Kidney failure risk equations show accuracy in geographically diverse patient population

Chronic kidney disease (CKD) is increasing in incidence and prevalence worldwide. Rates of progression to kidney failure varies among individuals with CKD. Interventions to slow CKD progression, planning for initiation of dialysis and transplant, and early creation of arteriovenous fistula (a surgically created access point for hemodialysis treatments) have been advocated, but these strategies may be expensive and are associated with risks. Treatment would ideally be recommended only for patients at high risk of progression and for whom the benefit exceeds the harm. Kidney failure risk equations were previously developed and validated in 2 Canadian cohorts. The equations include a number of variables, such as age, sex, estimated glomerular filtration rate (a measure of kidney function) and albuminuria (the presence of excessive protein in the urine), to help predict the risk of kidney failure. Validation of these equations in other regions is needed.

Josef Coresh, M.D., Ph.D., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues evaluated the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined in meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed.

During a median follow-up of 4 years, 23,829 cases of kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts; discrimination in subgroups by age, race, and diabetes status was similar. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 33 percent at 2 years and 16.5 percent at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively.

"There are important clinical and research implications to this study's findings," the authors write. "Clinicians can now use the 4- or 8-variable kidney failure risk equations, with the recalibration factor where applicable, that can inform patient-clinician communication and treatment decisions regarding the absolute risk of kidney failure, rather than the CKD stage alone. Decisions regarding access placement or transplant referral could be made once kidney failure risk thresholds are exceeded."