Living Donor Kidney Transplantation in High-Recurrence Kidney Diseases: Precision Risk Stratification and Management

Living-donor kidney transplantation (KT) offers the best outcomes for patients with kidney failure (KF). However, recurrence of primary kidney disease in the allograft remains a major concern and represents 1 of the leading causes of graft loss, significantly influencing donor and recipient selection. The recurrence risk varies substantially among kidney diseases and must be carefully assessed during pretransplant evaluation. For diseases associated with low-to-intermediate recurrence risk, such as lupus nephritis, antineutrophil cytoplasmic antibodies-associated vasculitis, or IgA nephropathy, living-donor KT is generally safe, although appropriate counseling remains essential. In contrast, diseases such as membranous nephropathy (MN), primary focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), primary hyperoxaluria (PH), and amyloid light-chain (AL) amyloidosis are associated with higher recurrence rates and often require complex, individualized assessment. Recent advances have significantly transformed this field. Biomarkers such as anti-phospholipase A2 receptor (anti-PLA2R) antibodies in MN and antinephrin antibodies in FSGS enable refined risk stratification and tailored pre- and post-transplant strategies. Complement gene analysis and targeted therapies, including eculizumab, have markedly improved outcomes in aHUS, whereas novel complement inhibitors show promise for recurrent C3G. RNA interference therapy has expanded kidney-alone transplantation options in PH, and modern hematologic therapies have improved post-transplant prognosis in AL amyloidosis. These developments are reshaping the decision-making landscape for living-donor KT in diseases with a high risk of recurrence, highlighting the need for multidisciplinary evaluation, individualized strategies, and transparent donor-recipient communication to optimize transplant outcomes.