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Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function.

ABSTRACT: OBJECTIVE: The structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria. RESEARCH DESIGN AND METHODS: In patients with normo- (n = 8) or microalbuminuria (n = 6), renal biopsies were performed according to a research protocol. In patients with macroalbuminuria (n = 17), biopsies were performed according to clinical indication. Findings were categorized according to the Fioretto classification: category 1 (C1), normal/near normal; category 2 (C2), typical diabetic nephropathy (DN) with predominantly glomerular changes; and category 3 (C3), atypical with disproportionately severe interstitial/tubular/vascular damage and with no/mild diabetic glomerular changes. RESULTS: In our study population (mean eGFR 35 mL/min/1.73 m2), typical glomerular changes (C2) of DN were observed in 22 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 subjects with normoalbuminuria (P = 0.002). By contrast, predominantly interstitial or vascular changes (C3) were seen in only 1 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 normoalbuminuric subjects (P = 0.08). Mesangial area increased progressively from normal controls to patients with type 2 diabetes and normo-, micro-, and macroalbuminuria. Varying degrees of arteriosclerosis, although not necessarily the predominant pattern, were seen in seven of eight subjects with normoalbuminuria. CONCLUSIONS: Typical renal structural changes of DN were observed in patients with type 2 diabetes and elevated albuminuria. By contrast, in normoalbuminuric renal insufficiency, these changes were seen less frequently, likely reflecting greater contributions from aging, hypertension, and arteriosclerosis.

SUBMITTER: Ekinci EI

PROVIDER: S-EPMC3816854 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function.

Ekinci Elif I EI Jerums George G Skene Alison A Crammer Paul P Power David D Cheong Karey Y KY Panagiotopoulos Sianna S McNeil Karen K Baker Scott T ST Fioretto Paola P Macisaac Richard J RJ

Diabetes care 20130708 11

<h4>Objective</h4>The structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria.<h4>Research design and methods</h4>In patients with normo- (n = 8) or microalbuminuria (n = 6), renal biopsies were performed according to a resear ...[more]

PMID: 23835690

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Project description:Objectives:As a screening index of diabetic kidney disease (DKD), urinary albumin/creatine ratio (UACR) is commonly used. However, approximately 23.3%-56.6% of DKD patients with estimated?glomerular?filtration?rate?(eGFR) < 60?ml/min per 1.73?m2 are normoalbuminuric. Thus, urinary biomarkers of nonalbuminuric renal insufficiency in type 2 diabetes mellitus (T2DM) patients are urgently needed. Methods:This cross-sectional study enrolled 209 T2DM patients with normoalbuminuria whose diabetes duration was more than 5 years. The patients were classified into two groups, NO-CKD (eGFR ? 60?ml/min per 1.73?m2, n = 165) and NA-DKD (eGFR < 60?ml/min per 1.73?m2, n = 44). Levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP), plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1), and E-cadherin were detected, and their correlations with eGFR, plasma TNF-?, IL-6, endothelin-1 (ET-1), and 8-hydroxydeoxyguanosine (8-OHdG) were assessed. Results:Among patients with renal insufficiency, 26.0% was normoalbuminuric. Compared to the NO-CKD group, the NA-DKD group was older with lower hemoglobin (HB) levels and higher systolic blood pressure (SBP), plasma TNF-?, IL-6, and 8-OHdG levels. Logistic regression analysis suggested that age, TNF-?, and 8-OHdG were independent risk factors for nonalbuminuric renal insufficiency. Compared to the NO-CKD group, the NA-DKD group exhibited significant increases in urinary NGAL and RBP levels but not PAI-1, VCAM-1, and E-cadherin. Urinary NGAL and RBP both correlated negatively with eGFR and positively with plasma IL-6 and 8-OHdG. Multiple linear regression indicated NGAL (? = -0.287, p = 0.008) and RBP (? = -44.545, p < 0.001) were independently correlated with eGFR. Conclusion:Age, plasma TNF-?, and 8-OHdG are independent risk factors for renal insufficiency in T2DM patients with normoalbuminuria. Urinary NGAL and RBP can serve as noninvasive biomarkers of normoalbuminuric renal insufficiency in T2DM.

Project description:INTRODUCTION:Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function. METHODS:For this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1-G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation. RESULTS:A total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064) after 2 years]. CONCLUSIONS:During long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from normal to end-stage renal disease, including those on dialysis, and improved glycemic control. TRIAL REGISTRATION NUMBER:Japic CTI-153047. FUNDING:Mitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co, Ltd.

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Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function.

Publications

Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function.

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