Cystatin C – an endogenous GFR marker and prognosis factor1)

Abstract

Abstract Glomerular filtration rate (GFR) is the most sensitive parameter of excretory kidney function. GFR reduction is usually detectable prior to the onset of clinical symptoms. Exact knowledge of GFR is helpful for pharmacotherapy and the use of contrast media. Everyday routine usually applies creatinine and creatinine-based equations to estimate GFR. However, because these equations were derived from patient cohorts with advanced renal insufficiency, they underestimate true GFR, if GFR is higher than 60 mL/min/1.73 m2. Moreover, serum creatinine concentrations are influenced by muscle mass, dietary protein intake, sex, age, and drugs thus limiting the precision of creatinine-based methods. An alternative endogenous parameter of GFR is cystatin C, which is a 13.3 kDa large cysteine proteinase inhibitor produced at a constant rate in virtually all nucleated cells. It is freely filtered by the glomerular membrane, reabsorbed in the proximal tubule, and catabolized to more than 99%. Its serum concentrations are virtually independent of body composition, sex, and age or inflammation. In routine diagnostics one single reference interval serves for males and females irrespective of ethnicity. Furthermore, serum concentrations of cystatin C are stable from the second year of life until the end of the fifth decade. Even subtle reductions of renal function in the creatinine-blind range can be diagnosed safely and are reproducible. In comparison to creatinine, cystatin C-based clearance formula allow for an easy estimation of GFR which is robust against diverse sources of error. Cystatin C also enables prognostic statements. This applies for acute renal failure due to shock, sepsis or surgical interventions, as well as for contrast media. Additionally, chronic renal failure and cardiovascular events may be predicted. In summary cystatin C is a reliable marker for GFR estimation and its diagnostic accuracy is less influenced than creatinine. Furthermore, it provides prognostic information on patients regarding all-cause mortality and cardiovascular risk, suggesting cystatin C as a potential screening parameter.