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Abstract: TH-PO479

Adult Male Patient of C1q Nephropathy with Heterozygous Pathogenic COL4A4 Variant

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Konishi, Kasumi, St. Luke's International Hospital, Tokyo, Japan
  • Fujimaru, Takuya, St. Luke's International Hospital, Tokyo, Japan
  • Aizawa, Chiharu, St. Luke's International Hospital, Tokyo, Japan
  • Kadota, Nozomi, St. Luke's International Hospital, Tokyo, Japan
  • Ito, Yugo, St. Luke's International Hospital, Tokyo, Japan
  • Nagahama, Masahiko, St. Luke's International Hospital, Tokyo, Japan
  • Taki, Fumika, St. Luke's International Hospital, Tokyo, Japan
  • Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan
  • Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan
  • Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan
  • Nakayama, Masaaki, St. Luke's International Hospital, Tokyo, Japan
Introduction

Autosomal dominant Alport syndrome (ADAS) is a disease with heterozygous pathogenic COL4A3 or COL4A4 variants.
ADAS is considered to have a better renal prognosis than X-linked Alport syndrome and less likely to develop focal and segmental glomerulosclerosis. However, ADAS could predispose to IgA glomerulonephritis (IgAN). We report an adult male patient of C1q nephropathy with ADAS.

Case Description

A 47-year-old man admitted our hospital for renal biopsy. He had hematuria and proteinuria since childhood. Six years before admission, he had hypertension and chronic kidney disease (serum Cr was around 2.5 mg/dL). His maternal grandmother, maternal aunt, son, and daughter had hematuria. No one, including him, suffered from hearing loss. One year before admission, his renal function deteriorated (Cr 3.37 mg/dL) and severe proteinuria appeared (5–7 g/day). Renal biopsy showed that 25% of glomeruli had global sclerosis and 60% had segmental glomerulosclerosis. Immunofluorescence shows global granular mesangial staining for C1q and IgM. Electron microscope revealed diffuse intra-membranous deposits with GBM thickening. Genetic analysis showed that he had heterozygous pathogenic variant in COL4A4 (c.2510G>C: p.Gly837Ala). We diagnosed him as C1q nephropathy with ADAS and started 1 mg/kg of corticosteroid for C1q nephropathy. We added cyclosporine after 1 month of treatment due to refractory proteinuria. However, because cyclosporine worsened renal function and he suffered from avascular necrosis of femoral head, immunosuppressive therapy was tapered.

Discussion

As far as we know, this is the first case of C1q nephropathy with ADAS. ADAS may also predispose to glomerulonephritis other than IgAN. Additionally, concomitant glomerulonephritis could worsen renal prognosis in ADAS patients.