Urinary Cystatin C and Tubular Proteinuria Predict Progression of Diabetic Nephropathy

Abstract

OBJECTIVEThe aim of this study was to evaluate the association of urinary cystatin C, a tubular damage marker, with the progression of type 2 diabetic nephropathy.RESERCH DESIGN AND METHODSThe baseline values of serum and urinary cystatin C were measured as primary parameters and those of urinary nonalbumin protein (NAP) were measured as secondary parameters. In this prospective observational study, a total of 237 type 2 diabetic patients were followed up for 29 months (13–44 months).RESULTSBoth the urinary cystatin C-to-creatinine ratio (CCR) and NAP-to-creatinine ratio (NAPCR) were significantly different according to the degree of albuminuria. Both markers had strongly positive correlations at baseline. After adjusting for several clinical factors, both urinary CCR and NAPCR had significant associations with the decline of the estimated glomerular filtration rate (eGFR) (r = 0.160, P = 0.021; r = 0.412, P < 0.001, respectively). Urinary CCR had positive correlations with the decline of eGFR in the subpopulation of patients with eGFR ≥60 mL/min/1.73 m2. In patients with eGFR ≥60 mL/min/1.73 m2 and normoalbuminuria, only urinary NAPCR showed a significant association with the decline of eGFR; urinary CCR did not. In multivariate regression analysis, the number of patients who progressed to chronic kidney disease stage 3 or greater was higher in those in the upper tertiles of both the urinary levels of cystatin C and NAP than in those in the lower tertiles.CONCLUSIONSThe results of this study suggest that urinary cystatin C and NAP may be predictors of the progression of type 2 diabetic nephropathy.

Novel Automated Immune Turbidimetric Assay for Routine Urinary Cystatin-C Determinations

“…In the diabetic patient group u-CYSC, data suggest that tubular damage has not been developed yet. Tubular damage might precede the appearance of microalbuminuria only in a few cases of diabetes where increased u-CYSC may be useful for the recognition of these patients [26]. Moreover, in certain cases with proteinuria it should be taken into consideration, that the competition between albumin and low molecular weight proteins for receptor-mediated reabsorption could elevate the urinary levels of CYSC as well [32].…”

“…Since spot urine samples were analyzed, it was reasonable to express results also as u-CYSC/u-CREAT ratio in order to exclude the effect of different hydration states (as it is reported by others) [4,8,[26][27][28]. However, it is future science group www.future-science.com known that in case of tubular damage the excretion of creatinine is also affected which may influence the urinary protein/u-CREAT values [29].…”

The role of novel biomarkers in predicting diabetic nephropathy: a review

“…103 For cystatin C, its urinary excretion suggests tubular injury as it is elevated early in diabetes and prediabetic nephropathy, together with NGAL. 104 Besides the predictive role of urinary cystatin C for the progression of DN, 105 its serum and urinary levels are useful biomarkers for assessing early nephropathy in T2DM. 106 Although KIM-1, as tubular transmembrane glycoprotein, is a well-known sensitive biomarker for acute kidney injury, 107 increased urinary levels have been reported in normoalbuminuric T2DM patients, indicating lesions of the proximal tubule in early stages of the disease.…”

Clinical Significance of Cystatin C-Based Estimates of Renal Function in Type 2 Diabetic Patients: Review

“…They concluded that urinary cystatin C level may be valuable marker for detection of microalbuminuria independent on any other tubular markers and independent of the degree of tubular dysfunction, and that it can be used as a good predictor for the presence of microalbuminuria in early DN [45]. Another study from type 2 diabetic patients found that increased urinary cystatin C was associated with decline in GFR, particularly at the early stages of DN in patients with an eGFR of ≥60 mL/min/1.73 m 2 and was associated with progressed to CKD stage 3 or greater, which indicated that higher urinary cystatin C excretion was a better predictor of early nephropathy [46].…”