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.
Bibliographical noteFunding Information:
We performed a prospective study of patients with iMN. For this study, 113 patients with renal biopsy-proven iMN and 43 healthy volunteers were enrolled between January 2002 and June 2012. Patients younger than 15 years or those with secondary MN were excluded. Healthy volunteers were participants in the study of ‘Korean coefficients for glomerular filtration rate estimation by MDRD study equations’ funded by the Korean Society of Nephrology , and its validation study funded by the Korea National Enterprise for Clinical Trials. They were defined as those who had no urinary abnormalities and had a systemic inulin clearance greater than ≥60 mL/min/1.73 m. Nephrotic range proteinuria was defined as a UPCR greater than 3.5 g/g Cr. 2
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