Unique proximal tubular cell injury and the development of acute kidney injury in adult patients with minimal change nephrotic syndrome

Yoshihide Fujigaki,Shigeru Shibata,Shigeyuki Arai,Michito Nagura,Yutaka Yamaguchi,Shunya Uchida,Fukuo Kondo,Yoshifuru Tamura,Tatsuru Ota

doi:10.1186/s12882-017-0756-6

Abstract

BackgroundAdult patients with minimal change nephrotic syndrome (MCNS) are often associated with acute kidney injury (AKI). To assess the mechanisms of AKI, we examined whether tubular cell injuries unique to MCNS patients exist.MethodsWe performed a retrospective analysis of clinical data and tubular cell changes using the immunohistochemical expression of vimentin as a marker of tubular injury and dedifferentiation at kidney biopsy in 37 adult MCNS patients. AKI was defined by the criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for AKI.ResultsThirteen patients (35.1%) were designated with AKI at kidney biopsy. No significant differences in age, history of hypertension, chronic kidney disease, diuretics use, proteinuria, and serum albumin were noted between the AKI and non-AKI groups. Urinary N-acetyl-β-D-glucosaminidase (uNAG) and urinary alpha1-microglobulin (uA1MG) as markers of tubular injury were increased in both groups, but the levels were significantly increased in the AKI group compared with the non-AKI group. The incidence of vimentin-positive tubules was comparable between AKI (84.6%) and non-AKI (58.3%) groups, but vimentin-positive tubular area per interstitial area was significantly increased in the AKI group (19.8%) compared with the non-AKI group (6.8%) (p = 0.011). Vimentin-positive injured tubules with tubular simplification (loss of brush-border of the proximal tubule/dilated tubule with flattening of tubular epithelium) were observed in the vicinity of glomeruli in both groups, suggesting that the proximal convoluted tubules were specifically injured. Two patients exhibited relatively severe tubular injuries with vimentin positivity and required dialysis within 2 weeks after kidney biopsy. The percentage of the vimentin-positive tubular area was positively correlated with uNAG but not with uA1MG in the non-AKI group.ConclusionsProximal tubular injuries with increased uNAG exist in MCNS patients without renal dysfunction and were more severe in the AKI group than they were in the non-AKI group. The unique tubular injuries probably due to massive proteinuria might be a predisposing factor for the development of severe AKI in adult MCNS patients.

Highlights

Adult patients with minimal change nephrotic syndrome (MCNS) are often associated with acute kidney injury (AKI)
AKI generally lasts longer in MCNS patients than it does in patients with ischaemic acute tubular necrosis (ATN) [8], and reduction of proteinuria is indispensable for recovery from AKI
No significant differences in age, gender, the presence of chronic kidney disease (CKD) and diuretics use were noted between AKI and non-AKI groups

Summary

Introduction

Adult patients with minimal change nephrotic syndrome (MCNS) are often associated with acute kidney injury (AKI). The pathogenesis of severe AKI remains uncertain and is suggested to include (1) ischaemic renal injury [2, 8], (2) tubular obstruction by surrounding interstitial edema [9], (3) redistribution of renal blood flow from cortical to juxtaglomerular nephrons [10] and (4) decrease in capillary filtration coefficient (Kf) [3, 6, 11] In addition to these functional and structural alterations in the kidney, proteinuria has been proposed to induce tubular cell injury and apoptosis [12,13,14]. Multiple factors may be involved in the pathophysiology of developing severe AKI in MCNS

Methods

Results

Discussion

Conclusion