Laurie Barclay, MD
October 22, 2010 — Three biomarkers that can be tested in a single blood sample may help identify patients at high risk for chronic kidney disease (CKD), according to the results of a study reported online October 21 in the Journal of the American Society of Nephrology.
"[CKD] affects 13 percent of the adult population in the United States and is an important risk factor for cardiovascular disease," lead author Caroline S. Fox, MD, MPH, from the National Heart, Lung, and Blood Institute's Framingham Heart Study, in Massachusetts, said in a news release. "It is difficult to identify early abnormalities using serum creatinine, the most commonly used measure to assess kidney function.... Our results identify biomarkers that can improve CKD risk prediction."
The study cohort consisted of 2345 participants who attended the sixth Framingham Offspring Study examination, conducted from 1995 to 1998. The investigators studied the association of 7 circulating biomarkers (C-reactive protein, aldosterone, renin, B-type natriuretic peptide [BNP], plasminogen-activator inhibitor type 1, fibrinogen, and homocysteine) to the incidence of CKD and microalbuminuria (MA) at follow-up from 2005 to 2008.
CKD was defined as estimated glomerular filtration rate (eGFR) of less than 60 mL/minute/1.73 m2, and MA as a urine albumin-to-creatinine ratio greater than or equal to 25 mg/g on spot urine samples in women, or 17 mg/g or higher in men. After adjustment for standard risk factors and baseline renal function, the investigators “identified a parsimonious set of markers related to outcomes” and determined their “incremental predictive utility.”
CKD developed in 213 participants and MA in 186 during follow-up of mean duration 9.5 years. The multimarker panel was associated with incident CKD (P < .001) and MA (P = .003), based on multivariable logistic regression models. Serum homocysteine and aldosterone were each significantly associated with CKD incidence, and log-transformed aldosterone, BNP, and homocysteine were each significantly associated with incident MA. Use of biomarkers led to a 7% increase in net risk reclassification and improvements in the c-statistics for both CKD and MA.
"[C]irculating homocysteine, aldosterone, and BNP provide incremental information regarding risk for incident CKD and MA beyond traditional risk factors," the study authors write. "[F]urther research is necessary to study whether homocysteine is along the causal pathway for the development of CKD and whether lowering homocysteine can reduce the development of CKD. In addition, additional research is warranted to evaluate whether targeting the BNP and aldosterone pathways can reduce the risk of CKD and MA."
Limitations of this study include that its participants were of European ancestry, limiting generalizability to multiethnic populations; lack of measurement of cystatin C (an alternative marker of CKD); and lack of a gold standard measure of GFR.
"Our results will require replication and testing in clinical trial settings, as well as in cost-effectiveness settings, before being brought into the clinical arena," the study authors conclude.
The National Heart, Lung, and Blood Institute’s Framingham Heart Study supported this trial. The study authors have disclosed no relevant financial relationships.