Crescentic Phase of Alport Syndrome: A Rare Glimpse into Rapid Progression

Introduction: Crescentic glomerulonephritis (GN) represents a rare histologic finding in Alport syndrome, especially among adults. We report a rare case of progressive chronic kidney disease (CKD) due to crescentic GN in a 22-year-old man with Alport syndrome. Case Description: This 22-year-old man with Alport syndrome complicated by bilateral hearing loss and CKD first presented to the hospital with hyperkalemia. He was diagnosed at age 8 via kidney biopsy showing glomerular basement membrane abnormalities consistent with Alport syndrome. He presented to Nephrology at his baseline serum creatinine of 1.8 mg/dL with estimated glomerular filtration rate (eGFR) of 51 ml/min due to hyperkalemia of 6.7 mmol/L. His hyperkalemia was medically managed without stopping enalapril. Over the next 12 months, his kidney function steadily declined with stable proteinuria of 5 g/g without nephrotic syndrome. He often missed clinic appointments and laboratory draws, which complicated management. Within 12 months, his serum creatinine rose to 9 mg/dL with eGFR was 7 ml/min, prompting admission to the hospital for initiation of dialysis. While hospitalized, he underwent kidney biopsy which revealed early segmental fibrocellular crescents, marked interstitial fibrosis and tubular atrophy (80%), and electron microscopy findings of extensive thinning and lamellation of the glomerular basement membranes consistent with Alport syndrome. Genetic testing confirmed hemizygous COL4A5 mutation. Serum antineutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibodies were sent and resulted negative. The relatively rapid progression of CKD to end-stage kidney disease was attributed to crescentic GN secondary to Alport syndrome, and he is currently awaiting kidney transplantation. Discussion: Crescentic GN is a rare histologic finding among patients with Alport syndrome. The few existing case reports often describe pediatric patients with nephritic or nephrotic syndrome. This patient had a more gradual presentation with progressively worsening CKD without nephritic or nephrotic syndrome. Crescentic GN is likely underdiagnosed in this population as patients don’t usually require biopsy for diagnosis and rarely undergo repeat biopsy. Given its rarity, it is unclear whether this entity should be treated different than non-crescentic Alport syndrome.Native kidney biopsy specimen demonstrating glomerulus with mesangial expansion, mesangial hypercellularity, and an early fibrocelluar crescent by light microscopy with Periodic acid–Schiff stain.