Serum creatinine, cystatin C, and beta-trace protein in diagnostic staging and prediction of progression of primary non-diabetic chronic kidney disease

Background: Chronic kidney disease (CKD) is a growing public health problem with increasing incidence and prevalence rates, poor outcomes and high health care costs. Impaired baseline kidney function is a well defined risk factor for progression of CKD. Measured glomerular filtration rate (GFR) is widely accepted as the best measure of overall renal function. Alternatively, serum markers, such as serum creatinine, or the newer low-molecular weight markers, cystatin C and beta-trace protein (BTP), are used to assess kidney function. We compared the diagnostic performance of creatinine, cystatin C, and BTP for staging kidney impairment measured by GFR and for predicting progression of CKD. Methods: Serum marker concentrations were measured in 227 patients with primary non-diabetic CKD and various degrees of renal impairment. 177 patients were followed prospectively for up to 7 years to assess progression of CKD. Results: At baseline, creatinine, cystatin C, and BTP were strongly correlated with GFR. Concentrations of all three markers increased progressively with decreasing GFR. Their diagnostic performance for the detection of even minor deteriorations of renal function (indicated by a GFR<90 mL/min/1.73m²) was similar. 65 patients experienced progression of CKD defined as doubling of baseline creatinine and/or terminal renal failure during follow-up. These patients had a lower GFR, higher serum creatinine, cystatin C, and BTP values at baseline (all P<0.001) compared to the patients who did not reach the predefined renal endpoint. Cox proportional hazard regression analysis revealed that all three clearance markers were equally strong predictors of CKD progression, even after adjustment for age, sex, GFR, and proteinuria. Conclusions: The diagnostic performance of serum creatinine, cystatin C or BTP for detecting even minor degrees of deterioration of renal function is good and these markers provide reliable risk prediction for progression of kidney disease in patients with CKD beyond the gold standard marker GFR.