Successful Kidney Transplantation in a Patient with Genetic Hypertension due to a Pathogenic Kelch-Like 3 Mutation: A Case Report.

Introduction: Gordon syndrome (or pseudohypoaldosteronism type II) is a rare form of hyperkalemic, hyperchloremic hypertension that is typically characterized by preserved kidney function. We report the first case of a successful paired exchange kidney transplant in a patient with an atypical presentation of Gordon syndrome due to a pathogenic KLHL-3 mutation who developed end-stage kidney disease, emphasizing the transplant outcomes and renal function. Case Presentation: A 24-year-old Caucasian male with early-onset hypertension since the age of 15 years, intermittent 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 blood pressure was 250/160 mm Hg. The laboratory results revealed a creatinine of 9.9 mg/dL, potassium of 3.0 mmol/L, sodium of 136 mmol/L, chloride of 91 mmol/L, bicarbonate of 18 mmol/L, hemoglobin of 10 g/dL, and platelet count of 87,000/μL. Renal ultrasound indicated increased echogenicity in both kidneys, and a glomerulonephritis workup was negative. Despite the use of aggressive antihypertensive therapy, progressive azotemia required hemodialysis. A kidney biopsy showed severe vascular and tubulointerstitial changes, consistent with hypertensive nephrosclerosis. Genetic testing confirmed a heterozygous pathogenic variant in the KLHL-3 gene, diagnosing Gordon syndrome. Five months later, the patient underwent successful living-unrelated kidney transplantation via a paired exchange program. Early post-transplant complications included acute allograft dysfunction due to volume depletion and mild 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, which was successfully treated with intravenous immunoglobulin, erythropoiesis-stimulating agents, and blood transfusions. At follow-up, the patient showed excellent allograft function and well-controlled blood pressure on a simplified antihypertensive regimen. Discussion and Conclusions: This case highlights an unexpected manifestation of an exceptionally rare disease, Gordon syndrome, due to a pathogenic KLHL-3 variant, uniquely leading to end-stage kidney disease and subsequent kidney transplantation. The impact of pathogenic KLHL-3 mutations on transplant outcomes remains undefined. However, our patient underwent kidney transplantation, resulting in excellent renal allograft function and optimal blood pressure control, thus demonstrating favorable renal transplant outcomes for patients with genetic hypertension.