Targeting complement in IgA nephropathy

Caravaca-Fontán, Fernando; Gutiérrez, Eduardo; Sevillano, Ángel M; Praga, Manuel

doi:10.1093/ckj/sfad198

Cited by 16 publications

(6 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study has the major limitation of a small sample size, which warrants for larger studies. However, low sC3 at the time of biopsy emerges as a clear predictor of CKD progression, strongly supporting the crucial role of complement overactivation/dysregulation as a driver of progression towards ESKD, further highlighting the rationale of ongoing pharmacological trials of complement blockade in IgAN (20).…”

Section: Discussionmentioning

confidence: 94%

The Relation Between C3 Hypocomplementemia, Thrombotic Microangiopathy And End-Stage Kidney Disease In Iga Nephropathy

Rossi,

Ricco,

Pisani

et al. 2024

Preprint

View full text Add to dashboard Cite

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN causes end-stage kidney disease (ESKD) in 20–40% of all cases. The activation of the complement system by pathological circulating IgAs, which is often associated with low serum C3 levels (LowC3), seems to play a crucial role. Previous studies have shown an association between histological evidence of TMA, which is the result of alternative complement activation, and poor outcome. However, it is not known to what extent the decrease in serum C3 levels reflects ongoing TMA injury. Our study aimed at assessing the association of LowC3 and ESKD and whether this association reflects ongoing TMA. We enrolled all patients with biopsy-proven IgAN and followed-up patients until last visit, ESKD or death. Of the 56 patients included in the study, 12 (21%) presented low serum C3 (LowC3) at the time of renal biopsy. TMA was significantly more frequent in the LowC3 group [7/12 (58%) vs 9/44 (20%), p=0.02]. After adjusting for potential confounders, LowC3 was strongly associated with an increased hazard of ESKD (hazard ratio [HR]: 5.84 [95%CI: 1.69,20.15; P=0.005). The association was not affected by adjusting for TMA. The estimated overall proportion of the relation between C3 and ESKD mediated by TMA was low and not statistically significant. Our study provides evidence that C3 hypocomplementemia is associated with an increased risk of ESKD with mechanisms that are largely independent from TMA.

show abstract

Section: Discussionmentioning

confidence: 94%

The Relation Between C3 Hypocomplementemia, Thrombotic Microangiopathy And End-Stage Kidney Disease In Iga Nephropathy

Rossi,

Ricco,

Pisani

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Our study has the major limitation of a small sample size, which warrants larger studies. However, low sC3 at the time of biopsy emerges as a clear predictor of CKD progression [29,30], strongly supporting the crucial role of complement overactivation/dysregulation as a driver of progression towards ESKD, further highlighting the rationale of ongoing pharmacological trials of complement blockade in IgAN [31].…”

Section: Discussionmentioning

confidence: 94%

C3 Hypocomplementemia Predicts the Progression of CKD towards End-Stage Kidney Disease in IgA Nephropathy, Irrespective of Histological Evidence of Thrombotic Microangiopathy

Rossi,

Ricco,

Pisani

et al. 2024

JCM

View full text Add to dashboard Cite

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN causes end-stage kidney disease (ESKD) in 30–40% of all cases. The activation of the complement system by pathological circulating IgAs, which is often associated with low serum C3 levels (LowC3), seems to play a crucial role. Previous studies have shown an association between histological evidence of TMA, which is the result of alternative complement activation, and poor outcomes. However, it is not known to what extent the decrease in serum C3 levels reflects ongoing TMA injury. Our study aimed at assessing the association between LowC3 and ESKD and whether this association reflects ongoing TMA. Methods: We enrolled all patients with biopsy-proven IgAN and followed-up patients until their last visit, ESKD, or death. Results: Of the 56 patients included in the study, 12 (21%) presented low serum C3 (LowC3) at the time of renal biopsy. TMA was significantly more frequent in the LowC3 group [7/12 (58%) vs. 9/44 (20%), p = 0.02]. After adjusting for potential confounders, LowC3 was strongly associated with an increased hazard of ESKD (hazard ratio [HR]: 5.84 [95%CI: 1.69, 20.15; p = 0.005). The association was not affected by adjusting for TMA. The estimated overall proportion of the relation between C3 and ESKD mediated by TMA was low and not statistically significant. Conclusions: Our study provides evidence that C3 hypocomplementemia is associated with an increased risk of ESKD through mechanisms that are largely independent from TMA.

show abstract

“…Understanding regional variations in IgAN patient survival is essential, especially with the development of various treatment classes in advanced trials. These include endothelin receptor antagonists, B-celldirected treatments, complement system inhibitors, SGLT2 inhibitors like dapagliflozin, and immunomodulatory drugs such as hydroxychloroquine [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Mortality in IgA Nephropathy: A Long-Term Follow-Up of an Eastern European Cohort

Ștefan,

Zugravu,

Stancu

2024

Medicina

View full text Add to dashboard Cite

Background and Objectives: IgA nephropathy (IgAN), the most common primary glomerulonephritis, has been extensively studied for renal outcomes, with limited data on patient survival, particularly in Eastern Europe. We aimed to investigate the long-term survival rate of patients with IgAN and the associated risk factors in an Eastern European cohort. Materials and Methods: We conducted a retrospective analysis of 215 IgAN patients (median age 44, 71% male) diagnosed at a Romanian tertiary center between 2010 and 2017. We assessed clinical and pathological attributes, including the Charlson comorbidity index, the prevalence of diabetes, renal function, and treatment with renin-angiotensin-system inhibitors (RASIs). Results: Over a median 7.3-year follow-up, 20% of patients died, mostly due to cardiovascular diseases. Survival rates at 1, 5, and 10 years were 93%, 84%, and 77%, respectively. Deceased patients had higher Charlson comorbidity index scores, greater prevalence of diabetes, and poorer renal function. They were less frequently treated with RASIs and more frequently reached end-stage kidney disease (ESKD). Conclusions: We report a 20% mortality rate in our Eastern European IgAN cohort, primarily due to cardiovascular diseases. Death correlates with increased age, comorbidity burden, decreased renal function at diagnosis, and the absence of RASI use. RASI treatment may potentially improve survival, highlighting its importance in managing IgAN.

show abstract

Targeting complement in IgA nephropathy

Cited by 16 publications

References 77 publications

The Relation Between C3 Hypocomplementemia, Thrombotic Microangiopathy And End-Stage Kidney Disease In Iga Nephropathy

The Relation Between C3 Hypocomplementemia, Thrombotic Microangiopathy And End-Stage Kidney Disease In Iga Nephropathy

C3 Hypocomplementemia Predicts the Progression of CKD towards End-Stage Kidney Disease in IgA Nephropathy, Irrespective of Histological Evidence of Thrombotic Microangiopathy

Mortality in IgA Nephropathy: A Long-Term Follow-Up of an Eastern European Cohort

Contact Info

Product

Resources

About