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Published in: Journal of Nephrology 3/2014

01-06-2014 | Original Article

Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function

Authors: Yizhi Chen, Li Tang, Zhe Feng, Xueying Cao, Xuefeng Sun, Moyan Liu, Shuwen Liu, Xueguang Zhang, Ping Li, Ribao Wei, Qiang Qiu, Guangyan Cai, Xiangmei Chen

Published in: Journal of Nephrology | Issue 3/2014

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Abstract

Background and objectives

The outcome of idiopathic membranous nephropathy (IMN) in adults with nephrotic-range proteinuria and decreased renal function has seldom been described and the predictive value of pathological features is debated. This study aimed to describe the clinical course of this patient subgroup and to identify independently predictive pathological features.

Materials and methods

We evaluated 129 adults with biopsy-proven IMN diagnosed from 2002 to 2011. All patients had chronic kidney disease (CKD) stages 2–4 and nephrotic-range proteinuria (≥3.5 g/day). Primary outcomes were a 20 or 50 % decline in renal function, progression to end-stage renal disease (ESRD), or all-cause mortality.

Results

Of 129 patients, 38 (30 %) presented with proteinuria ≥8.0 g/day and 37 (29 %) with CKD stages 3–4. Thirteen (10 %) presented with segmental sclerosis, 97 (75 %) with arteriosclerosis, 42 (33 %) with moderate-to-severe tubulointerstitial injury, and 86 (67 %) with C3 deposition. Over a median follow-up of 34 months (range 12–135), 51 patients (40 %) had a 20 % decline in renal function, 27 (21 %) a 50 % decline, 14 (11 %) developed ESRD, and 19 (15 %) died. Segmental sclerosis and tubulointerstitial injury but not arteriosclerosis or C3 deposition were independent risk factors for 20 and 50 % renal function decline and progression to ESRD.

Conclusions

Segmental sclerosis and tubulointerstitial injury predict renal outcomes independent of clinical data in nephrotic IMN patients with decreased renal function.
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Literature
1.
go back to reference Hofstra JM, Fervenza FC, Wetzels JF (2013) Treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 9(8):443–458PubMedCrossRef Hofstra JM, Fervenza FC, Wetzels JF (2013) Treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 9(8):443–458PubMedCrossRef
2.
go back to reference Pan X, Xu J, Ren H, Zhang W, Xu Y, Shen P, Li X, Wang W, Chen X, Wu P et al (2013) Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: a single-center study in China. Contrib Nephrol 181:22–30PubMedCrossRef Pan X, Xu J, Ren H, Zhang W, Xu Y, Shen P, Li X, Wang W, Chen X, Wu P et al (2013) Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: a single-center study in China. Contrib Nephrol 181:22–30PubMedCrossRef
3.
go back to reference van den Brand JA, Hofstra JM, Wetzels JF (2011) Low-molecular-weight proteins as prognostic markers in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 6(12):2846–2853PubMedCentralPubMedCrossRef van den Brand JA, Hofstra JM, Wetzels JF (2011) Low-molecular-weight proteins as prognostic markers in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 6(12):2846–2853PubMedCentralPubMedCrossRef
4.
go back to reference Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini S, Remuzzi G (1993) Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 329(2):85–89PubMedCrossRef Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini S, Remuzzi G (1993) Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 329(2):85–89PubMedCrossRef
5.
go back to reference Polanco N, Gutierrez E, Rivera F, Castellanos I, Baltar J, Lorenzo D, Praga M, Grupo de Estudio de las Enfermedades Glomerulares de la Sociedad Espanola de N (2012) Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment. Nephrol Dial Transplant 27(1):231–234PubMedCrossRef Polanco N, Gutierrez E, Rivera F, Castellanos I, Baltar J, Lorenzo D, Praga M, Grupo de Estudio de las Enfermedades Glomerulares de la Sociedad Espanola de N (2012) Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment. Nephrol Dial Transplant 27(1):231–234PubMedCrossRef
6.
go back to reference McQuarrie EP, Stirling CM, Geddes CC (2012) Idiopathic membranous nephropathy and nephrotic syndrome: outcome in the era of evidence-based therapy. Nephrol Dial Transplant 27(1):235–242PubMedCrossRef McQuarrie EP, Stirling CM, Geddes CC (2012) Idiopathic membranous nephropathy and nephrotic syndrome: outcome in the era of evidence-based therapy. Nephrol Dial Transplant 27(1):235–242PubMedCrossRef
7.
go back to reference Yoshimoto K, Yokoyama H, Wada T, Furuichi K, Sakai N, Iwata Y, Goshima S, Kida H (2004) Pathologic findings of initial biopsies reflect the outcomes of membranous nephropathy. Kidney Int 65(1):148–153PubMedCrossRef Yoshimoto K, Yokoyama H, Wada T, Furuichi K, Sakai N, Iwata Y, Goshima S, Kida H (2004) Pathologic findings of initial biopsies reflect the outcomes of membranous nephropathy. Kidney Int 65(1):148–153PubMedCrossRef
8.
go back to reference Shiiki H, Saito T, Nishitani Y, Mitarai T, Yorioka N, Yoshimura A, Yokoyama H, Nishi S, Tomino Y, Kurokawa K et al (2004) Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int 65(4):1400–1407PubMedCrossRef Shiiki H, Saito T, Nishitani Y, Mitarai T, Yorioka N, Yoshimura A, Yokoyama H, Nishi S, Tomino Y, Kurokawa K et al (2004) Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int 65(4):1400–1407PubMedCrossRef
9.
go back to reference Zuo K, Wu Y, Li SJ, Xu F, Zeng CH, Liu ZH (2013) Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population. Clin Nephrol 79(6):445–453PubMedCrossRef Zuo K, Wu Y, Li SJ, Xu F, Zeng CH, Liu ZH (2013) Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population. Clin Nephrol 79(6):445–453PubMedCrossRef
10.
go back to reference Horvatic I, Ljubanovic DG, Bulimbasic S, Knotek M, Prkacin I, Tisljar M, Galesic K (2012) Prognostic significance of glomerular and tubulointerstitial morphometry in idiopathic membranous nephropathy. Pathol Res Pract 208(11):662–667PubMedCrossRef Horvatic I, Ljubanovic DG, Bulimbasic S, Knotek M, Prkacin I, Tisljar M, Galesic K (2012) Prognostic significance of glomerular and tubulointerstitial morphometry in idiopathic membranous nephropathy. Pathol Res Pract 208(11):662–667PubMedCrossRef
11.
go back to reference Dumoulin A, Hill GS, Montseny JJ, Meyrier A (2003) Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis. Am J Kidney Dis 41(1):38–48PubMedCrossRef Dumoulin A, Hill GS, Montseny JJ, Meyrier A (2003) Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis. Am J Kidney Dis 41(1):38–48PubMedCrossRef
12.
go back to reference Troyanov S, Roasio L, Pandes M, Herzenberg AM, Cattran DC (2006) Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int 69(9):1641–1648PubMedCrossRef Troyanov S, Roasio L, Pandes M, Herzenberg AM, Cattran DC (2006) Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int 69(9):1641–1648PubMedCrossRef
13.
go back to reference Sprangers B, Bomback AS, Cohen SD, Radhakrishnan J, Valeri A, Markowitz GS, D’Agati V, Appel GB (2012) Idiopathic membranous nephropathy: clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center. Am J Nephrol 36(1):78–89PubMedCrossRef Sprangers B, Bomback AS, Cohen SD, Radhakrishnan J, Valeri A, Markowitz GS, D’Agati V, Appel GB (2012) Idiopathic membranous nephropathy: clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center. Am J Nephrol 36(1):78–89PubMedCrossRef
14.
go back to reference Hladunewich MA, Troyanov S, Calafati J, Cattran DC (2009) The natural history of the non-nephrotic membranous nephropathy patient. Clin J Am Soc Nephrol 4(9):1417–1422PubMedCentralPubMedCrossRef Hladunewich MA, Troyanov S, Calafati J, Cattran DC (2009) The natural history of the non-nephrotic membranous nephropathy patient. Clin J Am Soc Nephrol 4(9):1417–1422PubMedCentralPubMedCrossRef
15.
go back to reference Eriguchi M, Oka H, Mizobuchi T, Kamimura T, Sugawara K, Harada A (2009) Long-term outcomes of idiopathic membranous nephropathy in Japanese patients treated with low-dose cyclophosphamide and prednisolone. Nephrol Dial Transplant 24(10):3082–3088PubMedCrossRef Eriguchi M, Oka H, Mizobuchi T, Kamimura T, Sugawara K, Harada A (2009) Long-term outcomes of idiopathic membranous nephropathy in Japanese patients treated with low-dose cyclophosphamide and prednisolone. Nephrol Dial Transplant 24(10):3082–3088PubMedCrossRef
16.
go back to reference Heeringa SF, Branten AJ, Deegens JK, Steenbergen E, Wetzels JF (2007) Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome in patients with membranous nephropathy. Nephrol Dial Transplant 22(8):2201–2207PubMedCrossRef Heeringa SF, Branten AJ, Deegens JK, Steenbergen E, Wetzels JF (2007) Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome in patients with membranous nephropathy. Nephrol Dial Transplant 22(8):2201–2207PubMedCrossRef
17.
go back to reference Zent R, Nagai R, Cattran DC (1997) Idiopathic membranous nephropathy in the elderly: a comparative study. Am J Kidney Dis 29(2):200–206PubMedCrossRef Zent R, Nagai R, Cattran DC (1997) Idiopathic membranous nephropathy in the elderly: a comparative study. Am J Kidney Dis 29(2):200–206PubMedCrossRef
18.
go back to reference Polanco N, Gutierrez E, Covarsi A, Ariza F, Carreno A, Vigil A, Baltar J, Fernandez-Fresnedo G, Martin C, Pons S et al (2010) Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol 21(4):697–704PubMedCentralPubMedCrossRef Polanco N, Gutierrez E, Covarsi A, Ariza F, Carreno A, Vigil A, Baltar J, Fernandez-Fresnedo G, Martin C, Pons S et al (2010) Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol 21(4):697–704PubMedCentralPubMedCrossRef
19.
go back to reference Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC (2004) Idiopathic membranous nephropathy: definition and relevance of a partial remission. Kidney Int 66(3):1199–1205PubMedCrossRef Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC (2004) Idiopathic membranous nephropathy: definition and relevance of a partial remission. Kidney Int 66(3):1199–1205PubMedCrossRef
20.
go back to reference Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, Rambaldi A, Marasa M, Remuzzi G (2012) Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol 23(8):1416–1425PubMedCentralPubMedCrossRef Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, Rambaldi A, Marasa M, Remuzzi G (2012) Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol 23(8):1416–1425PubMedCentralPubMedCrossRef
21.
go back to reference Aaltonen S, Honkanen E (2011) Outcome of idiopathic membranous nephropathy using targeted stepwise immunosuppressive treatment strategy. Nephrol Dial Transplant 26(9):2871–2877PubMedCrossRef Aaltonen S, Honkanen E (2011) Outcome of idiopathic membranous nephropathy using targeted stepwise immunosuppressive treatment strategy. Nephrol Dial Transplant 26(9):2871–2877PubMedCrossRef
22.
go back to reference du Buf-Vereijken PW, Feith GW, Hollander D, Gerlag PG, Wirtz JJ, Noordzij TC, Wetzels JF (2004) Restrictive use of immunosuppressive treatment in patients with idiopathic membranous nephropathy: high renal survival in a large patient cohort. QJM 97(6):353–360PubMedCrossRef du Buf-Vereijken PW, Feith GW, Hollander D, Gerlag PG, Wirtz JJ, Noordzij TC, Wetzels JF (2004) Restrictive use of immunosuppressive treatment in patients with idiopathic membranous nephropathy: high renal survival in a large patient cohort. QJM 97(6):353–360PubMedCrossRef
23.
go back to reference du Buf-Vereijken PW, Branten AJ, Wetzels JF, Membranous Nephropathy Study Group (2004) Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate. Nephrol Dial Transplant 19(5):1142–1148PubMedCrossRef du Buf-Vereijken PW, Branten AJ, Wetzels JF, Membranous Nephropathy Study Group (2004) Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate. Nephrol Dial Transplant 19(5):1142–1148PubMedCrossRef
24.
go back to reference Paraskevakou H, Kavantzas N, Pavlopoulos PM, Voudiklari S, Zerefos N, Papagalanis N, Davaris P (2000) Membranous glomerulonephritis: a morphometric study. Pathol Res Pract 196(3):141–144PubMedCrossRef Paraskevakou H, Kavantzas N, Pavlopoulos PM, Voudiklari S, Zerefos N, Papagalanis N, Davaris P (2000) Membranous glomerulonephritis: a morphometric study. Pathol Res Pract 196(3):141–144PubMedCrossRef
25.
go back to reference Yang S, Xie L, Xue W, Yin A, Lu W (2013) Leflunomide plus oral prednisone in treatment of idiopathic membranous nephropathy: a retrospective clinical study of efficacy and safety. Nephrology (Carlton) 18:615–622CrossRef Yang S, Xie L, Xue W, Yin A, Lu W (2013) Leflunomide plus oral prednisone in treatment of idiopathic membranous nephropathy: a retrospective clinical study of efficacy and safety. Nephrology (Carlton) 18:615–622CrossRef
26.
go back to reference Chen Y, Gong Z, Chen X, Tang L, Zhao X, Yuan Q, Cai G (2013) Tripterygium wilfordii Hook F (a traditional Chinese medicine) for primary nephrotic syndrome. Cochrane Database Syst Rev 8:CD008568PubMed Chen Y, Gong Z, Chen X, Tang L, Zhao X, Yuan Q, Cai G (2013) Tripterygium wilfordii Hook F (a traditional Chinese medicine) for primary nephrotic syndrome. Cochrane Database Syst Rev 8:CD008568PubMed
27.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612PubMedCentralPubMedCrossRef Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612PubMedCentralPubMedCrossRef
28.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150CrossRef Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150CrossRef
29.
go back to reference Howman A, Chapman TL, Langdon MM, Ferguson C, Adu D, Feehally J, Gaskin GJ, Jayne DR, O’Donoghue D, Boulton-Jones M et al (2013) Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial. Lancet 381(9868):744–751PubMedCentralPubMedCrossRef Howman A, Chapman TL, Langdon MM, Ferguson C, Adu D, Feehally J, Gaskin GJ, Jayne DR, O’Donoghue D, Boulton-Jones M et al (2013) Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial. Lancet 381(9868):744–751PubMedCentralPubMedCrossRef
30.
go back to reference Cattran DC, Reich HN, Kim SJ, Troyanov S (2011) Have we changed the outcome in membranous nephropathy? A propensity study on the role of immunosuppressive therapy. Clin J Am Soc Nephrol 6(7):1591–1598PubMedCrossRef Cattran DC, Reich HN, Kim SJ, Troyanov S (2011) Have we changed the outcome in membranous nephropathy? A propensity study on the role of immunosuppressive therapy. Clin J Am Soc Nephrol 6(7):1591–1598PubMedCrossRef
31.
go back to reference Chen Y, Schieppati A, Cai G, Chen X, Zamora J, Giuliano GA, Braun N, Perna A (2013) Immunosuppression for membranous nephropathy: a systematic review and meta-analysis of 36 clinical trials. Clin J Am Soc Nephrol 8(5):787–796PubMedCentralPubMedCrossRef Chen Y, Schieppati A, Cai G, Chen X, Zamora J, Giuliano GA, Braun N, Perna A (2013) Immunosuppression for membranous nephropathy: a systematic review and meta-analysis of 36 clinical trials. Clin J Am Soc Nephrol 8(5):787–796PubMedCentralPubMedCrossRef
32.
go back to reference du Buf-Vereijken PW, Branten AJ, Wetzels JF (2005) Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis 46(6):1012–1029PubMedCrossRef du Buf-Vereijken PW, Branten AJ, Wetzels JF (2005) Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis 46(6):1012–1029PubMedCrossRef
Metadata
Title
Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function
Authors
Yizhi Chen
Li Tang
Zhe Feng
Xueying Cao
Xuefeng Sun
Moyan Liu
Shuwen Liu
Xueguang Zhang
Ping Li
Ribao Wei
Qiang Qiu
Guangyan Cai
Xiangmei Chen
Publication date
01-06-2014
Publisher
Springer International Publishing
Published in
Journal of Nephrology / Issue 3/2014
Print ISSN: 1121-8428
Electronic ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-014-0057-0

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