Prognostication for C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

Caravaca-Fontán, Fernando; Praga, Manuel

doi:10.2215/cjn.05490522

Cited by 2 publications

(4 citation statements)

References 13 publications

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“…We demonstrate, as shown previously, that eGFR and proteinuria are strongly associated with long-term outcomes. 18,20 However, our analysis also showed stronger relationships of these parameters at 6-24 months with long-term risk of KF, with the predictive value of proteinuria (and changes in proteinuria) particularly significant. We show associations between both eGFR percentage change and eGFR slope at 2 years and KF.…”

Section: Discussionmentioning

confidence: 48%

“…16 Finally, the C3G GLOSEN investigators demonstrated a ≥50% decrease in proteinuria over course of follow-up or within 6 and 12 months was associated with lower risk of KF. 20 While case series and small observational studies have suggested a potential benefit of corticosteroids and mycophenolate, it is not known why some patients respond and others do not, and long-term outcomes remain poor. 21,22 The community therefore awaits with great expectation the results of several ongoing complement inhibition trials.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Predictors of Long-term Outcomes in C3 Glomerulopathy and Immune-Complex Membranoproliferative Glomerulonephritis within the UK RaDaR Registry

Masoud,

Wong,

Downward

et al. 2024

Preprint

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Background C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare disorders that often result in kidney failure over the long-term. While there is much interest in the therapeutic potential of complement inhibition, the limited duration and necessarily small size of controlled trials, means there is a need to define how well short-term changes in eGFR and proteinuria predict clinically important outcomes such as kidney failure. We aimed to address this using longitudinal data from the UK National Registry of Rare Kidney Diseases (RaDaR). Methods 287 patients with biopsy-proven C3G (135, 47%) or IC-MPGN (152, 53%) were included. Analyses of kidney survival were conducted using Kaplan Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope. Results 85/135 (63%) C3G and 107/152 (70%) IC-MPGN patients reached kidney failure over follow-up after a median of 9.7 years (95% CI 7.6-12.4). Median time to first allograft loss following transplantation was 4.9 years (95% CI 1.7-6.5). Kidney survival was strongly associated with eGFR at baseline and 12-month timepoints (p<0.001). Proteinuria at diagnosis, although high, was not associated with long-term kidney failure risk. In contrast, both a time averaged 0.44g/g (50mg/mmol) and 50% reduction in UPCR at 12 months (from either diagnosis or 6 months) was strongly associated with a lower risk of kidney failure (≤0.002). Most notably those with a UPCR <0.88g/g (<100mg/mmol) at 12 months had a substantially lower rate of progression to kidney failure (HR adjusted for eGFR 0.13 (95% CI 0.03-0.56), p=0.007). Conclusions We quantified the relationships between early changes in both eGFR and proteinuria with long-term kidney survival. We demonstrate that proteinuria a short time after diagnosis is a strong predictor of long-term outcomes and that a UPCR <0.88g/g (<100mg/mol) at 1 year is associated with a substantially lower kidney failure risk.

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Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Clinical Predictors of Long-term Outcomes in C3 Glomerulopathy and Immune-Complex Membranoproliferative Glomerulonephritis within the UK RaDaR Registry

Masoud,

Wong,

Downward

et al. 2024

Preprint

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“…In this regard, there is a need in clinical settings not only to make prognoses but also to assist in decision‐making regarding the most appropriate therapeutic agents 267 . When developing novel treatments for complement‐driven diseases, it is important to consider which component of the cascade may be the most appropriate target.…”

Section: Discussionmentioning

confidence: 99%

“…3 In this regard, there is a need in clinical settings not only to make prognoses but also to assist in decision-making regarding the most appropriate therapeutic agents. 267 When developing novel treatments for complement-driven diseases, it is important to consider which component of the cascade may be the most appropriate target. For example, although inhibition of C5 impedes the C5a and MAC formation, this inhibition does not block the pro-inflammatory and opsonization actions of C3, because C5 acts downstream of C3 as part of the terminal cascade (Figure 1).…”

Section: Con Clus Ionsmentioning

confidence: 99%

Kidney diseases

Daina

Cortinovis

2022

Immunological Reviews

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The complement system, a central part of the innate immunity that serves as a first line of defense against foreign and altered host cells, is an extremely effective cell-killing and inflammation-provoking pathway. However, complement activation is a double-edged sword because uncontrolled stimulation can be highly detrimental to host tissues. [1][2][3] In order to avoid self-damage, a plethora of inhibitory mechanisms are known to prevent overwhelming activation at all stages of the complement cascade. The alternative pathway (AP) of complement is particularly significant for survival against invading pathogens and can be triggered by several other conditions, such as trauma, surgery, or pregnancy. Inappropriate AP activation may be

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Prognostication for C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

Cited by 2 publications

References 13 publications

Clinical Predictors of Long-term Outcomes in C3 Glomerulopathy and Immune-Complex Membranoproliferative Glomerulonephritis within the UK RaDaR Registry

Clinical Predictors of Long-term Outcomes in C3 Glomerulopathy and Immune-Complex Membranoproliferative Glomerulonephritis within the UK RaDaR Registry

Kidney diseases

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