Abstract
Idiopathic membranous nephropathy (iMN) is a common cause of nephrotic syndrome in adults. A biomarker to accurately indicate the severity of iMN and predict long-term prognosis is insufficient. Here, we evaluated the clinical significance of circulating tumor necrosis factor receptors (cTNFRs) as prognostic biomarkers of iMN with nephrotic syndrome. A total of 113 patients with biopsy-proven iMN and 43 healthy volunteers were enrolled in this study. Ninety patients with iMN had nephrotic range proteinuria. Levels of cTNFRs were measured by using serum samples collected at the time of initial diagnosis. Levels of cTNFRs were higher in the patients with nephrotic syndrome than in those with subnephrotic range proteinuria or in the healthy volunteers (P for trend <0.001). Estimated glomerular filtration rate and proteinuria tended to worsen as the cTNFRs levels increased. Having a cTNFR1 level within the highest tertile was a significant risk factor for renal progression after adjustment, in comparison with the other tertiles (hazard ratio [HR], 3.39; 95% confidence interval [95% CI], 1.48–7.78; P = 0.004). The cTNFR2 level within the highest tertile also significantly increased the risk of renal progression (HR, 3.29; 95% CI, 1.43–7.54; P = 0.005). Renal tubular TNFRs expression was associated with cTNFRs level. However, the cTNFRs levels were not associated with autoantibody against phospholipase A2 receptor reactivity/levels or treatment response. This study demonstrated that cTNFRs levels at the time of initial diagnosis could predict renal progression in patients with iMN.
Highlights
Idiopathic membranous nephropathy is a main cause of nephrotic syndrome in adults [1,2]
We found that the circulating tumor necrosis factor receptors (cTNFRs) levels in the patients with Idiopathic membranous nephropathy (iMN) were significantly higher in those with nephrotic syndrome than in those with subnephrotic proteinuria or in the healthy volunteers
The cTNFRs levels at the time of initial diagnosis were associated with renal progression, suggesting that cTNFRs levels at the time of initial diagnosis may forecast the renal progression of iMN
Summary
Idiopathic membranous nephropathy (iMN) is a main cause of nephrotic syndrome in adults [1,2]. Renal dysfunction, and severe histopathological lesions are known as risk factors for renal progression [3,6,7,8]. Autoantibody against phospholipase A2 receptor (anti-PLA2R) has been accepted as a primary mechanism of iMN accounting for the presence of immune complexes in the glomerular capillary wall [9]. This marker could not completely explain diverse clinical courses of iMN. Additional biomarkers for the prediction of renal progression or treatment response are needed
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