Drug-induced kidney disease: a study of the Japan Renal Biopsy Registry from 2007 to 2015

Clin Exp Nephrol. 2016 Oct;20(5):720-730. doi: 10.1007/s10157-015-1201-4. Epub 2015 Nov 21.

Abstract

Introduction: The Japan Renal Biopsy Registry (J-RBR) was started in 2007 by the Committee for the Standardization of Renal Pathological Diagnosis and the Committee for the Kidney Disease Registry of the Japanese Society of Nephrology. The purpose of this report is to clarify drug-induced kidney disease (DIKD) of renal biopsied cases in Japan.

Subjects and methods: We analyzed the data of 26,535 cases that were registered in the J-RBR from 2007 to 2015.

Results: Based on clinical and pathological diagnoses, 328 cases (176 males and 152 females) of renal biopsy-proven DIKD were registered in the J-RBR from 2007 to 2015 (1.24 % of all cases). The frequency of DIKD increased with age. The number of cases peaked in the 6th-8th decade in all pathological categories, except for the number of chronic tubulointerstitial lesions (CTIL), which peaked in the 4th-5th decade. Overall, the frequency of DIKD was 3 times higher in the 7th decade than in the 2nd decade (1.86 vs. 0.62 %). The main clinical diagnoses were DIKD in 150 cases (45.7 %), nephrotic syndrome in 66 cases (20.1 %), chronic nephritic syndrome in 55 cases (16.8 %), and rapidly progressive glomerulonephritis in 30 cases (9.1 %). DIKD was registered as a secondary diagnosis in 136 cases (41.5 %). The pathological findings of these cases were glomerular lesions in 105 cases (32.0 %), acute tubulointerstitial lesions (ATIL) in 87 cases (26.5 %), CTIL in 72 cases (22.0 %), and sclerotic glomerular lesions and/or nephrosclerosis in 18 cases (5.5 %). ATIL and CTIL were mainly found in cases in which DIKD was diagnosed on the basis of the patient's clinical findings. In addition, nephrotic syndrome-related membranous nephropathy (MN) was the major cause of renal damage in 59.4 % of the cases involving glomerular injuries. According to the CGA risk classification, high-risk (red zone) cases accounted for 56.1 % of all cases of DIKD and 75.9, 64.9, and 33.3 % of the cases involving ATIL, CTIL, and glomerular injuries, respectively. The causative drugs were identified in 102 cases, including bucillamine in 38 cases of MN, gemcitabine in 3 cases of thrombotic microangiopathy, and other anticancer drugs in 14 cases (anti-vascular endothelial growth factor drugs in 3 cases and propyl thiouracil in 3 cases of anti-neutrophil cytoplasmic antibody-related nephritis).

Conclusion: Our analysis of the J-RBR revealed that DIKD mainly affects elderly people in Japan. ATIL or CTIL were found in approximately half of the biopsied cases of DIKD, and one-third involved glomerular lesions, mainly MN or clinical nephrotic syndrome.

Keywords: Drug; Japanese; Kidney injury; Nephrotic syndrome; Tubulointerstitial nephritis.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Child
  • Female
  • Humans
  • Japan / epidemiology
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / diagnosis
  • Kidney Diseases / epidemiology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Registries
  • Risk Factors
  • Sex Distribution
  • Time Factors
  • Young Adult