Urine markers of renal tubular injury in idiopathic membranous nephropathy: A cross sectional study

Highlights

• Urine markers of tubular injury were increased in IMN.

• The level of urine tubular markers failed to reflect histological grades of tubular injury.

• Urinary RBP exhibited a weak relationship with parameters of renal function in IMN.

Abstract

Introduction

Idiopathic membranous nephropathy (IMN) is a primary glomerular disease and a major cause of adult nephrotic syndrome. Presently, little is known about the capabilities of the urine markers to reflect the severity of IMN. We aimed at establishing whether urinary N-acetyl-β-glucosaminidase (NAG), Retinol binding protein (RBP), Kidney injury molecule-1 (KIM-1) and Neutrophil gelatianse-associated lipocalin (NGAL) are related with renal parameters and the histological grades tubular injury.

Methods

The levels of urinary NAG, RBP, KIM-1 and NGAL were determined in 165 biopsy-proven patients and 64 healthy controls. Their levels were then compared between patients and healthy subjects, and between patients with and without nephrotic syndrome. Their linearity with renal parameters and associations with histological grades of renal tubular injury were also assessed.

Results

All biomarkers were significantly increased in patients (p < .001). However, no significant increase was observed between patients exhibiting moderate and severe grades tubular injury and those exhibiting mild histological grade. With exception of RBP, all biomarkers were higher in patients with nephrotic syndrome (p < .001) and significantly correlated with majority of renal parameters including proteinuria.

Conclusion

Our findings suggest that although urine markers of tubular injury are increased in IMN, they may not offer a reflection of histological grades.

Introduction

Idiopathic membranous nephropathy (IMN) is a subtype of mebranous nephropathy and a major cause of adult nephrotic syndrome [1]. Also known as primary membranous nephropathy, IMN is a glomerular disease whose pathogenesis is not yet fully clarified. It accounts for the biggest proportion of membranous nephropathy and is characterized by the subepithelial glomerular deposits whose composition is mainly immunoglobulin G and complement 3. In addition to glomerular injuries on which the severity of IMN is dependent, tubulointerstitial injury occurs and has recently been associated with its prognosis [2]. The role of renal tubular injury in the progression and prognosis of IMN has for so long been downplayed in spite of the existing body of evidence in other kidney diseases [[3], [4], [5], [6]]. Despite the apparent role of renal tubular injury in the progression of renal diseases, there is scanty information regarding the applicability of the urine markers in IMN, an important cause of nephrotic syndrome among adults. It is unknown whether the urine markers are capable of reflecting renal tubular injuries and the severity of IMN. Unknown also is their potential to predict IMN's course, the knowledge of which is crucial for timely treatment required to reduce the risk of end stage renal disease (ESRD) and avoiding unnecessary exposure of patients to immunosuppression therapy. Presently, the clinical course of IMN is predicted using proteinuria [7,8] the onset of which lags behind kidney injury. Accordingly, new biomarkers capable of predicting the course of IMN before significant renal damage are needed.

N-acetyl-β-D-glucosaminidase (NAG) and retinol-binding protein (RBP) are the urinary markers of renal tubular damage in current clinical practice. Kidney injury molecule 1(KIM-1) and neutrophil gelatianse-associated lipocalin (NGAL) are relatively new markers which, like NAG and RBP, have hardly been studied in IMN.