Recurrence of Type I Membranoproliferative Glomerulonephritis After Renal Transplantation

Andrésdóttir, Margrét B.; Assmann, K.J.M.; Hoitsma, Andries J.; Koene, R. A. P.; Wetzels, Jack F.M.

doi:10.1097/00007890-199706150-00016

Cited by 78 publications

(45 citation statements)

References 22 publications

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“…Patients with MPGN type II may remain stable clinically for long periods; however, relapses associated with acute inf lammatory changes within the kidney often result in a significant decline in renal function or threaten transplant kidney survival. Increased glomerular neutrophil numbers, often with crescent formation, are important features of MPGN type II (24,28) and of MPGN type II developing in transplant kidneys in the absence of transplant-related pathology (43). Furthermore, during rapidly progressive disease all glomerular deposits, including paramesangial deposits, react strongly with anti-C5 antibodies (11), suggesting that C5 activation is an important component of renal injury during acute inf lammatory episodes.…”

Section: Cfhmentioning

confidence: 99%

Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice

Pickering¹,

Warren²,

Rose³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

147

119

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Membranoproliferative glomerulonephritis (MPGN) type II (dense deposit disease) is an inflammatory renal disease characterized by electron-dense deposits and complement C3 on the glomerular basement membrane. There is no effective therapy. We investigated the role of C5 activation in a model of MPGN that develops spontaneously in complement factor H-deficient mice (Cfh ؊/؊ ). At 12 months there was a significant reduction in mortality, glomerular cellularity, neutrophil numbers, and serum creatinine levels in Cfh ؊/؊ mice deficient in C5. Excessive glomerular neutrophil numbers, frequently seen in patients with MPGN during disease flares, were also observed in Cfh ؊/؊ mice after the administration of an antiglomerular basement membrane antibody. This exaggerated injurious phenotype was absent in Cfh ؊/؊ mice deficient in C5 but not in Cfh ؊/؊ mice deficient in C6, indicating a key role for C5 activation in the induction of renal lesions. Importantly, the renal injury was completely reversed in Cfh ؊/؊ mice pretreated with an anti-murine C5 antibody. These results demonstrate an important role for C5 in both spontaneous MPGN and experimentally induced nephritis in factor H-deficient mice and provide preliminary evidence that C5 inhibition therapy might be useful in human MPGN type II.complement ͉ inflammation T he complement system is a key component of innate immunity contributing to host defenses against invading pathogens through multiple mechanisms, which include opsonization, cell lysis, and inflammatory cell recruitment, an action principally mediated through the anaphylatoxin C5a. Complement activation is regulated by a complex group of membrane-bound and fluid-phase proteins (1). Factor H is an abundant serum complement regulatory protein that inhibits the alternative pathway of complement activation. It achieves this through several mechanisms, which include inhibition of the alternative pathway C3 convertase enzyme complex (C3bBb) and acting as a cofactor for the factor I-mediated proteolytic degradation of activated C3 (termed C3b) (2, 3). Its critical importance as a regulator of C3 activation in vivo is illustrated by the complement profile reported in factor H-deficient individuals, where alternative pathway activation proceeds unhindered, resulting in markedly reduced C3 levels (4).Factor H deficiency in humans (5, 6), pigs (7), and mice (8) is associated with membranoproliferative glomerulonephritis (MPGN) type II (dense deposit disease). MPGN is characterized by glomerular capillary wall thickening with increased mesangial matrix and mesangial cells (9). Intramembranous glomerular basement membrane (GBM) deposits together with C3 (10), C5 (11), and C9 (12) staining along the GBM in the absence of Ig characterize type II MPGN (13). Patients typically have low C3 levels while C5 levels remain normal (14). MPGN type II is frequently associated with the presence of C3 nephritic factor (C3NeF), an autoantibody that stabilizes the alternative pathway C3 convertase, preventing its inactivation by factor...

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Section: Cfhmentioning

confidence: 99%

Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice

Pickering¹,

Warren²,

Rose³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

147

119

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“…5 Recurrence rates of MPGN type I after kidney transplantation range from 14% to 61%. [6][7][8][9][10] Patients with recurrence are at increased risk for graft loss, with rates ranging between 14% and 78%. 5,[7][8][9][10] Several studies have investigated factors associated with disease recurrence and graft loss.…”

mentioning

confidence: 99%

Recurrent Membranoproliferative Glomerulonephritis Type I After Kidney Transplantation

et al. 2015

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“…29 Graft loss has been reported in up to 40% of those with recurrence, and the risk of recurrence in subsequent grafts approaches 80%. 30 Significant geographic diversity in the risk of recurrence is evident, largely linked to the prevalence of HCV; much higher rates of graft loss due to recurrence are reported in areas where the majority of patients with MPGN are HCV positive, such as Spain, 29,31 compared with low HCV prevalence areas, such as Australia. 3 Patients receiving HLA-identical grafts appear to be at increased risk of recurrence in some series 29 but not in others.…”

Section: Membranoproliferative Glomerulonephritis Type Imentioning

confidence: 99%

Recurrent Disease in Kidney Transplantation

Chadban¹,

Vacher-Coponat²

2010

Comprehensive Clinical Nephrology

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Recurrence of Type I Membranoproliferative Glomerulonephritis After Renal Transplantation

Abstract: A n a l y s is o f t h e I n c i d e n c e , R i s k F a c t o r s , a n d I m p a c t o n G r a f t S u r v iv a l M a r g r e t B. An d r e s d o t t i r , 1,2 K a r e l J .M . A s s m a n n , A n d r ie s J. H o it s m a , R o b e r t A ,P. K o e n e , a n d J a c k F .M . W

Cited by 78 publications

References 22 publications

Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice

Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice

Recurrent Membranoproliferative Glomerulonephritis Type I After Kidney Transplantation

Recurrent Disease in Kidney Transplantation

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