Proteinuria May Help Predict Outcomes in Chronic Kidney Disease
By Lurie Barclay, MD
Medscape Medical News
February 16, 2010 — Proteinuria may help predict outcomes in chronic kidney disease (CKD) independent of estimated glomerular filtration rate (eGFR) level, according to the results of a community-based cohort study reported in the February 3 issue of the Journal of the American Medical Association.
"The current staging system for chronic kidney disease is based primarily on ...eGFR with lower eGFR associated with higher risk of adverse outcomes," write Brenda R. Hemmelgarn, MD, PhD, from University of Calgary in Alberta, Canada, and colleagues from the Alberta Kidney Disease Network. "Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system."
The goal of the study was to evaluate the association between reduced GFR, proteinuria, and poor clinical outcomes using a province-wide laboratory registry including eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. The study cohort consisted of 920,985 adults who did not require renal replacement therapy at baseline and who had at least 1?outpatient serum creatinine measurement.
Urine dipstick or albumin-creatinine ratio (ACR) was used to identify proteinuria. The main endpoints of the study were all-cause mortality, myocardial infarction, and progression to renal failure.
Most (89.1%) of the participants had an eGFR of at least 60 mL/minute/1.73 m2. During follow-up (median duration, 35 months; range, 0 - 59 months), there were 27,959 deaths (3.0%). Participants with lower eGFRs or heavier proteinuria had a higher fully adjusted rate of all-cause mortality. Compared with participants with an eGFR of 45 to 59.9 mL/minute/1.73 m2 and normal protein excretion, those with heavy proteinuria measured by urine dipstick and an eGFR of at least 60 mL/minute/1.73 m2 had adjusted mortality rates more than twice as high (rate, 7.2; 95% confidence interval [CI], 6.6 - 7.8 vs 2.9; 95% CI, 2.7 - 3.0 per 1000 person-years, respectively; rate ratio, 2.5; 95% CI, 2.3 - 2.7).
When proteinuria was measured by ACR, findings for adjusted mortality were similar (15.9; 95% CI, 14.0 - 18.1 and 7.0; 95% CI, 6.4 - 7.6 per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3; 95% CI, 2.0 - 2.6). Findings were also similar for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine levels.
Limitations of this study include observational design; failure to capture individuals who did not use medical services; difficulty distinguishing acute renal failure from progression of CKD; relatively short follow-up; and lack of data on use of alcohol, tobacco, and antihypertensive medications.
"The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria," the study authors write. "These findings suggest that future revisions of the classification system for CKD should incorporate information from proteinuria."
The Alberta Heritage Foundation for Medical Research (AHFMR) supported this study. Some of the study authors were also supported by awards from the Canadian Institutes of Health Research, by a joint initiative between Alberta Health and Wellness and the Universities of Alberta and Calgary, and/or by a KRESCENT and AHFMR Fellowship. The remaining study authors have disclosed no relevant financial relationships.
