Urinary cystatin C as a potential risk marker for cardiovascular disease and chronic kidney disease in patients with obesity and metabolic syndrome

Abstract

Background and objectives: Obesity and metabolic syndrome (MS) increase the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and all-cause mortality. Serum cystatin C (S-CysC), a marker of GFR, has been shown to be associated with CVD and CKD. This study was designed to elucidate the association of urinary CysC (U-CysC), a marker of renal tubular dysfunction, with CVD and CKD risk factors in patients with obesity and MS.

Design, setting, participants, & measurements: The U-CysC-creatinine ratio (UCCR) was examined in 343 Japanese obese outpatients enrolled in the multi-centered Japan Obesity and Metabolic Syndrome Study.

Results: UCCR was positively correlated with urine albumin-creatinine ratio (UACR) and S-CysC and negatively correlated with estimated GFR (eGFR). Among obese patients, UCCR was significantly higher in MS patients than in non-MS patients. UCCR had significant correlations with the number of components of MS and arterial stiffness, all of which are CVD predictors, similarly to UACR (P<0.05). Interestingly, diet- and exercise-induced weight reduction for 3 months significantly decreased only UCCR among all of the renal markers examined (P<0.01), in parallel with the decrease in BMI, HbA1c, and arterial stiffness, suggesting the beneficial effect of weight reduction on renal tubular dysfunction.

Conclusions: This study demonstrates that UCCR is significantly associated with renal dysfunction, the severity of MS, arterial stiffness, and weight change in obese patients. The data of this study suggest that U-CysC could serve as a CVD and CKD risk factor in patients with obesity and MS.

Figure 1.

The values of S-CysC (A), UACR (B), and UCCR (C) stratified according to the prognostic stages of CKD after gender and age adjustment. The data are shown as the means ± SEM. The differences between groups were assessed by ANCOVA. The open and closed bars indicate CKD and non-CKD according to the United States National Kidney Foundation guidelines, respectively.

Figure 2.

The values of eGFR (A), S-CysC (B), UACR (C), and UCCR (D) stratified according to the number of components of metabolic syndrome after gender and age adjustment. The data are shown as the means ± SEM. The differences between groups were assessed by ANCOVA. Nonmetabolic syndrome and metabolic syndrome are indicated by the open and closed bars, respectively.