Introduction:
IgA Nephropathy (IgAN) is the most common primary glomerulopathy worldwide. Significant advances have been made in understanding its pathophysiology and developing newer treatments. The accuracy of the International Risk-Prediction Tool in IgAN (IRP-IgAN) has been validated. However, the prognostic impact of extracapillary proliferation, particularly when affecting less than 25% of glomeruli, remains under investigation.
Methods:
Single-center retrospective observational cross-sectional study of patients with an histological diagnosis of IgAN between 2015 and 2023. The IRP-IgAN tool was used for patient stratification. Data on demographics, clinical presentation, histological characteristics, and follow-up were collected.
Results:
Over the eight-year period, 28 patients were diagnosed with IgAN. Mean age was 46 years (±12.2), 71.4% being male, predominantly Caucasian, with two patients of Asian and African descent, respectively. At presentation, 71.4% had hypertension, 14.3% presented with rapidly progressive renal insufficiency and 14.3% presented with nephrotic syndrome. Two patients (7.1%) required renal replacement therapy (RRT) at presentation. Mean GFR was 55.3 ml/min (±31.9), and mean protein-to-creatinine ratio was 2.42 g/g (±2.41). Hematuria was present in 82.1%, while C3 consumption was observed in one patient; 10 patients had isolated elevated IgA levels. Mean time between the first symptoms or documented clinical features and kidney biopsy was 2.9 years (±3.78). Regarding the MEST-C score, 71.4% had mesangial hypercellularity in >50% of the glomeruli (M1), 25% had endocapillary hypercellularity (E1), 17% had segmental glomerulosclerosis in at least one glomerulus (S1), 7% had interstitial fibrosis or tubular atrophy in 25-50% of the cortical area (T1), and 11% in >50% (T2). Additionally, 17.9% had crescents in <25% of the glomeruli (C1), and 2.6% in >25% (C2). Fibrinoid necrosis was noted in 7.1% of patients. IgA deposition in the mesangium on immunofluorescence was universal, and 64.3% had C3 co-staining. By the time of the clinical presentation diagnosis, half of the patients (46,4%) were already on ACEI or ARB and nearly all (92,9%) once diagnosis was established. SGTL-2 inhibitors were started in 42,9% of the patients. Eight patients started immunosuppression, all with corticosteroids, one patient was additionally under oral cyclophosphamide and another one under MMF. Using the IRP-IgAN, patients were stratified into low (35.7%), intermediate (10%), and high risk (8%) categories for kidney disease progression (GFR decline >50%) or ESKD. After a mean follow-up of 0.53 (±0.34) years, 28.6% (n=8) of patients required RRT. Six patients lost follow-up. Three patients died within a mean time of 1.2 years post-diagnosis, one due to immunosuppression-related adverse events. An association was found between higher risk group and progression to ESKD (p<0.001). However, the presence of crescents in less than 25% of glomeruli was not associated with worse renal outcomes.
Conclusions:
Supportive care in IgAN, even with new antiproteinuric approach, is insufficient for patients at high and intermediate risk. The IRP-IgAN tool is valuable for predicting kidney disease progression and the need for renal replacement therapy. The risk of progression to ESKD is indeed heterogeneous, necessitating close follow-up for these patients and novel therapies propose.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.