Background and aims: Microalbuminuria (MA) is not specific predictor of early stages of chronic kidney disease (CKD) in diabetes. We investigate several markers that might be useful in assessing early kidney damage in T1DM and T2DM patients additional to MA.
Materials and methods: We examined 111 patients (T1DM/T2DM: 51/60) with AER<20 mg/l (n=80); <199 mg/l (n=18); ≥200 mg/l (n=13). Biomarkers of kidney damage (collagen IV), nephrin, podocin, cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin, tissue inhibitor of metalloproteinases-1 (TIMP-1) were measured by ELISA in the morning urine and fasting plasma; overnight AER by immunoturbidimetry assay; glomerular filtration rate (GFR) was estimated by standard MDRD formula. All measurements were done in a triplicate and blinded manner. Statistical analyses performed by STATISTICA 8.0, using a MannWhitney test, correlations were analyzed using Spearman correlation coefficients, differences were considered significant at P<0.05.
Results: In T1DM podocin increased prior to MA [0.17; 0.08; 0.084; P<0.05]; collagens increase with CKD progression [3.86; 6.06; 8.663; P<0.05]. In plasma, we observed cystatin C increase [1060;1022; 2391; P<0.05]; significant increase of TIMP-1 observed at NA stage [2632; 2347; 2008; P<0.05]. Positive correlation was observed between the collagen with AER (r=0.48; P=0.002) and serum creatinine (r=0.51; P=0.001), KIM-1 with eGFR (r=0.41; P=0.05), NGAL with AER (r=0.44; P=0.05), uromodulin with eGFR (r=0.49; P=0.05). In T2DM, we observed significant distinctions in urine levels of podocin [0.192; 0.568; 0.084, p1-3, p2-3<0.05]; nephrin increase NAvs.MA [0.661; 0.904, P<0.05], KIM-1 increase NAvs. MA [373.02; 434.47; 1109.08, P<0.05], NGAL increase NA vs MA [1.74; 2.185; 14.66, P<0.05]. Biomarkers also had positive correlation with standard markers: collagen with AER (r=0.48; P=0.002), cystatin C, podocin and uromodulin with eGFR (r=0.48, P=0.002; r=0.39, P=0.015; r=0.49, P=0.0002, respectively).
Conclusion: We suggest that urinary levels of podocin, collagen IV, nephrin might be candidates biomarkers for early detection of CKD in diabetes.