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Triple-Biomarker Approach Improves Chronic Kidney Disease Prediction Accuracy

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Researchers have found that a combination biomarker approach improves risk prediction for chronic kidney disease (CKD). The study, published in the Journal of the American Medical Association (JAMA), concluded that adding cystatin C to the combination of creatinine and albumin-to-creatinine ratio (ACR) measures improved the predictive accuracy for all-cause mortality and end-stage renal disease.

CKD is currently defined as a creatinine-based estimated glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio (ACR) of 30 mg/g or higher. However, as serum creatinine levels are affected by muscle mass, age and race, estimated GFRs are less reliable for assessing renal function when GFR is more than 60 mL/min2. Serum cystatin C is an alternative biomarker of kidney function. Although it is not routinely used in the clinic, it is a better predictor of death and cardiovascular events than creatinine and is less affected by age, race, or muscle mass.

Researchers at the San Francisco VA Medical Center studied 26,643 subjects over a seven year period (January 2003 to January 2010) to evaluate the yield of combining creatinine, cystatin C, and urine ACR to forecast CKD risk compared to creatinine alone. Participants were categorized into 8 groups, defined by estimated GFR determined by creatinine and by certain levels of cystatin C and ACR. The primary outcomes measured were the incidence of end-stage renal disease and all-cause death.

The study participants had an average age of 65 years. Overall,11% (2,904) of participants were classified as having CKD based on creatinine alone. Among them, 24% (701) participants had CKD defined by creatininealone; 5% (148) had CKD defined by creatinine and ACR; 40% (1172) had CKD defined by creatinine and Cystatin C; and 30% (883) had CKD as defined by all biomarkers. Among the 23,739 participants with no CKD defined by creatinine, 16% (3,863) had CKD detected by ACR, cystatin C, or both.

Researchers found that the addition of cystatin C to creatinine and albuminuria for risk prediction enabled them to more accurately reclassify persons and distinguish important prognostic differences, namely a 3-fold risk of death and 4-fold risk of end-stage renal disease. Cystatin C and albuminuria were both strongly and independently associated with all-cause death among people with or without CKD defined by creatinine-based estimated GFR. Interestingly, highest risk group for end-stage renal disease was concentrated within the subset of participants who had CKD defined by all three markers; the second highest risk group for end-stage renal disease was missed by creatinine (the first marker used to stratify analyses) but was detected by cystatin C and ACR.

The authors note that several groups are currently advocating new international guidelines that more accurately reflect prognosis of CKD and have proposed adding ACR to the staging of CKD:

Our results suggest that a triple-marker approach using both ACR and cystatin C to confirm CKD more accurately discriminates prognosis for death and progression to end-stage renal disease than creatinine and ACR alone.

They add that the use of a triple-marker renal panel that improves prognostic ability could both reduce unwarranted referrals and unnecessary workups for low-risk individuals and would prioritize specialty care and interventions to individuals at highest risk.

Study: Detection of Chronic Kidney Disease With Creatinine, Cystatin C, and Urine Albumin-to-Creatinine Ratio and Association With Progression to End-Stage Renal Disease and Mortality

Pubmed: View abstract

Source: JAMA News