Kidney Week

Abstract: FR-PO0093

Severe Early-Onset Cystic Kidney Disease Associated with a De Novo Heterozygous NEK8 Variant: An ARPKD-Mimicking Phenotype

Session Information

• ADPKD and Cystic Kidney Disease - 2
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Lee, Hyun A, Seoul National University Children's Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Hyun A Lee, MD

• Min, Jeesu, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)

Jeesu Min, MD

• Choi, Naye, Seoul National University Children's Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Naye Choi, MD

• Kim, Ji hyun, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Ji hyun Kim, MD

• Kang, Hee Gyung, Seoul National University Children's Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Hee Gyung Kang, MD, PhD

• Ahn, Yo Han, Seoul National University Children's Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Yo Han Ahn, MD, PhD

Introduction

Polycystic kidney disease (PKD) in infants is a rare genetic disorder, most commonly caused by biallelic variants leading to autosomal recessive PKD (ARPKD). Infants with ARPKD often presents with pulmonary hypoplasia due to oligohydramnios, markedly enlarged kidneys, and early-onset renal dysfunction, sometimes accompanied by hepatic fibrosis or portal hypertension. Monoallelic NEK8 variants have recently been implicated in atypical cystic kidney disease, but the full phenotypic spectrum and pathogenic mechanism remain unclear. Here, we present a patient with de novo heterozygous NEK8 variant who experienced multiple severe complications.

Case Description

A 36-month-old boy was born at 36+4 weeks of gestation, weighing 3.25kg, following a pregnancy complicated by oligohydramnios. He required neonatal intensive care for respiratory failure due to prenatal pulmonary hypoplasia. Bilateral markedly enlarged polycystic kidneys were noted from birth. His kidney function had been progressively decreased requiring kidney replacement therapy by seven months of age. To create space for peritoneal dialysis, unilateral nephrectomy was performed; the resected kidney weighed 1.758kg, nearly nine times the normal adult kidney weight. Temporary hemodialysis following peritoneal catheter placement was complicated by esophageal bleeding and recurrent severe hypotension. He was suffered from severe urinary tract infections in the remaining kidney, which required hospitalization for septic shock and antibiotics-resistant bacterial infections. Following contralateral nephrectomy, he remained clinically stable with adequate dialysis clearance. Subsequent genetic testing identified a heterozygous de novo variant in NEK8 (NM_178170.3:c.626C>T, p.Pro209Leu), with no additional pathogenic variant detected.

Discussion

Pathogenic NEK8 variants are classically inherited in a biallelic manner and are associated with severe syndromic ciliopathy. This case expands the phenotypic spectrum of monoallelic NEK8-associated kidney disease, presenting with a severe infantile phenotype resembling ARPKD. The underlying pathogenic mechanism remains unclear, with possible roles of dominant-negative effects, undetected second hits, or additional genetic modifiers. NEK8 should be considered in the differential diagnosis of ARPKD-like presentations when no biallelic pathogenic variants are identified.