Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Ștefan, Gabriel; Alamartine, Eric; Mariat, Christophe; Maillard, Nicolas

doi:10.1016/j.ekir.2023.11.005

Cited by 1 publication

(2 citation statements)

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“…The reason for the association of the intensity of C3 staining mainly with chronicity might be related to the late diagnosis of IgAN in our cohort (with a mean age at the moment of kidney biopsy of over 40 years, a high prevalence of renal events and a short time for progression to ESRD). Other studies have confirmed our findings showing an association of intense mesangial C3 deposition with chronic lesions (S1 or T1-2) [ 33 ]. The association of mesangial hypercellularity with mesangial C3 deposition should be interpreted in the context that complement activation represents a key driver of autoimmune-mediated kidney injury.…”

Section: Discussionsupporting

confidence: 92%

“…The lectin and alternative pathways of the complement system have emerged as key mediators of kidney injury in IgAN that paved the way for the development of complement pathway inhibitors [ 32 ]. Accordingly, several studies have outlined that serum level of complement components or glomerular deposition of their fragments may be associated with a worse renal outcome, although with conflicting results [ 33 ]. In our study, the intensity of complement activation was mainly associated with chronic lesions, while those with intense C3 staining had a worse renal survival and a higher eGFR decline.…”

Section: Discussionmentioning

confidence: 99%

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Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition

Obrișcă,

Mocanu,

Jurubiță

et al. 2024

BMC Nephrol

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Background There is a clear need to refine the histological assessment in IgA Nephropathy (IgAN). We sought to investigate the clinical significance of the light microscopy (LM) pattern of glomerular injury and of the intensity of mesangial C3 staining in IgAN. Methods We conducted a retrospective, observational study that included all patients with biopsy-proven primary IgAN that had at least 12 months of follow-up. The LM pattern of glomerular injury was reevaluated based on a modified HAAS classification. Mesangial C3 deposition by immunofluorescence (IF) staining was scored semi-quantitatively. The study primary composite endpoint was defined as doubling of serum creatinine or ESRD (dialysis, renal transplant or eGFR < 15 ml/min). The secondary study endpoint was eGFR decline per year. Results This cohort included 214 patients with IgAN (mean age, 41.4 ± 12.6 years), with a mean eGFR and median 24-h proteinuria of 55.2 ± 31.5 ml/min/1.73m2 and 1.5 g/day (IQR:0.8–3.25), respectively. The most frequent LM pattern was the mesangioproliferative (37.4%), followed by the sclerotic (22.5%) and proliferative/necrotizing patterns (21.4%). Regarding the IF findings, mild-moderate and intense mesangial C3 staining was present in 30.6% and 61.1% of patients, respectively. Those with sclerosing and crescentic patterns had the worst renal survival (5-year renal survival of 48.8% and 42.9%) and the highest rate of eGFR change/year (-2.32 ml/min/y and − 2.16 ml/min/y, respectively) compared to those with other glomerular patterns of injury. In addition, those with intense C3 staining reached the composite endpoint more frequently compared to those without intense C3 staining (35.5% vs. 21.4%, p = 0.04). After multivariate adjustment, patients with crescentic and sclerosing patterns had a 3.6-fold and 2.1-fold higher risk for the composite endpoint compared to those with mesangioproliferative pattern, while an intense mesangial C3 deposition being also associated with a worse renal outcome (HR, 3.33; 95%CI, 1.21–9.2). Conclusions We have shown that the LM pattern of glomerular injury and the intensity of mesangial C3 deposition might stratify more accurately the renal outcome in patients with IgAN.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%