Successful Kidney Transplantation in a Patient with Genetic Hypertension Due to a Pathogenic KLHL3 Mutation: A Case Report

Introduction: We report a case of a successful paired exchange kidney transplant in a patient with Gordon syndrome due to a pathogenic KLHL3 mutation, who developed end-stage kidney disease (ESKD), highlighting the transplant outcomes and long-term renal function. Case Description: A 24-year-old Caucasian male with early-onset hypertension since age 16, hyperkalemia, and non-adherence to thiazide diuretics was admitted with abdominal pain and vomiting. His family history included early-onset hypertension in his brother, father, and paternal grandmother. His BP was 250/160 mmHg. Laboratory results showed a creatinine of 9.9 mg/dL, potassium of 3.0 mmol/L, sodium of 136 mmol/L, chloride of 91 mmol/L, CO2 of 18 mmol/L, hemoglobin of 10 g/dL, and platelet count of 87,000/µL. Renal ultrasound indicated increased echogenicity of both kidneys, and a glomerulonephritis workup was negative. Despite aggressive antihypertensive therapy, progressive azotemia required hemodialysis. A kidney biopsy showed severe vascular changes consistent with hypertensive nephrosclerosis, including marked arteriolar and arterial intimal thickening, moderate interstitial fibrosis, and 30-35% tubular atrophy. Genetic testing confirmed a heterozygous pathogenic variant in KLHL3, diagnosing Gordon syndrome. In September 2024, the patient underwent a successful living-unrelated kidney transplant via a paired exchange program. Early post-transplant complications included acute allograft dysfunction due to volume depletion and hydronephrosis, which improved with timely intervention, stabilizing creatinine at 1.1-1.2 mg/dL. The patient also developed severe post-transplant anemia secondary to parvovirus B19-infection, successfully treated with IVIG, ESA, and blood transfusions. At follow-up, the patient showed excellent allograft function and well-controlled BP on a simplified antihypertensive regimen. Discussion: This case highlights an atypical presentation of Gordon syndrome due to a pathogenic KLHL3 variant, leading to ESKD and requiring kidney transplantation. The impact of KLHL3 mutations on transplant outcomes remains undefined. Our patient underwent kidney transplantation, resulting in excellent long-term renal function and BP control, demonstrating favorable transplant outcomes for patients with genetic hypertension.