.

Q: In diabetic patients with incipient nephropathy (microalbuminuria, but GFR > 90 mL/min, more specifically), do evidence-based recommendations exist that suggest renal dosing parameters be followed in order to protect against progressive nephropathy? This, of course, would constitute a secondary prevention strategy, since (as most clinicians know) glycemic and blood pressure control are the most important primary steps toward prevention.

A patient with microalbuminuria and preserved renal function, according to the estimated GFR (eGFR), would be classified as having CKD stage 2. Currently, no medication dosing guidelines are available for patients at this stage of CKD; however, as providers, we should be aware that the presence of microalbuminuria has important clinical implications.

Microalbuminuria is associated with increased risk for cardiovascular disease and progression of CKD.⁴ Accordingly, medication selection should be targeted at avoiding renal insult, limiting progression of nephropathy through the use of ACE inhibitors or angiotensin receptor blockers (ARBs), and promptly addressing and modifying the risk factors for cardiovascular disease.

Blood pressure (BP), glycemic control, and lipids should all be managed aggressively. The JNC7 (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure)⁵ and the K/DOQI (Kidney Disease Outcomes Quality Initiative) guidelines⁶ recommend a target BP below 130/80 mm Hg for CKD patients with proteinuria of less than 1 g/24 h; and below 120/80 mm Hg for patients with proteinuria greater than 1 g/24 h. Unpublished guidelines from “Kidney Disease: Improving Global Outcomes” (see www.kdigo.org) are encouraging practitioners to give nonhypertensive diabetic patients with proteinuria an ACE inhibitor or an ARB.

Nephrotoxins, such as NSAIDs and aminoglycosides, should be avoided. Contrast dye and nephrotoxic chemotherapeutic agents should be used with caution and only if clinically justified. If they are used, renal precautions should be taken, including preprocedure and postprocedure hydration.⁷

Whenever possible, an ACE inhibitor or an ARB should be initiated early, as the greatest benefit in slowing the progression of nephrosclerosis is realized when these medications are initiated before irreversible scarring has occurred.^5,6 Initiating one of these agents is preferable while the serum creatinine level is below 1.2 mg/dL.⁸ Creatinine and potassium should be checked within two weeks of initiating or increasing ACE inhibitor or ARB dosing.

As CKD progresses, patients are at risk for acidemia and hyperkalemia. Typically, these concerns are greater in CKD stages 4 to 5 but can be seen as early as CKD stage 3. Metformin should be prescribed with caution in patients with CKD stage 2 and changed to an alternate antihyperglycemic agent for men whose serum creatinine exceeds 1.5 mg/dL and for women with serum creatinine greater than 1.4 mg/dL.⁸

Clinically, it is recommended that metformin be avoided in patients whose eGFR is below 60 to 70 mL/min.⁹ The eGFR is a better indicator of CKD stage than serum creatinine; using serum creatinine alone to calculate the CKD stage could lead to a very wrong result. For example, a thin, elderly white woman can have a very low eGFR but a serum creatinine of 1.4 mg/dL or less (which is essentially normal).

Diabetic patients in particular are susceptible to hyperkalemia, so spironolactone, potassium, and sulfamethoxazole should be prescribed with caution. Potassium levels should be monitored in patients receiving b-blockers, ACE inhibitors, or ARBs.

Renal medication dosing guidelines, as noted in the FDA information in each drug’s package insert, generally offer recommendations for adjustment in CKD stage 4 or 5, which correspond to an eGFR of < 30 mL/min or < 15 mL/min, respectively. FDA renal dosing guidelines are often based on serum creatinine, but eGFR can vary widely for a particular serum creatinine level, depending upon patient variables such as age, weight, race, and gender (as in the example above).

In summary, although no specific published guidelines exist for patients with CKD stage 2, the presence of microalbuminuria is an important clinical indicator that should inform the provider’s approach to patient management.
Alexis Chettiar, ACNP, East Bay Nephrology Medical Group, Oakland, CA

References
1. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov. Accessed November 18, 2011.

2. Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis. 2001;38(1):104-108.

3. Blommel ML, Blommel AL. Pregabalin: an antiepileptic agent useful for neuropathic pain. Am J Health-System Pharm. 2007;64(14):1475-1482.

4. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421-426.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

6. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 suppl 1):S1-290.

7. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI™). www.kidney.org/professionals/kdoqi. Accessed November 18, 2011.

8. Post TW, Rose BD. Overview of management of chronic kidney disease in adults. www.uptodate.com/contents/overview-of-the-management-of-chronic-kidney-disease-in-adults/contributors. Accessed November 18, 2011.

9. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303.

Chronic kidney disease (CKD) is the silent epidemic. It often follows hypertension, diabetes, and obesity. Patients with CKD are not seen exclusively in a nephrology practice. Often, they are not referred to a nephrologist until their glomerular filtration rate (GFR) is less than 60 mL/min/1.73m².

CKD affects 11.5% of the US population ages 20 and older,¹ which translates to some 23 million people. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 382,000 people were receiving dialysis in 2008,¹ and this number is expected to more than double by 2020. It is essential for the practitioner in any specialty to be aware of their patients’ renal status and any adjustments that may entail.

Q: In diabetic patients with incipient nephropathy (microalbuminuria, but GFR > 90 mL/min, more specifically), do evidence-based recommendations exist that suggest renal dosing parameters be followed in order to protect against progressive nephropathy? This, of course, would constitute a secondary prevention strategy, since (as most clinicians know) glycemic and blood pressure control are the most important primary steps toward prevention.

A patient with microalbuminuria and preserved renal function, according to the estimated GFR (eGFR), would be classified as having CKD stage 2. Currently, no medication dosing guidelines are available for patients at this stage of CKD; however, as providers, we should be aware that the presence of microalbuminuria has important clinical implications.

Microalbuminuria is associated with increased risk for cardiovascular disease and progression of CKD.⁴ Accordingly, medication selection should be targeted at avoiding renal insult, limiting progression of nephropathy through the use of ACE inhibitors or angiotensin receptor blockers (ARBs), and promptly addressing and modifying the risk factors for cardiovascular disease.

Blood pressure (BP), glycemic control, and lipids should all be managed aggressively. The JNC7 (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure)⁵ and the K/DOQI (Kidney Disease Outcomes Quality Initiative) guidelines⁶ recommend a target BP below 130/80 mm Hg for CKD patients with proteinuria of less than 1 g/24 h; and below 120/80 mm Hg for patients with proteinuria greater than 1 g/24 h. Unpublished guidelines from “Kidney Disease: Improving Global Outcomes” (see www.kdigo.org) are encouraging practitioners to give nonhypertensive diabetic patients with proteinuria an ACE inhibitor or an ARB.

Nephrotoxins, such as NSAIDs and aminoglycosides, should be avoided. Contrast dye and nephrotoxic chemotherapeutic agents should be used with caution and only if clinically justified. If they are used, renal precautions should be taken, including preprocedure and postprocedure hydration.⁷

Whenever possible, an ACE inhibitor or an ARB should be initiated early, as the greatest benefit in slowing the progression of nephrosclerosis is realized when these medications are initiated before irreversible scarring has occurred.^5,6 Initiating one of these agents is preferable while the serum creatinine level is below 1.2 mg/dL.⁸ Creatinine and potassium should be checked within two weeks of initiating or increasing ACE inhibitor or ARB dosing.

As CKD progresses, patients are at risk for acidemia and hyperkalemia. Typically, these concerns are greater in CKD stages 4 to 5 but can be seen as early as CKD stage 3. Metformin should be prescribed with caution in patients with CKD stage 2 and changed to an alternate antihyperglycemic agent for men whose serum creatinine exceeds 1.5 mg/dL and for women with serum creatinine greater than 1.4 mg/dL.⁸

Clinically, it is recommended that metformin be avoided in patients whose eGFR is below 60 to 70 mL/min.⁹ The eGFR is a better indicator of CKD stage than serum creatinine; using serum creatinine alone to calculate the CKD stage could lead to a very wrong result. For example, a thin, elderly white woman can have a very low eGFR but a serum creatinine of 1.4 mg/dL or less (which is essentially normal).

Diabetic patients in particular are susceptible to hyperkalemia, so spironolactone, potassium, and sulfamethoxazole should be prescribed with caution. Potassium levels should be monitored in patients receiving b-blockers, ACE inhibitors, or ARBs.

Renal medication dosing guidelines, as noted in the FDA information in each drug’s package insert, generally offer recommendations for adjustment in CKD stage 4 or 5, which correspond to an eGFR of < 30 mL/min or < 15 mL/min, respectively. FDA renal dosing guidelines are often based on serum creatinine, but eGFR can vary widely for a particular serum creatinine level, depending upon patient variables such as age, weight, race, and gender (as in the example above).

In summary, although no specific published guidelines exist for patients with CKD stage 2, the presence of microalbuminuria is an important clinical indicator that should inform the provider’s approach to patient management.
Alexis Chettiar, ACNP, East Bay Nephrology Medical Group, Oakland, CA

References
1. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov. Accessed November 18, 2011.

2. Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis. 2001;38(1):104-108.

3. Blommel ML, Blommel AL. Pregabalin: an antiepileptic agent useful for neuropathic pain. Am J Health-System Pharm. 2007;64(14):1475-1482.

4. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421-426.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

6. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 suppl 1):S1-290.

7. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI™). www.kidney.org/professionals/kdoqi. Accessed November 18, 2011.

8. Post TW, Rose BD. Overview of management of chronic kidney disease in adults. www.uptodate.com/contents/overview-of-the-management-of-chronic-kidney-disease-in-adults/contributors. Accessed November 18, 2011.

9. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303.

Chronic kidney disease (CKD) is the silent epidemic. It often follows hypertension, diabetes, and obesity. Patients with CKD are not seen exclusively in a nephrology practice. Often, they are not referred to a nephrologist until their glomerular filtration rate (GFR) is less than 60 mL/min/1.73m².

CKD affects 11.5% of the US population ages 20 and older,¹ which translates to some 23 million people. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 382,000 people were receiving dialysis in 2008,¹ and this number is expected to more than double by 2020. It is essential for the practitioner in any specialty to be aware of their patients’ renal status and any adjustments that may entail.

Q: In my primary care office, I saw a dialysis patient with peripheral neuropathy caused by her diabetes. I treated her with gabapentin 300 mg qd with an increase of 100 mg each week until her symptoms resolved. I received a note from the nephrology group that the dose I ordered was way too high, and they adjusted it down to 100 mg/d. Is that right? Would it have been better for me to prescribe pregabalin? I was trying to use an inexpensive medication because this patient has to take so many. 

Gabapentin has been used for years in the dialysis unit to treat patients with diabetes-related peripheral neuropathy.² It is one of the most commonly prescribed drugs for this population of patients due to its effectiveness and low adverse-effect profile. However, because gabapentin is cleared solely by renal excretion, it is recommended that patients on dialysis receive 200 to 300 mg after each four-hour hemodialysis session. This dose should be reached with gradual titration to avoid adverse effects, which include dizziness, ataxia, sedation, euphoria, ankle edema, and weight gain.

The risk for altered consciousness and myoclonus associated with gabapentin is increased in the dialysis population. When these adverse effects occur, the drug should be stopped. Doses above the recommended 200 to 300 mg per dialysis session have not been shown to provide any added analgesic effect and may increase adverse effects, putting patients at greater risk for falls, in addition to other side effects. Gabapentin has a much longer half-life in patients on dialysis, compared with those who have normal kidney function. These patients will benefit from a minimal dosing schedule as well as the prolonged pain control with gaba­pentin.

The efficacy of pregabalin (Lyrica^®) in the management of painful diabetic neuropathy has been established in several controlled clinical trials.³ Because it has not been in use as long as gabapentin, its safety profile has not yet been established. Pregabalin has better gastrointestinal absorption than gabapentin and offers more rapid pain relief; it can be administered twice daily. Pregabalin is cleared rapidly by dialysis and has a short half-life; therefore, an extra dose is required after each dialysis session. Pregabalin dosing must also be adjusted for creatinine clearance.*

Pregabalin is a Schedule V controlled substance because of its potential for abuse. It cannot be prescribed by advanced practitioners in all states.
Dawn McCombs, CRNP, Nephrology Associates, PC, Birmingham, AL

* Several sources are available on the Internet to determine creatinine clearance or stage of kidney disease if your lab does not calculate it for you.

References
1. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov. Accessed November 18, 2011.

2. Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis. 2001;38(1):104-108.

3. Blommel ML, Blommel AL. Pregabalin: an antiepileptic agent useful for neuropathic pain. Am J Health-System Pharm. 2007;64(14):1475-1482.

4. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421-426.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

6. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 suppl 1):S1-290.

7. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI™). www.kidney.org/professionals/kdoqi. Accessed November 18, 2011.

8. Post TW, Rose BD. Overview of management of chronic kidney disease in adults. www.uptodate.com/contents/overview-of-the-management-of-chronic-kidney-disease-in-adults/contributors. Accessed November 18, 2011.

9. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303.

Chronic kidney disease (CKD) is the silent epidemic. It often follows hypertension, diabetes, and obesity. Patients with CKD are not seen exclusively in a nephrology practice. Often, they are not referred to a nephrologist until their glomerular filtration rate (GFR) is less than 60 mL/min/1.73m².

CKD affects 11.5% of the US population ages 20 and older,¹ which translates to some 23 million people. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 382,000 people were receiving dialysis in 2008,¹ and this number is expected to more than double by 2020. It is essential for the practitioner in any specialty to be aware of their patients’ renal status and any adjustments that may entail.

Q: In my primary care office, I saw a dialysis patient with peripheral neuropathy caused by her diabetes. I treated her with gabapentin 300 mg qd with an increase of 100 mg each week until her symptoms resolved. I received a note from the nephrology group that the dose I ordered was way too high, and they adjusted it down to 100 mg/d. Is that right? Would it have been better for me to prescribe pregabalin? I was trying to use an inexpensive medication because this patient has to take so many. 

Gabapentin has been used for years in the dialysis unit to treat patients with diabetes-related peripheral neuropathy.² It is one of the most commonly prescribed drugs for this population of patients due to its effectiveness and low adverse-effect profile. However, because gabapentin is cleared solely by renal excretion, it is recommended that patients on dialysis receive 200 to 300 mg after each four-hour hemodialysis session. This dose should be reached with gradual titration to avoid adverse effects, which include dizziness, ataxia, sedation, euphoria, ankle edema, and weight gain.

The risk for altered consciousness and myoclonus associated with gabapentin is increased in the dialysis population. When these adverse effects occur, the drug should be stopped. Doses above the recommended 200 to 300 mg per dialysis session have not been shown to provide any added analgesic effect and may increase adverse effects, putting patients at greater risk for falls, in addition to other side effects. Gabapentin has a much longer half-life in patients on dialysis, compared with those who have normal kidney function. These patients will benefit from a minimal dosing schedule as well as the prolonged pain control with gaba­pentin.

The efficacy of pregabalin (Lyrica^®) in the management of painful diabetic neuropathy has been established in several controlled clinical trials.³ Because it has not been in use as long as gabapentin, its safety profile has not yet been established. Pregabalin has better gastrointestinal absorption than gabapentin and offers more rapid pain relief; it can be administered twice daily. Pregabalin is cleared rapidly by dialysis and has a short half-life; therefore, an extra dose is required after each dialysis session. Pregabalin dosing must also be adjusted for creatinine clearance.*

Pregabalin is a Schedule V controlled substance because of its potential for abuse. It cannot be prescribed by advanced practitioners in all states.
Dawn McCombs, CRNP, Nephrology Associates, PC, Birmingham, AL

* Several sources are available on the Internet to determine creatinine clearance or stage of kidney disease if your lab does not calculate it for you.

References
1. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov. Accessed November 18, 2011.

2. Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis. 2001;38(1):104-108.

3. Blommel ML, Blommel AL. Pregabalin: an antiepileptic agent useful for neuropathic pain. Am J Health-System Pharm. 2007;64(14):1475-1482.

4. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421-426.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

6. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 suppl 1):S1-290.

7. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI™). www.kidney.org/professionals/kdoqi. Accessed November 18, 2011.

8. Post TW, Rose BD. Overview of management of chronic kidney disease in adults. www.uptodate.com/contents/overview-of-the-management-of-chronic-kidney-disease-in-adults/contributors. Accessed November 18, 2011.

9. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303.

Chronic kidney disease (CKD) is the silent epidemic. It often follows hypertension, diabetes, and obesity. Patients with CKD are not seen exclusively in a nephrology practice. Often, they are not referred to a nephrologist until their glomerular filtration rate (GFR) is less than 60 mL/min/1.73m².

CKD affects 11.5% of the US population ages 20 and older,¹ which translates to some 23 million people. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 382,000 people were receiving dialysis in 2008,¹ and this number is expected to more than double by 2020. It is essential for the practitioner in any specialty to be aware of their patients’ renal status and any adjustments that may entail.

Q: In my primary care office, I saw a dialysis patient with peripheral neuropathy caused by her diabetes. I treated her with gabapentin 300 mg qd with an increase of 100 mg each week until her symptoms resolved. I received a note from the nephrology group that the dose I ordered was way too high, and they adjusted it down to 100 mg/d. Is that right? Would it have been better for me to prescribe pregabalin? I was trying to use an inexpensive medication because this patient has to take so many. 

Gabapentin has been used for years in the dialysis unit to treat patients with diabetes-related peripheral neuropathy.² It is one of the most commonly prescribed drugs for this population of patients due to its effectiveness and low adverse-effect profile. However, because gabapentin is cleared solely by renal excretion, it is recommended that patients on dialysis receive 200 to 300 mg after each four-hour hemodialysis session. This dose should be reached with gradual titration to avoid adverse effects, which include dizziness, ataxia, sedation, euphoria, ankle edema, and weight gain.

The risk for altered consciousness and myoclonus associated with gabapentin is increased in the dialysis population. When these adverse effects occur, the drug should be stopped. Doses above the recommended 200 to 300 mg per dialysis session have not been shown to provide any added analgesic effect and may increase adverse effects, putting patients at greater risk for falls, in addition to other side effects. Gabapentin has a much longer half-life in patients on dialysis, compared with those who have normal kidney function. These patients will benefit from a minimal dosing schedule as well as the prolonged pain control with gaba­pentin.

The efficacy of pregabalin (Lyrica^®) in the management of painful diabetic neuropathy has been established in several controlled clinical trials.³ Because it has not been in use as long as gabapentin, its safety profile has not yet been established. Pregabalin has better gastrointestinal absorption than gabapentin and offers more rapid pain relief; it can be administered twice daily. Pregabalin is cleared rapidly by dialysis and has a short half-life; therefore, an extra dose is required after each dialysis session. Pregabalin dosing must also be adjusted for creatinine clearance.*

Pregabalin is a Schedule V controlled substance because of its potential for abuse. It cannot be prescribed by advanced practitioners in all states.
Dawn McCombs, CRNP, Nephrology Associates, PC, Birmingham, AL

* Several sources are available on the Internet to determine creatinine clearance or stage of kidney disease if your lab does not calculate it for you.

References
1. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov. Accessed November 18, 2011.

2. Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis. 2001;38(1):104-108.

3. Blommel ML, Blommel AL. Pregabalin: an antiepileptic agent useful for neuropathic pain. Am J Health-System Pharm. 2007;64(14):1475-1482.

4. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421-426.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

6. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 suppl 1):S1-290.

7. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI™). www.kidney.org/professionals/kdoqi. Accessed November 18, 2011.

8. Post TW, Rose BD. Overview of management of chronic kidney disease in adults. www.uptodate.com/contents/overview-of-the-management-of-chronic-kidney-disease-in-adults/contributors. Accessed November 18, 2011.

9. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303.