Including Proteinuria May Improve Staging for Chronic Kidney Disease

Laurie Barclay, MD

January 06, 2011

January 6, 2011 — Including proteinuria may improve staging for chronic kidney disease (CKD), according to the results of a retrospective cohort study reported in the January 4 issue of the Annals of Internal Medicine.

"The staging system for ...CKD relies almost exclusively on estimated glomerular filtration rate (eGFR), although proteinuria is also associated with adverse outcomes," write Marcello Tonelli, MD, SM, from University of Alberta in Edmonton, Canada, and colleagues from the Alberta Kidney Disease Network.

Using a provincial laboratory registry in Alberta, Canada, and a representative sample of noninstitutionalized US adults, the investigators identified a derivation data set of 474,521 adult outpatients, 2 independent internal validation cohorts of 51,356 and 460,623 patients, respectively, and an external validation cohort of 14,358 patients.

The Modification of Diet in Renal Disease Study equation was used to determine eGFR, and urine albumin-to-creatinine ratio or dipstick urinalysis was used to detect proteinuria. All-cause mortality and a composite renal outcome of kidney failure or doubling of serum creatinine level were among the main study endpoints.

Higher risk categories defined by lower eGFR or greater proteinuria in the internal validation cohorts were associated with a graded increase in the risk for the composite renal outcome during follow-up (median duration, 38 months). By adding proteinuria, there were 3.9 million projected US adults assigned to risk categories 3 and 4 vs 16.3 million assigned to stages III and IV in the currently used staging system. This alternate system was more likely to correctly reclassify patients who did not go on to have the composite renal outcome than those who did. Despite being reclassified to a lower stage, however, some persons went on to have the composite renal outcome, but all analyses of patients reclassified to a lower stage indicated that markedly fewer such patients went on to have the renal outcome than those who did not.

Measuring proteinuria using the albumin-to-creatinine ratio vs dipstick testing was more likely to result in correct reclassification by the alternate system. Correct reclassification was also more likely to occur for the composite renal outcome vs mortality.

"Using proteinuria in combination with eGFR may reduce unnecessary referrals for care at the cost of not referring or delaying referral for some patients who go on to develop kidney failure," the study authors write.

Limitations of this study include short follow-up time and internal validation for renal outcomes.

In an accompanying editorial, Andrew S. Levey, MD, from Tufts Medical Center in Boston, Massachusetts, and colleagues discuss why they would not recommend substituting risk categories for the current GFR and albuminuria stages or relying on risk categories alone to predict clinical outcomes.

"We conclude that adding albuminuria stages to GFR stages enables better description of CKD for prognosis and management," the editorialists write. "...Grouping of GFR and albuminuria stages into risk categories may be a useful means of communication for clinicians, patients, and the public but requires more study to determine accuracy for a range of outcomes. Future studies should develop and validate quantitative risk prediction instruments and evaluate their utility for management of CKD."

An Alberta Heritage Foundation for Medical Research interdisciplinary research team grant supported this study, along with the Canadian Institutes of Health Research, a joint initiative between Alberta Health and Wellness and the Universities of Alberta and Calgary, and a Shire Biochem—KRESCENT Joint Fellowship. Disclosures of the study authors and editorialists can be viewed at the Annals of Internal Medicine Web site .

Ann Intern Med. 2011;154:12-21, 65-67. Abstract

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