Chronic Kidney Disease: Lifetime Risk Nears 60% in US

Selected by Pietro Cazzola

KidneyThe National Kidney Foundation (NKF) has called for annual screening for chronic kidney disease (CKD) after a new study showed a lifetime risk of 59.1% for CKD stage 3a+ in the United States. However, not everyone agrees more screening is the answer, and some experts raise concerns about overdiagnosis.

Morgan E. Grams, MD, MHS, from the Department of Medicine, Johns Hopkins University School of Medicine, and the Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, and colleagues reported the long-term risk analysis for CKD stages 3 to 5 in an article published in the August issue of American Journal of Kidney Diseases.
"Our findings reinforce that CKD is a very common disease with significant disparities in risk by race. While disease onset can be late, appreciation of the high lifetime risk should motivate early detection and prevention," senior author Josef Coresh, MD, PhD, told Medscape Medical News. Dr. Coresh is professor of epidemiology at the Welch Center for Prevention, Epidemiology, and Clinical Research; director, Cardiovascular Epidemiology Training Program; and director, Comstock Center for Public Health Research and Prevention, Johns Hopkins University, Baltimore.
The researchers applied a Markov Monte Carlo model simulation to data from the National Vital Statistics Report, the National Health and Nutrition Examination Survey, the US Renal Data System, and the US Census Bureau, comprising prevalence data on 37,475 individuals and mortality risk data from more than 2 million individuals. The investigators used a simulated cohort of 10,000 individuals of the specified baseline age, race, and sex to estimate the residual lifetime risks for CKD stage 3a+ (estimated glomerular filtration rate [eGFR], <60 mL/minute/1.73 m2), CKD stage 3b+ (eGFR ,45 mL/minute/1.73 m2), CKD stage 4+ (eGFR,30 mL/minute/1.73 m2), and end-stage renal disease (ESRD; chronic kidney failure treated by dialysis or transplantation).
Overall, the lifetime risks were 59.1% for CDK3a+, 33.6% for CKD 3b+, 11.5% for CKD 4+, and 3.6% for ESRD. Women had higher CKD risk but lower ESRD risk, apparently because of their longer life expectancy. Black participants of both sexes had significantly higher CKD 4+ (lifetime risk for white men, 9.3%; white women, 11.4%; black men, 15.8%; and black women, 18.5%) and ESRD (lifetime risk for white men, 3.3%; white women, 2.2%; black men, 8.5%; and black women, 7.8%) risks than whites. As expected, CKD risk increased with age, and about half of the CKD 3a+ cases occurred after age 70 years.

Low Kidney Function in Elderly Is a Drug Safety Hazard
"Low eGFR in the elderly as a patient safety hazard is the most clinically relevant aspect of the high lifetime risk described by Grams et al. Medication management that considers eGFR levels in the elderly is the most actionable patient safety hazard, since the majority of drugs are cleared by the kidney," write Joseph A. Vassalotti, MD, and Beth Piraino, MD, in an accompanying editorial. Dr. Vassalotti is chief medical officer of the NKF and serves on the Clinical Faculty of Medicine in the Division of Nephrology at Mount Sinai Medical Center in New York City. Dr. Piraino is president of the NKF and professor of medicine and associate dean of admissions at the University of Pittsburgh School of Medicine in Pennsylvania. "Medications that require caution in prescribing to those with decreased GFR include antihypertensive agents, analgesics (nonsteroidal anti-inflammatory drugs and opioids), antimicrobials, hypoglycemics, dyslipidemia therapy (statins and fibrates), chemotherapeutic agents (cisplatin, melphalan, and methotrexate), anticoagulants (low-molecular-weight heparins, oral thrombin inhibitors, oral factor Xa inhibitors, and warfarin), and others," Dr. Vassalotti and Dr. Piraino write. Increased risk for acute kidney injury during cardiac surgery with contrast administration is also a concern.

CKD Risk Now Greater Than Risk for Diabetes, Coronary Heart Disease, Cancer
"The knowledge that the cumulative incidence of CKD has surpassed diabetes mellitus should stimulate even greater interest in CKD as a population health problem," writes Bryce A. Kiberd, MD, in a second editorial. Dr. Kiberd is professor of medicine at Dalhousie University, staff physician at the Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada, and medical director of the Multi-Organ Transplant Program for Atlantic Canada.
According to Dr. Grams and colleagues, the predicted risk is 59% for CKD stage 3a+, 33% to 39% for diabetes, 32% to 49% for coronary heart disease (for a 40-year-old patient), and 38% to 45% for cancer. Dr. Kiberd wrote that although the utility of general population CKD screening is inconclusive, the data suggest that "screening in blacks should be reconsidered."

NKF Recommends Regular Urine Screening for Many Patients
The NKF responded to the new data by calling for annual urine screening for all Americans older than 60 years and for those with high blood pressure, diabetes, or family history of kidney failure requiring dialysis or transplantation. The NKF recommends that screenings be conducted as a part of an annual physical examination that should also include a blood test for kidney function.
However, other kidney experts expressed concern that this approach would lead to overdiagnosis. Expanding definitions of chronic kidney disease are "unnecessarily labelling many people as diseased," write Ray Moynihan, senior research fellow, Centre for Research in Evidence Based Practice, Bond University, Robina, Queensland, Australia, and colleagues (BMJ. Published online July 30, 2013).
"The current definitions may misclassify at least 30% of elderly people as having stage 3 disease, with those classified as stage 3A without albuminuria at highest risk of overdiagnosis," they add. Moreover, Moynihan and colleagues note that most people classified as having 3a CKD are older than 65 years, and many will have an eGFR within the normal range for their age.
"While accurate identification of those at risk for a disease that can have a material influence on the duration and quality of life and can be influenced by appropriate application of treatments proven to be safe and effective is highly laudable, what is missing from the NKF proposal is the expected benefit from 'true positive' risk identification (presumably from earlier interventions), the potential hazards of 'false positives,' and the inappropriate re-assurances of 'false negatives,' " coauthor Richard Glassock, MD, told Medscape Medical News. Dr. Glassock is emeritus professor of medicine at the University of California, Los Angeles, Geffen School of Medicine.
"Will such opportunistic screening lead ultimately to health benefits or to an epidemic of 'overdiagnosis,' an unnecessary anxiety, investigation, referrals, and expenses? Opportunistic screening for CKD is not like screening for cervical or colonic cancer, where benefits are known," said Dr. Glassock, who also noted that the US Preventive Services Task Force recommended against population-based CKD screening for exactly those reasons.
Dr. Coresh, though, stands by the recommendation for increased screening. "Rigorous analyses of large datasets have shown that CKD as currently defined is associated with risk across all age groups. The more abnormal markers the higher the risk, but even only mildly reduced kidney function without albuminuria is associated with risk. Kidney disease will benefit from more research, particularly clinical trials, but fortunately some treatments are known to work and some risks can be reduced."

Am J Kidney Dis. 2013;62:217-222, 245-252.