Clinicopathological Significance and Renal Outcomes of Light Microscopic Patterns in Complement Component 3 Glomerulopathy

Wani, Asif Sadiq; Zahir, Zafirah; Gupta, Amit; Agrawal, Vinita

doi:10.1159/000506290

Cited by 3 publications

(2 citation statements)

References 17 publications

(26 reference statements)

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“…With this mechanism, it is suggested that eculizumab may be an effective treatment of C3G [16,[62][63][64]. The etiologies of C3G can be classified into genetic causes (mutations/variants resulting in alternative complement pathway abnormalities) and acquired causes (C3Nef/autoantibodies) with possible triggering factors including infections, monoclonal immunoglobulin, and autoimmune diseases [16,26,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][85][86][87][88].…”

Section: Discussionmentioning

confidence: 99%

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Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review

et al. 2020

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Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. Methods: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). Results: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12–57%) after eculizumab, 42% (95% CI: 2–89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50–100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5–46%) after eculizumab, 56% (95% CI: 6–100%) after TPE, and 70% (95% CI: 24–100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0–100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7–64%) and 53% (95% CI: 28–77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. Conclusions: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.

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Section: Discussionmentioning

confidence: 99%

“…The prevalence in the United States (US) is estimated at 5 cases per million [21]. Although it is a rare disease, patients with C3G can develop worsening kidney function leading to end-stage kidney disease (ESKD) in up to 50% of patients [22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review

et al. 2020

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Pediatric C3 glomerulopathy: a 12-year single-center experience

et al. 2020

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C3 glomerulonephritis associated with ANCA positivity: a case report

Liu

Yang

et al. 2021

BMC Nephrol

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Background C3 glomerulopathy (C3G) is a recent disease classification that is characterized by the presence of glomerular deposits (composed of C3) in the absence of significant amounts of immunoglobulin and comprises dense deposit disease and C3 glomerulonephritis (C3GN). Most C3GN manifests as membranoproliferative, mesangial proliferative glomerulonephritis patterns via light microscopy. Pure membranous nephropathy (MN)-like glomerular lesions are rare manifestations of C3GN. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also seldomly reported to be positive in C3GN. Herein, we report the case of a C3GN patient presenting with an MN-like glomerular pattern with ANCA positivity. Case presentation A 68-year-old woman was admitted to a local hospital with elevated serum creatinine for two weeks. Laboratory tests showed a hemoglobin level of 85 g/L. Urinalysis was positive for 2 + protein and 360 RBCs/HPF. Blood biochemistry analysis revealed the following concentrations: albumin, 30.3 g/L; globulin, 46.2 g/L; blood urea nitrogen, 19.9 mmol/L; and serum creatinine, 234 µmol/L. The serum C3 level was 0.4950 g/L, and the serum C4 level was 0.1050 g/L. The direct Coombs test was positive. Serologic testing for ANCA revealed the presence of p-ANCA (1:10) by indirect immunofluorescence microscopy assay, as well as the presence of PR3 1.2 (normal range < 1) and MPO 3.5 (normal range < 1) by enzyme immunoassay. Renal biopsy sample pathology showed 2/6 cellular crescents and thickened glomerular basement membranes. Immunofluorescence testing revealed only diffuse, finely granular depositions of C3 along the glomerular capillary walls in frozen and paraffin-embedded tissue sections. Electron microscopy demonstrated the presence of subepithelial electron-dense deposits, similar to those that are observed in membranous nephropathy. Corticosteroid and cyclophosphamide were administered, with a subsequent improvement in renal function. Conclusions We present the rare case of a patient with MN-like C3GN with ANCA positivity. C3GN with ANCA positivity may be represented by more crescents, severe renal dysfunction and more extrarenal manifestations. More cases are needed to elucidate the clinicopathologic features and optimal treatments of these patients.

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Clinicopathological Significance and Renal Outcomes of Light Microscopic Patterns in Complement Component 3 Glomerulopathy

Cited by 3 publications

References 17 publications

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review

Pediatric C3 glomerulopathy: a 12-year single-center experience

C3 glomerulonephritis associated with ANCA positivity: a case report

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