Cystatin C Levels in U.S. Adults, 1988–1994 Versus 1999–2002: NHANES

Background and objectives: Creatinine-based estimates of GFR suggest an evolving epidemic of chronic kidney disease (CKD) in U.S. adults that is inadequately explained by conventional, modifiable risk factors. Cystatin C has recently emerged as a promising measure of GFR. To enable further insights into the evolution of CKD in the U.S. population, this study aimed to examine cystatin C levels in U.S. adults.Design, setting, participants, and measurements: Stored serum samples, measured in 2006, were used to compare cystatin C levels among adult participants in the National Health and Nutrition Examination Survey (NHANES) in two time periods, 1988–1994 (n = 6877) and 1999–2002 (n = 4563).Results: Mean cystatin C levels (0.9 versus 0.9 mg/L, P = 0.65) and urinary albumin-creatinine ratios were similar (5.8 versus 5.9 mg/g, P = 0.19) in the 2 study eras. In contrast, standardized serum creatinine (0.8 versus 0.9 mg/dl, P < 0.0001) was higher and estimated GFR (93.2 versus 87.6 ml/min/1.73 m², P < 0.001) was lower in 1999–2002. Similar discrepancies in population trends (when cystatin C and creatinine-based methods were used to define GFR) were present when categories of kidney function were considered, and when adjustment was made for demography and comorbid illness.Conclusions: The disparity between temporal trends when kidney function is assessed with different measurements suggests that estimating trends in disease burden remains an open question.Chronic kidney disease (CKD) may be important from a public health perspective; it is common, and associated with cardiovascular disease, end-stage kidney disease, death risks in community settings, and substantial health care expenditure (1–5). In the last decade, incidence of end-stage kidney disease treated with renal replacement therapy has increased substantially (5,6), as has the population-wide burden of treatable CKD risk factors, principally hypertension (7), obesity, and diabetes (8,9). However, trends in the burden of CKD are unlikely to be accurately inferred from trends in incidence of end-stage kidney disease. For example, in one notable study comparing 1976–1980 and 1988–1994, CKD prevalence did not keep pace with incidence of end-stage kidney disease treated with renal replacement therapy (10).Precise estimates of disease trends are desirable for disease management at a public health level. In this regard, recent observations have generated concern that kidney function in representative U.S. adults may be declining without adequate explanation (11). These twin observations (increasing disease burden; inability to explain this burden with easily identifiable, modifiable risk factors) may be a cause for concern from a public health perspective.Cystatin C is a low-molecular-weight protein with attractive properties as a measure of GFR, including near-constant production rates and free filtration by the glomerulus (12); in addition, cystatin C levels appear to be independent of sex and race, and the contribution of lean-body mass to cystatin C appears to be less than one-tenth that of true GFR in healthy adults (13).Cystatin C levels were measured in a large, systematically sampled group of National Health and Nutrition Examination Survey (NHANES) participants from 1988–1994 and 1999–2002, enabling further insights into the evolution of CKD in the U.S. population.