Skip to main content
Top
Published in: Clinical and Experimental Nephrology 6/2019

01-06-2019 | Glomerulonephritis | Original article

Characteristics of membranoproliferative glomerulonephritis based on a new classification at a single center

Authors: Marie Nakano, Kazunori Karasawa, Takahito Moriyama, Keiko Uchida, Kosaku Nitta

Published in: Clinical and Experimental Nephrology | Issue 6/2019

Login to get access

Abstract

Background

Recently, a new classification has been established for membranoproliferative glomerulonephritis (MPGN). However, the effect of the new classification on MPGN treatment is not fully understood.

Methods

We conducted a retrospective study of 87 patients with biopsies diagnosed as MPGN. We reclassified 87 MPGN patients diagnosed between 1977 and 2014 at our hospital, according to the new classification, and analyzed both primary immune complex (IC)- and complement (CP)-mediated MPGN in terms of clinicopathological features, treatment, and renal prognosis.

Results

Proteinuria was abundant in the IC-mediated MPGN group (p = 0.0063), and the serum albumin level was significantly lower in the IC-mediated MPGN group (p = 0.0186). The serum C3 value was significantly lower in the CP-mediated MPGN group (p = 0.0317). Serum CH50 values were also lower in the CP-mediated MPGN group (p = 0.0404). However, glomerular deposition of C3 showed no significant differences in immunofluorescence findings. The 148.6-month renal survival rate was similar in both groups (p = 0.445).

Conclusion

These results suggested no significant differences in complement activation of the solid phase in local glomeruli and therefore no equivalence in renal prognosis.
Appendix
Available only for authorised users
Literature
2.
go back to reference Sugiyama H, Yokoyama H, Sato H, Saito T, Kohda Y, Nishi S, Tsuruya K, Kiyomoto H, Iida H, Sasaki T, Higuchi M, Hattori M, Oka K, Kagami S, Nagata M, Kawamura T, Honda M, Fukasawa Y, Fukatsu A, Morozumi K, Yoshikawa N, Yuzawa Y, Matsuo S, Kiyohara Y, Joh K, Taguchi T, Makino H. Committee for standardization of renal pathological diagnosis and Working Group for Renal Biopsy Database, Japanese Society of Nephrology, Tokyo, Japan. Japan Renal Biopsy Registry: the first nationwide, web-based, and prospective registry system of renal biopsies in Japan. Clin Exp Nephrol. 2011;15(4):493–503.CrossRefPubMed Sugiyama H, Yokoyama H, Sato H, Saito T, Kohda Y, Nishi S, Tsuruya K, Kiyomoto H, Iida H, Sasaki T, Higuchi M, Hattori M, Oka K, Kagami S, Nagata M, Kawamura T, Honda M, Fukasawa Y, Fukatsu A, Morozumi K, Yoshikawa N, Yuzawa Y, Matsuo S, Kiyohara Y, Joh K, Taguchi T, Makino H. Committee for standardization of renal pathological diagnosis and Working Group for Renal Biopsy Database, Japanese Society of Nephrology, Tokyo, Japan. Japan Renal Biopsy Registry: the first nationwide, web-based, and prospective registry system of renal biopsies in Japan. Clin Exp Nephrol. 2011;15(4):493–503.CrossRefPubMed
3.
go back to reference Takei T, Itabashi M, Moriyama T, Shimizu A, Tsuruta Y, Ochi A, Nakayama K, Iwasaki C, Uchida K, Nitta K. Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis. Clin Exp Nephrol. 2013;17(1):92–8.CrossRefPubMed Takei T, Itabashi M, Moriyama T, Shimizu A, Tsuruta Y, Ochi A, Nakayama K, Iwasaki C, Uchida K, Nitta K. Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis. Clin Exp Nephrol. 2013;17(1):92–8.CrossRefPubMed
4.
go back to reference Sethi S, Nester CM, Smith RJ. Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int. 2012;81(5):434–41.CrossRefPubMed Sethi S, Nester CM, Smith RJ. Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int. 2012;81(5):434–41.CrossRefPubMed
5.
go back to reference Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol. 2011;31(4):341–8.CrossRefPubMed Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol. 2011;31(4):341–8.CrossRefPubMed
6.
go back to reference Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis—a new look at an old entity. N Engl J Med. 2012;366(12):1119–31.CrossRefPubMed Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis—a new look at an old entity. N Engl J Med. 2012;366(12):1119–31.CrossRefPubMed
7.
go back to reference Bomback AS, Appel GB. Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol. 8(11):634–42. Bomback AS, Appel GB. Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol. 8(11):634–42.
8.
go back to reference Hou J, Markowitz GS, Bomback AS, Appel GB, Herlitz LC, Barry Stokes M, D’Agati VD. Toward a working definition of C3 glomerulopathy by immunofluorescence. Kidney Int. 2014;85(2):450–6.CrossRefPubMed Hou J, Markowitz GS, Bomback AS, Appel GB, Herlitz LC, Barry Stokes M, D’Agati VD. Toward a working definition of C3 glomerulopathy by immunofluorescence. Kidney Int. 2014;85(2):450–6.CrossRefPubMed
9.
go back to reference Cook HT, Pickering MC. Clusters not classifications: making sense of complement-mediated kidney injury. J Am Soc Nephrol. 2018;29(1):9–12.CrossRefPubMed Cook HT, Pickering MC. Clusters not classifications: making sense of complement-mediated kidney injury. J Am Soc Nephrol. 2018;29(1):9–12.CrossRefPubMed
10.
go back to reference Fervenza FC, Sethi S, Glassock RJ. Idiopathic membranoproliferative glomerulonephritis: does it exist? Nephrol Dial Transplant. 2012;27(12):4288–94.CrossRefPubMed Fervenza FC, Sethi S, Glassock RJ. Idiopathic membranoproliferative glomerulonephritis: does it exist? Nephrol Dial Transplant. 2012;27(12):4288–94.CrossRefPubMed
11.
go back to reference Nakagawa N, Hasebe N, Hattori M, Nagata M, Yokoyama H, Sato H, Sugiyama H, Shimizu A, Isaka Y, Maruyama S, Narita I. Clinical features and pathogenesis of membranoproliferative glomerulonephritis: a nationwide analysis of the Japan renal biopsy registry from 2007 to 2015. Clin Exp Nephrol. 2018;22(4):797–807.CrossRefPubMed Nakagawa N, Hasebe N, Hattori M, Nagata M, Yokoyama H, Sato H, Sugiyama H, Shimizu A, Isaka Y, Maruyama S, Narita I. Clinical features and pathogenesis of membranoproliferative glomerulonephritis: a nationwide analysis of the Japan renal biopsy registry from 2007 to 2015. Clin Exp Nephrol. 2018;22(4):797–807.CrossRefPubMed
13.
go back to reference Sheerin NS, Springall T, Carroll M, Sacks SH. Altered distribution of intraglomerular immune complexes in C3-deficient mice. Immunology. 1999;97(3):393–9.CrossRefPubMedPubMedCentral Sheerin NS, Springall T, Carroll M, Sacks SH. Altered distribution of intraglomerular immune complexes in C3-deficient mice. Immunology. 1999;97(3):393–9.CrossRefPubMedPubMedCentral
14.
go back to reference Clynes R, Dumitru C, Ravetch JV. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science. 1998;279(5353):1052–4.CrossRefPubMed Clynes R, Dumitru C, Ravetch JV. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science. 1998;279(5353):1052–4.CrossRefPubMed
15.
go back to reference Meyer-Schwesinger C, Dehde S, Klug P, Becker JU, Mathey S, Arefi K, Balabanov S, Venz S, Endlich KH, Pekna M, Gessner JE, Thaiss F, Meyer TN. Nephrotic syndrome and subepithelial deposits in a mouse model of immune-mediated anti-podocyte glomerulonephritis. J Immunol. 2011;187(6):3218–29.CrossRefPubMed Meyer-Schwesinger C, Dehde S, Klug P, Becker JU, Mathey S, Arefi K, Balabanov S, Venz S, Endlich KH, Pekna M, Gessner JE, Thaiss F, Meyer TN. Nephrotic syndrome and subepithelial deposits in a mouse model of immune-mediated anti-podocyte glomerulonephritis. J Immunol. 2011;187(6):3218–29.CrossRefPubMed
16.
go back to reference Iatropoulos P, Daina E, Curreri M, Piras R, Valoti E, Mele C, Bresin E, Gamba S, Alberti M, Breno M, Perna A, Bettoni S, Sabadini E, Murer L, Vivarelli M, Noris M, Remuzzi G. Registry of membranoproliferative glomerulonephritis/C3 glomerulopathy; Nastasi. Cluster analysis identifies distinct pathogenetic patterns in C3 glomerulopathies/immune complex-mediated membranoproliferative GN. J Am Soc Nephrol. 2018;29(1):283–94.CrossRefPubMed Iatropoulos P, Daina E, Curreri M, Piras R, Valoti E, Mele C, Bresin E, Gamba S, Alberti M, Breno M, Perna A, Bettoni S, Sabadini E, Murer L, Vivarelli M, Noris M, Remuzzi G. Registry of membranoproliferative glomerulonephritis/C3 glomerulopathy; Nastasi. Cluster analysis identifies distinct pathogenetic patterns in C3 glomerulopathies/immune complex-mediated membranoproliferative GN. J Am Soc Nephrol. 2018;29(1):283–94.CrossRefPubMed
18.
go back to reference Servais A, Noël LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grünfeld JP, Niaudet P, Lesavre P, Frémeaux-Bacchi V. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. 2012;82(4):454–64.CrossRefPubMed Servais A, Noël LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grünfeld JP, Niaudet P, Lesavre P, Frémeaux-Bacchi V. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. 2012;82(4):454–64.CrossRefPubMed
19.
go back to reference Ito N, Ohashi R, Nagata M. C3 glomerulopathy and current dilemmas. Clin Exp Nephrol. 2017;21(4):541–51.CrossRefPubMed Ito N, Ohashi R, Nagata M. C3 glomerulopathy and current dilemmas. Clin Exp Nephrol. 2017;21(4):541–51.CrossRefPubMed
20.
go back to reference Zhang Y, Nester CM, Martin B, Skjoedt MO, Meyer NC, Shao D, Borsa N, Palarasah Y, Smith RJ. Defining the complement biomarker profile of C3 glomerulopathy. Clin J Am Soc Nephrol. 2014;9(11):1876–82.CrossRefPubMedPubMedCentral Zhang Y, Nester CM, Martin B, Skjoedt MO, Meyer NC, Shao D, Borsa N, Palarasah Y, Smith RJ. Defining the complement biomarker profile of C3 glomerulopathy. Clin J Am Soc Nephrol. 2014;9(11):1876–82.CrossRefPubMedPubMedCentral
21.
go back to reference Bomback AS, Santoriello D, Avasare RS, Regunathan-Shenk R, Canetta PA, Ahn W, Radhakrishnan J, Marasa M, Rosenstiel PE, Herlitz LC, Markowitz GS, D’Agati VD, Appel GB. C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy. Kidney Int. 2018;93(4):977–85.CrossRefPubMed Bomback AS, Santoriello D, Avasare RS, Regunathan-Shenk R, Canetta PA, Ahn W, Radhakrishnan J, Marasa M, Rosenstiel PE, Herlitz LC, Markowitz GS, D’Agati VD, Appel GB. C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy. Kidney Int. 2018;93(4):977–85.CrossRefPubMed
22.
go back to reference Sethi S, Fervenza FC, Zhang Y, Zand L, Vrana JA, Nasr SH, Theis JD, Dogan A, Smith RJ. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012;82(4):465–73.CrossRefPubMedPubMedCentral Sethi S, Fervenza FC, Zhang Y, Zand L, Vrana JA, Nasr SH, Theis JD, Dogan A, Smith RJ. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012;82(4):465–73.CrossRefPubMedPubMedCentral
23.
go back to reference Iatropoulos P, Noris M, Mele C, Piras R, Valoti E, Bresin E, Curreri M, Mondo E, Zito A, Gamba S, Bettoni S, Murer L, Fremeaux-Bacchi V, Vivarelli M, Emma F, Daina E, Remuzzi G. Complement gene variants determine the risk of immunoglobulin-associated MPGN and C3 glomerulopathy and predict long-term renal outcome. Mol Immunol. 2016;71:131–42.CrossRefPubMed Iatropoulos P, Noris M, Mele C, Piras R, Valoti E, Bresin E, Curreri M, Mondo E, Zito A, Gamba S, Bettoni S, Murer L, Fremeaux-Bacchi V, Vivarelli M, Emma F, Daina E, Remuzzi G. Complement gene variants determine the risk of immunoglobulin-associated MPGN and C3 glomerulopathy and predict long-term renal outcome. Mol Immunol. 2016;71:131–42.CrossRefPubMed
24.
go back to reference Levin A. Management of membranoproliferative glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. 1999;70:41-6. Levin A. Management of membranoproliferative glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. 1999;70:41-6.
25.
go back to reference Faedda R, Satta A, Tanda F, Pirisi M, Bartoli E. Immunosuppressive treatment of membranoproliferative glomerulonephritis. Nephron. 1994;67(1):59–65.CrossRefPubMed Faedda R, Satta A, Tanda F, Pirisi M, Bartoli E. Immunosuppressive treatment of membranoproliferative glomerulonephritis. Nephron. 1994;67(1):59–65.CrossRefPubMed
26.
go back to reference Imtiaz S, Dhrolia MF, Nasir K, Salman B, Ahmad A. Type of immune and complement deposits and response of immunosuppressive treatment on membranoproliferative glomerulonephritis—a single centre experience. J Pak Med Assoc. 2015;65(9):995–1000.PubMed Imtiaz S, Dhrolia MF, Nasir K, Salman B, Ahmad A. Type of immune and complement deposits and response of immunosuppressive treatment on membranoproliferative glomerulonephritis—a single centre experience. J Pak Med Assoc. 2015;65(9):995–1000.PubMed
27.
go back to reference Braun MC, West CD, Strife CF. Differences between membranoproliferative glomerulonephritis types I and III in long-term response to an alternate-day prednisone regimen. Am J Kidney Dis. 1999;34(6):1022–32.CrossRefPubMed Braun MC, West CD, Strife CF. Differences between membranoproliferative glomerulonephritis types I and III in long-term response to an alternate-day prednisone regimen. Am J Kidney Dis. 1999;34(6):1022–32.CrossRefPubMed
28.
go back to reference Radhakrishnan S, Lunn A, Kirschfink M, Thorner P, Hebert D, Langlois V, Pluthero F, Licht C. Eculizumab and refractory membranoproliferative glomerulonephritis. N Engl J Med. 2012;366(12):1165–6.CrossRefPubMed Radhakrishnan S, Lunn A, Kirschfink M, Thorner P, Hebert D, Langlois V, Pluthero F, Licht C. Eculizumab and refractory membranoproliferative glomerulonephritis. N Engl J Med. 2012;366(12):1165–6.CrossRefPubMed
29.
go back to reference Herlitz LC, Bomback AS, Markowitz GS, Stokes MB, Smith RN, Colvin RB, Appel GB, D’Agati VD. Pathology after eculizumab in dense deposit disease and C3 GN. J Am Soc Nephrol. 2012;23(7):1229–37.CrossRefPubMedPubMedCentral Herlitz LC, Bomback AS, Markowitz GS, Stokes MB, Smith RN, Colvin RB, Appel GB, D’Agati VD. Pathology after eculizumab in dense deposit disease and C3 GN. J Am Soc Nephrol. 2012;23(7):1229–37.CrossRefPubMedPubMedCentral
30.
go back to reference Mizuno M, Suzuki Y, Ito Y. Complement regulation and kidney diseases: recent knowledge of the double-edged roles of complement activation in nephrology. Clin Exp Nephrol. 2018;22(1):3–14.CrossRefPubMed Mizuno M, Suzuki Y, Ito Y. Complement regulation and kidney diseases: recent knowledge of the double-edged roles of complement activation in nephrology. Clin Exp Nephrol. 2018;22(1):3–14.CrossRefPubMed
Metadata
Title
Characteristics of membranoproliferative glomerulonephritis based on a new classification at a single center
Authors
Marie Nakano
Kazunori Karasawa
Takahito Moriyama
Keiko Uchida
Kosaku Nitta
Publication date
01-06-2019
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 6/2019
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-019-01716-7

Other articles of this Issue 6/2019

Clinical and Experimental Nephrology 6/2019 Go to the issue