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Abstract: PO1641

One Disease Cannot Exclude the Other: The Coexistence of IgA Nephropathy and Alport Syndrome

Session Information

Category: Trainee Case Report

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Patel, Jayesh B., University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Jenigiri, Sreedevi koppisetti, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Rastogi, Prerna, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Thomas, Christie P., University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
Introduction

Alport syndrome and IgA nephropathy (IgAN) have shared clinical characteristics such as persistent hematuria, proteinuria, and progressive renal failure. We describe a case that histologically was diagnosed as IgAN, genetic testing and segregation analysis confirmed the coexistence of Alport. The additional diagnosis came to light when the daughter, a kidney donor candidate presented with persistent microscopic hematuria (MH).

Case Description

A 61-year-old female with diabetes, hypertension and ESRD presented for evaluation of transplant candidacy. The patient was diagnosed with IgAN after a biopsy at age 50. A second biopsy at the age of 61 years, showed granular mesangial and para-mesangial IgA staining, foot process effacement and irregular thickening of the glomerular basement membrane (GBM). Her daughter presented for evaluation as a live kidney donor and reported MH. She had normal renal function and imaging. Cystoscopy and urine cytology were negative. To evaluate the hematuria further, her mother was first screened with a renal genetic panel, KidneySeq™ which demonstrated a likely pathogenic variant in the COL4A3 gene, c.361 G>A, p. Gly121Ser. The donor underwent focused screening and was positive for this familial variant. Subsequently obtained FH revealed that a maternal aunt had early onset deafness, and another had CKD. The donor’s daughter was found to have MH. The results suggested that both the transplant candidate and her daughter had a genetic diagnosis consistent with Alport type nephropathy.

Discussion

Pathogenic or likely pathogenic variants in COL4A3 and COL4A4 cause FSGS and AR and AD Alport syndrome. Up to 50% of causal variants are a substitution of glycine in the Gly-X-Y repeat sequence disrupting the triple helical structure of the collagen fiber and causing anomalies in the GBM. Heterozygous carriers of these variants may also manifest with thin basement membrane disease. In this transplant candidate with IgAN and GBM abnormalities, the relative contribution of the COL4A3 variant to her CKD cannot be ascertained. Consequently, the daughter’s long-term renal outcome cannot be predicted. The co-existence of both IgAN and Alport syndrome is rarely described in the literature and the importance of the consideration of genetic renal disease is emphasized here in the context of living donor safety.