Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15

Licht, Christoph; Weyersberg, Annic; Heinen, Stefan; Stapenhorst, Ludwig; Devenge, Jacqueline; Beck, Bodo B.; Waldherr, R; Kirschfink, Michael; Zipfel, Peter F.; Höppe, Bernd

doi:10.1053/j.ajkd.2004.10.018

Cited by 115 publications

(81 citation statements)

References 29 publications

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“…Indeed, replacement of defective CFH with normal CFH protein through plasma exchange has been shown to be effective in preventing further disease episodes and normalizing kidney function in MPGN II and atypical hemolytic uremic syndrome (aHUS) patients harboring loss of function CFH mutations (Gerber et al 2003;Licht et al 2005;Pickering and Cook 2008;Stratton and Warwicker 2002). Similar results have been obtained in Yorkshire pigs with an inherited deficiency of CFH that develop lethal glomerulonephritis (Hegasy et al 2002;Jansen et al 1998).…”

Section: Options For Therapysupporting

confidence: 72%

Complement Factor H: Using Atomic Resolution Structure to Illuminate Disease Mechanisms

Barlow

Hageman

Lea

2008

Advances in Experimental Medicine and Biology

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Complement Factor H has recently come to the fore with variant forms implicated in a range of serious disease states. This review aims to bring together recent data concerning the structure and biological activity of this molecule to highlight the way in which a molecular understanding of function may open novel therapeutic possibilities. In particular we examine the evidence for and against the hypothesis that sequence variations in factor H may predispose to disease if they perturb its ability to recognise and respond appropriately to polyanionic carbohydrates on host surfaces that require protection from complement-mediated damage.

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Section: Options For Therapysupporting

confidence: 72%

Complement Factor H: Using Atomic Resolution Structure to Illuminate Disease Mechanisms

Barlow

Hageman

Lea

2008

Advances in Experimental Medicine and Biology

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“…In particular, treatment details were inadequately documented in some cases, which may explain why, in contrast with previous reports (9,11), we did not identify an effect of treatment on renal outcome. It is also noteworthy that only three patients received plasma exchange, a therapeutic option for DDD patients with specific CFH mutations (16). Similarly, no patient received eculizumab, an anti-complement therapy recently reported to mitigate disease in selected patients with C3 glomerulopathy (17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

C3 Glomerulopathy

Medjeral-Thomas

O’Shaughnessy

O’Regan

et al. 2014

Clinical Journal of the American Society of Nephrology

218

200

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SummaryBackground and objectives The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome.Design, setting, participants, & measurements All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model.Results Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age .16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD.Conclusions Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be used to stratify patients, enabling application of emerging mechanism-based therapies to patients at high risk for poor renal outcome.

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“…There was also a realization that whether because of initial renal injury, incomplete protection from HUS, or other unknown reasons, chronic plasma exchange had not been able to protect the native kidneys from long-term decline. In the literature, variability in response to plasma therapy has been reported (27,29,30). Intravenous Ig (IVIG) might ameliorate TMA (31)(32)(33), possibly related to its ability to decrease complement activation (34,35).…”

Section: Discussionmentioning

confidence: 99%

Successful Split Liver-Kidney Transplant for Factor H Associated Hemolytic Uremic Syndrome

Saland¹,

Shneider²,

Bromberg³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: A male infant with a family history of thrombotic microangiopathy developed atypical hemolytic uremic syndrome (aHUS).Design, setting, participants, & measurements: Case report. Results: Genetic analysis demonstrated a heterozygous mutation (S1191L) of CFH, the gene coding complement factor H (CFH). The child suffered many episodes of HUS, each treated with plasma exchange. In time, despite initiation of a prophylactic regimen of plasma exchange, his renal function declined significantly. At the age of 4 yr he received a (split liver) combined liver-kidney transplant (LKT) with preoperative plasma exchange and enoxaparin anticoagulation. Initial function of both grafts was excellent and is maintained for nearly 2 yr.Conclusions: This report adds to the small but growing number of individuals in whom LKT has provided a favorable outcome for aHUS associated with CFH mutation, expands the technique of using a split liver graft, and describes the unique histologic features of subclinical liver disease in HUS.

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Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15

Cited by 115 publications

References 29 publications

Complement Factor H: Using Atomic Resolution Structure to Illuminate Disease Mechanisms

Complement Factor H: Using Atomic Resolution Structure to Illuminate Disease Mechanisms

C3 Glomerulopathy

Successful Split Liver-Kidney Transplant for Factor H Associated Hemolytic Uremic Syndrome

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