Beyond Living Donor Kidney Transplantation in COL4 Nephropathy - A Real-World Clinical Dilemma in Light of Current...

Area of Science:

• Nephrology
• Genetics
• Transplantation

Background:

• Kidney transplantation is the optimal treatment for end-stage kidney disease (ESKD).
• Hereditary conditions, such as COL4 nephropathy (Alport syndrome), complicate living kidney donor selection.
• Autosomal recessive COL4 nephropathy presents unique challenges for donor evaluation.

Purpose of the Study:

• To review a clinical dilemma concerning living kidney donation in a family with autosomal recessive COL4 nephropathy.
• To analyze the clinical spectrum and prevalence of COL4 nephropathy in North Macedonia.
• To evaluate current and updated guidelines for living kidney donor selection in hereditary kidney diseases.

Main Methods:

• Case review of a 24-year-old male with autosomal recessive COL4 nephropathy and his heterozygous carrier mother.
• Analysis of next-generation sequencing (NGS) data from 92 identified patients in North Macedonia.
• Evaluation of Kidney Disease: Improving Global Outcomes (KDIGO) and European Renal Best Practice (ERBP) / European Society of Paediatric Nephrology (ESPN) / European Renal Association (ERA) guidelines.

Main Results:

• COL4A5 mutations were the most prevalent (67.4%) among 92 identified COL4 nephropathy patients in North Macedonia.
• Current KDIGO guidelines offer limited specific guidance for hereditary conditions in living donor evaluation.
• Updated 2025 ERBP/ESPN/ERA criteria suggest donation may be considered for selected carriers over 40 with preserved kidney function and no subclinical damage.

Conclusions:

• Individualized evaluation of potential living kidney donors from affected families is crucial.
• Updated guidelines provide a framework for considering donation in selected heterozygous carriers.
• This approach is vital in contexts of organ shortages and limited deceased-donor transplant access.