Paratubular basement membrane insudative lesions predict renal prognosis in patients with type 2 diabetes and biopsy-proven diabetic nephropathy

PLoS One. 2017 Aug 15;12(8):e0183190. doi: 10.1371/journal.pone.0183190. eCollection 2017.

Abstract

Aims: Glomerular insudative lesions are a pathological hallmark of diabetic nephropathy (DN). However, paratubular basement membrane insudative lesions (PTBMIL) have not attracted much attention, and the association between such lesions and the renal prognosis remains unclear.

Methods: Among 142 patients with biopsy-proven DN and type 2 diabetes encountered from 1998 to 2011, 136 patients were enrolled in this study. Patients were classified into 3 groups (Group 1: mild, Group 2: moderate, Group 3: severe) according to the extent of cortical and medullary PTBMIL. The endpoint was a decline of the estimated glomerular filtration rate (eGFR) by ≥ 40% from baseline or commencement of dialysis for end-stage renal disease. The Cox proportional hazard model was employed to calculate hazard ratios (HRs) and 95% confidence interval (CIs) for the death-censored endpoint.

Results: During a median follow-up period of 1.8 years (IQR: 0.9-3.5), the endpoint occurred in 104 patients. Baseline mean eGFR was 43.9 ± 22.8 ml/min/1.73 m2, and 125 patients (92%) had overt proteinuria. After adjusting for known indicators of DN progression, the HR for the endpoint was 2.32 (95% CI: 1.20-4.51) in PTBMIL Group 2 and 3.12 (1.48-6.58) in PTBMIL Group 3 versus PTBMIL Group 1. Furthermore, adding the PTBMIL Group to a multivariate model including known promoters of DN progression improved prediction of the endpoint (c-index increased by 0.02 [95% CI: 0.00-0.04]).

Conclusions: PTBMIL may be useful for predicting the renal prognosis of patients with biopsy-proven DN, but further investigation of these lesions in various stages of DN is needed.

MeSH terms

  • Aged
  • Antihypertensive Agents / pharmacology
  • Biopsy*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Nephropathies / diagnosis*
  • Diabetic Nephropathies / mortality
  • Diabetic Nephropathies / pathology*
  • Female
  • Glomerular Filtration Rate / physiology
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors

Substances

  • Antihypertensive Agents

Grants and funding

A Grant-in-Aid for Practical Research Project for Renal Disease, from the Japanese Agency for Medical Research and Development (grant no: 15ek0310003h0001), Grants for young researchers from Japan Association for Diabetes Education and Care, a grant from Okinaka Memorial Institute for Medical Research, and a grant from The Kidney Foundation, Japan (grant no: JKFB15-16).