Is There a Role for IgA/C3 Ratio in IgA Nephropathy Prognosis? An Outcome Analysis on An European Population.

INTRODUCTION: Serum immunoglobulin A (IgA)/C3 ratio has been reported as a predictor of histological lesions and prognosis in asian patients with IgA nephropathy (IgAN). Since its validity in other populations is unclear, we aimed to evaluate the relationship between IgA/C3 ratio and renal outcome in Caucasian European patients with biopsy-proven IgAN. METHODS: We conducted a retrospective, observational study on 95 patients with primary IgAN patients diagnosed between 2010 to 2017 (70% male, age 41 (34 to 49) years, eGFR 39.4 (25.2 to 56.5) mL/ min, proteinuria 1.7 (0.8 to 3.0) g/g). The primary study composite end-point was doubling of serum creatinine, ESRD (dialysis or renal transplant) or death, whichever came first. RESULTS: Median follow-up was 30 (95% CI: 27.5 to 32.4) months; 11% developed ESRD, 10% experienced serum creatinine doubling, and 1% died. The endpoint was reached by 21% of the patients. They had lower eGFR, higher proteinuria and hematuria, and lower serum albumin. The distribution in Oxford classes was alike. The AUROC for IgA/C3 ratio was 0.60 (95% CI: 0.45 to 0.74) and generated an optimal cut-off of 2.91 (sensitivity 68%, specificity 55%). The mean event-free survival of the whole cohort was 5.2 (95% CI: 4.7 to 5.8) years. Patients with IgA/C3 ratio < 2.9 had a tendency to better renal survival (P > .05). In Cox proportional hazard ratio model, the independent predictors of a poorer eventfree survival were higher serum creatinine, higher proteinuria and increased IgA/C3 ratio, while renin angiotensin system inhibitors predicted better outcome. CONCLUSION: Our study reports evidence that supports IgA/C3 ratio as a reasonable predictor of IgAN prognosis in European patients.

"Associated" or "Secondary" IgA nephropathy? An outcome analysis.

BACKGROUND: Whether differences in outcome between primary (pIgAN) and secondary IgA nephropathy (sIgAN) exist is uncertain. METHODS: We conducted a retrospective, observational study that included all histologically diagnosed IgAN patients between 2010-2017 (N = 306), 248 with pIgAN and 58 with sIgAN. To obtain samples with similar risk of progression, sIgAN patients were grouped as liver disease and autoimmune/viral disease and propensity score matched to corresponding pIgAN samples. Univariate (Kaplan Meier) and multivariate time-dependent (Cox modelling) analyses were performed to identify predictors of the composite end-point (doubling of serum creatinine, end-stage kidney disease or death). RESULTS: Of the whole cohort, 20% had sIgAN (6% alcoholic cirrhosis, 6% autoimmune disease and 8% viral infections). sIgAN patients were older, had more comorbidities, lower proteinuria and higher haematuria, but similar distribution in MESTC lesions and eGFR as those with pIgAN. They reached the end-point in similar proportions with those with pIgAN (43 vs. 30%; p = 0.09) but their mortality was higher (19 vs. 3%; p<0.0001). Both in unmatched (HR 0.80, 95%CI 0.42-1.52; p = 0.5) and matched samples (log-rank test: liver disease-IgAN vs. pIgAN, p = 0.1; autoimmune/viral-IgAN vs. pIgAN, p = 0.3), sIgAN was not predictive for end-point. In analyses restricted only to sIgAN, those with viral infections (HR, 10.98; 95% CI, 1.12-107.41; p = 0.03) and lower eGFR (HR, 0.94; 95%CI, 0.89-0.98; p = 0.007) had a worse prognosis. Immunosuppression did not influence outcome. CONCLUSIONS: The differences in MESTC score and outcome between pIgAN and sIgAN seems to be minimal, suggesting that "associated" describes better than "secondary" the relationship among the two. Immunosuppression did not to influence outcome of sIgAN.