Diabetic nephropathy: Traditional to proteomic markers

Moresco, Rafael Noal; Sangoi, Manuela B.; Carvalho, José Antônio Mainardi de; Tatsch, Etiane; Bochi, Guilherme Vargas

doi:10.1016/j.cca.2013.02.019

Cited by 107 publications

(104 citation statements)

References 231 publications

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“…2013). The increased creatinine clearance observed in this study is in agreement with several other studies that correlated with DN (Hiragushi et al.…”

Section: Discussionmentioning

confidence: 99%

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

et al. 2017

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Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC‐5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24‐h urine sample by calculating clearance and fractional excretion of solutes. The RNA and protein contents of ClC‐5, CFTR, megalin, and cubilin were determined in the renal proximal tubule and cortex using real‐time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin, and transferrin in the DM group than in the CTRL group. Furthermore, the renal cortex and proximal tubule of diabetic animals showed downregulation of megalin, cubilin, ClC‐5, and CFTR, critical components of the endocytic apparatus. These data suggest dysfunction in proximal tubule low‐molecular‐weight endocytosis and protein glomerulus filtration in the kidney of diabetic rats.

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“…2013). The increased creatinine clearance observed in this study is in agreement with several other studies that correlated with DN (Hiragushi et al.…”

Section: Discussionmentioning

confidence: 99%

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

et al. 2017

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“…Because of its relatively high molecular mass (.130 kD), NAG is not filtered through the glomeruli, and it is only released into the urine after renal tubular injury (6,7). Urinary NAG excretion is also associated with inflammation, such as that related to NF-kB activation, which is important in the pathophysiology of DN (8).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Mise

Hoshino²,

Ueno³

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Some biomarkers of renal tubular injury are reported to be useful for predicting renal prognosis in the early stage of diabetic nephropathy (DN). Our study compared predictions of the renal prognosis by such biomarkers and by histologic tubulointerstitial damage.Design, setting, participants, & measurements Among 210 patients with type 2 diabetes and biopsy-proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-b-D-glucosaminidase (NAG) and urinary b2-microglobulin (b2-MG) data at the time of renal biopsy were enrolled. The primary outcome was a decline in eGFR of $50% from baseline or commencement of dialysis for ESRD.Results The median follow-up period was 2.3 years (interquartile range, 1.1-5.3), and the primary outcome was noted in 94 patients. Mean eGFR was 46.3623.2 ml/min per 1.73 m 2 , and 132 patients (89%) had overt proteinuria at baseline. Cox proportional hazards analysis revealed that the association of urinary NAG and b2-MG with the outcome was attenuated after adjustment for known promoters of progression (+1 SD for log NAG: hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.84 to 1.55; +1 SD for log b2-MG: HR, 1.23; 95% CI, 0.94 to 1.62). In contrast, the interstitial fibrosis and tubular atrophy (IFTA) score was still significantly correlated with the outcome after adjustment for the same covariates (+1 for IFTA score: HR, 2.31; 95% CI, 1.56 to 3.43). Moreover, adding the IFTA score to a model containing known progression indicators improved prediction of the outcome (increase of concordance index by 0.02; 95% CI, 0.00 to 0.05; category-free net reclassification improvement by 0.54; 95% CI, 0.03 to 1.05; and relative integrated discrimination improvement by 0.07; 95% CI, 20.08 to 0.22).Conclusions Adding urinary NAG and b2-MG excretion to known promoters of progression did not improve prognostication, whereas adding the IFTA score did. The IFTA score may be superior to these tubulointerstitial markers for predicting the renal prognosis in advanced DN.

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“…It has now been confirmed that many inflammatory cytokines and cell signaling pathways have a relationship with DN (Horbinski et al, 2010;Cohen-Bucay and Viswanathan, 2012;Ogawa and Makino, 2012;Kanasaki et al, 2013;Moresco et al, 2013). Microalbuminuria is not, however, an ideal indicator of DN because there are renal pathological changes and progressive renal functions present during impaired glucose tolerance that are not reflected in urinary albumin levels.…”

Section: Discussionmentioning

confidence: 99%

Correlation between serum YKL-40 levels and albuminuria in type 2 diabetes

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We explored the correlation between serum YKL-40 levels and albuminuria in type 2 diabetes mellitus (T2DM) and its clinical significance. This study used a cross-sectional survey method. According to the American Diabetes Association 2007 Clinical Practice Recommendations, 738 patients with T2DM were divided into three groups: a normoalbuminuria group [albumin-to-creatinine ratio (ACR) <30 μg/mg, N = 360], a microalbuminuria group (ACR 30-300 μg/mg, N = 246), and a macroalbuminuria group (ACR ≥ 300 μg/mg, N = 332). The serum YKL-40 levels were determined by a quantitative sandwich enzyme-linked immunosorbent assay in all the cases and in 210 control subjects. Serum YKL-40 levels were significantly higher in the T2DM group vs the control group (P < 0.05), the macroalbuminuria group vs the microalbuminuria group (P < 0.05), and the microalbuminuria group vs the normoalbuminuria group (P < 0.05). Serum YKL-40 levels correlated with ACR in all 18597 Correlation between YKL-40 and albuminuria in T2DM ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 18596-18603 (2015) participants. Significant correlation of YKL-40 was found with ACR, 2-h plasma glucose, glycated hemoglobin, fasting blood glucose, homeostatic model assessment of insulin resistance index, systolic blood pressure, duration, diastolic blood pressure, age, triglycerides, and high-density lipoprotein cholesterol (r-values: 0.713, 0.524, 0.515, 0.467, 0.438, 0.409, 0.407, 0.374, 0.112, 0.097, and -0.123, respectively). ACR correlated with serum YKL-40 levels (Beta = 0.555, P < 0.001). YKL-40 may be involved in the occurrence and development of diabetic nephropathy and would be useful as a new marker for the disease.

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Diabetic nephropathy: Traditional to proteomic markers

Cited by 107 publications

References 231 publications

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Correlation between serum YKL-40 levels and albuminuria in type 2 diabetes

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