Mild CKD Ups Risks of Renal, Urothelial Cancers

SAN FRANCISCO – Chronic kidney disease, even on the milder end of the spectrum, is an independent risk factor for urinary cancers and may therefore be useful for targeting screening, the results of a large observational study suggest.

In the study of nearly 1.2 million adults in the Kaiser Permanente Renal Registry, none of whom were on dialysis, the risks of urinary cancers increased in stepwise fashion with decreasing estimated glomerular filtration rate (GFR), Dr. William T. Lowrance reported at the Genitourinary Cancers Symposium.

After adjustments, patients having the lowest estimated GFRs had a more than 100% increase in the risk of renal cell cancer and a 35% increase in the risk of urothelial cancer. The risks of other types of cancers – breast, lung, prostate, and colorectal – and of cancer overall increased with decreasing estimated GFR in univariate analyses but not in multivariate analyses.

"We found an independent, graded increased risk of renal and urothelial cancer as you went to a lower estimated GFR, and this was especially true when your estimated GFR was less than 45 mL/min per 1.73 m2, in this large diverse population-based cohort," said Dr. Lowrance of the Huntsman Cancer Institute at the University of Utah, Salt Lake City.

"Estimated GFRs may play a role in identifying patients at higher risk for renal and urothelial malignancies," he added. "Certainly, prospective studies are needed to further assess any net clinical benefit of targeted cancer screening in these patients with CKD. And we also need to try and elucidate the etiology of this mechanism: Is there some underlying biological process that explains this association?"

"As far as I could determine on a literature search, this is the largest number of patients in a study to date," commented Thomas E. Hutson, D.O., Pharm.D., of the Baylor Sammons Cancer Center in Dallas, who was invited to discuss the study.

"We are used to screening patients with end-stage renal disease already, using renal ultrasounds, looking for renal tumors," he noted. This new study suggests that "GFR may play a role in identifying patients at higher risk, and therefore we may want to use that as a potential screening mechanism," a practice that should be studied prospectively, he agreed.

End-stage renal disease is a known risk factor for cancer, according to Dr. Lowrance. And previous studies have implicated CKD generally in cancer risk, "but they are somewhat limited by their size and their ability to control for important factors that may confound the association between CKD and cancer," he maintained.

The investigators studied adults aged 40 years or older who were in the Kaiser Permanente Renal Registry and had at least one outpatient, non–emergency department measurement of serum creatinine level between 2000 and 2008. Those who had cancer or a history of dialysis or renal transplantation were excluded.

Estimated GFR values within 3 months of cancer diagnosis and incident cancers in the first 2 years of follow-up were excluded from analysis to minimize the possibility of cancer affecting kidney function.

Results were based on 1.2 million patients with a median age of 55 years. A total of 76,809 cancers were diagnosed during a median follow-up of 5.3 years.

Univariate analyses showed increasing rates of various types of common cancers and of cancer overall with decreasing GFR, which was estimated with the CKD-Epi equation.

Multivariate analysis – adjusted for numerous potential confounders, such as proteinuria, comorbidities (including diabetes), smoking status, prescription medications taken, and health care use – showed that patients having an estimated GFR of 59 mL/min per 1.73 m² or lower had a significantly increased risk of renal cell cancer, and patients having an estimated GFR of 44 mL/min per 1.73 m² or lower had a significantly increased risk of urothelial cancer – both compared with their counterparts having an estimated GFR of 60 to 89 mL/min per 1.73 m².

Those with the poorest renal function – an estimated GFR of less than 30 mL/min per 1.73 m² – had a significant 2.09-fold increased risk of renal cell cancer and a significant 1.35-fold increased risk of urothelial cancer.

"A big concern [in such a study] is potential detection bias, meaning subjects with worse renal function may be followed more closely than those with normal renal function, and as a result, we are likely to diagnose more cancers in those patients," Dr. Lowrance acknowledged. However, analyses took into account numbers of outpatient visits and hospitalizations (although not specifically hematuria tests or imaging tests), reducing this possible source of bias.

The Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Lowrance disclosed that he had no relevant conflicts of interest. Dr. Hutson disclosed that he is a consultant to and receives honoraria from Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx, Pfizer, and Wyeth, and that he receives research funding from GlaxoSmithKline, Pfizer, and Wyeth.

SAN FRANCISCO – Chronic kidney disease, even on the milder end of the spectrum, is an independent risk factor for urinary cancers and may therefore be useful for targeting screening, the results of a large observational study suggest.

In the study of nearly 1.2 million adults in the Kaiser Permanente Renal Registry, none of whom were on dialysis, the risks of urinary cancers increased in stepwise fashion with decreasing estimated glomerular filtration rate (GFR), Dr. William T. Lowrance reported at the Genitourinary Cancers Symposium.

After adjustments, patients having the lowest estimated GFRs had a more than 100% increase in the risk of renal cell cancer and a 35% increase in the risk of urothelial cancer. The risks of other types of cancers – breast, lung, prostate, and colorectal – and of cancer overall increased with decreasing estimated GFR in univariate analyses but not in multivariate analyses.

"We found an independent, graded increased risk of renal and urothelial cancer as you went to a lower estimated GFR, and this was especially true when your estimated GFR was less than 45 mL/min per 1.73 m2, in this large diverse population-based cohort," said Dr. Lowrance of the Huntsman Cancer Institute at the University of Utah, Salt Lake City.

"Estimated GFRs may play a role in identifying patients at higher risk for renal and urothelial malignancies," he added. "Certainly, prospective studies are needed to further assess any net clinical benefit of targeted cancer screening in these patients with CKD. And we also need to try and elucidate the etiology of this mechanism: Is there some underlying biological process that explains this association?"

"As far as I could determine on a literature search, this is the largest number of patients in a study to date," commented Thomas E. Hutson, D.O., Pharm.D., of the Baylor Sammons Cancer Center in Dallas, who was invited to discuss the study.

"We are used to screening patients with end-stage renal disease already, using renal ultrasounds, looking for renal tumors," he noted. This new study suggests that "GFR may play a role in identifying patients at higher risk, and therefore we may want to use that as a potential screening mechanism," a practice that should be studied prospectively, he agreed.

End-stage renal disease is a known risk factor for cancer, according to Dr. Lowrance. And previous studies have implicated CKD generally in cancer risk, "but they are somewhat limited by their size and their ability to control for important factors that may confound the association between CKD and cancer," he maintained.

The investigators studied adults aged 40 years or older who were in the Kaiser Permanente Renal Registry and had at least one outpatient, non–emergency department measurement of serum creatinine level between 2000 and 2008. Those who had cancer or a history of dialysis or renal transplantation were excluded.

Estimated GFR values within 3 months of cancer diagnosis and incident cancers in the first 2 years of follow-up were excluded from analysis to minimize the possibility of cancer affecting kidney function.

Results were based on 1.2 million patients with a median age of 55 years. A total of 76,809 cancers were diagnosed during a median follow-up of 5.3 years.

Univariate analyses showed increasing rates of various types of common cancers and of cancer overall with decreasing GFR, which was estimated with the CKD-Epi equation.

Multivariate analysis – adjusted for numerous potential confounders, such as proteinuria, comorbidities (including diabetes), smoking status, prescription medications taken, and health care use – showed that patients having an estimated GFR of 59 mL/min per 1.73 m² or lower had a significantly increased risk of renal cell cancer, and patients having an estimated GFR of 44 mL/min per 1.73 m² or lower had a significantly increased risk of urothelial cancer – both compared with their counterparts having an estimated GFR of 60 to 89 mL/min per 1.73 m².

Those with the poorest renal function – an estimated GFR of less than 30 mL/min per 1.73 m² – had a significant 2.09-fold increased risk of renal cell cancer and a significant 1.35-fold increased risk of urothelial cancer.

"A big concern [in such a study] is potential detection bias, meaning subjects with worse renal function may be followed more closely than those with normal renal function, and as a result, we are likely to diagnose more cancers in those patients," Dr. Lowrance acknowledged. However, analyses took into account numbers of outpatient visits and hospitalizations (although not specifically hematuria tests or imaging tests), reducing this possible source of bias.

The Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Lowrance disclosed that he had no relevant conflicts of interest. Dr. Hutson disclosed that he is a consultant to and receives honoraria from Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx, Pfizer, and Wyeth, and that he receives research funding from GlaxoSmithKline, Pfizer, and Wyeth.

SAN FRANCISCO – Chronic kidney disease, even on the milder end of the spectrum, is an independent risk factor for urinary cancers and may therefore be useful for targeting screening, the results of a large observational study suggest.

In the study of nearly 1.2 million adults in the Kaiser Permanente Renal Registry, none of whom were on dialysis, the risks of urinary cancers increased in stepwise fashion with decreasing estimated glomerular filtration rate (GFR), Dr. William T. Lowrance reported at the Genitourinary Cancers Symposium.

After adjustments, patients having the lowest estimated GFRs had a more than 100% increase in the risk of renal cell cancer and a 35% increase in the risk of urothelial cancer. The risks of other types of cancers – breast, lung, prostate, and colorectal – and of cancer overall increased with decreasing estimated GFR in univariate analyses but not in multivariate analyses.

"We found an independent, graded increased risk of renal and urothelial cancer as you went to a lower estimated GFR, and this was especially true when your estimated GFR was less than 45 mL/min per 1.73 m2, in this large diverse population-based cohort," said Dr. Lowrance of the Huntsman Cancer Institute at the University of Utah, Salt Lake City.

"Estimated GFRs may play a role in identifying patients at higher risk for renal and urothelial malignancies," he added. "Certainly, prospective studies are needed to further assess any net clinical benefit of targeted cancer screening in these patients with CKD. And we also need to try and elucidate the etiology of this mechanism: Is there some underlying biological process that explains this association?"

"As far as I could determine on a literature search, this is the largest number of patients in a study to date," commented Thomas E. Hutson, D.O., Pharm.D., of the Baylor Sammons Cancer Center in Dallas, who was invited to discuss the study.

"We are used to screening patients with end-stage renal disease already, using renal ultrasounds, looking for renal tumors," he noted. This new study suggests that "GFR may play a role in identifying patients at higher risk, and therefore we may want to use that as a potential screening mechanism," a practice that should be studied prospectively, he agreed.

End-stage renal disease is a known risk factor for cancer, according to Dr. Lowrance. And previous studies have implicated CKD generally in cancer risk, "but they are somewhat limited by their size and their ability to control for important factors that may confound the association between CKD and cancer," he maintained.

The investigators studied adults aged 40 years or older who were in the Kaiser Permanente Renal Registry and had at least one outpatient, non–emergency department measurement of serum creatinine level between 2000 and 2008. Those who had cancer or a history of dialysis or renal transplantation were excluded.

Estimated GFR values within 3 months of cancer diagnosis and incident cancers in the first 2 years of follow-up were excluded from analysis to minimize the possibility of cancer affecting kidney function.

Results were based on 1.2 million patients with a median age of 55 years. A total of 76,809 cancers were diagnosed during a median follow-up of 5.3 years.

Univariate analyses showed increasing rates of various types of common cancers and of cancer overall with decreasing GFR, which was estimated with the CKD-Epi equation.

Multivariate analysis – adjusted for numerous potential confounders, such as proteinuria, comorbidities (including diabetes), smoking status, prescription medications taken, and health care use – showed that patients having an estimated GFR of 59 mL/min per 1.73 m² or lower had a significantly increased risk of renal cell cancer, and patients having an estimated GFR of 44 mL/min per 1.73 m² or lower had a significantly increased risk of urothelial cancer – both compared with their counterparts having an estimated GFR of 60 to 89 mL/min per 1.73 m².

Those with the poorest renal function – an estimated GFR of less than 30 mL/min per 1.73 m² – had a significant 2.09-fold increased risk of renal cell cancer and a significant 1.35-fold increased risk of urothelial cancer.

"A big concern [in such a study] is potential detection bias, meaning subjects with worse renal function may be followed more closely than those with normal renal function, and as a result, we are likely to diagnose more cancers in those patients," Dr. Lowrance acknowledged. However, analyses took into account numbers of outpatient visits and hospitalizations (although not specifically hematuria tests or imaging tests), reducing this possible source of bias.

The Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Lowrance disclosed that he had no relevant conflicts of interest. Dr. Hutson disclosed that he is a consultant to and receives honoraria from Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx, Pfizer, and Wyeth, and that he receives research funding from GlaxoSmithKline, Pfizer, and Wyeth.