Skip to main content
Top
Published in: BMC Nephrology 1/2019

Open Access 01-12-2019 | Research article

Focal segmental glomerulosclerosis, excluding atypical lesion, is a predictor of renal outcome in patients with membranous nephropathy: a retrospective analysis of 716 cases

Authors: Hong-Guang He, Chao-Qing Wu, Kun Ye, Chun Zeng, Yi-Yun Huang, Shu-Wen Luo, Wu Yin, Qiu-Rong Ye, Xiao-Mei Peng

Published in: BMC Nephrology | Issue 1/2019

Login to get access

Abstract

Background

Focal segmental lesions (FSLs) are not uncommon in idiopathic membranous nephropathy (IMN). The reported percentage of IMN patients with focal segmental glomerulosclerosis (FSGS) lesions varies widely between studies. The objective of this study was to differentiate atypical FSL (aFSL) from typical FSGS in IMN and to analyse the clinicopathological predictors of primary outcome of IMN patients.

Methods

A total of 716 patients with biopsy-proven IMN between January 1, 2007 and December 31, 2017 were enrolled in the study. An atypical focal segmental lesion was defined as pure synechia, segmental hyperplasia of podocytes or thickening of the GBM accompanied by proliferation of the mesangial matrix, and absence of typical FSGS. The patients were divided into three groups: patients without FSL (FSL), patients with typical FSGS (FSGS+), and patients with aFSL (aFSL+).The primary outcome was a 50% decline in the initial estimated glomerular filtration rate or end-stage renal disease (ESRD) incidence. Secondary outcomes included all-cause death and ESRD.

Results

FSGS was present in 174 patients, while aFSL was noted in 161 patients. Systolic blood pressure was higher in both aFSL+ group and FSGS+ groups compared with the FSL group. IMN patients without FSL and with aFSL had lower serum creatinine levels than IMN patients with FSGS. Both the FSGS+ and aFSL+ groups had higher levels of proteinuria and lower albumin levels than the FSL group. Renal tissue lesions, including tubulointerstitial fibrosis, glomerular obsolescence, and vascular sclerosis were significantly more severe in the FSGS+ group. Cox multivariate analysis showed that older age ≥ 60 years, eGFR< 60 ml/(min·1.73m2), tubulointerstitial fibrosis area ≥ 15% and FSGS at biopsy were independent risk factors for the primary outcome.

Conclusions

No significant difference in outcome was found between the FSL and aFSL+ groups, although the patients with aFSL had lower levels of serum albumin and eGFR, higher level of urinary protein, more severe renal lesions with proliferation of the mesangial area,tubulointerstitial fibrosis and vascular sclerosis. FSGS, excluding atypical lesions, was an independent predictor of the primary outcome.
Literature
1.
go back to reference Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976–1979 and 1995–1997. Am J Kidney Dis. 1997;30:621–31.CrossRef Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976–1979 and 1995–1997. Am J Kidney Dis. 1997;30:621–31.CrossRef
2.
go back to reference Pan X, Xu J, Ren H, Zhang W, Xu Y, Shen P, et al. Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: a single center study in China. Contrib Nephrol. 2013;181:22–30.CrossRef Pan X, Xu J, Ren H, Zhang W, Xu Y, Shen P, et al. Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: a single center study in China. Contrib Nephrol. 2013;181:22–30.CrossRef
3.
go back to reference Ehrenreich T, Churg J. Focal sclerosis in membranous nephropathy. Am J Pathol. 1977;86:37A abstr. Ehrenreich T, Churg J. Focal sclerosis in membranous nephropathy. Am J Pathol. 1977;86:37A abstr.
4.
go back to reference Van Damme B, Tardanico R, Vanrenterghem Y, Desmet V. Adhesions, focal sclerosis,protein crescents, and capsular lesions in membranous nephropathy. J Pathol. 1990;161:47–56.CrossRef Van Damme B, Tardanico R, Vanrenterghem Y, Desmet V. Adhesions, focal sclerosis,protein crescents, and capsular lesions in membranous nephropathy. J Pathol. 1990;161:47–56.CrossRef
5.
go back to reference Iwahashi C. Clinico-pathological study of focal glomerular sclerotic lesions in idiopathic membranous nephropathy. Nippon Jinzo Gakkai Shi. 1991;33:139–43.PubMed Iwahashi C. Clinico-pathological study of focal glomerular sclerotic lesions in idiopathic membranous nephropathy. Nippon Jinzo Gakkai Shi. 1991;33:139–43.PubMed
6.
go back to reference Wakai S, Magil AB. Focal glomerulosclerosis in idiopathic membranous glomerulonephritis. Kidney Int. 1992;41:428–34.CrossRef Wakai S, Magil AB. Focal glomerulosclerosis in idiopathic membranous glomerulonephritis. Kidney Int. 1992;41:428–34.CrossRef
7.
go back to reference Dumoulin A, Hill GS, Montseny JJ, Meyrier A. Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis. Am J Kidney Dis. 2003;41:38–48.CrossRef Dumoulin A, Hill GS, Montseny JJ, Meyrier A. Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis. Am J Kidney Dis. 2003;41:38–48.CrossRef
8.
go back to reference Yoshimoto K, Yokoyama H, Wada T, Furuichi K, Sakai N, Iwata Y, et al. Pathologic findings of initial biopsies reflect the outcomes of membranous nephropathy. Kidney Int. 2004;65:148–53.CrossRef Yoshimoto K, Yokoyama H, Wada T, Furuichi K, Sakai N, Iwata Y, et al. Pathologic findings of initial biopsies reflect the outcomes of membranous nephropathy. Kidney Int. 2004;65:148–53.CrossRef
9.
go back to reference D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004;43:368–82.CrossRef D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004;43:368–82.CrossRef
10.
go back to reference Shiiki H, Saito T, Nishitani Y, Mitarai T, Yorioka N, Yoshimura A, et al. Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int. 2004;65:1400–7.CrossRef Shiiki H, Saito T, Nishitani Y, Mitarai T, Yorioka N, Yoshimura A, et al. Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int. 2004;65:1400–7.CrossRef
11.
go back to reference Troyanov S, Roasio L, Pandes M, Herzenberg AM, Cattran DC. Renal pathology in idiopathic membranous nephropathy:a new perspective. Kidney Int. 2006;69:1641–8.CrossRef Troyanov S, Roasio L, Pandes M, Herzenberg AM, Cattran DC. Renal pathology in idiopathic membranous nephropathy:a new perspective. Kidney Int. 2006;69:1641–8.CrossRef
12.
go back to reference Heeringa SF, Branten AJ, Deegens JK, Steenbergen E, Wetzels JF. Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome in patients with membranous nephropathy. Nephrol Dial Transplant. 2007;22:2201–7.CrossRef Heeringa SF, Branten AJ, Deegens JK, Steenbergen E, Wetzels JF. Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome in patients with membranous nephropathy. Nephrol Dial Transplant. 2007;22:2201–7.CrossRef
13.
go back to reference Sprangers B, Bomback AS, Cohen SD, Radhakrishnan J, Valeri A, Markowitz GS, et al. Idiopathic membranous nephropathy: clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center. Am J Nephrol. 2012;36:78–89.CrossRef Sprangers B, Bomback AS, Cohen SD, Radhakrishnan J, Valeri A, Markowitz GS, et al. Idiopathic membranous nephropathy: clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center. Am J Nephrol. 2012;36:78–89.CrossRef
14.
go back to reference Gu QH, Cui Z, Huang J, Zhang YM, Qu Z, Wang F, et al. Patients with combined membranous nephropathy and focal segmental glomerulosclerosis have comparable clinical and autoantibody profiles with primary membranous nephropathy. Medicine (Baltimore). 2016;95(21):e3786.CrossRef Gu QH, Cui Z, Huang J, Zhang YM, Qu Z, Wang F, et al. Patients with combined membranous nephropathy and focal segmental glomerulosclerosis have comparable clinical and autoantibody profiles with primary membranous nephropathy. Medicine (Baltimore). 2016;95(21):e3786.CrossRef
15.
go back to reference Chen Y, Tang L, Feng Z, Cao X, Sun X, Liu M, et al. Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function. J Nephrol. 2014;27:307–16.CrossRef Chen Y, Tang L, Feng Z, Cao X, Sun X, Liu M, et al. Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function. J Nephrol. 2014;27:307–16.CrossRef
16.
go back to reference Zheng CX, Chen ZH, Zeng CH, Qin WS, Li LS, Liu ZH. Triptolide protects podocytes from puromycinaminonucleoside induced injury in vivo and in vitro. Kidney Int. 2008;74:596–612.CrossRef Zheng CX, Chen ZH, Zeng CH, Qin WS, Li LS, Liu ZH. Triptolide protects podocytes from puromycinaminonucleoside induced injury in vivo and in vitro. Kidney Int. 2008;74:596–612.CrossRef
17.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. CKD-EPI (chronic kidney disease epidemiology collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRef Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. CKD-EPI (chronic kidney disease epidemiology collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRef
18.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.CrossRef Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.CrossRef
19.
go back to reference Gupta R, Sharma A, Mahanta PJ, Jacob TG, Agarwal SK, Roy TS, et al. Focal segmental glomerulosclerosis in idiopathic membranous glomerulonephritis: a clinico-pathological and stereological study. Nephrol Dial Transplant. 2010;25:444–9.CrossRef Gupta R, Sharma A, Mahanta PJ, Jacob TG, Agarwal SK, Roy TS, et al. Focal segmental glomerulosclerosis in idiopathic membranous glomerulonephritis: a clinico-pathological and stereological study. Nephrol Dial Transplant. 2010;25:444–9.CrossRef
20.
go back to reference Morita M, Mii A, Shimizu A, Yasuda F, Shoji J, Masuda Y, et al. Glomerular endothelial cell injury and focal segmental glomerulosclerosis lesion in idiopathic membranous nephropathy. PLoS One. 2015;10(4):e0116700.CrossRef Morita M, Mii A, Shimizu A, Yasuda F, Shoji J, Masuda Y, et al. Glomerular endothelial cell injury and focal segmental glomerulosclerosis lesion in idiopathic membranous nephropathy. PLoS One. 2015;10(4):e0116700.CrossRef
21.
go back to reference Wharram BL, Goyal M, Wiggins JE, Sanden SK, Hussain S, Filipiak WE, et al. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol. 2005;16:2941–52.CrossRef Wharram BL, Goyal M, Wiggins JE, Sanden SK, Hussain S, Filipiak WE, et al. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol. 2005;16:2941–52.CrossRef
22.
go back to reference Nochy D, Heudes D, Glotz D, Lemoine R, Gentric D, Bruneval P, et al. Preeclampsia associated focal and segmental glomerulosclerosis and glomerular hypertrophy: a morphometric analysis. Clin Nephrol. 1994;42:9–17.PubMed Nochy D, Heudes D, Glotz D, Lemoine R, Gentric D, Bruneval P, et al. Preeclampsia associated focal and segmental glomerulosclerosis and glomerular hypertrophy: a morphometric analysis. Clin Nephrol. 1994;42:9–17.PubMed
23.
go back to reference Nishimoto K, Shiiki H, Nishino T, Kimura T, Sasaki Y, Yamasaki M, et al. Glomerular hypertrophy in preeclamptic patients with focal segmental glomerulosclerosis. A morphometric analysis. ClinNephrol. 1999;51:209–19. Nishimoto K, Shiiki H, Nishino T, Kimura T, Sasaki Y, Yamasaki M, et al. Glomerular hypertrophy in preeclamptic patients with focal segmental glomerulosclerosis. A morphometric analysis. ClinNephrol. 1999;51:209–19.
24.
go back to reference Daehn I, Casalena G, Zhang T, Shi S, Fenninger F, Barasch N, et al. Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis. J Clin Invest. 2014;124:1608–21.CrossRef Daehn I, Casalena G, Zhang T, Shi S, Fenninger F, Barasch N, et al. Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis. J Clin Invest. 2014;124:1608–21.CrossRef
25.
go back to reference Howie AJ, Ferreira MA, Majumdar A, Lipkin GW. Glomerular prolapse as precursor of one type of segmental sclerosing lesions. J Pathol. 2000;190:478–83.CrossRef Howie AJ, Ferreira MA, Majumdar A, Lipkin GW. Glomerular prolapse as precursor of one type of segmental sclerosing lesions. J Pathol. 2000;190:478–83.CrossRef
26.
go back to reference Smeets B, Stucker F, Wetzels J, Brocheriou I, Ronco P, Gröne HJ, et al. Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease. J Am J Pathol. 2014;184:3239–48.CrossRef Smeets B, Stucker F, Wetzels J, Brocheriou I, Ronco P, Gröne HJ, et al. Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease. J Am J Pathol. 2014;184:3239–48.CrossRef
27.
go back to reference Zuo K, Wu Y, Li SJ, Xu F, Zeng CH, Liu ZH. Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population. Clin Nephrol. 2013;79:445–53.CrossRef Zuo K, Wu Y, Li SJ, Xu F, Zeng CH, Liu ZH. Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population. Clin Nephrol. 2013;79:445–53.CrossRef
28.
go back to reference Eriguchi M, Oka H, Mizobuchi T, Kamimura T, Sugawara K, Harada A. Long-term outcomes of idiopathic membranous nephropathy in Japanese patients treated with low-dose cyclophosphamide and prednisolone. Nephrol Dial Transplant. 2009;24:3082–8.CrossRef Eriguchi M, Oka H, Mizobuchi T, Kamimura T, Sugawara K, Harada A. Long-term outcomes of idiopathic membranous nephropathy in Japanese patients treated with low-dose cyclophosphamide and prednisolone. Nephrol Dial Transplant. 2009;24:3082–8.CrossRef
29.
go back to reference Paraskevakou H, Kavantzas N, Pavlopoulos PM, Voudiklari S, Zerefos N, Papagalanis N, et al. Membranous glomerulonephritis: a morphometric study. Pathol Res Pract. 2000;196:141–4.CrossRef Paraskevakou H, Kavantzas N, Pavlopoulos PM, Voudiklari S, Zerefos N, Papagalanis N, et al. Membranous glomerulonephritis: a morphometric study. Pathol Res Pract. 2000;196:141–4.CrossRef
30.
go back to reference Horvatic I, Ljubanovic DG, Bulimbasic S, Knotek M, Prkacin I, Tisljar M, et al. Prognostic significance of glomerular and tubulointerstitial morphometry in idiopathic membranous nephropathy. Pathol Res Pract. 2012;208:662–7.CrossRef Horvatic I, Ljubanovic DG, Bulimbasic S, Knotek M, Prkacin I, Tisljar M, et al. Prognostic significance of glomerular and tubulointerstitial morphometry in idiopathic membranous nephropathy. Pathol Res Pract. 2012;208:662–7.CrossRef
Metadata
Title
Focal segmental glomerulosclerosis, excluding atypical lesion, is a predictor of renal outcome in patients with membranous nephropathy: a retrospective analysis of 716 cases
Authors
Hong-Guang He
Chao-Qing Wu
Kun Ye
Chun Zeng
Yi-Yun Huang
Shu-Wen Luo
Wu Yin
Qiu-Rong Ye
Xiao-Mei Peng
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2019
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-019-1498-4

Other articles of this Issue 1/2019

BMC Nephrology 1/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.