Kidney Week

Abstract: PUB274

A Family with Variants in Multiple ADPKD Genes

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Tanaka, Hisae, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan

Hisae Tanaka, MD, PhD

• Wada, Takehiko, Nephrology Center, Toranomon Hospital, Tokyo, Japan

Takehiko Wada, MD, PhD

• Nakamura, Michio, Department of Transplant Surgery, Tokai University School of Medicine, Isehara, Japan

Michio Nakamura, DrMed, PhD

• Ohnuki, Yuko, Department of Medical Ethics, Tokai University School of Medicine, Isehara, Japan

Yuko Ohnuki, MD, PhD

• Sekine, Akinari, Nephrology Center, Toranomon Hospital, Tokyo, Japan

Akinari Sekine, MD

• Fujimaru, Takuya, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Takuya Fujimaru, MD, PhD

• Mori, Takayasu, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Takayasu Mori, MD, PhD

• Sohara, Eisei, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Eisei Sohara, MD, PhD

• Uchida, Shinichi, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Shinichi Uchida, MD, PhD

• Fukagawa, Masafumi, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan

Masafumi Fukagawa, MD, PhD, FASN

• Komaba, Hirotaka, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan

Hirotaka Komaba, MD, PhD

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by progressive cyst formation and enlargement of the kidneys, often leading to end-stage kidney disease (ESKD). ADPKD is thought to be caused by mutations in one of two genes (PKD1 or PKD2). Recent advances in genetic technologies have enabled the identification of new variants of the ADPKD genes and revealed the complexity of the genetic inheritance of this disease.

Case Description

A 30-year-old female was referred to our hospital for evaluation of progressively worsening kidney function and potential living donor kidney transplantation. She was diagnosed with multicystic dysplastic kidney of the right kidney in her fetal period. At the age of 4, a renal cyst developed in the left kidney and the number of cysts increased with age. Later, her kidney function gradually declined and she developed ESKD in her late 20s. Laboratory tests showed a serum creatinine of 3.75 mg/dL, an eGFR of 13 mL/min/1.73m², and a urine protein/creatinine ratio of 2.6. Abdominal CT showed multiple kidney cysts in both kidneys with only one small hepatic cyst. It was later recognized that her biological father had been clinically diagnosed with ADPKD and had been on hemodialysis since the age of 50. Next-generation sequencing revealed a heterozygous PKD2 pathogenic variant, accompanied by PKD1 and IFT140 variants of uncertain clinical significance, in both the patient and her father, but not in her mother. The patient eventually received a kidney transplant from her mother.

Discussion

Genetic testing could help identify the cause of ESKD in this patient and exclude genetic risk in her mother, a kidney donor candidate. The lack of genetic difference between this patient and her father does not support the possibility that digenic effects of PKD1 and/or IFT140 variants led to the atypical ADPKD manifestations in this patient. Further studies are required to investigate the putative impact of these variants on the development of ADPKD.