Cystatin C May Better Reflect the Effect of Obesity on Renal Function

Abstract

TO THE EDITOR: We read with interest an article by Naour et al. titled “Potential Contribution of Adipose Tissue to Elevated Serum Cystatin C in Human Obesity” (1). advocating the elevation of serum cystatin C (Scys) with adiposity. However, we would like to draw attention to some issues that needs to be carefully reviewed. First, in order to confirm the association between obesity and elevated Scys, the authors attempted to discriminate the influence of reduced renal function by estimating glomerular filtration rate (GFR) based on serum creatinine (Scr). The authors found the GFR values of the participants in the range associated with normal to moderately impaired renal function. According to the K/DOQI guidelines this range concerns stage 1–3 of chronic kidney disease (CKD) (2). At stage 3, we already have a markedly affected kidney function. However, the authors reported none of the subjects had stage 3–5 of CKD. Second, the authors showed that three subjects with very low estimated GFR ( 60 ml/min, in which MDRD equation is not precise to estimate GFR (3). Finally, to determine cystatin C gene expression and secretion in adipose tissue, the authors did not mention the current renal status of the subjects recruited from the gastric surgery program. In response to hypoxic stress, the adipocytes secrete proinflammatory cytokines and adipokines. These adipokines are linked to the genesis of insulin resistance, endothelial dysfunction, metabolic syndrome, all of which have been connected with CKD and may explain the link between adipose tissue and Scys (4). Elevated Scys may be associated with the presence of early signs of atherosclerotic and end-organ damages (5). Moreover, Scys may identify an early stage defined as “preclinical kidney disease”, in which it is associated with an increased risk of CKD progression and cardiovascular mortality, more than creatinine or estimated GFR (3). A few epidemiological studies have reported positive associations of Scys with BMI in different populations and stages of CKD (6,7). However, none of these studies have used the direct measurement of GFR which means they were unable to determine if there is a bias in the estimation of GFR using creatinineor cystatin C-based equations. By contrast, other studies using direct measurement of GFR have found no association of BMI with Scys, and strong association of age with Scys and renal function, even in healthy individuals (8–10). Currently, there is no concrete evidence that would link elevated Scys to human obesity and adiposity other than its correlation with GFR. Therefore, we disagree with the authors that cystatin C may be dependent of body fat composition. DIsclOsuRE The authors declared no conflict of interest.