Immunosuppressive Treatment in C3 Glomerulopathy: Is it Really Effective?

Abstract

Background: C3 glomerulopathy (C3GP) is a recently identified and described disease that has a high risk of progressing into end-stage renal disease. We aimed to evaluate the effects of various immunosuppressive regimens on C3GP progression because there are conflicting data on the treatment modalities. Methods: In this retrospective study of 66 patients with C3GP, 27 patients received mycophenolate mofetil (MMF)-based treatment, 23 received non-MMF-based treatment (prednisolone or cyclophosphamide), and 16 received conservative care. The study groups were compared with each other with specific focus on primary outcomes defined as (1) kidney failure and (2) estimated glomerular filtration rate (eGFR) decline ≥50% from the baseline value. Results: Overall, 17 (25.8%) patients reached the primary outcome after a median period of 28 months. The number of patients who reached the primary outcome were similar among the study groups (MMF-based: 8/27 [29.6%], non-MMF-based: 4/23 [17.4%], and conservative care: 5/16 [31.3%], p = 0.520). In the Cox regression analysis, age (HR 0.912, p = 0.006), eGFR (HR 0.945, p = 0.001), and proteinuria levels (HR 1.418, p = 0.015) at the time of biopsy, percentage of crescentic (HR 1.035, p = 0.001) and sclerotic glomeruli (HR 1.041, p = 0.006), severity of interstitial fibrosis (HR 1.981, p = 0.048), as well as no remission of proteinuria (HR 2.418, p = 0.002) predicted the primary outcome. Conclusion: Although patients receiving immunosuppressive treatments had higher proteinuria and lower serum albumin at baseline, there were no differences between these patients and those receiving conservative care alone in proteinuria remission or in the decline of renal function. Younger age, higher proteinuria, lower eGFR, and the presence of crescentic and sclerotic glomeruli, severity of interstitial fibrosis, and no remission of proteinuria predicted the progression of kidney disease.

Evaluation of Clinical, Laboratory and Treatment Modalities in C3 Glomerulopathy: Single Center Experience

“…al. showed that MMF based and non-MMF based cellular immunosuppressant treatments have similar clinical success to treat C3GP [17]. Similar to our study, they found that MMF based treatment had 40.7% complete remission rates.…”

“…Similarly, the need for RRT at the time of the diagnosis was determined to be predictor of ESRD. In the previous studies, age, nephrotic range proteinuria, and low eGFR were suggested as an independent predictor for kidney failure [7,14,17]. On the contrary, this study could not show nephrotic range proteinuria as a predictor of ESRD.…”

Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

“…Treatment of active disease with MMF and corticosteroids has shown promise in 2 retrospective case series, 44,45 but was not found to be effective in a third case series in patients with more severe baseline kidney disease. 46 For patients with C3G and monoclonal gammopathy, a recent retrospective case series found superior hematologic and renal response rates, as well as renal survival, for patients treated with clone-directed chemotherapy compared with conservative or immunosuppressive treatment. 47 Monoclonal Gammopathies of Renal Significance Pathogenesis.…”

A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease

“…Because of the low frequency of C3 GP, patient cohort studies are important and can provide valuable information regarding clinical presentation, pathological and laboratory features, and their correlation with disease outcomes. Table 1 shows the clinical and laboratory data of patients affected by C3 GP in different cohorts, as described by many investigators [23,25,29,[31][32][33][34][35][36]. C3 GP involves mainly children and young people and may develop after an infectious episode (i.e., streptococcal infection) of the upper respiratory tract.…”

“…Patients with nephrotic syndrome and a decline in renal function should receive oral CYC or MMF plus a low dose of daily or alternate-day corticosteroids [33]. If despite this treatment nephrotic syndrome persists or the renal function impairs, tacrolimus or RTX can be considered although the percentage of its beneficial effect is very low [35,70].…”