Decreased Expression of Urinary Mammalian Target of Rapamycin mRNA Is Related to Chronic Renal Fibrosis in IgAN.

Yuhan Cao,Yinhua Liu,Guifa Zhang,Daoqin Liu,Xiaomei Chen,Sufen Wang,Cong Fu,Xinjian Zhu,Yuwei Wang

doi:10.1155/2019/2424751

Abstract

Background Renal fibrosis is a common outcome of all pathological types of chronic kidney disease (CKD). However, the noninvasive detection of renal fibrosis remains a challenge. Methods We collected urine samples from 154 biopsy-proven IgA nephropathy (IgAN) patients and 61 healthy controls. The expression of mTOR was measured and the correlation with renal function parameter and pathological indicators. The receiver operating characteristic (ROC) curve for the diagnosis of IgAN and renal fibrosis was calculated. Results The urinary mammalian target of rapamycin (mTOR) expression was decreased in IgAN patients. The expression of mTOR was correlated with serum creatinine, blood urea nitrogen, estimated glomerular filtration rate, 24 h proteinuria, and cystatin C. Further, the urinary mTOR expression was significantly decreased in severe renal fibrosis patients compared with mild or moderate renal fibrosis patients. Urinary mTOR expression was correlated with score of tubulointerstitial fibrosis (TIF) and score of glomerular sclerosis. The ROC curve showed that mTOR can diagnose IgAN at a cut-off value of 0.930 with the sensitivity of 90.2% and specificity of 73.8% and renal fibrosis at a cut-off value of 0.301 with the sensitivity of 71.7% and specificity of 64.8%. Conclusion Urinary mTOR mRNA expression was a potential biomarker for diagnosis of IgAN and renal fibrosis in IgAN patients.

Highlights

Chronic kidney disease (CKD) is a major public health problem worldwide and in China
The IgA nephropathy (IgAN) group had a significant decrease in the estimated glomerular filtration rate compared with controls. eGFR was calculated using modified MDRD equations for Chinese patients [20]
The results showed that the urinary mammalian target of rapamycin (mTOR) mRNA level effectively distinguished E1 from E0 (Figure 6(a)), with the largest AUC of 0.841, higher than that of eGFR (AUC of 0.551; 95% CI: 0.457-0.644; P = 0 281), serum creatinine (Scr) (AUC of 0.476; 95% CI: 0.385-0.568; P = 0 617), blood urea nitrogen (BUN) (AUC of 0.488; 95% CI: 0.396-0.580; P = 0 799), 24 h proteinuria (AUC of 0.707; 95% CI: 0.610-0.804; P = 0 051), and cystatin C (Cys-c) (AUC of 0.362; 95% CI: 0.273-0.450; P = 0 063). mTOR displayed the sensitivity of 91.2% and specificity of 86.0% at the optimal cut-off value of 0.308

Summary

Introduction

Chronic kidney disease (CKD) is a major public health problem worldwide and in China. IgA nephropathy (IgAN) is the major pathological type of CKD. Tubulointerstitial fibrosis (TIF), is the common histological outcome of all types of CKD [9]. Accurate and early diagnosis of IgAN and renal fibrosis is important for treating and monitoring the progression of CKD. Renal fibrosis is a common outcome of all pathological types of chronic kidney disease (CKD). The urinary mammalian target of rapamycin (mTOR) expression was decreased in IgAN patients. Urinary mTOR expression was correlated with score of tubulointerstitial fibrosis (TIF) and score of glomerular sclerosis. The ROC curve showed that mTOR can diagnose IgAN at a cut-off value of 0.930 with the sensitivity of 90.2% and specificity of 73.8% and renal fibrosis at a cut-off value of 0.301 with the sensitivity of 71.7% and specificity of 64.8%. Urinary mTOR mRNA expression was a potential biomarker for diagnosis of IgAN and renal fibrosis in IgAN patients

Methods

Results

Conclusion