Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model

Abstract

This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically differential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group (n = 248) and non-MN group (n = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.

Keywords

multiparameter analysis / diagnosis / model / membranous nephropathy

参考文献

[1] Ronco P, Debiec H. Pathophysiological advances in membranous nephropathy: time for a shift in patient’s care. Lancet 2015; 385(9981): 1983–1992

[2] Beck LH Jr, Salant DJ. Membranous nephropathy: recent travels and new roads ahead. Kidney Int 2010; 77(9): 765–770

[3] Pan X, Xu J, Ren H, Zhang W, Xu Y, Shen P, Li X, Wang W, Chen X, Wu P, Feng X, Hao C, Chen N. Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: a single-center study in China. Contrib Nephrol 2013; 181(24): 22–30

[4] Xie J, Chen N. Primary glomerulonephritis in mainland China: an overview. Contrib Nephrol 2013; 181(43): 1–11

[5] Ponticelli C. Membranous nephropathy. J Nephrol 2007; 20(3): 268–287

[6] Ronco P, Debiec H. First identification of an antigen in autoimmune idiopathic membranous nephropathy: toward targeted therapy? Am J Kidney Dis 2010; 55(5): 820–823

[7] Bazzi C, Wight R. Urinary N-acetyl-β-glucosaminidase and eGFR may identify patients to be treated with immuno-suppression at diagnosis in idiopathic membranous nephropathy. Nephrology (Carlton) 2018; 23(2):175–182

[8] Wu X, Wen S, Zhu X, Yuan S, Xu X, Yang D, Sun L, Liu H, Liu F. Diagnostic value of renal phospholipase A2 receptor and serum anti-phospholipase A2 receptor antibody in membranous nephropathy. Med J Cent South Univ (Zhong Nan Da Xue Xue Bao Yi Xue Ban) 2017; 42(4): 395–399 (in Chinese)

[9] Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361(1): 11–21

[10] Ortega LM, Schultz DR, Lenz O, Pardo V, Contreras GN. Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions. Lupus 2010; 19(5): 557–574

[11] Iwakura T, Fujigaki Y, Katahashi N, Sato T, Ishigaki S, Tsuji N, Naito Y, Isobe S, Ono M, Sakao Y, Tsuji T, Ohashi N, Kato A, Miyajima H, Yasuda H. Membranous nephropathy with an enhanced granular expression of thrombospondin type-1 domain-containing 7A in a pregnant woman. Intern Med 2016; 55(18): 2663–2668

[12] Li Q, Lin X, Wu Z, He L, Wang W, Cao Q, Zhang J. Immuno-histochemistry analysis of Helicobacter pylori antigen in renal biopsy specimens from patients with glomerulonephritis. Saudi J Kidney Dis Transpl 2013; 24(4): 751–758

[13] Li LS, Liu ZH. Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int 2004; 66(3): 920–923

[14] Knehtl M, Debiec H, Kamgang P, Callard P, Cadranel J, Ronco P, Boffa JJ. A case of phospholipase A₂ receptor-positive membranous nephropathy preceding sarcoid-associated granulomatous tubulointerstitial nephritis. Am J Kidney Dis 2011; 57(1): 140–143

[15] Ponticelli C, Passerini P. Can prognostic factors assist therapeutic decisions in idiopathic membranous nephropathy? J Nephrol 2010; 23(2): 156–163

[16] Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H. Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy. Nephrol Dial Transplant 2013; 28(7): 1839–1844

[17] Hofstra JM, Wetzels JF. Phospholipase A2 receptor antibodies in membranous nephropathy: unresolved issues. J Am Soc Nephrol 2014; 25(6): 1137–1139

[18] Dähnrich C, Komorowski L, Probst C, Seitz-Polski B, Esnault V, Wetzels JF, Hofstra JM, Hoxha E, Stahl RA, Lambeau G, Stöcker W, Schlumberger W. Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy. Clin Chim Acta 2013; 421(11): 213–218

[19] Quintana LF, Blasco M, Seras M, Pérez NS, López-Hoyos M, Villarroel P, Rodrigo E, Viñas O, Ercilla G, Diekmann F, Gómez-Roman JJ, Fernandez-Fresnedo G, Oppenheimer F, Arias M, Campistol JM. Antiphospholipase A2 receptor antibody levels predict the risk of posttransplantation recurrence of membranous nephropathy. Transplantation 2015; 99(8): 1709–1714

[20] Na W, Yi K, Song YS, Park MH. Dissecting the relationships of IgG subclasses and complements in membranous lupus nephritis and idiopathic membranous nephropathy. PLoS One 2017; 12(3): e0174501

[21] Li XL, Yan TK, Li HF, Xu PC, Jia JY, Wei L, Shang WY, Lin S. IgG4-related membranous nephropathy with high blood and low urine IgG4/IgG ratio: a case report and review of the literature. Clin Rheumatol 2014; 33(1): 145–148

[22] Branten AJ, du Buf-Vereijken PW, Klasen IS, Bosch FH, Feith GW, Hollander DA, Wetzels JF. Urinary excretion of β2-microglobulin and IgG predict prognosis in idiopathic membranous nephropathy: a validation study. J Am Soc Nephrol 2005; 16(1): 169–174

[23] Suzuki H, Moldoveanu Z, Hall S, Brown R, Julian BA, Wyatt RJ, Tomana M, Tomino Y, Novak J, Mestecky J. IgA nephropathy: characterization of IgG antibodies specific for galactose-deficient IgA1. Contrib Nephrol 2007; 157: 129–133

[24] Gu QH, Cui Z, Huang J, Zhang YM, Qu Z, Wang F, Wang X, Wang SX, Liu G, Zhao MH. Patients with combined membranous nephropathy and focal segmental glomerulosclerosis have comparable clinical and autoantibody profiles with primary membranous nephropathy: a retrospective observational study. Medicine (Baltimore) 2016; 95(21): e3786

[25] Lemley KV, Bagnasco SM, Nast CC, Barisoni L, Conway CM, Hewitt SM, Song PX. Morphometry predicts early GFR change in primary proteinuric glomerulopathies: a longitudinal cohort study using generalized estimating equations. PLoS One 2016; 11(6): e0157148

[26] Wong E, Lasica M, He SZ, Bajel A, Roberts AW, Mason KD, Ritchie DS, Szer J. Nephrotic syndrome as a complication of chronic graft-versus-host disease after allogeneic haemopoietic stem cell transplantation. Intern Med J 2016; 46(6): 737–741

[27] Wang B, Yang H, Shen L, Wang J, Pu W, Chen Z, Shen X, Fu J, Zhuang Z. Rs56288038 (C/G) in 3'UTR of IRF-1 regulated by miR-502-5p promotes gastric cancer development. Cell Physiol Biochem 2016; 40(1-2): 391–399

[28] Togo K, Ueo T, Yonemasu H, Honda H, Ishida T, Tanabe H, Yao K, Iwashita A, Murakami K. Two cases of adenocarcinoma occurring in sporadic fundic gland polyps observed by magnifying endoscopy with narrow band imaging. World J Gastroenterol 2016; 22(40): 9028–9034

[29] Tabata N, Sueta D, Akasaka T, Arima Y, Sakamoto K, Yamamoto E, Izumiya Y, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Morita K, Oniki K, Saruwatari J, Nakagawa K, Hokimoto S. Helicobacter pylori seropositivity in patients with interleukin-1 polymorphisms is significantly associated with ST-segment elevation myocardial infarction. PLoS One 2016; 11(11): e0166240

[30] Dong HR, Wang YY, Cheng XH, Wang GQ, Sun LJ, Cheng H, Chen YP. Retrospective study of phospholipase A2 receptor and IgG subclasses in glomerular deposits in Chinese patients with membranous nephropathy. PLoS One 2016; 11(5): e0156263

[31] Bastard JP, Fellahi S, Lescure FX, Capeau J, Ronco P, Plaisier E. Interest of the combined measurement of selected urinary proteins in the diagnosis approach in nephrology. Ann Biol Clin (Paris) 2017; 75(3): 327–333

Acknowledgements

This study was supported by (1) National Key R&D Program of China (No. 2016YFC1305500), (2) the National Natural Science Foundation of China (Nos. 61471399 and 61671479), (3) Innovation Nursery Fund of PLA General Hospital (No. 15KMZ04), and (4) the National Natural Science Foundation of China (No. 81401719).

Compliance with ethics guidelines

Hanyu Zhu, Bo Fu, Yong Wang, Jing Gao, Qiuxia Han, Wenjia Geng, Xiaoli Yang, Guangyan Cai, Xiangmei Chen, and Dong Zhang declare that they have no conflict of interest. This study was approved by the Ethics Committee of the Chinese PLA General Hospital. Written informed consent was obtained from each patient.

版权

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