Kidney Week

Abstract: TH-PO1039

Successful Kidney Transplantation in a Patient with Combined COL4A4 and COL4A5 Pathogenic Variants, CYP3A5 Expression, and a Conflicting Heterozygous FN1 Variant

Session Information

• Transplantation: Clinical - Outcomes, Malignancy, and Pathology
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2002 Transplantation: Clinical

Authors

• ElSharkawy, Magdy, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Magdy ElSharkawy, MD, PhD, FASN

• Teama, Nahla Mohamed, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Nahla Mohamed Teama

• Ahmed, Fatma Abdelrahman, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Fatma Abdelrahman Ahmed, PhD

• Elsharabasy, Reem Mohsen, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Reem Mohsen Elsharabasy, MD, MBChB

• Emara, Ahmed, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Ahmed Emara, MD, FASN

• Elbraky, Abdelrahman, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Abdelrahman Elbraky, MBChB

• Abd El-Mohsen, Mohamed Atef, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Mohamed Atef Abd El-Mohsen, MD, MBChB, MSc

• Tohami, Nahla Hussein, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Nahla Hussein Tohami, MD, PhD

• Adel, Wedad, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Wedad Adel, MD, PhD

• Fathy, Salma, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Salma Fathy, PhD

• Abd El Azim, Mahmoud Nady Abd El Aziz, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Mahmoud Nady Abd El Aziz Abd El Azim, MD, MBChB, MSc

• Abdallah, Shaimaa Zaki abdelmegied, Ain Shams University Faculty of Medicine, Cairo, Cairo Governorate, Egypt

Shaimaa Zaki abdelmegied Abdallah, MD

Introduction

Alport syndrome is an inherited disorder caused by mutations in COL4A3, COL4A4, and COL4A5. Fibronectin glomerulopathy is a rare autosomal dominant glomerular disease linked to FN1 mutations and is associated with a risk of early post-transplant recurrence. Differentiating between these disorders is essential because transplant outcomes and recurrence risks differ significantly.

Case Description

A 20-year-old Sudanese male was referred for kidney transplant evaluation. Kidney disease was first detected at the age of 8 years, when he presented with persistent hematuria and proteinuria. The renal function progressively deteriorated, leading to end-stage renal disease (ESRD) in 2025. Family history was remarkable for ESRD affecting multiple maternal relatives. His mother underwent kidney transplantation but experienced early graft rejection and died; a maternal uncle lost his graft after 3 years. The patient’s parents were Consanguineous.

Whole-exome sequencing (WES) was performed to determine the underlying cause before transplantation. WES revealed combined pathogenic variants in COL4A4 and COL4A5, supporting a diagnosis of Alport syndrome, in addition to a heterozygous FN1 mutation with conflicting interpretation regarding pathogenicity for Fibronectin glomerulopathy. The native kidney biopsy was done; it demonstrated advanced global glomerulosclerosis with pathological findings consistent with Alport syndrome and without evidence supporting fibronectin glomerulopathy. Correlation of genetic findings with the clinico-pathological phenotype favored Alport syndrome as the primary diagnosis.

The patient underwent successful living-related kidney transplantation with immediate graft function. Delayed achievement of therapeutic tacrolimus levels prompted pharmacogenomics reassessment, which identified CYP3A5 expresser status requiring higher tacrolimus dosing with adjunctive verapamil and vonoprazan. At 6-month follow-up, serum creatinine was 1.02 mg/dL with stable graft function and no rejection episodes.

Discussion

This case highlights the importance of comprehensive genotype–phenotype correlation in resolving diagnostic uncertainty, enabling accurate risk stratification and successful kidney transplantation. It also demonstrates the value of pharmacogenomic-guided tacrolimus optimization in transplant recipients.