First Treatment of Relapsing Rapidly Progressive IgA Nephropathy With Eculizumab After Living Kidney Donation: A Case Report

Herzog, Anna Laura; Wanner, Christoph; Amann, Kerstin; Lopau, Kai

doi:10.1016/j.transproceed.2017.02.044

Cited by 32 publications

(20 citation statements)

References 17 publications

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“…Severe vascular lesions and shear stress-induced endothelial injury have been shown to activate the classical pathway, and several proteins in the coagulation cascade have bi-directional interactions with the complement system, causing a vicious cycle that can be particularly harmful in patients who lack adequate complement regulation [49,50]. This is particularly interesting given the recent case reports showing that complement-inhibiting therapeuticswhich are known to benefit patients with systemic microangiopathy-are also beneficial to at least some patients with IgA nephropathy, including patients with complementmediated microangiopathy [15][16][17][18]51]. In our study, there were 11 patients with liver disease prior to the diagnosis of IgA nephropathy or IgA vasculitis with nephritis.…”

Section: Discussionmentioning

confidence: 99%

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Complement-mediated microangiopathy in IgA nephropathy and IgA vasculitis with nephritis

et al. 2019

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Complement factor C4d was recently observed in renal biopsies from patients who had IgA nephropathy and a poor prognosis. We previously reported that C4d is a common denominator in microangiopathies. In this retrospective cohort study, we investigated whether C4d is a marker of microangiopathy in both IgA nephropathy and IgA vasculitis with nephritis, and whether patients with C4d and microangiopathy have poor renal outcome. We examined 128 renal biopsies from adult and pediatric patients, including normotensive and hypertensive patients, who presented with IgA nephropathy or IgA vasculitis with nephritis. Biopsies were re-evaluated in accordance with the Oxford classification, scored for additional lesions, and stained for complement proteins using immunohistochemistry, including C4d and C5b-9. Clinical data were collected with a mean (±SD) follow-up period of 51 ± 39 months. Changes in estimated glomerular filtration rate over time were compared using linear mixed-effects models. Renal survival was analyzed using multivariable Cox regression. Microangiopathic lesions were present in 20% of all biopsies (23% and 9% of patients with IgA nephropathy and IgA vasculitis with nephritis, respectively). Microangiopathy was associated with C4d and C5b-9 deposits, a higher number of chronic lesions, and hypertension (all p < 0.05). Patients with C4d and microangiopathic lesions had significantly poorer renal survival than patients without these findings, corrected for hypertension (p < 0.01). In conclusion, patients with IgA nephropathy or IgA vasculitis with nephritis with a combination of C4d positivity and microangiopathy comprise a clinical subgroup with an increased number of chronic lesions, lower estimated glomerular filtration rate, and poorer renal survival, even when corrected for hypertension. These data suggest that complement activation is involved in the development of microangiopathy in patients with IgA nephropathy and IgA vasculitis with nephritis, and that complement-mediated microangiopathy contributes to disease progression.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, some patients with IgA nephropathy have been reported to have genetic deficiencies in complementregulatory proteins [7,[9][10][11][12][13][14]. Moreover, recent case reports suggest that some patients with IgA nephropathy may benefit from complement-inhibiting therapy [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Complement-mediated microangiopathy in IgA nephropathy and IgA vasculitis with nephritis

et al. 2019

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“…Identifying and understanding this heterogeneity of complement activity might be clinically important because we now have the ability to target complement activation at specific points in the activation sequence. For example, OMS721, a monoclonal antibody targeting MASP-2, was recently designated breakthrough therapy status for IgAN treatment; Eculizumab, a C5 inhibitor, has been used in recurrent 61 and progressive 62 , 63 IgAN; and factor D inhibitors are in clinical trials for C3 glomerulopathy. 64 …”

Section: Discussionmentioning

confidence: 99%

Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin–Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H–Related Protein-5 (FHR5) Deposition

Medjeral-Thomas

Troldborg

Constantinou

et al. 2018

Kidney International Reports

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IntroductionIgA nephropathy (IgAN) is characterized by glomerular deposition of galactose-deficient IgA1 and complement proteins and leads to renal impairment. Complement deposition through the alternative and lectin activation pathways is associated with renal injury.MethodsTo elucidate the contribution of the lectin pathway to IgAN, we measured the 11 plasma lectin pathway components in a well-characterized cohort of patients with IgAN.ResultsM-ficolin, L-ficolin, mannan-binding lectin (MBL)–associated serine protease (MASP)-1 and MBL-associated protein (MAp) 19 were increased, whereas plasma MASP-3 levels were decreased in patients with IgAN compared with healthy controls. Progressive disease was associated with low plasma MASP-3 levels and increased glomerular staining for C3b/iC3b/C3c, C3d, C4d, C5b-9, and factor H–related protein 5 (FHR5). Glomerular FHR5 deposition positively correlated with glomerular C3b/iC3b/C3c, C3d, and C5b-9 deposition, but not with glomerular C4d. These observations, together with the finding that glomerular factor H (fH) deposition was reduced in progressive disease, are consistent with a role for fH deregulation by FHR5 in renal injury in IgAN.ConclusionOur data indicate that circulating MASP-3 levels could be used as a biomarker of disease severity in IgAN and that glomerular staining for FHR5 could both indicate alternative complement pathway activation and be a tissue marker of disease severity.

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“…It has been proposed that it may also benefit patients with IgAN [15] who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide, and PE. Contrary eculizumab was not effective in treating IgAN recurrence after transplantation [16]. We believe that the present case provides proof of principle that complement inhibition by eculizumab may be beneficial for the treatment of a patient with aHUS associated with CFH mutation and partially with IgAN, considering the pathogenesis of the 2 diseases.…”

Section: Discussionmentioning

confidence: 69%

Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation and IgA Nephropathy: A Case Report Successfully Treated with Eculizumab

Nakamura

Anayama

Makino

et al. 2017

Nephron

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We present a rare case of IgA nephropathy in a patient who developed atypical hemolytic uremic syndrome (aHUS) associated with a complement factor H (CFH) gene mutation, and who was successfully treated with eculizmab. A 76-year-old man was admitted as the patients had thrombotic microangiopathies findings. The patient was treated with plasma exchange, hemodialysis and methylprednisolone. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 level was not decreased. Light microscopy findings were consistent with hemolytic uremic syndrome and immunofluorescence analysis revealed IgA and C3 were detected. Genetic analysis revealed that mutation of p.Arg1215Gln in CFH was identified. The diagnosis of aHUS was confirmed and eculizmab therapy was currently effective for 5 months.

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First Treatment of Relapsing Rapidly Progressive IgA Nephropathy With Eculizumab After Living Kidney Donation: A Case Report

Cited by 32 publications

References 17 publications

Complement-mediated microangiopathy in IgA nephropathy and IgA vasculitis with nephritis

Complement-mediated microangiopathy in IgA nephropathy and IgA vasculitis with nephritis

Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin–Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H–Related Protein-5 (FHR5) Deposition

Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation and IgA Nephropathy: A Case Report Successfully Treated with Eculizumab

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