Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study.

Novel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM). A prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up. The composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38-6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40- 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers. Patients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.

Satirapoj B ，Pooluea P ，Nata N ，Supasyndh O ... -  《-》

Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients.

The aim of this study was to evaluate the association of urinary tubular markers, interleukin-18 (IL-18) and angiotensinogen with albuminuria in early nephropathy of type 2 diabetics. Urine levels of tubular markers (kidney injury molecule [KIM]-1, neutrophil gelatinase-associated lipocalin [NGAL] and liver-type fatty acid-binding protein [L-FABP]), proinflammatory marker (IL-18), and a marker of intrarenal renin-angiotensin system (RAS) status (angiotensinogen) were determined in 118 patients with type 2 diabetes mellitus and 25 non-diabetic controls with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m(2). Urinary levels of KIM-1, NGAL, IL-18 and angiotensinogen were significantly higher in macroalbuminuria group compared with control and normo- and microalbuminuria groups but not significantly different between control and normoalbuminuria group. Urinary tubular markers were positively correlated with urinary IL-18 and angiotensinogen, respectively. The urinary albuminuria was correlated with all investigated urinary markers in univariate analysis. After adjusting for several clinical parameters, urinary KIM-1, NGAL and angiotensinogen were significantly associated with albuminuria. The results of this study suggest that urinary tubular markers may be independently associated with albuminuria in the early stage of nephropathy in type 2 diabetics (eGFR ≥ 60 mL/min/1.73 m(2)) and may reflect inflammatory processing and the activation of the intrarenal RAS.

Kim SS ，Song SH ，Kim IJ ，Yang JY ，Lee JG ，Kwak IS ，Kim YK ... -  《-》

Markers of Glomerular and Tubular Damage in the Early Stage of Kidney Disease in Type 2 Diabetic Patients.

Żyłka A ，Dumnicka P ，Kuśnierz-Cabala B ，Gala-Błądzińska A ，Ceranowicz P ，Kucharz J ，Ząbek-Adamska A ，Maziarz B ，Drożdż R ，Kuźniewski M ... -  《-》

Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus.

Fufaa GD ，Weil EJ ，Nelson RG ，Hanson RL ，Bonventre JV ，Sabbisetti V ，Waikar SS ，Mifflin TE ，Zhang X ，Xie D ，Hsu CY ，Feldman HI ，Coresh J ，Vasan RS ，Kimmel PL ，Liu KD ，Chronic Kidney Disease Biomarkers Consortium Investigators ... -  《-》

Nonalbuminuric proteinuria as a biomarker for tubular damage in early development of nephropathy with type 2 diabetic patients.

The aim of this study was to evaluate the association between urinary nonalbumin protein (NAP) and urinary tubular markers in early diabetic nephropathy. Urinary NAP was measured in 118 patients with type 2 diabetes with estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m². Urine levels of tubular markers [kidney injury molecule (KIM)-1, neutrophil gelatinase-assoicated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP)] were measured by using an Enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups according to urinary NAP values. The urine levels of KIM-1, NGAL and L-FABP were significantly higher in the third tertile group than in the first tertile group (all p < 0.001). There was a significant positive correlation between NAP and each tubular marker (KIM-1, NGAL and L-FABP) in univariate analysis (all p < 0.001). Urinary NAP was positively correlated with all urinary tubular markers after adjustment for age, duration of diabetes, systolic blood pressure, eGFR, low-density lipoprotein cholesterol, HbA1c and albumin-to-creatinine ratio (KIM-1 r = 0.170, p < 0.001; NGAL r = 0.142, p < 0.015 and L-FABP r = 0.262, p < 0.001). In normoalbuminuric patients (n = 58), urinary NAP was also significantly correlated with NGAL and L-FABP in multivariate regression analyses (r = 0.302, p = 0.030 and r = 0.430, p = 0.001). These findings suggest that urinary NAP reflects tubular damage in the early-stage type 2 diabetic nephropathy (eGFR ≥ 60 mL/min/1.73 m²). We suggest that urinary NAP could be used as a biomarker for tubular damage in clinical practice.

Kim SS ，Song SH ，Kim IJ ，Kim WJ ，Jeon YK ，Kim BH ，Kwak IS ，Lee EK ，Kim YK ... -  《-》