# IgA Nephropathy With Membranoproliferative Pattern and Resistance to Immunosuppressive Therapy in Two Patients With Cofactor I Pathogenic Variant

## TL;DR

Two IgA nephropathy patients with a rare CFI gene variant showed kidney damage patterns and treatment resistance, highlighting the need for detailed genetic and clinical analysis.

## Contribution

Reports two novel cases of IgAN with CFI pathogenic variants and membranoproliferative features, not previously documented.

## Key findings

- Patients showed membranoproliferative pattern and isolated C3 hypocomplementemia.
- Both patients had resistance to immunosuppressive therapy and a family history of kidney disease.
- Pathogenic CFI variants were identified, suggesting a role in IgAN with TMA-like features.

## Abstract

Complement system (CS) overactivation is one of the main causes of kidney damage in IgA nephropathy (IgAN), and it mainly involves the alternative pathway (AP). Additionally, pathogenic complement variants in CS‐related genes are reported in IgAN with associated thrombotic microangiopathy (TMA). Here we report two patients with IgAN presenting membranoproliferative pattern, isolated C3 hypocomplementemia, resistance to multiple lines of immunosuppressive therapy, familiarity for proteinuric chronic kidney disease and pathogenic rare variants in cofactor I (CFI). To the best of our knowledge, no other cases of IgAN patients with a similar phenotype and genotype were previously reported in the literature. This work highlights the essential role of deep phenotyping and genotyping in providing tailored treatment strategies in IgAN patients.