Nephrology

Peginesatide, a long-acting erythropoiesis-stimulating agent, has been approved as a treatment for anemia caused by chronic kidney disease in adults who are on dialysis, the Food and Drug Administration announced March 27.

This is the first erythropoiesis-stimulating agent (ESA) approved for this indication since 2001, Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in a statement. The product "offers patients and health care providers the convenience of receiving ESA therapy just once per month instead of more frequent injections," he noted.

The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) that consists of educational elements for health care professionals and a requirement to assess data on how the drug is used, the statement said. The FDA can require a REMS for a product when the agency determines certain measures are needed to ensure that a drug’s benefits outweigh its risks.

Peginesatide is not approved for treating anemia in patients with chronic kidney disease (CKD) who are not on dialysis, for patients who are being treated for cancer and whose anemia is not caused by CKD, or for use instead of a red blood cell transfusion in patients who require immediate correction of anemia – which are approved indications for other ESAs. The label also states that treatment with peginesatide has not been shown to "improve symptoms, physical functioning, or health-related quality of life."

Peginesatide, which will be marketed as Omontys by Affymax Inc., is administered once a month, intravenously or subcutaneously. Treatment is started when the hemoglobin level is below 10 g/dL, according to the prescribing information.

Approval was based on two randomized open-label studies of 1,608 patients with CKD who were on dialysis, who, after their hemoglobin levels were stabilized with epoetin, were randomized to continue treatment with epoetin or peginesatide. Treatment with peginesatide was "as safe and effective as epoetin in maintaining hemoglobin levels within the studies’ prespecified range of 10 to 12 g/dL," according to the FDA statement. Diarrhea, vomiting, hypertension, and arthralgias were among the most common adverse effects reported in 10% or more of the patients on dialysis treated with peginesatide.

At a meeting in December 2011, the majority of an FDA advisory panel voted that peginesatide had a favorable risk-benefit profile for the approved indication. At that meeting, panelists were concerned about the higher rate of serious adverse events in patients treated with peginesatide, compared with those treated with darbepoetin, in studies of patients with anemia from CKD who were not on dialysis. But in the two studies of patients on dialysis, panelists agreed that the safety and efficacy of peginesatide were comparable with epoetin and cited the convenience of once-a-month dosing for patients.

Darbepoetin alfa, marketed as Aranesp, and epoetin alfa, marketed as Epogen and Procrit, are the ESAs approved in the United States; they are administered as often as one to three times per week. A pegylated epoetin beta (Mircera) is not available in the United States.

Like the other ESAs, the peginesatide prescribing information includes a boxed warning about the increased risks of deaths and serious cardiovascular events when higher hemoglobin levels are targeted, and the recommendation to use the lowest dose needed to reduce the need for transfusions.

Peginesatide, a long-acting erythropoiesis-stimulating agent, has been approved as a treatment for anemia caused by chronic kidney disease in adults who are on dialysis, the Food and Drug Administration announced March 27.

This is the first erythropoiesis-stimulating agent (ESA) approved for this indication since 2001, Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in a statement. The product "offers patients and health care providers the convenience of receiving ESA therapy just once per month instead of more frequent injections," he noted.

The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) that consists of educational elements for health care professionals and a requirement to assess data on how the drug is used, the statement said. The FDA can require a REMS for a product when the agency determines certain measures are needed to ensure that a drug’s benefits outweigh its risks.

Peginesatide is not approved for treating anemia in patients with chronic kidney disease (CKD) who are not on dialysis, for patients who are being treated for cancer and whose anemia is not caused by CKD, or for use instead of a red blood cell transfusion in patients who require immediate correction of anemia – which are approved indications for other ESAs. The label also states that treatment with peginesatide has not been shown to "improve symptoms, physical functioning, or health-related quality of life."

Peginesatide, which will be marketed as Omontys by Affymax Inc., is administered once a month, intravenously or subcutaneously. Treatment is started when the hemoglobin level is below 10 g/dL, according to the prescribing information.

Approval was based on two randomized open-label studies of 1,608 patients with CKD who were on dialysis, who, after their hemoglobin levels were stabilized with epoetin, were randomized to continue treatment with epoetin or peginesatide. Treatment with peginesatide was "as safe and effective as epoetin in maintaining hemoglobin levels within the studies’ prespecified range of 10 to 12 g/dL," according to the FDA statement. Diarrhea, vomiting, hypertension, and arthralgias were among the most common adverse effects reported in 10% or more of the patients on dialysis treated with peginesatide.

At a meeting in December 2011, the majority of an FDA advisory panel voted that peginesatide had a favorable risk-benefit profile for the approved indication. At that meeting, panelists were concerned about the higher rate of serious adverse events in patients treated with peginesatide, compared with those treated with darbepoetin, in studies of patients with anemia from CKD who were not on dialysis. But in the two studies of patients on dialysis, panelists agreed that the safety and efficacy of peginesatide were comparable with epoetin and cited the convenience of once-a-month dosing for patients.

Darbepoetin alfa, marketed as Aranesp, and epoetin alfa, marketed as Epogen and Procrit, are the ESAs approved in the United States; they are administered as often as one to three times per week. A pegylated epoetin beta (Mircera) is not available in the United States.

Like the other ESAs, the peginesatide prescribing information includes a boxed warning about the increased risks of deaths and serious cardiovascular events when higher hemoglobin levels are targeted, and the recommendation to use the lowest dose needed to reduce the need for transfusions.

Peginesatide, a long-acting erythropoiesis-stimulating agent, has been approved as a treatment for anemia caused by chronic kidney disease in adults who are on dialysis, the Food and Drug Administration announced March 27.

This is the first erythropoiesis-stimulating agent (ESA) approved for this indication since 2001, Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in a statement. The product "offers patients and health care providers the convenience of receiving ESA therapy just once per month instead of more frequent injections," he noted.

The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) that consists of educational elements for health care professionals and a requirement to assess data on how the drug is used, the statement said. The FDA can require a REMS for a product when the agency determines certain measures are needed to ensure that a drug’s benefits outweigh its risks.

Peginesatide is not approved for treating anemia in patients with chronic kidney disease (CKD) who are not on dialysis, for patients who are being treated for cancer and whose anemia is not caused by CKD, or for use instead of a red blood cell transfusion in patients who require immediate correction of anemia – which are approved indications for other ESAs. The label also states that treatment with peginesatide has not been shown to "improve symptoms, physical functioning, or health-related quality of life."

Peginesatide, which will be marketed as Omontys by Affymax Inc., is administered once a month, intravenously or subcutaneously. Treatment is started when the hemoglobin level is below 10 g/dL, according to the prescribing information.

Approval was based on two randomized open-label studies of 1,608 patients with CKD who were on dialysis, who, after their hemoglobin levels were stabilized with epoetin, were randomized to continue treatment with epoetin or peginesatide. Treatment with peginesatide was "as safe and effective as epoetin in maintaining hemoglobin levels within the studies’ prespecified range of 10 to 12 g/dL," according to the FDA statement. Diarrhea, vomiting, hypertension, and arthralgias were among the most common adverse effects reported in 10% or more of the patients on dialysis treated with peginesatide.

At a meeting in December 2011, the majority of an FDA advisory panel voted that peginesatide had a favorable risk-benefit profile for the approved indication. At that meeting, panelists were concerned about the higher rate of serious adverse events in patients treated with peginesatide, compared with those treated with darbepoetin, in studies of patients with anemia from CKD who were not on dialysis. But in the two studies of patients on dialysis, panelists agreed that the safety and efficacy of peginesatide were comparable with epoetin and cited the convenience of once-a-month dosing for patients.

Darbepoetin alfa, marketed as Aranesp, and epoetin alfa, marketed as Epogen and Procrit, are the ESAs approved in the United States; they are administered as often as one to three times per week. A pegylated epoetin beta (Mircera) is not available in the United States.

Like the other ESAs, the peginesatide prescribing information includes a boxed warning about the increased risks of deaths and serious cardiovascular events when higher hemoglobin levels are targeted, and the recommendation to use the lowest dose needed to reduce the need for transfusions.

MINNEAPOLIS – Azithromycin and doxycycline appear to be equally effective for men with nongonococcal urethritis.

In a randomized placebo-controlled trial, both drugs had good overall effectiveness, with an 84% clinical cure rate for azithromycin and a 78% rate for doxycycline. But some pathogens were more resistant to the drugs than others, Lisa Manhart, Ph.D., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

The Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA) trial enrolled 606 men with nongonococcal urethritis from 2007 to 2011. The main end points of the trial were clinical and microbiological cure of urethritis associated with M. genitalium infection, when treated with the standard therapy recommended by the Centers for Disease Control and Prevention: a single dose of 1 g of azithromycin, or a 7-day regimen of 100 mg of doxycycline taken twice a day.

Several pathogens cause nongonococcal urethritis, said Dr. Manhart, an epidemiologist at the University of Washington, Seattle. Among them are Chlamydia trachomatis, M. genitalium, the recently differentiated Ureaplasma urealyticum, and Trichomonas vaginalis. In some infections, no pathogen can be identified. In addition to presenting the end points for M. genitalium infections, Dr. Manhart broke the results out by other pathogens.

The mean age of the men in the trial was 34 years. Most (67%) were heterosexual, 28% were homosexual, and about 5% were bisexual. They reported a mean of six sexual partners in the past 12 months.

The most common infectious pathogen was chlamydia (26%), followed by U. urealyticum (24%). M. genitalium was present in 14% of the study group, and T. vaginalis in 2%. The remainder of the group had an idiopathic urethritis.

Treatment consisted of either a placebo azithromycin and active doxycycline or active azithromycin and placebo doxycycline. If men still showed symptoms or microbiological failure after treatment, they were offered reverse therapy (i.e., a treatment pack with the opposite active and placebo drugs), and returned for a follow-up visit in 3 weeks. If they were still not clinically or microbiologically cured, they received a course of moxifloxacin.

Overall, there was no statistically significant difference in cure rates between the two drugs. Nor were there significant differences among men with chlamydia infections, with a clinical cure rate of 87% for azithromycin and 78% for doxycycline. For microbiological cure, the rates were 86% and 90%, respectively.

Both clinical and microbiological cures rates were much lower in men infected with M. genitalium, but the rates were not significantly different between the two drugs. Clinical cure rates were 68% for azithromycin and 48% for doxycycline. For microbiological cure, the rates were 39% and 30%, respectively.

Men with U. urealyticum infections fared a little better, but again, the cure rates were not significantly different between the drugs. A clinical cure occurred in 85% of the azithromycin group and 75% of the doxycycline group. Microbiological cure rates were 75% and 69%, respectively.

For those with idiopathic urethritis, the cure rate for both drugs was identical: 87%.

Reverse therapy was still not effective in some men with U. urealyticum or M. genitalium infections. Three weeks after that treatment, 51% of those with M. genitalium and 57% of those with U. urealyticum were still positive for the pathogen. These men received a course of moxifloxacin.

"Moxifloxacin was quite effective, but at the end of the trial, we still had two men with M. genitalium and four with U. urealyticum who did not clear their infections," Dr. Manhart said.

Moxifloxacin, although highly effective, is too expensive to be used as first-time therapy in a public health department setting, she noted. "Its preinsurance cost runs up to $150, so we are still faced with a conundrum when treating these infections."

Dr. Manhart had no financial declarations.

MINNEAPOLIS – Azithromycin and doxycycline appear to be equally effective for men with nongonococcal urethritis.

In a randomized placebo-controlled trial, both drugs had good overall effectiveness, with an 84% clinical cure rate for azithromycin and a 78% rate for doxycycline. But some pathogens were more resistant to the drugs than others, Lisa Manhart, Ph.D., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

The Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA) trial enrolled 606 men with nongonococcal urethritis from 2007 to 2011. The main end points of the trial were clinical and microbiological cure of urethritis associated with M. genitalium infection, when treated with the standard therapy recommended by the Centers for Disease Control and Prevention: a single dose of 1 g of azithromycin, or a 7-day regimen of 100 mg of doxycycline taken twice a day.

Several pathogens cause nongonococcal urethritis, said Dr. Manhart, an epidemiologist at the University of Washington, Seattle. Among them are Chlamydia trachomatis, M. genitalium, the recently differentiated Ureaplasma urealyticum, and Trichomonas vaginalis. In some infections, no pathogen can be identified. In addition to presenting the end points for M. genitalium infections, Dr. Manhart broke the results out by other pathogens.

The mean age of the men in the trial was 34 years. Most (67%) were heterosexual, 28% were homosexual, and about 5% were bisexual. They reported a mean of six sexual partners in the past 12 months.

The most common infectious pathogen was chlamydia (26%), followed by U. urealyticum (24%). M. genitalium was present in 14% of the study group, and T. vaginalis in 2%. The remainder of the group had an idiopathic urethritis.

Treatment consisted of either a placebo azithromycin and active doxycycline or active azithromycin and placebo doxycycline. If men still showed symptoms or microbiological failure after treatment, they were offered reverse therapy (i.e., a treatment pack with the opposite active and placebo drugs), and returned for a follow-up visit in 3 weeks. If they were still not clinically or microbiologically cured, they received a course of moxifloxacin.

Overall, there was no statistically significant difference in cure rates between the two drugs. Nor were there significant differences among men with chlamydia infections, with a clinical cure rate of 87% for azithromycin and 78% for doxycycline. For microbiological cure, the rates were 86% and 90%, respectively.

Both clinical and microbiological cures rates were much lower in men infected with M. genitalium, but the rates were not significantly different between the two drugs. Clinical cure rates were 68% for azithromycin and 48% for doxycycline. For microbiological cure, the rates were 39% and 30%, respectively.

Men with U. urealyticum infections fared a little better, but again, the cure rates were not significantly different between the drugs. A clinical cure occurred in 85% of the azithromycin group and 75% of the doxycycline group. Microbiological cure rates were 75% and 69%, respectively.

For those with idiopathic urethritis, the cure rate for both drugs was identical: 87%.

Reverse therapy was still not effective in some men with U. urealyticum or M. genitalium infections. Three weeks after that treatment, 51% of those with M. genitalium and 57% of those with U. urealyticum were still positive for the pathogen. These men received a course of moxifloxacin.

"Moxifloxacin was quite effective, but at the end of the trial, we still had two men with M. genitalium and four with U. urealyticum who did not clear their infections," Dr. Manhart said.

Moxifloxacin, although highly effective, is too expensive to be used as first-time therapy in a public health department setting, she noted. "Its preinsurance cost runs up to $150, so we are still faced with a conundrum when treating these infections."

Dr. Manhart had no financial declarations.

MINNEAPOLIS – Azithromycin and doxycycline appear to be equally effective for men with nongonococcal urethritis.

In a randomized placebo-controlled trial, both drugs had good overall effectiveness, with an 84% clinical cure rate for azithromycin and a 78% rate for doxycycline. But some pathogens were more resistant to the drugs than others, Lisa Manhart, Ph.D., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

The Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA) trial enrolled 606 men with nongonococcal urethritis from 2007 to 2011. The main end points of the trial were clinical and microbiological cure of urethritis associated with M. genitalium infection, when treated with the standard therapy recommended by the Centers for Disease Control and Prevention: a single dose of 1 g of azithromycin, or a 7-day regimen of 100 mg of doxycycline taken twice a day.

Several pathogens cause nongonococcal urethritis, said Dr. Manhart, an epidemiologist at the University of Washington, Seattle. Among them are Chlamydia trachomatis, M. genitalium, the recently differentiated Ureaplasma urealyticum, and Trichomonas vaginalis. In some infections, no pathogen can be identified. In addition to presenting the end points for M. genitalium infections, Dr. Manhart broke the results out by other pathogens.

The mean age of the men in the trial was 34 years. Most (67%) were heterosexual, 28% were homosexual, and about 5% were bisexual. They reported a mean of six sexual partners in the past 12 months.

The most common infectious pathogen was chlamydia (26%), followed by U. urealyticum (24%). M. genitalium was present in 14% of the study group, and T. vaginalis in 2%. The remainder of the group had an idiopathic urethritis.

Treatment consisted of either a placebo azithromycin and active doxycycline or active azithromycin and placebo doxycycline. If men still showed symptoms or microbiological failure after treatment, they were offered reverse therapy (i.e., a treatment pack with the opposite active and placebo drugs), and returned for a follow-up visit in 3 weeks. If they were still not clinically or microbiologically cured, they received a course of moxifloxacin.

Overall, there was no statistically significant difference in cure rates between the two drugs. Nor were there significant differences among men with chlamydia infections, with a clinical cure rate of 87% for azithromycin and 78% for doxycycline. For microbiological cure, the rates were 86% and 90%, respectively.

Both clinical and microbiological cures rates were much lower in men infected with M. genitalium, but the rates were not significantly different between the two drugs. Clinical cure rates were 68% for azithromycin and 48% for doxycycline. For microbiological cure, the rates were 39% and 30%, respectively.

Men with U. urealyticum infections fared a little better, but again, the cure rates were not significantly different between the drugs. A clinical cure occurred in 85% of the azithromycin group and 75% of the doxycycline group. Microbiological cure rates were 75% and 69%, respectively.

For those with idiopathic urethritis, the cure rate for both drugs was identical: 87%.

Reverse therapy was still not effective in some men with U. urealyticum or M. genitalium infections. Three weeks after that treatment, 51% of those with M. genitalium and 57% of those with U. urealyticum were still positive for the pathogen. These men received a course of moxifloxacin.

"Moxifloxacin was quite effective, but at the end of the trial, we still had two men with M. genitalium and four with U. urealyticum who did not clear their infections," Dr. Manhart said.

Moxifloxacin, although highly effective, is too expensive to be used as first-time therapy in a public health department setting, she noted. "Its preinsurance cost runs up to $150, so we are still faced with a conundrum when treating these infections."

Dr. Manhart had no financial declarations.

Men who are circumcised before their first sexual intercourse have a significantly lower risk for prostate cancer than do uncircumcised men or those who are circumcised after their first sexual encounter, according to an analysis of data on 3,399 men.

The finding of a 15% reduction in relative risk points to sexually transmitted infections and inflammation as possible risk factors for prostate cancer, the authors suggested in a study published online in the journal Cancer.

"These findings are consistent with research showing that an infectious/inflammatory pathway may be involved in prostate carcinogenesis," wrote Dr. Jonathan L. Wright and colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle (Cancer 2012 March 12 [doi:10.1002/cncr.26653]).

The authors had hypothesized that circumcision reduces the risk for transmission of a sexually transmitted infection (STI), "and that if a [prostate cancer] develops as a result of the STI, only circumcision prior to first sexual intercourse can potentially alter risk" of prostate cancer.

They borrowed data from two population-based, case-control studies of men with prostate cancer, identifying a total of 1,754 cases in the Seattle–Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry. For the 1,645 controls, they used random-digit dialing to identify men from the same area with no prostate cancer, age-matched in 5-year groups.

In all, 68.8% of cases and 71.5% of controls were circumcised. Among all men who reported being circumcised, 91% had the procedure shortly after birth. Circumcision was performed after first sexual intercourse in 3.9% of cases and 2.5% of controls. Circumcision was also more commonly reported in white men (69%) than in black men (43%).

In multivariate regression analysis, the investigators controlled for age, race, prostate-specific antigen (PSA) test within 5 years of diagnosis or reference data, family history of prostate cancer, history of STIs, prior prostatitis, and number of female and male sexual partners. They found that the overall odds ratio for prostate cancer among men who were circumcised before their first sexual intercourse was 0.88 (95% confidence interval, 0.73-0.99).

The researchers also looked at prostate cancer and circumcision status by aggressiveness of disease, with "aggressive" defined as a composite of Gleason score of 7 (4 + 3) or greater; nonlocalized stage; or PSA level greater than 20 ng/mL at the time of diagnosis.

They saw that preintercourse circumcision had borderline associations with lower risk for both less-aggressive (OR, 0.88; 95% CI, 0.74-1.04) and more-aggressive cancers (OR, 0.82; 95% CI, 0.66-1.00).

The reduction in prostate cancer risk with circumcision before first intercourse was observed in whites (OR, 0.87; 95% CI, 0.73-1.02); and blacks (OR, 0.64; 95% CI, 0.39-1.08).

Circumcision has been shown in other studies to be linked to lower rates of STIs, including HIV/AIDS, herpes simplex, syphilis, and chancroid, the authors noted. They suggested that the mucosal lining of the prepuce, which is thin, may develop small tears that provide pathogens with a route to the bloodstream.

"Circumcision may reduce these injuries due to the significant keratinization that occurs following the procedure," they speculated. "In addition, the moist environment under the preputial skin may help pathogens survive for extended periods prior to direct infection. Circumcision removes this protective environment."

The authors pointed to other studies linking circumcision to reduced prostate cancer risk, including a 1987 case-control study in which circumcision was associated with a 50% reduction in relative risk among whites, and a near 40% reduction in blacks (J Natl Cancer Inst. 1987;78:869-74).

The study was supported by National Institute of Health grants and the Fred Hutchinson Cancer Research Center. The authors reported no conflicts of interest. Dr. Freedland said that he had no conflicts of interest.

Men who are circumcised before their first sexual intercourse have a significantly lower risk for prostate cancer than do uncircumcised men or those who are circumcised after their first sexual encounter, according to an analysis of data on 3,399 men.

The finding of a 15% reduction in relative risk points to sexually transmitted infections and inflammation as possible risk factors for prostate cancer, the authors suggested in a study published online in the journal Cancer.

"These findings are consistent with research showing that an infectious/inflammatory pathway may be involved in prostate carcinogenesis," wrote Dr. Jonathan L. Wright and colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle (Cancer 2012 March 12 [doi:10.1002/cncr.26653]).

The authors had hypothesized that circumcision reduces the risk for transmission of a sexually transmitted infection (STI), "and that if a [prostate cancer] develops as a result of the STI, only circumcision prior to first sexual intercourse can potentially alter risk" of prostate cancer.

They borrowed data from two population-based, case-control studies of men with prostate cancer, identifying a total of 1,754 cases in the Seattle–Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry. For the 1,645 controls, they used random-digit dialing to identify men from the same area with no prostate cancer, age-matched in 5-year groups.

In all, 68.8% of cases and 71.5% of controls were circumcised. Among all men who reported being circumcised, 91% had the procedure shortly after birth. Circumcision was performed after first sexual intercourse in 3.9% of cases and 2.5% of controls. Circumcision was also more commonly reported in white men (69%) than in black men (43%).

In multivariate regression analysis, the investigators controlled for age, race, prostate-specific antigen (PSA) test within 5 years of diagnosis or reference data, family history of prostate cancer, history of STIs, prior prostatitis, and number of female and male sexual partners. They found that the overall odds ratio for prostate cancer among men who were circumcised before their first sexual intercourse was 0.88 (95% confidence interval, 0.73-0.99).

The researchers also looked at prostate cancer and circumcision status by aggressiveness of disease, with "aggressive" defined as a composite of Gleason score of 7 (4 + 3) or greater; nonlocalized stage; or PSA level greater than 20 ng/mL at the time of diagnosis.

They saw that preintercourse circumcision had borderline associations with lower risk for both less-aggressive (OR, 0.88; 95% CI, 0.74-1.04) and more-aggressive cancers (OR, 0.82; 95% CI, 0.66-1.00).

The reduction in prostate cancer risk with circumcision before first intercourse was observed in whites (OR, 0.87; 95% CI, 0.73-1.02); and blacks (OR, 0.64; 95% CI, 0.39-1.08).

Circumcision has been shown in other studies to be linked to lower rates of STIs, including HIV/AIDS, herpes simplex, syphilis, and chancroid, the authors noted. They suggested that the mucosal lining of the prepuce, which is thin, may develop small tears that provide pathogens with a route to the bloodstream.

"Circumcision may reduce these injuries due to the significant keratinization that occurs following the procedure," they speculated. "In addition, the moist environment under the preputial skin may help pathogens survive for extended periods prior to direct infection. Circumcision removes this protective environment."

The authors pointed to other studies linking circumcision to reduced prostate cancer risk, including a 1987 case-control study in which circumcision was associated with a 50% reduction in relative risk among whites, and a near 40% reduction in blacks (J Natl Cancer Inst. 1987;78:869-74).

The study was supported by National Institute of Health grants and the Fred Hutchinson Cancer Research Center. The authors reported no conflicts of interest. Dr. Freedland said that he had no conflicts of interest.

Men who are circumcised before their first sexual intercourse have a significantly lower risk for prostate cancer than do uncircumcised men or those who are circumcised after their first sexual encounter, according to an analysis of data on 3,399 men.

The finding of a 15% reduction in relative risk points to sexually transmitted infections and inflammation as possible risk factors for prostate cancer, the authors suggested in a study published online in the journal Cancer.

"These findings are consistent with research showing that an infectious/inflammatory pathway may be involved in prostate carcinogenesis," wrote Dr. Jonathan L. Wright and colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle (Cancer 2012 March 12 [doi:10.1002/cncr.26653]).

The authors had hypothesized that circumcision reduces the risk for transmission of a sexually transmitted infection (STI), "and that if a [prostate cancer] develops as a result of the STI, only circumcision prior to first sexual intercourse can potentially alter risk" of prostate cancer.

They borrowed data from two population-based, case-control studies of men with prostate cancer, identifying a total of 1,754 cases in the Seattle–Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry. For the 1,645 controls, they used random-digit dialing to identify men from the same area with no prostate cancer, age-matched in 5-year groups.

In all, 68.8% of cases and 71.5% of controls were circumcised. Among all men who reported being circumcised, 91% had the procedure shortly after birth. Circumcision was performed after first sexual intercourse in 3.9% of cases and 2.5% of controls. Circumcision was also more commonly reported in white men (69%) than in black men (43%).

In multivariate regression analysis, the investigators controlled for age, race, prostate-specific antigen (PSA) test within 5 years of diagnosis or reference data, family history of prostate cancer, history of STIs, prior prostatitis, and number of female and male sexual partners. They found that the overall odds ratio for prostate cancer among men who were circumcised before their first sexual intercourse was 0.88 (95% confidence interval, 0.73-0.99).

The researchers also looked at prostate cancer and circumcision status by aggressiveness of disease, with "aggressive" defined as a composite of Gleason score of 7 (4 + 3) or greater; nonlocalized stage; or PSA level greater than 20 ng/mL at the time of diagnosis.

They saw that preintercourse circumcision had borderline associations with lower risk for both less-aggressive (OR, 0.88; 95% CI, 0.74-1.04) and more-aggressive cancers (OR, 0.82; 95% CI, 0.66-1.00).

The reduction in prostate cancer risk with circumcision before first intercourse was observed in whites (OR, 0.87; 95% CI, 0.73-1.02); and blacks (OR, 0.64; 95% CI, 0.39-1.08).

Circumcision has been shown in other studies to be linked to lower rates of STIs, including HIV/AIDS, herpes simplex, syphilis, and chancroid, the authors noted. They suggested that the mucosal lining of the prepuce, which is thin, may develop small tears that provide pathogens with a route to the bloodstream.

"Circumcision may reduce these injuries due to the significant keratinization that occurs following the procedure," they speculated. "In addition, the moist environment under the preputial skin may help pathogens survive for extended periods prior to direct infection. Circumcision removes this protective environment."

The authors pointed to other studies linking circumcision to reduced prostate cancer risk, including a 1987 case-control study in which circumcision was associated with a 50% reduction in relative risk among whites, and a near 40% reduction in blacks (J Natl Cancer Inst. 1987;78:869-74).

The study was supported by National Institute of Health grants and the Fred Hutchinson Cancer Research Center. The authors reported no conflicts of interest. Dr. Freedland said that he had no conflicts of interest.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: What is the renal diet? Should my patients with chronic kidney disease (CKD) restrict their protein consumption?

The CKD nondialysis diet aims to preserve remaining kidney function. A person living with kidney disease can continue to enjoy a variety of foods, including whole grains, fruits, and vegetables. These foods must be restricted only when phosphorus, parathyroid hormone, and/or potassium levels become elevated. However, many advanced practitioners recommend avoiding dark sodas because of their high phosphorus content. Sodium is limited to help maintain blood pressure control and decrease fluid buildup.

Fluid intake is not restricted unless fluid retention becomes an issue. Adequate caloric intake from carbohydrates and healthy fats is essential so as to spare protein for growth and repair. Aiming for a healthy weight through appropriate caloric intake and regular physical activity is important. A water-soluble vitamin B complex and a vitamin C supplement may be recommended as the diet becomes more restrictive. Supplemental vitamin D requirements and iron needs are based on findings from laboratory studies.

As is always the case when advising patients on food choices, the emphasis should be on optimizing nutrition and avoiding empty calories. A review of how to interpret a food label is often helpful to patients and their families.

Dietary protein recommendations continue to be controversial in CKD stages 1 through 4 (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²). The renal diet emphasizes high-quality proteins but limits protein intake to approximately 0.6 to 0.8 g/kg/d so as to decrease the workload on the kidneys and reduce urea waste production. The National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for nutrition in patients with CKD¹ recommend that patients who have an eGFR between 25 and 55 mL/min/1.73 m² should eat at least 0.8 g/kg/d of protein; and that those whose eGFR is less than 25 mL/min/1.73 m² and who are not receiving dialysis consume 0.6 g/kg/d. If a patient cannot tolerate the diet or is unable to maintain an adequate caloric intake, then protein intake can be 0.75 g/kg/d.

Once a patient is undergoing dialysis, the protein requirements may change, depending on the patient’s needs and type of dialysis. Fortunately, the renal dietician, an essential member of the interdisciplinary dialysis team, offers great assistance to the advanced practitioner in addressing the patient’s nutritional needs.

However, referral to a renal dietitian is recommended before dialysis, as diet is an important part of CKD treatment. A Medicare recipient with stage 3 or 4 CKD can see a registered dietitian through the Medical Nutrition Therapy benefit.²

Individualizing nutritional therapy is essential to optimize health in people living with the complexities of CKD. It is also very important, when assessing, monitoring, and intervening to avoid or treat malnutrition in these patients, to provide care as an interprofessional team that includes a renal dietician. (To provide the best evidence available, an experienced renal dietician was asked to contribute to this response.)
Debra Hain, PhD, APRN, GNP-BC
Assistant Professor, Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton; Nurse Practitioner, Cleveland Clinic Florida, Weston
Susan Meese-Morris, RD, LD/N
Renal Dietitian, Pine Island, Weston, and Miramar, Florida

REFERENCES

1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: What is the renal diet? Should my patients with chronic kidney disease (CKD) restrict their protein consumption?

The CKD nondialysis diet aims to preserve remaining kidney function. A person living with kidney disease can continue to enjoy a variety of foods, including whole grains, fruits, and vegetables. These foods must be restricted only when phosphorus, parathyroid hormone, and/or potassium levels become elevated. However, many advanced practitioners recommend avoiding dark sodas because of their high phosphorus content. Sodium is limited to help maintain blood pressure control and decrease fluid buildup.

Fluid intake is not restricted unless fluid retention becomes an issue. Adequate caloric intake from carbohydrates and healthy fats is essential so as to spare protein for growth and repair. Aiming for a healthy weight through appropriate caloric intake and regular physical activity is important. A water-soluble vitamin B complex and a vitamin C supplement may be recommended as the diet becomes more restrictive. Supplemental vitamin D requirements and iron needs are based on findings from laboratory studies.

As is always the case when advising patients on food choices, the emphasis should be on optimizing nutrition and avoiding empty calories. A review of how to interpret a food label is often helpful to patients and their families.

Dietary protein recommendations continue to be controversial in CKD stages 1 through 4 (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²). The renal diet emphasizes high-quality proteins but limits protein intake to approximately 0.6 to 0.8 g/kg/d so as to decrease the workload on the kidneys and reduce urea waste production. The National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for nutrition in patients with CKD¹ recommend that patients who have an eGFR between 25 and 55 mL/min/1.73 m² should eat at least 0.8 g/kg/d of protein; and that those whose eGFR is less than 25 mL/min/1.73 m² and who are not receiving dialysis consume 0.6 g/kg/d. If a patient cannot tolerate the diet or is unable to maintain an adequate caloric intake, then protein intake can be 0.75 g/kg/d.

Once a patient is undergoing dialysis, the protein requirements may change, depending on the patient’s needs and type of dialysis. Fortunately, the renal dietician, an essential member of the interdisciplinary dialysis team, offers great assistance to the advanced practitioner in addressing the patient’s nutritional needs.

However, referral to a renal dietitian is recommended before dialysis, as diet is an important part of CKD treatment. A Medicare recipient with stage 3 or 4 CKD can see a registered dietitian through the Medical Nutrition Therapy benefit.²

Individualizing nutritional therapy is essential to optimize health in people living with the complexities of CKD. It is also very important, when assessing, monitoring, and intervening to avoid or treat malnutrition in these patients, to provide care as an interprofessional team that includes a renal dietician. (To provide the best evidence available, an experienced renal dietician was asked to contribute to this response.)
Debra Hain, PhD, APRN, GNP-BC
Assistant Professor, Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton; Nurse Practitioner, Cleveland Clinic Florida, Weston
Susan Meese-Morris, RD, LD/N
Renal Dietitian, Pine Island, Weston, and Miramar, Florida

REFERENCES

1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: What is the renal diet? Should my patients with chronic kidney disease (CKD) restrict their protein consumption?

The CKD nondialysis diet aims to preserve remaining kidney function. A person living with kidney disease can continue to enjoy a variety of foods, including whole grains, fruits, and vegetables. These foods must be restricted only when phosphorus, parathyroid hormone, and/or potassium levels become elevated. However, many advanced practitioners recommend avoiding dark sodas because of their high phosphorus content. Sodium is limited to help maintain blood pressure control and decrease fluid buildup.

Fluid intake is not restricted unless fluid retention becomes an issue. Adequate caloric intake from carbohydrates and healthy fats is essential so as to spare protein for growth and repair. Aiming for a healthy weight through appropriate caloric intake and regular physical activity is important. A water-soluble vitamin B complex and a vitamin C supplement may be recommended as the diet becomes more restrictive. Supplemental vitamin D requirements and iron needs are based on findings from laboratory studies.

As is always the case when advising patients on food choices, the emphasis should be on optimizing nutrition and avoiding empty calories. A review of how to interpret a food label is often helpful to patients and their families.

Dietary protein recommendations continue to be controversial in CKD stages 1 through 4 (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²). The renal diet emphasizes high-quality proteins but limits protein intake to approximately 0.6 to 0.8 g/kg/d so as to decrease the workload on the kidneys and reduce urea waste production. The National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for nutrition in patients with CKD¹ recommend that patients who have an eGFR between 25 and 55 mL/min/1.73 m² should eat at least 0.8 g/kg/d of protein; and that those whose eGFR is less than 25 mL/min/1.73 m² and who are not receiving dialysis consume 0.6 g/kg/d. If a patient cannot tolerate the diet or is unable to maintain an adequate caloric intake, then protein intake can be 0.75 g/kg/d.

Once a patient is undergoing dialysis, the protein requirements may change, depending on the patient’s needs and type of dialysis. Fortunately, the renal dietician, an essential member of the interdisciplinary dialysis team, offers great assistance to the advanced practitioner in addressing the patient’s nutritional needs.

However, referral to a renal dietitian is recommended before dialysis, as diet is an important part of CKD treatment. A Medicare recipient with stage 3 or 4 CKD can see a registered dietitian through the Medical Nutrition Therapy benefit.²

Individualizing nutritional therapy is essential to optimize health in people living with the complexities of CKD. It is also very important, when assessing, monitoring, and intervening to avoid or treat malnutrition in these patients, to provide care as an interprofessional team that includes a renal dietician. (To provide the best evidence available, an experienced renal dietician was asked to contribute to this response.)
Debra Hain, PhD, APRN, GNP-BC
Assistant Professor, Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton; Nurse Practitioner, Cleveland Clinic Florida, Weston
Susan Meese-Morris, RD, LD/N
Renal Dietitian, Pine Island, Weston, and Miramar, Florida

REFERENCES

1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: Our practice received a flyer for kidney disease education classes offered by the local nephrology group. Can you tell me more about these classes?

Patient education in kidney disease has been shown to delay disease progression and improve patient outcomes.⁴ Because of this, the Medicare Improvements for Patients and Providers Act (­MIPPA) of 2008⁵ provided for classes for patients with stage 4 CKD (GFR, 15 to 29 mL/min/1.73 m²) to receive six hours of education over their lifetime.

Classes can be taught by a physician or an advanced practitioner (a PA, an NP, or a clinical nurse specialist). Four broad areas are covered: management of comorbidities that occur with CKD; prevention of complications, including an explanation of how the kidneys work and a review of medications; renal replacement modalities, including hemodialysis, peritoneal dialysis, and transplantation; and opportunities to empower the patients as active partners in their own health care.⁶ Classes also include information on managing anemia, hypertension, and bone mineral disease.⁷

Class structure is up to the provider. Most practices offer classes to all stage 4 CKD patients, regardless of Medicare status. Classes can be taught on a one-to-one basis or in a group setting.⁸

Some practices design their own format, while others use programs designed for CKD education. The National Kidney Foundation developed a slide set called Your Treatment, Your Choice,⁸ while the Cleveland Clinic, the Mayo Clinic, and the University of Alabama at Birmingham (among others, no doubt), have developed their own in-house programs. All these programs have a prepared Power Point slide deck, and most include evaluation tools.
Tricia Howard, MHS, PA-C
South University, Savannah, Georgia

REFERENCES
1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: Our practice received a flyer for kidney disease education classes offered by the local nephrology group. Can you tell me more about these classes?

Patient education in kidney disease has been shown to delay disease progression and improve patient outcomes.⁴ Because of this, the Medicare Improvements for Patients and Providers Act (­MIPPA) of 2008⁵ provided for classes for patients with stage 4 CKD (GFR, 15 to 29 mL/min/1.73 m²) to receive six hours of education over their lifetime.

Classes can be taught by a physician or an advanced practitioner (a PA, an NP, or a clinical nurse specialist). Four broad areas are covered: management of comorbidities that occur with CKD; prevention of complications, including an explanation of how the kidneys work and a review of medications; renal replacement modalities, including hemodialysis, peritoneal dialysis, and transplantation; and opportunities to empower the patients as active partners in their own health care.⁶ Classes also include information on managing anemia, hypertension, and bone mineral disease.⁷

Class structure is up to the provider. Most practices offer classes to all stage 4 CKD patients, regardless of Medicare status. Classes can be taught on a one-to-one basis or in a group setting.⁸

Some practices design their own format, while others use programs designed for CKD education. The National Kidney Foundation developed a slide set called Your Treatment, Your Choice,⁸ while the Cleveland Clinic, the Mayo Clinic, and the University of Alabama at Birmingham (among others, no doubt), have developed their own in-house programs. All these programs have a prepared Power Point slide deck, and most include evaluation tools.
Tricia Howard, MHS, PA-C
South University, Savannah, Georgia

REFERENCES
1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: Our practice received a flyer for kidney disease education classes offered by the local nephrology group. Can you tell me more about these classes?

Patient education in kidney disease has been shown to delay disease progression and improve patient outcomes.⁴ Because of this, the Medicare Improvements for Patients and Providers Act (­MIPPA) of 2008⁵ provided for classes for patients with stage 4 CKD (GFR, 15 to 29 mL/min/1.73 m²) to receive six hours of education over their lifetime.

Classes can be taught by a physician or an advanced practitioner (a PA, an NP, or a clinical nurse specialist). Four broad areas are covered: management of comorbidities that occur with CKD; prevention of complications, including an explanation of how the kidneys work and a review of medications; renal replacement modalities, including hemodialysis, peritoneal dialysis, and transplantation; and opportunities to empower the patients as active partners in their own health care.⁶ Classes also include information on managing anemia, hypertension, and bone mineral disease.⁷

Class structure is up to the provider. Most practices offer classes to all stage 4 CKD patients, regardless of Medicare status. Classes can be taught on a one-to-one basis or in a group setting.⁸

Some practices design their own format, while others use programs designed for CKD education. The National Kidney Foundation developed a slide set called Your Treatment, Your Choice,⁸ while the Cleveland Clinic, the Mayo Clinic, and the University of Alabama at Birmingham (among others, no doubt), have developed their own in-house programs. All these programs have a prepared Power Point slide deck, and most include evaluation tools.
Tricia Howard, MHS, PA-C
South University, Savannah, Georgia

REFERENCES
1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: We scheduled a total knee replacement for a patient on dialysis, and anesthesia balked because the patient had a potassium level of 5.5 mEq/L. The nephrology practice, apparently not concerned, agreed to dialyze the patient, but only because anesthesia insisted. If the practice uses our facility, where 5.3 mEq/L is the upper limit of serum potassium, how can a potassium level of 5.5 mEq/L not be of concern in a hemodialysis patient?

This is a question that occurs frequently regarding patients receiving dialysis. Hyperkalemia is a problem faced by many dialysis patients as a result of the kidneys’ inability to remove potassium with the loss of renal function. Patients’ potassium levels are monitored routinely, and low-potassium diets are a staple of any nephrology clinic or dialysis unit.

For patients in our dialysis unit, the normal potassium range is 3.5 to 6.0 mEq/L, which is 0.9 mEq/L higher than for a patient without end-stage renal disease (ESRD). Dialysis patients with ESRD often have an increased tolerance for hyperkalemia.

When potassium levels are elevated, a 12-lead ECG is used to detect any physiological cardiac changes. These are generally not seen until the serum potassium exceeds 6.0 to 6.5 mEq/L. ECG changes seen in hyperkalemia include peaked T waves, a prolonged PR interval, and absent P waves with a widened QRS complex. These changes, which can lead to ventricular tachycardia or ventricular fibrillation, are not based on numbers or values of serum potassium, but are thought to reflect the transcellular potassium gradient.³

When questioning a potassium level in a dialysis patient and considering whether presurgical dialysis is needed, it is important to consider the surgery planned. In surgeries during which potassium might be released secondary to tissue trauma, potassium levels can rise higher during surgery.³

It is important to assess hypokalemia as well. Arrhythmias such as premature atrial and ventricular beats, sinus bradycardia, paroxysmal atrial or junctional tachycardia, atrioventricular block, and ventricular tachycardia or fibrillation can occur with hypokalemia. ECG changes include depression of the ST segment, a decrease in the amplitude of the T wave, and an increase in the amplitude of U waves, which occur at the end of the T wave. U waves are often seen in the lateral precordial leads V4 to V6.³
Laura MacGregor, RN, MS, NP-C
Grand Street Medical Associates, Kingston, New York

REFERENCES

1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: We scheduled a total knee replacement for a patient on dialysis, and anesthesia balked because the patient had a potassium level of 5.5 mEq/L. The nephrology practice, apparently not concerned, agreed to dialyze the patient, but only because anesthesia insisted. If the practice uses our facility, where 5.3 mEq/L is the upper limit of serum potassium, how can a potassium level of 5.5 mEq/L not be of concern in a hemodialysis patient?

This is a question that occurs frequently regarding patients receiving dialysis. Hyperkalemia is a problem faced by many dialysis patients as a result of the kidneys’ inability to remove potassium with the loss of renal function. Patients’ potassium levels are monitored routinely, and low-potassium diets are a staple of any nephrology clinic or dialysis unit.

For patients in our dialysis unit, the normal potassium range is 3.5 to 6.0 mEq/L, which is 0.9 mEq/L higher than for a patient without end-stage renal disease (ESRD). Dialysis patients with ESRD often have an increased tolerance for hyperkalemia.

When potassium levels are elevated, a 12-lead ECG is used to detect any physiological cardiac changes. These are generally not seen until the serum potassium exceeds 6.0 to 6.5 mEq/L. ECG changes seen in hyperkalemia include peaked T waves, a prolonged PR interval, and absent P waves with a widened QRS complex. These changes, which can lead to ventricular tachycardia or ventricular fibrillation, are not based on numbers or values of serum potassium, but are thought to reflect the transcellular potassium gradient.³

When questioning a potassium level in a dialysis patient and considering whether presurgical dialysis is needed, it is important to consider the surgery planned. In surgeries during which potassium might be released secondary to tissue trauma, potassium levels can rise higher during surgery.³

It is important to assess hypokalemia as well. Arrhythmias such as premature atrial and ventricular beats, sinus bradycardia, paroxysmal atrial or junctional tachycardia, atrioventricular block, and ventricular tachycardia or fibrillation can occur with hypokalemia. ECG changes include depression of the ST segment, a decrease in the amplitude of the T wave, and an increase in the amplitude of U waves, which occur at the end of the T wave. U waves are often seen in the lateral precordial leads V4 to V6.³
Laura MacGregor, RN, MS, NP-C
Grand Street Medical Associates, Kingston, New York

REFERENCES

1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

Your renal practitioners/department editors have chosen three typical situations you might encounter in practice. 

• Nutrition and diet help control kidney disease, but also heart disease, diabetes, and other comorbid states.

• Renal patients, like many others, often require surgeries; what specific concerns exist for surgical patients requiring dialysis?

• The Medicare education benefit has been a particular bonus for advanced practitioners, as we teach many of the classes.

We welcome your questions and comments.

Q: We scheduled a total knee replacement for a patient on dialysis, and anesthesia balked because the patient had a potassium level of 5.5 mEq/L. The nephrology practice, apparently not concerned, agreed to dialyze the patient, but only because anesthesia insisted. If the practice uses our facility, where 5.3 mEq/L is the upper limit of serum potassium, how can a potassium level of 5.5 mEq/L not be of concern in a hemodialysis patient?

This is a question that occurs frequently regarding patients receiving dialysis. Hyperkalemia is a problem faced by many dialysis patients as a result of the kidneys’ inability to remove potassium with the loss of renal function. Patients’ potassium levels are monitored routinely, and low-potassium diets are a staple of any nephrology clinic or dialysis unit.

For patients in our dialysis unit, the normal potassium range is 3.5 to 6.0 mEq/L, which is 0.9 mEq/L higher than for a patient without end-stage renal disease (ESRD). Dialysis patients with ESRD often have an increased tolerance for hyperkalemia.

When potassium levels are elevated, a 12-lead ECG is used to detect any physiological cardiac changes. These are generally not seen until the serum potassium exceeds 6.0 to 6.5 mEq/L. ECG changes seen in hyperkalemia include peaked T waves, a prolonged PR interval, and absent P waves with a widened QRS complex. These changes, which can lead to ventricular tachycardia or ventricular fibrillation, are not based on numbers or values of serum potassium, but are thought to reflect the transcellular potassium gradient.³

When questioning a potassium level in a dialysis patient and considering whether presurgical dialysis is needed, it is important to consider the surgery planned. In surgeries during which potassium might be released secondary to tissue trauma, potassium levels can rise higher during surgery.³

It is important to assess hypokalemia as well. Arrhythmias such as premature atrial and ventricular beats, sinus bradycardia, paroxysmal atrial or junctional tachycardia, atrioventricular block, and ventricular tachycardia or fibrillation can occur with hypokalemia. ECG changes include depression of the ST segment, a decrease in the amplitude of the T wave, and an increase in the amplitude of U waves, which occur at the end of the T wave. U waves are often seen in the lateral precordial leads V4 to V6.³
Laura MacGregor, RN, MS, NP-C
Grand Street Medical Associates, Kingston, New York

REFERENCES

1. National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure (2000). www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_nut.html. Accessed February 16, 2012.

2. Medicare.gov. Medical nutrition therapy. www.medicare.gov/navigation/manage-your-health/preventive-services/medical-nutrition-therapy.aspx?AspxAutoDetectCookieSupport=1. Accessed February 16, 2012.

3. Soundararajan R, Golper T. Medical management of the dialysis patient undergoing surgery. www.uptodate.com/contents/medical-management-of-the-dialysis-patient-undergoing-surgery. Accessed February 16, 2012.

4. Young HN, Chan MR, Yevzlin AS, Becker BN. The rationale, implementation and effects of the Medicare CKD education benefit. Am J Kidney Dis. 2011;57(3):381-386.

5. H. R. 6331: Medicare Improvements for Patients and Providers Act of 2008. www.govtrack.us/congress/bill.xpd?bill=h110-6331. Accessed February 16, 2012.

6. §410.48. Kidney disease education services. Federal Register. 2009;74(226):62003.

7. Lazarus JM. National health care policy and its effect on renal care. Presented at: NKFI Multi-Disciplinary Conference; September 24, 2009; Chicago, IL.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed February 16, 2012.

SAN FRANCISCO – Healthy middle-aged and older men who take vitamin E supplements have an increased risk of prostate cancer, although the risk takes some time to emerge, suggests an update of the randomized SELECT prevention trial.

At a median follow-up of 7 years – or 1.5 years after the trial had been closed early for futility and men had been told to stop taking supplements – those who had taken vitamin E had a significant 17% greater risk of prostate cancer than those who had taken a placebo. The risk had been increased, although not significantly so, at the time of trial closure.

Photo credit: Juanmonino/iStockphoto

In absolute terms, the elevated risk from taking vitamin E translated to 11 more cancers for every 1,000 men over a 7-year period, Dr. Eric A. Klein said at the Genitourinary Cancers Symposium.

The findings serve as a cautionary tale, he said. "Nutritional supplements are biologically active and may in fact be harmful, and importantly, the effect may continue after the intervention stops," Dr. Klein commented.

More than half of U.S. men over age 60 take vitamin E, with about one-quarter taking at least 400 IU daily (Ann. Intern. Med. 2005;143:116-20), the dose used in the trial. "Consumers should be skeptical about health claims for unregulated over-the-counter products in the absence of strong evidence of benefit from clinical trials," said Dr. Klein at the meeting, which was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

In other updated results, men who took selenium with vitamin E and men who took selenium alone did not have any significant increase in the risk of prostate cancer. And baseline plasma levels of various tocopherols (forms of vitamin E) modified prostate cancer risk: Within the vitamin E group, for example, higher levels of alpha-tocopherol were protective, whereas higher levels of gamma-tocopherol were deleterious.

The obvious question now is, how does vitamin E increase prostate cancer risk? said Dr. Klein, who is chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. Theories that have been advanced include the possibility that antioxidants become carcinogenic pro-oxidants at high doses; there may be interplay between the different types of tocopherols; high doses of vitamin E may inhibit absorption of other, protective fat-soluble vitamins; and genetic susceptibility may affect the actions of antioxidants. A related, as yet unanswered question is why adding selenium to vitamin E abolishes the excess risk.

"We need to sort all of this out," Dr. Klein said, pointing to the SELECT (Selenium and Vitamin E Cancer Prevention Trial) Biorepository, which contains a wealth of information about the men studied and is being offered as a resource. "I invite anybody in the scientific community to float a hypothesis. If it passes scientific muster, we will give you access to the Biorepository to help us answer [these questions]." More than a half dozen studies have already been approved, he said.

In SELECT, 35,533 healthy North American men aged 50 years or older if black or 55 years or older if of other races/ethnicities who had an average risk of prostate cancer were randomized to four groups: vitamin E (400 IU/day, all rac-alpha-tocopherol acetate), selenium (200 mcg/day from l-selenomethionine), the combination, or a placebo.

"It was recommended, but not required in this trial, unlike in the PCPT [Prostate Cancer Prevention Trial], that men be screened yearly with PSA and digital rectal exam," Dr. Klein noted. "One of the strengths of the trial is that the screening interval and the trigger for biopsy were not prescribed by the trial; they were left to local community standards at these 400-plus sites."

At the time that the trial was halted early, men in the vitamin E group had a marginally increased risk of prostate cancer compared with men in the placebo group (hazard ratio, 1.13; P = .06) (JAMA 2009;301:39-51). But with the additional follow-up, despite cessation of supplement use, the trend continued and became significant (hazard ratio, 1.17; P = .008) (JAMA 2011;306:1549-56).

"There was no difference in tumor aggressiveness across the four arms as assessed by tumor stage and grade," Dr. Klein reported. "And the increased risk of being diagnosed with prostate cancer in the vitamin E arm was not accounted for by more intense screening or an increasing rate of biopsy."

In the vitamin E group, the risk of prostate cancer generally decreased with each additional quintile of alpha-tocopherol at baseline. In contrast, within the selenium and combination groups, the risk increased with quintile, and within the placebo group, risk was unaffected.

The results were "somewhat opposite" for plasma gamma-tocopherol levels at baseline. In the vitamin E group, the risk generally increased with quintile. In contrast, within all the other groups, the risk decreased with quintile.

The findings have noteworthy implications for the design of clinical trials, said Dr. Klein.

"There were interactions between selenium and vitamin E with respect to risk, and a factorial design would not have captured that. So it’s important that these be powered to allow for these interactions to be tested for," he explained. "And maybe most importantly, for agents whose biology we don’t really understand and don’t really understand what the time line of the effect is, that postintervention follow-up is critical: If we had not continued to follow these men beyond the 5.5 years that they took the supplements, we would not have discovered [the elevated risk with vitamin E]".

Dr. Klein disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – Healthy middle-aged and older men who take vitamin E supplements have an increased risk of prostate cancer, although the risk takes some time to emerge, suggests an update of the randomized SELECT prevention trial.

At a median follow-up of 7 years – or 1.5 years after the trial had been closed early for futility and men had been told to stop taking supplements – those who had taken vitamin E had a significant 17% greater risk of prostate cancer than those who had taken a placebo. The risk had been increased, although not significantly so, at the time of trial closure.

Photo credit: Juanmonino/iStockphoto

In absolute terms, the elevated risk from taking vitamin E translated to 11 more cancers for every 1,000 men over a 7-year period, Dr. Eric A. Klein said at the Genitourinary Cancers Symposium.

The findings serve as a cautionary tale, he said. "Nutritional supplements are biologically active and may in fact be harmful, and importantly, the effect may continue after the intervention stops," Dr. Klein commented.

More than half of U.S. men over age 60 take vitamin E, with about one-quarter taking at least 400 IU daily (Ann. Intern. Med. 2005;143:116-20), the dose used in the trial. "Consumers should be skeptical about health claims for unregulated over-the-counter products in the absence of strong evidence of benefit from clinical trials," said Dr. Klein at the meeting, which was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

In other updated results, men who took selenium with vitamin E and men who took selenium alone did not have any significant increase in the risk of prostate cancer. And baseline plasma levels of various tocopherols (forms of vitamin E) modified prostate cancer risk: Within the vitamin E group, for example, higher levels of alpha-tocopherol were protective, whereas higher levels of gamma-tocopherol were deleterious.

The obvious question now is, how does vitamin E increase prostate cancer risk? said Dr. Klein, who is chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. Theories that have been advanced include the possibility that antioxidants become carcinogenic pro-oxidants at high doses; there may be interplay between the different types of tocopherols; high doses of vitamin E may inhibit absorption of other, protective fat-soluble vitamins; and genetic susceptibility may affect the actions of antioxidants. A related, as yet unanswered question is why adding selenium to vitamin E abolishes the excess risk.

"We need to sort all of this out," Dr. Klein said, pointing to the SELECT (Selenium and Vitamin E Cancer Prevention Trial) Biorepository, which contains a wealth of information about the men studied and is being offered as a resource. "I invite anybody in the scientific community to float a hypothesis. If it passes scientific muster, we will give you access to the Biorepository to help us answer [these questions]." More than a half dozen studies have already been approved, he said.

In SELECT, 35,533 healthy North American men aged 50 years or older if black or 55 years or older if of other races/ethnicities who had an average risk of prostate cancer were randomized to four groups: vitamin E (400 IU/day, all rac-alpha-tocopherol acetate), selenium (200 mcg/day from l-selenomethionine), the combination, or a placebo.

"It was recommended, but not required in this trial, unlike in the PCPT [Prostate Cancer Prevention Trial], that men be screened yearly with PSA and digital rectal exam," Dr. Klein noted. "One of the strengths of the trial is that the screening interval and the trigger for biopsy were not prescribed by the trial; they were left to local community standards at these 400-plus sites."

At the time that the trial was halted early, men in the vitamin E group had a marginally increased risk of prostate cancer compared with men in the placebo group (hazard ratio, 1.13; P = .06) (JAMA 2009;301:39-51). But with the additional follow-up, despite cessation of supplement use, the trend continued and became significant (hazard ratio, 1.17; P = .008) (JAMA 2011;306:1549-56).

"There was no difference in tumor aggressiveness across the four arms as assessed by tumor stage and grade," Dr. Klein reported. "And the increased risk of being diagnosed with prostate cancer in the vitamin E arm was not accounted for by more intense screening or an increasing rate of biopsy."

In the vitamin E group, the risk of prostate cancer generally decreased with each additional quintile of alpha-tocopherol at baseline. In contrast, within the selenium and combination groups, the risk increased with quintile, and within the placebo group, risk was unaffected.

The results were "somewhat opposite" for plasma gamma-tocopherol levels at baseline. In the vitamin E group, the risk generally increased with quintile. In contrast, within all the other groups, the risk decreased with quintile.

The findings have noteworthy implications for the design of clinical trials, said Dr. Klein.

"There were interactions between selenium and vitamin E with respect to risk, and a factorial design would not have captured that. So it’s important that these be powered to allow for these interactions to be tested for," he explained. "And maybe most importantly, for agents whose biology we don’t really understand and don’t really understand what the time line of the effect is, that postintervention follow-up is critical: If we had not continued to follow these men beyond the 5.5 years that they took the supplements, we would not have discovered [the elevated risk with vitamin E]".

Dr. Klein disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – Healthy middle-aged and older men who take vitamin E supplements have an increased risk of prostate cancer, although the risk takes some time to emerge, suggests an update of the randomized SELECT prevention trial.

At a median follow-up of 7 years – or 1.5 years after the trial had been closed early for futility and men had been told to stop taking supplements – those who had taken vitamin E had a significant 17% greater risk of prostate cancer than those who had taken a placebo. The risk had been increased, although not significantly so, at the time of trial closure.

Photo credit: Juanmonino/iStockphoto

In absolute terms, the elevated risk from taking vitamin E translated to 11 more cancers for every 1,000 men over a 7-year period, Dr. Eric A. Klein said at the Genitourinary Cancers Symposium.

The findings serve as a cautionary tale, he said. "Nutritional supplements are biologically active and may in fact be harmful, and importantly, the effect may continue after the intervention stops," Dr. Klein commented.

More than half of U.S. men over age 60 take vitamin E, with about one-quarter taking at least 400 IU daily (Ann. Intern. Med. 2005;143:116-20), the dose used in the trial. "Consumers should be skeptical about health claims for unregulated over-the-counter products in the absence of strong evidence of benefit from clinical trials," said Dr. Klein at the meeting, which was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

In other updated results, men who took selenium with vitamin E and men who took selenium alone did not have any significant increase in the risk of prostate cancer. And baseline plasma levels of various tocopherols (forms of vitamin E) modified prostate cancer risk: Within the vitamin E group, for example, higher levels of alpha-tocopherol were protective, whereas higher levels of gamma-tocopherol were deleterious.

The obvious question now is, how does vitamin E increase prostate cancer risk? said Dr. Klein, who is chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. Theories that have been advanced include the possibility that antioxidants become carcinogenic pro-oxidants at high doses; there may be interplay between the different types of tocopherols; high doses of vitamin E may inhibit absorption of other, protective fat-soluble vitamins; and genetic susceptibility may affect the actions of antioxidants. A related, as yet unanswered question is why adding selenium to vitamin E abolishes the excess risk.

"We need to sort all of this out," Dr. Klein said, pointing to the SELECT (Selenium and Vitamin E Cancer Prevention Trial) Biorepository, which contains a wealth of information about the men studied and is being offered as a resource. "I invite anybody in the scientific community to float a hypothesis. If it passes scientific muster, we will give you access to the Biorepository to help us answer [these questions]." More than a half dozen studies have already been approved, he said.

In SELECT, 35,533 healthy North American men aged 50 years or older if black or 55 years or older if of other races/ethnicities who had an average risk of prostate cancer were randomized to four groups: vitamin E (400 IU/day, all rac-alpha-tocopherol acetate), selenium (200 mcg/day from l-selenomethionine), the combination, or a placebo.

"It was recommended, but not required in this trial, unlike in the PCPT [Prostate Cancer Prevention Trial], that men be screened yearly with PSA and digital rectal exam," Dr. Klein noted. "One of the strengths of the trial is that the screening interval and the trigger for biopsy were not prescribed by the trial; they were left to local community standards at these 400-plus sites."

At the time that the trial was halted early, men in the vitamin E group had a marginally increased risk of prostate cancer compared with men in the placebo group (hazard ratio, 1.13; P = .06) (JAMA 2009;301:39-51). But with the additional follow-up, despite cessation of supplement use, the trend continued and became significant (hazard ratio, 1.17; P = .008) (JAMA 2011;306:1549-56).

"There was no difference in tumor aggressiveness across the four arms as assessed by tumor stage and grade," Dr. Klein reported. "And the increased risk of being diagnosed with prostate cancer in the vitamin E arm was not accounted for by more intense screening or an increasing rate of biopsy."

In the vitamin E group, the risk of prostate cancer generally decreased with each additional quintile of alpha-tocopherol at baseline. In contrast, within the selenium and combination groups, the risk increased with quintile, and within the placebo group, risk was unaffected.

The results were "somewhat opposite" for plasma gamma-tocopherol levels at baseline. In the vitamin E group, the risk generally increased with quintile. In contrast, within all the other groups, the risk decreased with quintile.

The findings have noteworthy implications for the design of clinical trials, said Dr. Klein.

"There were interactions between selenium and vitamin E with respect to risk, and a factorial design would not have captured that. So it’s important that these be powered to allow for these interactions to be tested for," he explained. "And maybe most importantly, for agents whose biology we don’t really understand and don’t really understand what the time line of the effect is, that postintervention follow-up is critical: If we had not continued to follow these men beyond the 5.5 years that they took the supplements, we would not have discovered [the elevated risk with vitamin E]".

Dr. Klein disclosed that he had no relevant conflicts of interest.