Nephrology

PARIS — Prophylactic use of heparin made no difference in the incidence of symptomatic deep vein thrombosis and/or pulmonary embolism after 4,609 laparoscopic radical prostatectomies reviewed by the International Laparoscopy Prostate Cancer Working Group.

Eleven centers in seven countries contributed patients to the ongoing study. Dr. Fernando P. Secin presented an interim analysis of the study data at the annual congress of the European Association of Urology.

The overall rate of deep vein thrombosis and/or pulmonary embolism (DVT/PE) was low: 0.6%, according to Dr. Secin, a urology fellow at Memorial Sloan-Kettering Cancer Center in New York.

Dr. Secin speculated that most patients undergoing laparoscopic radical prostatectomies are probably at low risk for thromboembolic events.

“Most prostate cancers [that] are operated [on] are early prostate cancers, so the impact of the cancer itself on the thrombotic mechanism may not be that serious,” he said in an interview at the meeting.

Although heparin use was not a statistically significant factor in univariate or multivariate analyses, the latter did identify the following risk factors as being significant for DVT/PE in patients undergoing laparoscopic radical prostatectomy:

▸ Patients undergoing a reexploration were 20 times more likely to have a thromboembolic event.

▸ The odds were 13 times greater for those with a prior history of DVT.

▸ Every 10-g increase in prostate size raised the odds ratio by 1.2.

The investigators concluded that the data do not support heparin prophylaxis in patients who do not have these risk factors. Randomized trials are needed to establish its utility, they said.

Centers in France, Belgium, Austria, the United Kingdom, Spain, Sweden, and the United States contributed patients to the analysis. Dr. Secin said he hopes to accumulate another 1,000 patients before completing the study.

Prophylaxis protocols ranged from no heparin use to both preoperative and postoperative use of heparin, with no discernible relationship to the rate of DVT/PE at each hospital. All the institutions used mechanical prophylaxis: either a pneumatic compression device or a gradual compression stocking.

The lowest and highest DVT/PE rates (0% and 1.4%, respectively) were both found at centers that administered heparin before and after surgery. At the Cleveland Clinic, where heparin prophylaxis was not used, the rate was 0.5%.

Patients receiving preoperative heparin had significantly higher intraoperative mean blood loss, compared with those given postoperative heparin or no heparin: 444 mL vs. 332 mL.

This difference in blood loss did not translate into longer hospital stays or higher transfusion or reoperation rates, according to Dr. Secin.

Estimating the cost of heparin at $80 per dose, the investigators calculated the total cost as $2,955,057 for the 11 centers that contributed data.

“You spend so much money and there isn't any use for that,” said Dr. Bertrand D. Guillonneau, the study's senior author and section head of minimally invasive surgery, department of urology, Memorial Sloan-Kettering.

PARIS — Prophylactic use of heparin made no difference in the incidence of symptomatic deep vein thrombosis and/or pulmonary embolism after 4,609 laparoscopic radical prostatectomies reviewed by the International Laparoscopy Prostate Cancer Working Group.

Eleven centers in seven countries contributed patients to the ongoing study. Dr. Fernando P. Secin presented an interim analysis of the study data at the annual congress of the European Association of Urology.

The overall rate of deep vein thrombosis and/or pulmonary embolism (DVT/PE) was low: 0.6%, according to Dr. Secin, a urology fellow at Memorial Sloan-Kettering Cancer Center in New York.

Dr. Secin speculated that most patients undergoing laparoscopic radical prostatectomies are probably at low risk for thromboembolic events.

“Most prostate cancers [that] are operated [on] are early prostate cancers, so the impact of the cancer itself on the thrombotic mechanism may not be that serious,” he said in an interview at the meeting.

Although heparin use was not a statistically significant factor in univariate or multivariate analyses, the latter did identify the following risk factors as being significant for DVT/PE in patients undergoing laparoscopic radical prostatectomy:

▸ Patients undergoing a reexploration were 20 times more likely to have a thromboembolic event.

▸ The odds were 13 times greater for those with a prior history of DVT.

▸ Every 10-g increase in prostate size raised the odds ratio by 1.2.

The investigators concluded that the data do not support heparin prophylaxis in patients who do not have these risk factors. Randomized trials are needed to establish its utility, they said.

Centers in France, Belgium, Austria, the United Kingdom, Spain, Sweden, and the United States contributed patients to the analysis. Dr. Secin said he hopes to accumulate another 1,000 patients before completing the study.

Prophylaxis protocols ranged from no heparin use to both preoperative and postoperative use of heparin, with no discernible relationship to the rate of DVT/PE at each hospital. All the institutions used mechanical prophylaxis: either a pneumatic compression device or a gradual compression stocking.

The lowest and highest DVT/PE rates (0% and 1.4%, respectively) were both found at centers that administered heparin before and after surgery. At the Cleveland Clinic, where heparin prophylaxis was not used, the rate was 0.5%.

Patients receiving preoperative heparin had significantly higher intraoperative mean blood loss, compared with those given postoperative heparin or no heparin: 444 mL vs. 332 mL.

This difference in blood loss did not translate into longer hospital stays or higher transfusion or reoperation rates, according to Dr. Secin.

Estimating the cost of heparin at $80 per dose, the investigators calculated the total cost as $2,955,057 for the 11 centers that contributed data.

“You spend so much money and there isn't any use for that,” said Dr. Bertrand D. Guillonneau, the study's senior author and section head of minimally invasive surgery, department of urology, Memorial Sloan-Kettering.

PARIS — Prophylactic use of heparin made no difference in the incidence of symptomatic deep vein thrombosis and/or pulmonary embolism after 4,609 laparoscopic radical prostatectomies reviewed by the International Laparoscopy Prostate Cancer Working Group.

Eleven centers in seven countries contributed patients to the ongoing study. Dr. Fernando P. Secin presented an interim analysis of the study data at the annual congress of the European Association of Urology.

The overall rate of deep vein thrombosis and/or pulmonary embolism (DVT/PE) was low: 0.6%, according to Dr. Secin, a urology fellow at Memorial Sloan-Kettering Cancer Center in New York.

Dr. Secin speculated that most patients undergoing laparoscopic radical prostatectomies are probably at low risk for thromboembolic events.

“Most prostate cancers [that] are operated [on] are early prostate cancers, so the impact of the cancer itself on the thrombotic mechanism may not be that serious,” he said in an interview at the meeting.

Although heparin use was not a statistically significant factor in univariate or multivariate analyses, the latter did identify the following risk factors as being significant for DVT/PE in patients undergoing laparoscopic radical prostatectomy:

▸ Patients undergoing a reexploration were 20 times more likely to have a thromboembolic event.

▸ The odds were 13 times greater for those with a prior history of DVT.

▸ Every 10-g increase in prostate size raised the odds ratio by 1.2.

The investigators concluded that the data do not support heparin prophylaxis in patients who do not have these risk factors. Randomized trials are needed to establish its utility, they said.

Centers in France, Belgium, Austria, the United Kingdom, Spain, Sweden, and the United States contributed patients to the analysis. Dr. Secin said he hopes to accumulate another 1,000 patients before completing the study.

Prophylaxis protocols ranged from no heparin use to both preoperative and postoperative use of heparin, with no discernible relationship to the rate of DVT/PE at each hospital. All the institutions used mechanical prophylaxis: either a pneumatic compression device or a gradual compression stocking.

The lowest and highest DVT/PE rates (0% and 1.4%, respectively) were both found at centers that administered heparin before and after surgery. At the Cleveland Clinic, where heparin prophylaxis was not used, the rate was 0.5%.

Patients receiving preoperative heparin had significantly higher intraoperative mean blood loss, compared with those given postoperative heparin or no heparin: 444 mL vs. 332 mL.

This difference in blood loss did not translate into longer hospital stays or higher transfusion or reoperation rates, according to Dr. Secin.

Estimating the cost of heparin at $80 per dose, the investigators calculated the total cost as $2,955,057 for the 11 centers that contributed data.

“You spend so much money and there isn't any use for that,” said Dr. Bertrand D. Guillonneau, the study's senior author and section head of minimally invasive surgery, department of urology, Memorial Sloan-Kettering.

ATLANTA — An annual dose of zoledronic acid can prevent bone loss in men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer, Dr. M. Dror Michaelson reported at the annual meeting of the American Society of Clinical Oncology.

Investigators randomized 40 men who were being treated with gonadotropin-releasing hormone (GnRH) agonists to a single 4-mg intravenous dose of zoledronic acid (Zometa) or placebo.

Twelve months later, the men treated with zoledronic acid had average bone mineral density (BMD) increases of 4% in the lumbar spine and 0.7% in the total hip. The placebo group lost 3.1% of BMD in the lumbar spine and 1.9% in the total hip.

Two bone turnover markers, serum N-telopeptide and bone alkaline phosphatase, decreased during this same period in the men given zoledronic acid and increased in the placebo group. The differences were statistically significant.

“Annual zoledronic acid should be considered in GnRH-agonist treated men who may be at risk for osteoporosis,” Dr. Michaelson, of Massachusetts General Hospital Cancer Center, said on behalf of coinvestigators from his institution and the Dana-Farber Cancer Institute, both in Boston.

Dr. Michaelson said concern about side effects drew the group to explore annual dosing as an alternative to more frequent bisphosphonate use in these patients.

GnRH agonists are known to decrease bone mineral density while increasing bone turnover and fracture risk. Studies have shown that pamidronate as well as zoledronic acid can increase BMD in prostate cancer patients receiving hormonal therapy. Frequent bisphosphonate use can cause serious side effects, however, particularly renal insufficiency and osteonecrosis of the jaw. An annual dose of zoledronic acid had been shown to prevent bone loss in postmenopausal women, but Dr. Michaelson said the strategy had not been tested in men.

The trial excluded prostate cancer patients with metastatic bone disease, prostate-specific antigen evidence of progression, or osteoporosis. The men enrolled had an average age in the mid-60s. All patients in both arms of the study were encouraged to take daily supplements of calcium and vitamin D, Dr. Michaelson said.

In a discussion of the trial, Dr. Ian F. Tannock said the biomarkers were a reasonable surrogate end point for fracture risk. Although small, the trial probably was large enough to produce significant findings, he said, noting that the results are consistent with those of other studies. “I think those conclusions are reasonable,” said Dr. Tannock, the Daniel E. Bergsagel professor of medical oncology at Princess Margaret Hospital and the University of Toronto.

Estimating the cost of 4 mg of zoledronic acid to be about $600, he asked whether less-frequent dosing also could be effective in men with metastatic prostate cancer. “I think we should consider using that very expensive medication less often in that group of men, also,” he said.

Novartis Oncology and the Prostate Cancer Foundation supported the study.

ATLANTA — An annual dose of zoledronic acid can prevent bone loss in men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer, Dr. M. Dror Michaelson reported at the annual meeting of the American Society of Clinical Oncology.

Investigators randomized 40 men who were being treated with gonadotropin-releasing hormone (GnRH) agonists to a single 4-mg intravenous dose of zoledronic acid (Zometa) or placebo.

Twelve months later, the men treated with zoledronic acid had average bone mineral density (BMD) increases of 4% in the lumbar spine and 0.7% in the total hip. The placebo group lost 3.1% of BMD in the lumbar spine and 1.9% in the total hip.

Two bone turnover markers, serum N-telopeptide and bone alkaline phosphatase, decreased during this same period in the men given zoledronic acid and increased in the placebo group. The differences were statistically significant.

“Annual zoledronic acid should be considered in GnRH-agonist treated men who may be at risk for osteoporosis,” Dr. Michaelson, of Massachusetts General Hospital Cancer Center, said on behalf of coinvestigators from his institution and the Dana-Farber Cancer Institute, both in Boston.

Dr. Michaelson said concern about side effects drew the group to explore annual dosing as an alternative to more frequent bisphosphonate use in these patients.

GnRH agonists are known to decrease bone mineral density while increasing bone turnover and fracture risk. Studies have shown that pamidronate as well as zoledronic acid can increase BMD in prostate cancer patients receiving hormonal therapy. Frequent bisphosphonate use can cause serious side effects, however, particularly renal insufficiency and osteonecrosis of the jaw. An annual dose of zoledronic acid had been shown to prevent bone loss in postmenopausal women, but Dr. Michaelson said the strategy had not been tested in men.

The trial excluded prostate cancer patients with metastatic bone disease, prostate-specific antigen evidence of progression, or osteoporosis. The men enrolled had an average age in the mid-60s. All patients in both arms of the study were encouraged to take daily supplements of calcium and vitamin D, Dr. Michaelson said.

In a discussion of the trial, Dr. Ian F. Tannock said the biomarkers were a reasonable surrogate end point for fracture risk. Although small, the trial probably was large enough to produce significant findings, he said, noting that the results are consistent with those of other studies. “I think those conclusions are reasonable,” said Dr. Tannock, the Daniel E. Bergsagel professor of medical oncology at Princess Margaret Hospital and the University of Toronto.

Estimating the cost of 4 mg of zoledronic acid to be about $600, he asked whether less-frequent dosing also could be effective in men with metastatic prostate cancer. “I think we should consider using that very expensive medication less often in that group of men, also,” he said.

Novartis Oncology and the Prostate Cancer Foundation supported the study.

ATLANTA — An annual dose of zoledronic acid can prevent bone loss in men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer, Dr. M. Dror Michaelson reported at the annual meeting of the American Society of Clinical Oncology.

Investigators randomized 40 men who were being treated with gonadotropin-releasing hormone (GnRH) agonists to a single 4-mg intravenous dose of zoledronic acid (Zometa) or placebo.

Twelve months later, the men treated with zoledronic acid had average bone mineral density (BMD) increases of 4% in the lumbar spine and 0.7% in the total hip. The placebo group lost 3.1% of BMD in the lumbar spine and 1.9% in the total hip.

Two bone turnover markers, serum N-telopeptide and bone alkaline phosphatase, decreased during this same period in the men given zoledronic acid and increased in the placebo group. The differences were statistically significant.

“Annual zoledronic acid should be considered in GnRH-agonist treated men who may be at risk for osteoporosis,” Dr. Michaelson, of Massachusetts General Hospital Cancer Center, said on behalf of coinvestigators from his institution and the Dana-Farber Cancer Institute, both in Boston.

Dr. Michaelson said concern about side effects drew the group to explore annual dosing as an alternative to more frequent bisphosphonate use in these patients.

GnRH agonists are known to decrease bone mineral density while increasing bone turnover and fracture risk. Studies have shown that pamidronate as well as zoledronic acid can increase BMD in prostate cancer patients receiving hormonal therapy. Frequent bisphosphonate use can cause serious side effects, however, particularly renal insufficiency and osteonecrosis of the jaw. An annual dose of zoledronic acid had been shown to prevent bone loss in postmenopausal women, but Dr. Michaelson said the strategy had not been tested in men.

The trial excluded prostate cancer patients with metastatic bone disease, prostate-specific antigen evidence of progression, or osteoporosis. The men enrolled had an average age in the mid-60s. All patients in both arms of the study were encouraged to take daily supplements of calcium and vitamin D, Dr. Michaelson said.

In a discussion of the trial, Dr. Ian F. Tannock said the biomarkers were a reasonable surrogate end point for fracture risk. Although small, the trial probably was large enough to produce significant findings, he said, noting that the results are consistent with those of other studies. “I think those conclusions are reasonable,” said Dr. Tannock, the Daniel E. Bergsagel professor of medical oncology at Princess Margaret Hospital and the University of Toronto.

Estimating the cost of 4 mg of zoledronic acid to be about $600, he asked whether less-frequent dosing also could be effective in men with metastatic prostate cancer. “I think we should consider using that very expensive medication less often in that group of men, also,” he said.

Novartis Oncology and the Prostate Cancer Foundation supported the study.

ATLANTA — A single prostate-specific antigen screening measurement of 3 ng/mL or higher is sufficient to justify a biopsy of the prostate without a repeat measurement of the PSA, researchers reported at the annual meeting of the American Urological Association.

Traditional wisdom has been that the serum PSA, if elevated, should be measured again before biopsy, on the theory that PSA levels could normalize before the second test. This premise is not valid, said Dr. Freddie C. Hamdy, head of urology at Sheffield (England) University.

He reported data from the ongoing Prostate Testing for Cancer and Treatment (Protect) study, a large randomized controlled trial in the United Kingdom. The study is scheduled to complete recruitment in 2008.

He and his associates analyzed the value of a repeat PSA test in 7,383 asymptomatic men aged 50–69 years during the feasibility phase of the Protect study. PSA testing was done between 1999 and 2001. Of the men, 723 (10%) had a PSA level of at least 3 ng/mL. All of these men were biopsied after the first PSA test, and 224 (31%) were found to have cancer. Repeat PSA measures were performed, but it was the first measure that triggered the biopsies.

If the criterion of PSA normalization had led to deferred biopsy, prostate cancer would have been missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher and in 11.1% of men biopsied after a PSA level of 4 ng/mL or higher.

Cancer could be missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher that later normalized. DR. HAMDY

ATLANTA — A single prostate-specific antigen screening measurement of 3 ng/mL or higher is sufficient to justify a biopsy of the prostate without a repeat measurement of the PSA, researchers reported at the annual meeting of the American Urological Association.

Traditional wisdom has been that the serum PSA, if elevated, should be measured again before biopsy, on the theory that PSA levels could normalize before the second test. This premise is not valid, said Dr. Freddie C. Hamdy, head of urology at Sheffield (England) University.

He reported data from the ongoing Prostate Testing for Cancer and Treatment (Protect) study, a large randomized controlled trial in the United Kingdom. The study is scheduled to complete recruitment in 2008.

He and his associates analyzed the value of a repeat PSA test in 7,383 asymptomatic men aged 50–69 years during the feasibility phase of the Protect study. PSA testing was done between 1999 and 2001. Of the men, 723 (10%) had a PSA level of at least 3 ng/mL. All of these men were biopsied after the first PSA test, and 224 (31%) were found to have cancer. Repeat PSA measures were performed, but it was the first measure that triggered the biopsies.

If the criterion of PSA normalization had led to deferred biopsy, prostate cancer would have been missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher and in 11.1% of men biopsied after a PSA level of 4 ng/mL or higher.

Cancer could be missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher that later normalized. DR. HAMDY

ATLANTA — A single prostate-specific antigen screening measurement of 3 ng/mL or higher is sufficient to justify a biopsy of the prostate without a repeat measurement of the PSA, researchers reported at the annual meeting of the American Urological Association.

Traditional wisdom has been that the serum PSA, if elevated, should be measured again before biopsy, on the theory that PSA levels could normalize before the second test. This premise is not valid, said Dr. Freddie C. Hamdy, head of urology at Sheffield (England) University.

He reported data from the ongoing Prostate Testing for Cancer and Treatment (Protect) study, a large randomized controlled trial in the United Kingdom. The study is scheduled to complete recruitment in 2008.

He and his associates analyzed the value of a repeat PSA test in 7,383 asymptomatic men aged 50–69 years during the feasibility phase of the Protect study. PSA testing was done between 1999 and 2001. Of the men, 723 (10%) had a PSA level of at least 3 ng/mL. All of these men were biopsied after the first PSA test, and 224 (31%) were found to have cancer. Repeat PSA measures were performed, but it was the first measure that triggered the biopsies.

If the criterion of PSA normalization had led to deferred biopsy, prostate cancer would have been missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher and in 11.1% of men biopsied after a PSA level of 4 ng/mL or higher.

Cancer could be missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher that later normalized. DR. HAMDY

CHICAGO — Despite recommendations to the contrary, prostate-specific antigen screening is being performed in many elderly men who are not in good health and have limited life expectancies.

That conclusion was drawn from an analysis of data collected during a cohort study of 597,824 veterans aged 70 years and older who were seen at 104 Veterans Affairs medicalcenters in 2002 and 2003. The subjects did not have a history of prostate cancer, elevated prostate-specific antigen (PSA) levels, or prostate symptoms.

Most guidelines recommend that PSA screening not be performed in elderly men with a life expectancy of fewer than 10 years—most of those over age 80 years, and men aged 70 years or older in poor health—because the known harms outweigh the potential benefits, Dr. Louise Walter and her associates said at the annual meeting of the American Geriatrics Society.

PSA levels are often inaccurate, leading to unnecessary biopsies due to false-positive results. This can cause psychological distress and treatment of irrelevant cancers, which may lead to incontinence or impotence, said Dr. Walter, of the geriatrics division at the University of California, San Francisco, and staff physician at the San Francisco VA Medical Center.

The mean age of the men in the VA-supported study was 77 years, and 333,041 (56%) had a PSA test performed in 2003. Health status was measured with the Charlson-Deyo index using 2002 VA and Medicare claims. The men were stratified into three groups, from best health (score of 0) to worst health (score of 4 or more).

PSA screening rates decreased significantly with advancing age, ranging from 64% in men aged 70–74 years to 27% in men aged 90 or older. But screening rates did not decline with worsening health, she said. Among men aged 85–89 years, 36% in the best-health group had a PSA test, compared with 37% in the worst-health group.

Although men aged 80 years or older in the worst health have less than a 10% chance of living 10 years, 11,391 (41%) of these men had a PSA test.

CHICAGO — Despite recommendations to the contrary, prostate-specific antigen screening is being performed in many elderly men who are not in good health and have limited life expectancies.

That conclusion was drawn from an analysis of data collected during a cohort study of 597,824 veterans aged 70 years and older who were seen at 104 Veterans Affairs medicalcenters in 2002 and 2003. The subjects did not have a history of prostate cancer, elevated prostate-specific antigen (PSA) levels, or prostate symptoms.

Most guidelines recommend that PSA screening not be performed in elderly men with a life expectancy of fewer than 10 years—most of those over age 80 years, and men aged 70 years or older in poor health—because the known harms outweigh the potential benefits, Dr. Louise Walter and her associates said at the annual meeting of the American Geriatrics Society.

PSA levels are often inaccurate, leading to unnecessary biopsies due to false-positive results. This can cause psychological distress and treatment of irrelevant cancers, which may lead to incontinence or impotence, said Dr. Walter, of the geriatrics division at the University of California, San Francisco, and staff physician at the San Francisco VA Medical Center.

The mean age of the men in the VA-supported study was 77 years, and 333,041 (56%) had a PSA test performed in 2003. Health status was measured with the Charlson-Deyo index using 2002 VA and Medicare claims. The men were stratified into three groups, from best health (score of 0) to worst health (score of 4 or more).

PSA screening rates decreased significantly with advancing age, ranging from 64% in men aged 70–74 years to 27% in men aged 90 or older. But screening rates did not decline with worsening health, she said. Among men aged 85–89 years, 36% in the best-health group had a PSA test, compared with 37% in the worst-health group.

Although men aged 80 years or older in the worst health have less than a 10% chance of living 10 years, 11,391 (41%) of these men had a PSA test.

CHICAGO — Despite recommendations to the contrary, prostate-specific antigen screening is being performed in many elderly men who are not in good health and have limited life expectancies.

That conclusion was drawn from an analysis of data collected during a cohort study of 597,824 veterans aged 70 years and older who were seen at 104 Veterans Affairs medicalcenters in 2002 and 2003. The subjects did not have a history of prostate cancer, elevated prostate-specific antigen (PSA) levels, or prostate symptoms.

Most guidelines recommend that PSA screening not be performed in elderly men with a life expectancy of fewer than 10 years—most of those over age 80 years, and men aged 70 years or older in poor health—because the known harms outweigh the potential benefits, Dr. Louise Walter and her associates said at the annual meeting of the American Geriatrics Society.

PSA levels are often inaccurate, leading to unnecessary biopsies due to false-positive results. This can cause psychological distress and treatment of irrelevant cancers, which may lead to incontinence or impotence, said Dr. Walter, of the geriatrics division at the University of California, San Francisco, and staff physician at the San Francisco VA Medical Center.

The mean age of the men in the VA-supported study was 77 years, and 333,041 (56%) had a PSA test performed in 2003. Health status was measured with the Charlson-Deyo index using 2002 VA and Medicare claims. The men were stratified into three groups, from best health (score of 0) to worst health (score of 4 or more).

PSA screening rates decreased significantly with advancing age, ranging from 64% in men aged 70–74 years to 27% in men aged 90 or older. But screening rates did not decline with worsening health, she said. Among men aged 85–89 years, 36% in the best-health group had a PSA test, compared with 37% in the worst-health group.

Although men aged 80 years or older in the worst health have less than a 10% chance of living 10 years, 11,391 (41%) of these men had a PSA test.

ATLANTA — A prostate-specific antigen velocity threshold of approximately 0.4 ng/mL a year is a useful predictor of prostate cancer risk in men under the age of 60 years who have lower median PSA levels, according to research presented at the annual meeting of the American Urological Association.

“A decade ago, it was thought that a PSA velocity threshold of 0.75 ng/mL per year was useful to distinguish between prostate cancer and benign conditions and that total PSA levels between 4 and 10 warranted a biopsy. However, in the modern era, many men present with lower total PSA levels, particularly younger men,” said the lead author, Dr. Stacy Loeb of Georgetown University, Washington.

Dr. Loeb and her colleagues have previously shown in a large screening study that the median PSA level is 0.7 ng/mL for men in their 40s and 0.9 ng/mL for men in their 50s. “Thus, we felt that the traditional PSA velocity threshold of 0.75 ng/mL a year might be too high in these young men,” she said.

The researchers examined this issue in 6,488 men aged 60 or younger (mean age, 54 years). The median PSA velocity and performance characteristics of various PSA velocity thresholds were compared between men with prostate cancer and those with benign conditions.

Overall, 346 (5%) of the men under the age of 60 were diagnosed with prostate cancer during the study period, which was from 1991 to 2001. The median total PSA level was 2.8 ng/mL in men with prostate cancer, compared with 1.0 ng/mL in men who did not develop prostate cancer. In addition, a significantly greater number of men with prostate cancer presented with a PSA level greater than 4 ng/mL, Dr. Loeb said.

The median PSA velocity was 0.8 ng/mL a year in men with prostate cancer, versus 0.1 ng/mL a year in men with benign conditions. This difference was statistically significant.

The PSA velocity was useful in detecting prostate cancer. Cancer detection rates increased continuously as the PSA velocity increased from 0.4 ng/mL to 2 ng/mL a year.

A PSA velocity of 0.4 ng/mL a year had the optimal sensitivity and specificity for prostate cancer detection in men under the age of 60 years, Dr. Loeb reported. This threshold was associated with 57% sensitivity and 81% specificity for prostate cancer detection.

A PSA velocity greater than 0.4 ng/mL a year is a significant independent predictor of prostate cancer in young men, along with total PSA level and race, Dr. Loeb added.

“This means that a young man with a PSA velocity greater than 0.4 ng/mL a year has a 6.7-fold increased risk of prostate cancer over a young man with a PSA velocity less than 0.4. Furthermore, these results indicate that PSA velocity is a stronger predictor of prostate cancer in young men than race, total PSA, age, or family history,” she said.

The PSA velocity is also a highly significant independent predictor in the subgroup of men with total PSA levels less than 4 ng/mL. In these men, there was a 4.3-fold increased risk of prostate cancer if the PSA velocity was greater than 0.4 ng/mL a year, compared with men whose PSA velocity was less than 0.4 ng/mL a year.

Dr. Loeb noted that “4 ng/mL is a very high total PSA threshold, especially for young men, but this is what many people in the community still use. … In fact, part of what we are trying to disseminate through this paper is that the median PSA levels are much lower in young men, so lower total PSA and PSA velocity thresholds should be used in these men.”

In addition, there is controversy over the management of men with total PSA levels less than 4 ng/mL, so “this is another reason we chose to do a separate multivariate model for them, to show the message that even in this controversial group, PSA velocity is useful,” Dr. Loeb said in an interview.

ATLANTA — A prostate-specific antigen velocity threshold of approximately 0.4 ng/mL a year is a useful predictor of prostate cancer risk in men under the age of 60 years who have lower median PSA levels, according to research presented at the annual meeting of the American Urological Association.

“A decade ago, it was thought that a PSA velocity threshold of 0.75 ng/mL per year was useful to distinguish between prostate cancer and benign conditions and that total PSA levels between 4 and 10 warranted a biopsy. However, in the modern era, many men present with lower total PSA levels, particularly younger men,” said the lead author, Dr. Stacy Loeb of Georgetown University, Washington.

Dr. Loeb and her colleagues have previously shown in a large screening study that the median PSA level is 0.7 ng/mL for men in their 40s and 0.9 ng/mL for men in their 50s. “Thus, we felt that the traditional PSA velocity threshold of 0.75 ng/mL a year might be too high in these young men,” she said.

The researchers examined this issue in 6,488 men aged 60 or younger (mean age, 54 years). The median PSA velocity and performance characteristics of various PSA velocity thresholds were compared between men with prostate cancer and those with benign conditions.

Overall, 346 (5%) of the men under the age of 60 were diagnosed with prostate cancer during the study period, which was from 1991 to 2001. The median total PSA level was 2.8 ng/mL in men with prostate cancer, compared with 1.0 ng/mL in men who did not develop prostate cancer. In addition, a significantly greater number of men with prostate cancer presented with a PSA level greater than 4 ng/mL, Dr. Loeb said.

The median PSA velocity was 0.8 ng/mL a year in men with prostate cancer, versus 0.1 ng/mL a year in men with benign conditions. This difference was statistically significant.

The PSA velocity was useful in detecting prostate cancer. Cancer detection rates increased continuously as the PSA velocity increased from 0.4 ng/mL to 2 ng/mL a year.

A PSA velocity of 0.4 ng/mL a year had the optimal sensitivity and specificity for prostate cancer detection in men under the age of 60 years, Dr. Loeb reported. This threshold was associated with 57% sensitivity and 81% specificity for prostate cancer detection.

A PSA velocity greater than 0.4 ng/mL a year is a significant independent predictor of prostate cancer in young men, along with total PSA level and race, Dr. Loeb added.

“This means that a young man with a PSA velocity greater than 0.4 ng/mL a year has a 6.7-fold increased risk of prostate cancer over a young man with a PSA velocity less than 0.4. Furthermore, these results indicate that PSA velocity is a stronger predictor of prostate cancer in young men than race, total PSA, age, or family history,” she said.

The PSA velocity is also a highly significant independent predictor in the subgroup of men with total PSA levels less than 4 ng/mL. In these men, there was a 4.3-fold increased risk of prostate cancer if the PSA velocity was greater than 0.4 ng/mL a year, compared with men whose PSA velocity was less than 0.4 ng/mL a year.

Dr. Loeb noted that “4 ng/mL is a very high total PSA threshold, especially for young men, but this is what many people in the community still use. … In fact, part of what we are trying to disseminate through this paper is that the median PSA levels are much lower in young men, so lower total PSA and PSA velocity thresholds should be used in these men.”

In addition, there is controversy over the management of men with total PSA levels less than 4 ng/mL, so “this is another reason we chose to do a separate multivariate model for them, to show the message that even in this controversial group, PSA velocity is useful,” Dr. Loeb said in an interview.

ATLANTA — A prostate-specific antigen velocity threshold of approximately 0.4 ng/mL a year is a useful predictor of prostate cancer risk in men under the age of 60 years who have lower median PSA levels, according to research presented at the annual meeting of the American Urological Association.

“A decade ago, it was thought that a PSA velocity threshold of 0.75 ng/mL per year was useful to distinguish between prostate cancer and benign conditions and that total PSA levels between 4 and 10 warranted a biopsy. However, in the modern era, many men present with lower total PSA levels, particularly younger men,” said the lead author, Dr. Stacy Loeb of Georgetown University, Washington.

Dr. Loeb and her colleagues have previously shown in a large screening study that the median PSA level is 0.7 ng/mL for men in their 40s and 0.9 ng/mL for men in their 50s. “Thus, we felt that the traditional PSA velocity threshold of 0.75 ng/mL a year might be too high in these young men,” she said.

The researchers examined this issue in 6,488 men aged 60 or younger (mean age, 54 years). The median PSA velocity and performance characteristics of various PSA velocity thresholds were compared between men with prostate cancer and those with benign conditions.

Overall, 346 (5%) of the men under the age of 60 were diagnosed with prostate cancer during the study period, which was from 1991 to 2001. The median total PSA level was 2.8 ng/mL in men with prostate cancer, compared with 1.0 ng/mL in men who did not develop prostate cancer. In addition, a significantly greater number of men with prostate cancer presented with a PSA level greater than 4 ng/mL, Dr. Loeb said.

The median PSA velocity was 0.8 ng/mL a year in men with prostate cancer, versus 0.1 ng/mL a year in men with benign conditions. This difference was statistically significant.

The PSA velocity was useful in detecting prostate cancer. Cancer detection rates increased continuously as the PSA velocity increased from 0.4 ng/mL to 2 ng/mL a year.

A PSA velocity of 0.4 ng/mL a year had the optimal sensitivity and specificity for prostate cancer detection in men under the age of 60 years, Dr. Loeb reported. This threshold was associated with 57% sensitivity and 81% specificity for prostate cancer detection.

A PSA velocity greater than 0.4 ng/mL a year is a significant independent predictor of prostate cancer in young men, along with total PSA level and race, Dr. Loeb added.

“This means that a young man with a PSA velocity greater than 0.4 ng/mL a year has a 6.7-fold increased risk of prostate cancer over a young man with a PSA velocity less than 0.4. Furthermore, these results indicate that PSA velocity is a stronger predictor of prostate cancer in young men than race, total PSA, age, or family history,” she said.

The PSA velocity is also a highly significant independent predictor in the subgroup of men with total PSA levels less than 4 ng/mL. In these men, there was a 4.3-fold increased risk of prostate cancer if the PSA velocity was greater than 0.4 ng/mL a year, compared with men whose PSA velocity was less than 0.4 ng/mL a year.

Dr. Loeb noted that “4 ng/mL is a very high total PSA threshold, especially for young men, but this is what many people in the community still use. … In fact, part of what we are trying to disseminate through this paper is that the median PSA levels are much lower in young men, so lower total PSA and PSA velocity thresholds should be used in these men.”

In addition, there is controversy over the management of men with total PSA levels less than 4 ng/mL, so “this is another reason we chose to do a separate multivariate model for them, to show the message that even in this controversial group, PSA velocity is useful,” Dr. Loeb said in an interview.

Nondiabetic patients with advanced renal insufficiency showed evidence of renal protection from benazepril therapy, along with conventional antihypertensive treatment, reported Dr. Fan Fan Hou of the Nanfang Hospital of Southern Medical University in Guangzhou, China, and associates.

The investigators reported that they observed substantial renal benefits in patients with advanced (stage 4 chronic) renal insufficiency in a randomized, double-blind controlled trial of benazepril (N. Engl. J. Med. 2006;354:131–40).

Based on the findings of the study, Dr. Hou and co-investigators suggested that treatment with ACE inhibitors be initiated at earlier stages of chronic kidney disease. ACE inhibitors have been shown to slow the progression of chronic kidney disease, but until now they have been limited to patients with serum creatinine levels of 3.0 mg/dL or less.

The 3-year study was conducted at the Nanfang (China) Hospital renal division. Patients were aged 18–70 years and had not received ACE inhibitors or angiotensin II-receptor antagonists for at least 6 weeks before screening. They had persistent proteinuria with serum creatinine levels of 1.5–5.0 mg/dL and creatinine clearance of 20–70 mL/min per 1.73 m

The study excluded patients if they had conditions such as renovascular disease, connective tissue disease, or obstructive uropathy, as well as patients being treated with corticosteroids, nonsteroidal anti-inflammatory drugs, or immunosuppressive drugs in the year preceding the trial.

The patients were divided into two groups: group 1 included patients with serum creatinine levels of 1.5–3.0 mg/dL, and group 2 consisted of patients with levels of 3.1–5.0 mg/dL.

During an 8-week run-in phase, patients were given benazepril 10 mg/day for 4 weeks with close monitoring. Then the dosage of the medication was increased to 10 mg twice a day for 4 weeks, and open-label antihypertensive agents were added as necessary.

After the run-in phase, benazepril was discontinued for 3 weeks. Antihypertensive agents were continued to control blood pressure.

After the 3 weeks, all patients in group 1 were given 10 mg of benazepril twice a day. Group 2 patients received either 10 mg of benazepril twice daily or placebo and antihypertensive agents.

“[The] primary efficacy measure was the time to the first event in the composite end point of a doubling of the serum creatinine level, end-stage renal disease or death,” they said.

Of the 422 patients who participated in the run-in phase, 104 in group 1 and 112 in group 2 were assigned to benazepril 20 mg/day; another 112 in group 2 were assigned to placebo.

After a mean follow-up of 3 years, 107 patients assigned to benazepril in group 2 and 108 assigned to placebo were included in the efficacy analysis.

A total of 44 patients in group 2 assigned to benazepril reached the primary end point, compared with 65 patients on placebo.

Although all patients who received benazepril took the same dose, renal outcome was worse in group 2 than in group 1.

Benazepril treatment of the participants in group 2 resulted in a 43% reduction in the risk of reaching the primary end point, compared with placebo, and reduced the risk of end-stage renal disease by 40%. Also in group 2, benazepril was associated with reduced severity of proteinuria, compared with placebo, and was associated with a 23% reduction in the rate of decline in renal function.

Dry cough and an acute increase in serum creatinine level were reported mainly in the first 2 months of benazepril therapy. The incidence of hyperkalemia in group 2 was similar for patients who received benazepril and those who received placebo.

In an editorial comment accompanying the report, Dr. Lee Hebert of Ohio State University, Columbus, wrote that “although their results indicate that it may be time to change our practice, a number of caveats should be considered before we do so” (N. Engl. J. Med. 2006;354:189–91).

He said that the researchers used only half the maximal recommended dose of benazepril for patients with chronic kidney disease, as well as a twice-daily regimen that provides little opportunity for nocturnal recovery from any hyperkalemia.

Dr. Hebert added that although the results of the study support the continuation of the ACE inhibitor benazepril for treatment of chronic kidney disease, whether other types of ACE inhibitors would achieve the same results is not clear.

Nondiabetic patients with advanced renal insufficiency showed evidence of renal protection from benazepril therapy, along with conventional antihypertensive treatment, reported Dr. Fan Fan Hou of the Nanfang Hospital of Southern Medical University in Guangzhou, China, and associates.

The investigators reported that they observed substantial renal benefits in patients with advanced (stage 4 chronic) renal insufficiency in a randomized, double-blind controlled trial of benazepril (N. Engl. J. Med. 2006;354:131–40).

Based on the findings of the study, Dr. Hou and co-investigators suggested that treatment with ACE inhibitors be initiated at earlier stages of chronic kidney disease. ACE inhibitors have been shown to slow the progression of chronic kidney disease, but until now they have been limited to patients with serum creatinine levels of 3.0 mg/dL or less.

The 3-year study was conducted at the Nanfang (China) Hospital renal division. Patients were aged 18–70 years and had not received ACE inhibitors or angiotensin II-receptor antagonists for at least 6 weeks before screening. They had persistent proteinuria with serum creatinine levels of 1.5–5.0 mg/dL and creatinine clearance of 20–70 mL/min per 1.73 m

The study excluded patients if they had conditions such as renovascular disease, connective tissue disease, or obstructive uropathy, as well as patients being treated with corticosteroids, nonsteroidal anti-inflammatory drugs, or immunosuppressive drugs in the year preceding the trial.

The patients were divided into two groups: group 1 included patients with serum creatinine levels of 1.5–3.0 mg/dL, and group 2 consisted of patients with levels of 3.1–5.0 mg/dL.

During an 8-week run-in phase, patients were given benazepril 10 mg/day for 4 weeks with close monitoring. Then the dosage of the medication was increased to 10 mg twice a day for 4 weeks, and open-label antihypertensive agents were added as necessary.

After the run-in phase, benazepril was discontinued for 3 weeks. Antihypertensive agents were continued to control blood pressure.

After the 3 weeks, all patients in group 1 were given 10 mg of benazepril twice a day. Group 2 patients received either 10 mg of benazepril twice daily or placebo and antihypertensive agents.

“[The] primary efficacy measure was the time to the first event in the composite end point of a doubling of the serum creatinine level, end-stage renal disease or death,” they said.

Of the 422 patients who participated in the run-in phase, 104 in group 1 and 112 in group 2 were assigned to benazepril 20 mg/day; another 112 in group 2 were assigned to placebo.

After a mean follow-up of 3 years, 107 patients assigned to benazepril in group 2 and 108 assigned to placebo were included in the efficacy analysis.

A total of 44 patients in group 2 assigned to benazepril reached the primary end point, compared with 65 patients on placebo.

Although all patients who received benazepril took the same dose, renal outcome was worse in group 2 than in group 1.

Benazepril treatment of the participants in group 2 resulted in a 43% reduction in the risk of reaching the primary end point, compared with placebo, and reduced the risk of end-stage renal disease by 40%. Also in group 2, benazepril was associated with reduced severity of proteinuria, compared with placebo, and was associated with a 23% reduction in the rate of decline in renal function.

Dry cough and an acute increase in serum creatinine level were reported mainly in the first 2 months of benazepril therapy. The incidence of hyperkalemia in group 2 was similar for patients who received benazepril and those who received placebo.

In an editorial comment accompanying the report, Dr. Lee Hebert of Ohio State University, Columbus, wrote that “although their results indicate that it may be time to change our practice, a number of caveats should be considered before we do so” (N. Engl. J. Med. 2006;354:189–91).

He said that the researchers used only half the maximal recommended dose of benazepril for patients with chronic kidney disease, as well as a twice-daily regimen that provides little opportunity for nocturnal recovery from any hyperkalemia.

Dr. Hebert added that although the results of the study support the continuation of the ACE inhibitor benazepril for treatment of chronic kidney disease, whether other types of ACE inhibitors would achieve the same results is not clear.

Nondiabetic patients with advanced renal insufficiency showed evidence of renal protection from benazepril therapy, along with conventional antihypertensive treatment, reported Dr. Fan Fan Hou of the Nanfang Hospital of Southern Medical University in Guangzhou, China, and associates.

The investigators reported that they observed substantial renal benefits in patients with advanced (stage 4 chronic) renal insufficiency in a randomized, double-blind controlled trial of benazepril (N. Engl. J. Med. 2006;354:131–40).

Based on the findings of the study, Dr. Hou and co-investigators suggested that treatment with ACE inhibitors be initiated at earlier stages of chronic kidney disease. ACE inhibitors have been shown to slow the progression of chronic kidney disease, but until now they have been limited to patients with serum creatinine levels of 3.0 mg/dL or less.

The 3-year study was conducted at the Nanfang (China) Hospital renal division. Patients were aged 18–70 years and had not received ACE inhibitors or angiotensin II-receptor antagonists for at least 6 weeks before screening. They had persistent proteinuria with serum creatinine levels of 1.5–5.0 mg/dL and creatinine clearance of 20–70 mL/min per 1.73 m

The study excluded patients if they had conditions such as renovascular disease, connective tissue disease, or obstructive uropathy, as well as patients being treated with corticosteroids, nonsteroidal anti-inflammatory drugs, or immunosuppressive drugs in the year preceding the trial.

The patients were divided into two groups: group 1 included patients with serum creatinine levels of 1.5–3.0 mg/dL, and group 2 consisted of patients with levels of 3.1–5.0 mg/dL.

During an 8-week run-in phase, patients were given benazepril 10 mg/day for 4 weeks with close monitoring. Then the dosage of the medication was increased to 10 mg twice a day for 4 weeks, and open-label antihypertensive agents were added as necessary.

After the run-in phase, benazepril was discontinued for 3 weeks. Antihypertensive agents were continued to control blood pressure.

After the 3 weeks, all patients in group 1 were given 10 mg of benazepril twice a day. Group 2 patients received either 10 mg of benazepril twice daily or placebo and antihypertensive agents.

“[The] primary efficacy measure was the time to the first event in the composite end point of a doubling of the serum creatinine level, end-stage renal disease or death,” they said.

Of the 422 patients who participated in the run-in phase, 104 in group 1 and 112 in group 2 were assigned to benazepril 20 mg/day; another 112 in group 2 were assigned to placebo.

After a mean follow-up of 3 years, 107 patients assigned to benazepril in group 2 and 108 assigned to placebo were included in the efficacy analysis.

A total of 44 patients in group 2 assigned to benazepril reached the primary end point, compared with 65 patients on placebo.

Although all patients who received benazepril took the same dose, renal outcome was worse in group 2 than in group 1.

Benazepril treatment of the participants in group 2 resulted in a 43% reduction in the risk of reaching the primary end point, compared with placebo, and reduced the risk of end-stage renal disease by 40%. Also in group 2, benazepril was associated with reduced severity of proteinuria, compared with placebo, and was associated with a 23% reduction in the rate of decline in renal function.

Dry cough and an acute increase in serum creatinine level were reported mainly in the first 2 months of benazepril therapy. The incidence of hyperkalemia in group 2 was similar for patients who received benazepril and those who received placebo.

In an editorial comment accompanying the report, Dr. Lee Hebert of Ohio State University, Columbus, wrote that “although their results indicate that it may be time to change our practice, a number of caveats should be considered before we do so” (N. Engl. J. Med. 2006;354:189–91).

He said that the researchers used only half the maximal recommended dose of benazepril for patients with chronic kidney disease, as well as a twice-daily regimen that provides little opportunity for nocturnal recovery from any hyperkalemia.

Dr. Hebert added that although the results of the study support the continuation of the ACE inhibitor benazepril for treatment of chronic kidney disease, whether other types of ACE inhibitors would achieve the same results is not clear.

Simultaneous kidney-pancreas transplant patients may be at risk for long-term kidney dysfunction if they continue to meet criteria for metabolic syndrome 1 year after the procedure, according to a prospective study.

The risk of long-term kidney dysfunction was especially high if patients had both metabolic syndrome and pancreas graft failure 1 year after transplantation. Poor selection of the pancreas graft or technical failures during surgery may contribute to pancreas graft loss and incomplete correction of metabolic syndrome in patients, according to surgeons who were interviewed.

In the study, Dr. Jeffrey Rogers, then at the Medical University of South Carolina, Charleston, and his colleagues used data from 241 insulin-dependent (mostly type 1) diabetic patients who were participating in a randomized, double-blind trial that tested different dosing regimens of daclizumab after simultaneous kidney-pancreas transplantation (Transplant. Proc. 2005;37:3549–51).

The incidence of metabolic syndrome in the patients decreased from 59% pretransplantation to 19% 1 year after the procedure.

But all of the patients could have potentially been free from metabolic syndrome had they received adequate pancreas grafts, Dr. David Sutherland said in an interview.

Two scenarios could explain why these patients developed metabolic syndrome, suggested Dr. Sutherland, director of the Diabetes Institute for Immunology and Transplantation at the University of Minnesota, Minneapolis. Some patients may have had a severe form of metabolic syndrome in which their insulin resistance or need for insulin was so high that even a normal pancreas could not have reduced their blood glucose level. Other patients may have had a form of metabolic syndrome that could have been reversed by receipt of a normal, healthy pancreas. Imperfect testing of deceased donors may be the reason these patients continued to have metabolic syndrome after transplant, he said.

Brain-dead donors on life support often have hyperglycemia because they receive drugs that raise blood glucose levels, such as steroids, Dr. Sutherland said. At the University of Minnesota, donors are given insulin so that hyperglycemia doesn't damage the beta islet cells of the pancreas. Donors who require hundreds of units of insulin to decrease their blood glucose level have extreme insulin resistance but may actually have a good pancreas, he said.

One can be more certain that donors who require 4 or 5 units of insulin to reduce their blood glucose level have a bad pancreas because the organ was not able to produce that amount of insulin itself.

Yet “most people think the opposite,” Dr. Sutherland said. “If it takes 4 to 5 units for blood glucose to come down, they think, 'Oh, good, we'll use the pancreas.' Actually, that's the one I wouldn't use.”

One can be “absolutely sure” that a pancreas is healthy when a donor does not need any insulin and has a normal blood glucose level despite the stress of brain death, he said.

Data on the donors were not provided in the current study.

Many of the donors were likely hyperglycemic when the organs were procured, and probably little attention was paid to how much insulin it would take to correct hyperglycemia in those donors, Dr. Sutherland surmised.

None of the patients with metabolic syndrome who developed pancreas graft failure at 1 year had a prior documented episode of kidney or pancreas rejection. Pancreas graft failure in these patients did not develop secondary to rejection of the organ.

“To me, that means that they got bum pancreases to begin with,” Dr. Sutherland said.

In the study, the presence of metabolic syndrome in patients after 1 year was significantly associated with several changes 3 years after transplant, including decreased glomerular filtration rate, increased HbA_1c levels, a lower rate of pancreas graft survival, and a higher rate of acute pancreas graft rejection.

When rejection is diagnosed in one graft in simultaneous kidney-pancreas recipients, most of the time rejection is present in the other grafts as well, Dr. Rogers said in an interview. But in the current study, metabolic syndrome patients with and without pancreas graft failure at 1 year had similar rates of kidney rejection, which suggests that kidney rejection did not play a role in the difference in kidney function.

Pancreas grafts probably failed early in patients with metabolic syndrome because of thrombosis or other technical problems, said Dr. Rogers, who is now in the surgery department at Wake Forest University, Winston-Salem, N.C.

Dr. Rogers suggested using low-dose anticoagulation postoperatively, and being cautious about using pancreases that are fatty, are from older donors, or are from donors who died of a stroke.

Simultaneous kidney-pancreas transplant patients may be at risk for long-term kidney dysfunction if they continue to meet criteria for metabolic syndrome 1 year after the procedure, according to a prospective study.

The risk of long-term kidney dysfunction was especially high if patients had both metabolic syndrome and pancreas graft failure 1 year after transplantation. Poor selection of the pancreas graft or technical failures during surgery may contribute to pancreas graft loss and incomplete correction of metabolic syndrome in patients, according to surgeons who were interviewed.

In the study, Dr. Jeffrey Rogers, then at the Medical University of South Carolina, Charleston, and his colleagues used data from 241 insulin-dependent (mostly type 1) diabetic patients who were participating in a randomized, double-blind trial that tested different dosing regimens of daclizumab after simultaneous kidney-pancreas transplantation (Transplant. Proc. 2005;37:3549–51).

The incidence of metabolic syndrome in the patients decreased from 59% pretransplantation to 19% 1 year after the procedure.

But all of the patients could have potentially been free from metabolic syndrome had they received adequate pancreas grafts, Dr. David Sutherland said in an interview.

Two scenarios could explain why these patients developed metabolic syndrome, suggested Dr. Sutherland, director of the Diabetes Institute for Immunology and Transplantation at the University of Minnesota, Minneapolis. Some patients may have had a severe form of metabolic syndrome in which their insulin resistance or need for insulin was so high that even a normal pancreas could not have reduced their blood glucose level. Other patients may have had a form of metabolic syndrome that could have been reversed by receipt of a normal, healthy pancreas. Imperfect testing of deceased donors may be the reason these patients continued to have metabolic syndrome after transplant, he said.

Brain-dead donors on life support often have hyperglycemia because they receive drugs that raise blood glucose levels, such as steroids, Dr. Sutherland said. At the University of Minnesota, donors are given insulin so that hyperglycemia doesn't damage the beta islet cells of the pancreas. Donors who require hundreds of units of insulin to decrease their blood glucose level have extreme insulin resistance but may actually have a good pancreas, he said.

One can be more certain that donors who require 4 or 5 units of insulin to reduce their blood glucose level have a bad pancreas because the organ was not able to produce that amount of insulin itself.

Yet “most people think the opposite,” Dr. Sutherland said. “If it takes 4 to 5 units for blood glucose to come down, they think, 'Oh, good, we'll use the pancreas.' Actually, that's the one I wouldn't use.”

One can be “absolutely sure” that a pancreas is healthy when a donor does not need any insulin and has a normal blood glucose level despite the stress of brain death, he said.

Data on the donors were not provided in the current study.

Many of the donors were likely hyperglycemic when the organs were procured, and probably little attention was paid to how much insulin it would take to correct hyperglycemia in those donors, Dr. Sutherland surmised.

None of the patients with metabolic syndrome who developed pancreas graft failure at 1 year had a prior documented episode of kidney or pancreas rejection. Pancreas graft failure in these patients did not develop secondary to rejection of the organ.

“To me, that means that they got bum pancreases to begin with,” Dr. Sutherland said.

In the study, the presence of metabolic syndrome in patients after 1 year was significantly associated with several changes 3 years after transplant, including decreased glomerular filtration rate, increased HbA_1c levels, a lower rate of pancreas graft survival, and a higher rate of acute pancreas graft rejection.

When rejection is diagnosed in one graft in simultaneous kidney-pancreas recipients, most of the time rejection is present in the other grafts as well, Dr. Rogers said in an interview. But in the current study, metabolic syndrome patients with and without pancreas graft failure at 1 year had similar rates of kidney rejection, which suggests that kidney rejection did not play a role in the difference in kidney function.

Pancreas grafts probably failed early in patients with metabolic syndrome because of thrombosis or other technical problems, said Dr. Rogers, who is now in the surgery department at Wake Forest University, Winston-Salem, N.C.

Dr. Rogers suggested using low-dose anticoagulation postoperatively, and being cautious about using pancreases that are fatty, are from older donors, or are from donors who died of a stroke.

Simultaneous kidney-pancreas transplant patients may be at risk for long-term kidney dysfunction if they continue to meet criteria for metabolic syndrome 1 year after the procedure, according to a prospective study.

The risk of long-term kidney dysfunction was especially high if patients had both metabolic syndrome and pancreas graft failure 1 year after transplantation. Poor selection of the pancreas graft or technical failures during surgery may contribute to pancreas graft loss and incomplete correction of metabolic syndrome in patients, according to surgeons who were interviewed.

In the study, Dr. Jeffrey Rogers, then at the Medical University of South Carolina, Charleston, and his colleagues used data from 241 insulin-dependent (mostly type 1) diabetic patients who were participating in a randomized, double-blind trial that tested different dosing regimens of daclizumab after simultaneous kidney-pancreas transplantation (Transplant. Proc. 2005;37:3549–51).

The incidence of metabolic syndrome in the patients decreased from 59% pretransplantation to 19% 1 year after the procedure.

But all of the patients could have potentially been free from metabolic syndrome had they received adequate pancreas grafts, Dr. David Sutherland said in an interview.

Two scenarios could explain why these patients developed metabolic syndrome, suggested Dr. Sutherland, director of the Diabetes Institute for Immunology and Transplantation at the University of Minnesota, Minneapolis. Some patients may have had a severe form of metabolic syndrome in which their insulin resistance or need for insulin was so high that even a normal pancreas could not have reduced their blood glucose level. Other patients may have had a form of metabolic syndrome that could have been reversed by receipt of a normal, healthy pancreas. Imperfect testing of deceased donors may be the reason these patients continued to have metabolic syndrome after transplant, he said.

Brain-dead donors on life support often have hyperglycemia because they receive drugs that raise blood glucose levels, such as steroids, Dr. Sutherland said. At the University of Minnesota, donors are given insulin so that hyperglycemia doesn't damage the beta islet cells of the pancreas. Donors who require hundreds of units of insulin to decrease their blood glucose level have extreme insulin resistance but may actually have a good pancreas, he said.

One can be more certain that donors who require 4 or 5 units of insulin to reduce their blood glucose level have a bad pancreas because the organ was not able to produce that amount of insulin itself.

Yet “most people think the opposite,” Dr. Sutherland said. “If it takes 4 to 5 units for blood glucose to come down, they think, 'Oh, good, we'll use the pancreas.' Actually, that's the one I wouldn't use.”

One can be “absolutely sure” that a pancreas is healthy when a donor does not need any insulin and has a normal blood glucose level despite the stress of brain death, he said.

Data on the donors were not provided in the current study.

Many of the donors were likely hyperglycemic when the organs were procured, and probably little attention was paid to how much insulin it would take to correct hyperglycemia in those donors, Dr. Sutherland surmised.

None of the patients with metabolic syndrome who developed pancreas graft failure at 1 year had a prior documented episode of kidney or pancreas rejection. Pancreas graft failure in these patients did not develop secondary to rejection of the organ.

“To me, that means that they got bum pancreases to begin with,” Dr. Sutherland said.

In the study, the presence of metabolic syndrome in patients after 1 year was significantly associated with several changes 3 years after transplant, including decreased glomerular filtration rate, increased HbA_1c levels, a lower rate of pancreas graft survival, and a higher rate of acute pancreas graft rejection.

When rejection is diagnosed in one graft in simultaneous kidney-pancreas recipients, most of the time rejection is present in the other grafts as well, Dr. Rogers said in an interview. But in the current study, metabolic syndrome patients with and without pancreas graft failure at 1 year had similar rates of kidney rejection, which suggests that kidney rejection did not play a role in the difference in kidney function.

Pancreas grafts probably failed early in patients with metabolic syndrome because of thrombosis or other technical problems, said Dr. Rogers, who is now in the surgery department at Wake Forest University, Winston-Salem, N.C.

Dr. Rogers suggested using low-dose anticoagulation postoperatively, and being cautious about using pancreases that are fatty, are from older donors, or are from donors who died of a stroke.

Accepting living kidney donors with mild hypertension or proteinuria would increase the transplantation rate by only 3%, according to a review of cases from four transplant centers.

But increasing live donor awareness and overcoming immunologic barriers may more successfully mitigate the effects of donor organ shortage in patients who need kidney transplants, Dr. Martin Karpinski of the University of Manitoba, Winnipeg, and his associates wrote (Am. J. Kidney Dis. 2006;47:317–23).

Yet even a 3% increase indicates that the glass is “half full” rather than “half empty,” because transplants increase longevity and improve quality of life, Dr. Arthur J. Matas of the University of Minnesota, Minneapolis, wrote in an editorial (Am. J. Kidney Dis. 2006;47:353–5).

In the study of 352 wait-listed patients with end-stage renal disease, 31 potential living kidney donors were turned down because of hypertension or proteinuria. The researchers identified 12 (3%) donors with acceptable levels of hypertension (untreated blood pressure between 140/90 mm Hg and 150/100 mm Hg or treated with a single antihypertensive medication to less than 140/90 mm Hg) or proteinuria (protein 0.15–0.30 g/day).

Only 124 (35%) of the 352 patients on the wait list had at least 1 potential living donor evaluated. Overall, 180 potential donors for these 124 patients were evaluated and excluded. Positive crossmatch and blood group type incompatibility accounted for 55% of the donor exclusions.

Efforts to make greater use of living donors need not be mutually exclusive, because each of the potential ways of addressing the problem has its own set of issues, Dr. Matas wrote.

“There is no reason why transplant centers could not simultaneously work to increase living donor rates, overcome immunologic barriers, and accept living donors with mild hypertension,” he said.

The long-term effects of these types of kidney transplants are not yet known, nor is it clear whether recipients fare better by continuing with dialysis until a deceased donor kidney is available, Dr. Matas and Dr. Karpinski and his colleagues noted.

A study of 24 white living kidney donors with essential hypertension found no adverse effects of the donation on blood pressure after a mean of 282 days of follow-up (Transplantation 2004;78:276–82). Longer follow-up will be necessary to accept such living donors, Dr. Matas wrote.

Any centers that want to take on these challenges must have systems in place for adequate evaluation, counseling, education, and long-term follow-up of prospective living donors and recipients, he added.

Accepting living kidney donors with mild hypertension or proteinuria would increase the transplantation rate by only 3%, according to a review of cases from four transplant centers.

But increasing live donor awareness and overcoming immunologic barriers may more successfully mitigate the effects of donor organ shortage in patients who need kidney transplants, Dr. Martin Karpinski of the University of Manitoba, Winnipeg, and his associates wrote (Am. J. Kidney Dis. 2006;47:317–23).

Yet even a 3% increase indicates that the glass is “half full” rather than “half empty,” because transplants increase longevity and improve quality of life, Dr. Arthur J. Matas of the University of Minnesota, Minneapolis, wrote in an editorial (Am. J. Kidney Dis. 2006;47:353–5).

In the study of 352 wait-listed patients with end-stage renal disease, 31 potential living kidney donors were turned down because of hypertension or proteinuria. The researchers identified 12 (3%) donors with acceptable levels of hypertension (untreated blood pressure between 140/90 mm Hg and 150/100 mm Hg or treated with a single antihypertensive medication to less than 140/90 mm Hg) or proteinuria (protein 0.15–0.30 g/day).

Only 124 (35%) of the 352 patients on the wait list had at least 1 potential living donor evaluated. Overall, 180 potential donors for these 124 patients were evaluated and excluded. Positive crossmatch and blood group type incompatibility accounted for 55% of the donor exclusions.

Efforts to make greater use of living donors need not be mutually exclusive, because each of the potential ways of addressing the problem has its own set of issues, Dr. Matas wrote.

“There is no reason why transplant centers could not simultaneously work to increase living donor rates, overcome immunologic barriers, and accept living donors with mild hypertension,” he said.

The long-term effects of these types of kidney transplants are not yet known, nor is it clear whether recipients fare better by continuing with dialysis until a deceased donor kidney is available, Dr. Matas and Dr. Karpinski and his colleagues noted.

A study of 24 white living kidney donors with essential hypertension found no adverse effects of the donation on blood pressure after a mean of 282 days of follow-up (Transplantation 2004;78:276–82). Longer follow-up will be necessary to accept such living donors, Dr. Matas wrote.

Any centers that want to take on these challenges must have systems in place for adequate evaluation, counseling, education, and long-term follow-up of prospective living donors and recipients, he added.

Accepting living kidney donors with mild hypertension or proteinuria would increase the transplantation rate by only 3%, according to a review of cases from four transplant centers.

But increasing live donor awareness and overcoming immunologic barriers may more successfully mitigate the effects of donor organ shortage in patients who need kidney transplants, Dr. Martin Karpinski of the University of Manitoba, Winnipeg, and his associates wrote (Am. J. Kidney Dis. 2006;47:317–23).

Yet even a 3% increase indicates that the glass is “half full” rather than “half empty,” because transplants increase longevity and improve quality of life, Dr. Arthur J. Matas of the University of Minnesota, Minneapolis, wrote in an editorial (Am. J. Kidney Dis. 2006;47:353–5).

In the study of 352 wait-listed patients with end-stage renal disease, 31 potential living kidney donors were turned down because of hypertension or proteinuria. The researchers identified 12 (3%) donors with acceptable levels of hypertension (untreated blood pressure between 140/90 mm Hg and 150/100 mm Hg or treated with a single antihypertensive medication to less than 140/90 mm Hg) or proteinuria (protein 0.15–0.30 g/day).

Only 124 (35%) of the 352 patients on the wait list had at least 1 potential living donor evaluated. Overall, 180 potential donors for these 124 patients were evaluated and excluded. Positive crossmatch and blood group type incompatibility accounted for 55% of the donor exclusions.

Efforts to make greater use of living donors need not be mutually exclusive, because each of the potential ways of addressing the problem has its own set of issues, Dr. Matas wrote.

“There is no reason why transplant centers could not simultaneously work to increase living donor rates, overcome immunologic barriers, and accept living donors with mild hypertension,” he said.

The long-term effects of these types of kidney transplants are not yet known, nor is it clear whether recipients fare better by continuing with dialysis until a deceased donor kidney is available, Dr. Matas and Dr. Karpinski and his colleagues noted.

A study of 24 white living kidney donors with essential hypertension found no adverse effects of the donation on blood pressure after a mean of 282 days of follow-up (Transplantation 2004;78:276–82). Longer follow-up will be necessary to accept such living donors, Dr. Matas wrote.

Any centers that want to take on these challenges must have systems in place for adequate evaluation, counseling, education, and long-term follow-up of prospective living donors and recipients, he added.

CHICAGO — As the demand for kidney transplants for patients with end-stage renal disease continues to increase, disparities in transplantation rates among U.S. minority populations continue.

Dr. Robert S. Gaston, a nephrologist whose transplant team at the University of Alabama, Birmingham, has performed more than 7,000 kidney transplants, said that thousands of people have asked him when they can have a transplant.

Most patients would prefer having a kidney transplant to remaining on dialysis.

“Patients will tell us a lot about therapeutic modalities if we'll listen to them,” Dr. Gaston said at a meeting on clinical nephrology sponsored by the National Kidney Foundation.

The prevalence of end-stage renal disease (ESRD) is four to five times greater in blacks than in whites, yet black and other minority patients do not undergo nearly as many transplants as white patients do. “White patients are 50% more likely to receive a transplant within 2 years of being wait-listed,” compared with other racial groups, Dr. Gaston said.

He cited 2002 data on ESRD prevalence that further underscore the disparities. At that time, more than 80% of the African American population with ESRD was on dialysis, while less than 20% had undergone a kidney transplant. At the same time, only 62% of the comparable white population was on dialysis, while 38% had received a kidney transplant.

All patients who might need a kidney transplant go through a process that involves a referral to a transplant center and a medical evaluation, Dr. Gaston explained. Patients who are approved after the evaluation are then placed on a waiting list. But the process goes more smoothly for some patients than others. “At each step along the pathway, the evaluation process can be challenging,” he said.

Dr. Gaston provided details on many of the barriers to transplantation that minority patients face.

First, fewer African American patients than white patients learn about the transplantation option.

In addition, the high cost of a transplant is also an important factor, and patients with higher-paying private insurance are much more likely to get a transplant than patients who have only Medicare.

Also, those ESRD patients who have been placed on multiple transplant lists have an increased likelihood of ultimately receiving a transplant. But African American patients are 70% less likely to be on multiple waiting lists.

Possibly the biggest obstacle to receiving a transplant is that minority patients have less access to living donors than white patients do. Dr. Gaston cited a study done at his institution that revealed that while 33% of white patients received a kidney from a living donor, only 13% of African American patients were able to undergo this type of transplant.

Ultimately, patients who receive a transplanted kidney from a living donor have the best outcomes. Studies show that the greatest survival benefit occurs in ESRD patients who receive a living donor transplant before starting dialysis.

Under the new organ allocation system, Dr. Gaston noted, transplant access for minorities has increased and overall outcomes have also improved.

Data show a 10.3% increase in renal transplants in black patients since the rules have changed by relaxing HLA matching requirements, said Friedrich K. Port, president of University Renal Research and Education Association in Ann Arbor, Mich.

CHICAGO — As the demand for kidney transplants for patients with end-stage renal disease continues to increase, disparities in transplantation rates among U.S. minority populations continue.

Dr. Robert S. Gaston, a nephrologist whose transplant team at the University of Alabama, Birmingham, has performed more than 7,000 kidney transplants, said that thousands of people have asked him when they can have a transplant.

Most patients would prefer having a kidney transplant to remaining on dialysis.

“Patients will tell us a lot about therapeutic modalities if we'll listen to them,” Dr. Gaston said at a meeting on clinical nephrology sponsored by the National Kidney Foundation.

The prevalence of end-stage renal disease (ESRD) is four to five times greater in blacks than in whites, yet black and other minority patients do not undergo nearly as many transplants as white patients do. “White patients are 50% more likely to receive a transplant within 2 years of being wait-listed,” compared with other racial groups, Dr. Gaston said.

He cited 2002 data on ESRD prevalence that further underscore the disparities. At that time, more than 80% of the African American population with ESRD was on dialysis, while less than 20% had undergone a kidney transplant. At the same time, only 62% of the comparable white population was on dialysis, while 38% had received a kidney transplant.

All patients who might need a kidney transplant go through a process that involves a referral to a transplant center and a medical evaluation, Dr. Gaston explained. Patients who are approved after the evaluation are then placed on a waiting list. But the process goes more smoothly for some patients than others. “At each step along the pathway, the evaluation process can be challenging,” he said.

Dr. Gaston provided details on many of the barriers to transplantation that minority patients face.

First, fewer African American patients than white patients learn about the transplantation option.

In addition, the high cost of a transplant is also an important factor, and patients with higher-paying private insurance are much more likely to get a transplant than patients who have only Medicare.

Also, those ESRD patients who have been placed on multiple transplant lists have an increased likelihood of ultimately receiving a transplant. But African American patients are 70% less likely to be on multiple waiting lists.

Possibly the biggest obstacle to receiving a transplant is that minority patients have less access to living donors than white patients do. Dr. Gaston cited a study done at his institution that revealed that while 33% of white patients received a kidney from a living donor, only 13% of African American patients were able to undergo this type of transplant.

Ultimately, patients who receive a transplanted kidney from a living donor have the best outcomes. Studies show that the greatest survival benefit occurs in ESRD patients who receive a living donor transplant before starting dialysis.

Under the new organ allocation system, Dr. Gaston noted, transplant access for minorities has increased and overall outcomes have also improved.

Data show a 10.3% increase in renal transplants in black patients since the rules have changed by relaxing HLA matching requirements, said Friedrich K. Port, president of University Renal Research and Education Association in Ann Arbor, Mich.

CHICAGO — As the demand for kidney transplants for patients with end-stage renal disease continues to increase, disparities in transplantation rates among U.S. minority populations continue.

Dr. Robert S. Gaston, a nephrologist whose transplant team at the University of Alabama, Birmingham, has performed more than 7,000 kidney transplants, said that thousands of people have asked him when they can have a transplant.

Most patients would prefer having a kidney transplant to remaining on dialysis.

“Patients will tell us a lot about therapeutic modalities if we'll listen to them,” Dr. Gaston said at a meeting on clinical nephrology sponsored by the National Kidney Foundation.

The prevalence of end-stage renal disease (ESRD) is four to five times greater in blacks than in whites, yet black and other minority patients do not undergo nearly as many transplants as white patients do. “White patients are 50% more likely to receive a transplant within 2 years of being wait-listed,” compared with other racial groups, Dr. Gaston said.

He cited 2002 data on ESRD prevalence that further underscore the disparities. At that time, more than 80% of the African American population with ESRD was on dialysis, while less than 20% had undergone a kidney transplant. At the same time, only 62% of the comparable white population was on dialysis, while 38% had received a kidney transplant.

All patients who might need a kidney transplant go through a process that involves a referral to a transplant center and a medical evaluation, Dr. Gaston explained. Patients who are approved after the evaluation are then placed on a waiting list. But the process goes more smoothly for some patients than others. “At each step along the pathway, the evaluation process can be challenging,” he said.

Dr. Gaston provided details on many of the barriers to transplantation that minority patients face.

First, fewer African American patients than white patients learn about the transplantation option.

In addition, the high cost of a transplant is also an important factor, and patients with higher-paying private insurance are much more likely to get a transplant than patients who have only Medicare.

Also, those ESRD patients who have been placed on multiple transplant lists have an increased likelihood of ultimately receiving a transplant. But African American patients are 70% less likely to be on multiple waiting lists.

Possibly the biggest obstacle to receiving a transplant is that minority patients have less access to living donors than white patients do. Dr. Gaston cited a study done at his institution that revealed that while 33% of white patients received a kidney from a living donor, only 13% of African American patients were able to undergo this type of transplant.

Ultimately, patients who receive a transplanted kidney from a living donor have the best outcomes. Studies show that the greatest survival benefit occurs in ESRD patients who receive a living donor transplant before starting dialysis.

Under the new organ allocation system, Dr. Gaston noted, transplant access for minorities has increased and overall outcomes have also improved.

Data show a 10.3% increase in renal transplants in black patients since the rules have changed by relaxing HLA matching requirements, said Friedrich K. Port, president of University Renal Research and Education Association in Ann Arbor, Mich.