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      Serum NGAL and Cystatin C Comparison With Urinary Albumin-to-Creatinine Ratio and Inflammatory Biomarkers as Early Predictors of Renal Dysfunction in Patients With Type 2 Diabetes

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          Abstract

          Introduction

          Diabetic nephropathy is associated with specific histological changes. Early detection of poor glomerular and tubular function can be achieved with biomarkers of diabetes. The aim of this study was to evaluate the accuracy of kidney dysfunction biomarkers in type 2 diabetes (T2D).

          Methods

          Patients with T2D were grouped according to their glycated hemoglobin level. Patients’ urine and blood samples were taken to measure cystatin C (CysC), neutrophil gelatinase-associated lipocalin, beta-trace protein levels, and the first morning void albumin-to-creatinine ratio. Patients in the end stage of renal disease or receiving dialysis were not included. Receiver operating characteristic curves were generated, and the areas under the curve were compared with the performance of the biomarkers used to evaluate kidney dysfunction in T2D.

          Results

          Ninety patients with T2D were chosen. CysC was positively correlated with creatinine ( P < 0.001), estimated glomerular filtration rate ( P < 0.001), and urinary beta-trace protein ( P = 0.01). The area under the curve was 0.635 for CysC, 0.621 for serum neutrophil gelatinase-associated lipocalin, and 0.660 for the albumin-to-creatinine ratio. A crude logistic regression model showed a positive association between serum CysC ( P = 0.01) and serum neutrophil gelatinase-associated lipocalin ( P < 0.001). A linear regression model showed a positive association between serum CysC, creatinine, and estimated glomerular filtration rate ( P < 0.001) but did not show a positive association with glycated hemoglobin ( P = 0.892).

          Discussion

          Neutrophil gelatinase-associated lipocalin and serum CysC were positively associated with the presence of renal dysfunction and had better performance on receiver operating characteristic analysis than the other markers evaluated in patients with T2D without kidney dysfunction.

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          Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease.

          Giuseppe Coppolino, Richard Fazio, G Nicocia … (2009)
          Chronic kidney disease (CKD) has recently assumed epidemic proportion, becoming a troubling emerging cause of morbidity, especially if it progresses to terminal stage (ESRD). The authors aimed to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD. Serum and urinary NGAL levels, together with a series of putative progression factors, were evaluated in a cohort of 96 patients (mean age: 57 +/- 16 years) affected by nonterminal CKD (eGFR > or =15 ml/min/1.73 m(2)) of various etiology. Progression of CKD, assessed as doubling of baseline serum creatinine and/or onset of ESRD, was evaluated during follow-up. At baseline, both serum and urinary NGAL were inversely, independently, and closely related to eGFR. After a median follow-up of 18.5 mo (range 1.01 to 20), 31 patients (32%) reached the composite endpoint. At baseline, these patients were significantly older and showed increased serum creatinine, calcium-phosphate product, C-reactive protein, fibrinogen, daily proteinuria, and NGAL levels, whereas eGFR values were significantly lower. Univariate followed by multivariate Cox proportional hazard regression analysis showed that urinary NGAL and sNGAL predicted CKD progression independently of other potential confounders, including eGFR and age. In patients with CKD, NGAL closely reflects the entity of renal impairment and represents a strong and independent risk marker for progression of CKD.
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            Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes.

            M. Luiza Caramori, Youngki Kim, Chunmei Huang … (2002)
            This study was designed to elucidate the cellular basis of risk of or protection from nephropathy in patients with type 1 diabetes. Entry criteria included diabetes duration of > or =8 years (mean duration, 22.5 years) and glomerular filtration rate (GFR) >30 ml x min(-1) x 1.73 m(-2). Patients were classified, on the basis of the estimated rate of mesangial expansion, as "fast-track" (upper quintile) or "slow-track" (lower quintile). A total of 88 patients were normoalbuminuric, 17 were microalbuminuric, and 19 were proteinuric. All three groups had increased glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(Mes/glom)], with increasing severity from normoalbuminuria to microalbuminuria to proteinuria but with considerable overlap among groups. Vv(Mes/glom) (r = 0.75, P < 0.001) and GBM width (r = 0.63, P < 0.001) correlated with albumin excretion rate (AER), whereas surface density of peripheral GBM per glomerulus [Sv(PGBM/glom)] (r = 0.50, P < 0.001) and Vv(Mes/glom) (r = -0.48, P < 0.001) correlated with GFR. Vv(Mes/glom) and GBM width together explained 59% of AER variability. GFR was predicted by Sv(PGBM/glom), AER, and sex. Fast-track patients had worse glycemic control, higher AER, lower GFR, more hypertension and retinopathy, and, as expected, worse glomerular lesions than slow-track patients. Thus, there are strong relationships between glomerular structure and renal function across the spectrum of AER, but there is considerable structural overlap among AER categories. Given that normoalbuminuric patients may have advanced glomerulopathy, the selection of slow-track patients based on glomerular structure may better identify protected patients than AER alone.
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              Serum Cystatin C and Tubular Urinary Enzymes as Biomarkers of Renal Dysfunction in Type 2 Diabetes Mellitus

              Heba Assal, Salwa Tawfeek, Enas A. Rasheed … (2013)
              Renal tubulointerstitium plays an important role in the development and progression of diabetic nephropathy. The aim of this study was to assess serum cystatin C and 2 renal tubular enzymes, neutrophil gelatinase associated lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG), as screening markers for early renal dysfunction in patients with type 2 diabetes mellitus (T2DM). ROC curve analysis showed that urinary NAG is the most sensitive marker of microalbuminuria and early renal damage with sensitivity of 83.3%, while serum cystatin C was the most sensitive and specific marker of macroalbuminuria and damage progress with sensitivity of 70.8% and specificity of 83.3% versus 70.6% and 83.3% for uNGAL; and 64.7% and 66.7% for NAG, respectively. Our data indicate that urinary NAG is the most sensitive marker for early renal damage in diabetic patients. However, for damage progress, serum cystatin C is the most sensitive and specific marker for follow-up and monitoring renal dysfunction.
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                Author and article information

                Contributors
                Marcelo R. Bacci
                Journal
                Journal ID (nlm-ta): Kidney Int Rep
                Journal ID (iso-abbrev): Kidney Int Rep
                Title: Kidney International Reports
                Publisher: Elsevier
                ISSN (Electronic): 2468-0249
                Publication date PMC-release: 15 October 2016
                Publication date Collection: March 2017
                Publication date (Electronic): 15 October 2016
                Volume: 2
                Issue: 2
                Pages: 152-158
                Affiliations
                [1 ]Department of General Practice, Faculdade de Medicina do ABC, Santo André, Brazil
                [2 ]Earth Sciense’s Department of UNIFESP, São Paulo, Brazil
                [3 ]Clinical Analysis Laboratory of Faculdade de Medicina do ABC, Santo André, Brazil
                Author notes
                [∗ ] Correspondence: Marcelo R. Bacci, Faculdade de Medicina do ABC, Av. Príncipe de Gales n 821, Vila Príncipe de Gales, Santo André, São Paulo, Brazil.Faculdade de Medicina do ABCAv. Príncipe de Gales n 821Vila Príncipe de GalesSanto AndréSão PauloBrazil mr.bacci1@ 123456hotmail.com
                Article
                Publisher ID: S2468-0249(16)30146-2
                DOI: 10.1016/j.ekir.2016.10.001
                PMC ID: 5678634
                PubMed ID: 29142952
                SO-VID: 2fbcd052-50bc-4cd1-9ab5-3a42d64227b3
                Copyright © © 2016 International Society of Nephrology. Published by Elsevier Inc.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 20 June 2016
                Date revision received : 12 September 2016
                Date accepted : 7 October 2016
                Categories
                Subject: Clinical Research

                Keywords: albuminuria,biomarkers,cystatin c,diabetic kidney disease,ngal
                Data availability:
                Keywords: albuminuria, biomarkers, cystatin c, diabetic kidney disease, ngal

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