IgA Vasculitis Nephritis in a Patient With Alport Syndrome: An Association or a Just a Coincidence?

ABSTRACT

Introduction: Alport syndrome is a rare inherited disorder manifested by persistent microscopic hematuria, nephritis, sensorineural deafness, and ocular abnormalities. IgA nephropathy has been reported in a small percentage of patients with Alport syndrome, however, IgA vasculitis nephritis (IgA-VN) has not been reported. We report a rare case of Alport syndrome with crescentic IgA-VN. Case Description A 48-year-old male with a history of deep vein thrombosis (on warfarin) was followed by nephrology clinic for chronic kidney disease (CKD). Due to concerns of risks associated with holding warfarin, genetic testing was done in lieu of kidney biopsy which was positive for a hemizygous pathogenic mutation in the X-linked COL4A5 gene for Alport Syndrome. He did not have any sensorineural deafness, ocular abnormalities, or a family history of kidney disease. He was admitted to the hospital for acute kidney injury (creatinine 14.6 mg/dL from a baseline of 2 mg/dL), nephrotic range proteinuria (microalbumin/creatinine ratio 3,689 mg/g, normal < 200 mg/g) and microscopic hematuria. A full serological workup was unremarkable. He developed newonset bilateral lower extremity purpura which was biopsied showing leukocytoclastic IgA Vasculitis. Kidney biopsy showed IgA-dominant glomerulonephritis with 70% interstitial fibrosis and tubular atrophy, 80% crescents, and no electron microscopy findings suggestive of Alport Syndrome. Four days after the kidney biopsy, he was started on dialysis and immunosuppression (IV Methylprednisolone and Cyclophosphamide) after ruling out infection. He was discharged with a plan to continue immunosuppression and dialysis as an outpatient. Unfortunately, he developed COVID-19 prompting a delay in further immunosuppressive therapy. Discussion(s) Although extremely rare, mutations in the COL4A3, COL4A4, and COL4A5 genes have been implicated in cases of familial IgA Nephropathy and Alport Syndrome. We report a novel patient with IgA-VN and COL4A5 variant. It is unclear whether his underlying COL4A5 variant contributed to his severe presentation with IgAVN. Genome-wide association studies in patients with coexisting pathologies are needed to discover both diseases' possible common genetic connection.