Donor Klotho KL-VS Polymorphism Predicts Allograft Glomerulosclerosis and Early Post-Transplant Kidney Function

Area of Science:

• Nephrology
• Genetics
• Transplantation Immunology

Background:

• The Klotho protein, encoded by the KL gene, has antiaging and antifibrotic properties.
• The KL-VS genotype is linked to reduced Klotho expression and adverse health outcomes, including cardiovascular disease and kidney disease progression.
• Investigating donor Klotho polymorphisms' impact on renal allograft outcomes is crucial for understanding transplant success.

Purpose of the Study:

• To determine the association between donor Klotho rs9536314 and rs9527025 polymorphisms (KL-VS genotype) and early renal allograft morphology and function.
• To analyze the impact of specific Klotho gene variants on kidney transplant recipients within the initial post-transplant period.

Main Methods:

• Retrieved clinical data and biopsy reports from 170 deceased donor kidney transplantations.
• Genotyped donor DNA for rs9527025 and rs9536314 single nucleotide polymorphisms (SNPs) using custom TaqMan assays.
• Analyzed the association between donor SNPs, allograft morphology, and kidney function at 3 months post-transplant.

Main Results:

• The rs9527025 SNP was in full linkage with rs9536314; results reported for rs9536314.
• G allele carriers of rs9536314 showed significantly higher incidence of chronic glomerulopathy (>0 score) compared to TT haplotype (12.2% vs 3.2%, P=.023).
• G allele carriers exhibited lower estimated glomerular filtration rate (median 35.0 mL/min vs 46.3 mL/min, P=.001) and higher proteinuria incidence (24.4% vs 9.5%, P=.030) at 3 months post-transplant.

Conclusions:

• Deceased donor KL-VS polymorphism influences early renal transplant glomerular lesions and function.
• The KL-VS genotype, affecting Klotho protein dimerization and coreceptor function, serves as a predictor of early post-transplant outcomes.
• Further research is needed to evaluate the long-term effects of this polymorphism on renal allograft durability.