Testing Kidney Function Using an Alternative Filtration Marker

A new method of testing kidney function using cystatin-C, an endogenous protein produced by almost all nucleated cells, is shown to be more effective than measuring serum creatinine…. 

Diabetic kidney disease accounts for 40 percent of prevalent chronic kidney disease (CKD) and 50 percent of incident end-stage renal disease (ESRD) in the United States. Individuals with diabetes and CKD are at an even greater risk of morbidity and mortality. In practice, kidney function is estimated rather than measured; estimated glomerular filtration rate (eGFR) using serum creatinine is the most common method of testing the kidney’s function. When using serum creatinine to measure kidney function, age, muscle mass, sex and race are factors in kidney function. A valid alternative to using serum creatinine would be to use cystatin-C, an endogenous protein produced by almost all nucleated cells. Cystatin-C is less affected by age, race and muscle mass; however, BMI, diabetes and inflammation may affect cystatin levels.

There have been many previous studies concerning the effectiveness of eGFR. A recent study analyzed true glomerular filtration rate (GFR) versus urinary creatinine clearance and found that the common method of estimating GFR demonstrated poor precision in critical care patients. Many researchers are analyzing more accurate and precise methods to measure kidney. In 2007, researchers tested iohexol blood spot clearance as a new potential method of estimating GFR.

This study analyzed participants, aged 20 and older, from the 1999 – 2002 National Health and Nutrition Examination Survey (NHANES) with available cystatin C. Researchers compared the performance of eGFR using cystatin-C to eGFR using creatinine in the identification of kidney function in diabetic participants. There were 4,457 participants with preserved or reduced kidney function that were analyzed in this study; 778 of the participants had diabetes. Preserved kidney function was determined to be an eGFR of greater than 60 mL/min/1.73m² and reduced eGR was any value less than 60 mL/min/1.73m².

Of the 778 participants with diabetes, the prevalence of reduced kidney functions was greatest among the estimated glomerular filtration rate using cystatin (eGFR_cys). There was a 22 percent prevalence of reduced kidney function using cystatin-C and a 16.5 percent prevalence using creatinine. Other results showed more persons with diabetes were re-classified from preserved kidney function using creatinine to reduced kidney function using cystatin-C. There was strong association between lower eGFR and higher prevalence of complications. Complications presented in this study include: albuminuria, retinopathy, peripheral arterial disease and coronary artery disease; these complications were higher regardless of filtration method used.

In conclusion, this study found that using cystatin-C filtration when estimating glomerular filtration rate leads to more diabetic patients being classified with reduced kidney function than by using creatinine filtration as an estimator.

• Studies have shown that cystatin-c based eGFR correlates more closely to clinical outcomes and when combined with creatinine it improves the accuracy of eGFR.
• Suitable candidates for cystatin-c based eGFR include: adults with creatinine based eGFR of 45-50 mL/min/1.73m² and no indication of kidney damage and patients who are being considered for or receiving nephrotoxic medications.
• Cyclosporine can decrease cystatin-c levels which may cause inaccurate lab test values; rheumatic and malignant diseases in the absence of kidney disease may lead to elevated cystatin-c levels.

Tsai C, Grams M, Inker L, et. al. Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate, Vascular Disease, and Mortality in Persons with Diabetes in the U.S. Diabetes Care. 2014 Mar. 37:1002-1008. Doi:10.2337/dc13-1910.