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Kidney Week

Abstract: PO2408

LIMS1 Gene Mismatching and Risk of Rejection in Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Caliskan, Yasar, Saint Louis University, Saint Louis, Missouri, United States
  • Mirioglu, Safak, Istanbul University, Istanbul, Istanbul, Turkey
  • Yazici, Halil, Istanbul University, Istanbul, Istanbul, Turkey
  • Dirim, Ahmet Burak, Istanbul University, Istanbul, Istanbul, Turkey
  • Demir, Erol, Istanbul University, Istanbul, Istanbul, Turkey
  • Oto, Ozgur Akin, Istanbul University, Istanbul, Istanbul, Turkey
  • Edwards, John C., Saint Louis University, Saint Louis, Missouri, United States
  • Ouseph, Rosemary, Saint Louis University, Saint Louis, Missouri, United States
  • Turkmen, Aydin, Istanbul University, Istanbul, Istanbul, Turkey
  • Lentine, Krista L., Saint Louis University, Saint Louis, Missouri, United States
Background

Recent advances in precision medicine have provided new insights into the pathogenesis of kidney transplant (KTx) rejection such as the potential role of genetic risk variants in LIM Zinc Finger Domain Containing 1 (LIMS1). We aimed to evaluate the relationship between donor and recipient LIMS1 genotype matching status and allograft rejection and survival.

Methods

We genotyped 41 prevalent living KTx recipient [24 (59%) males; mean age 34±13 years] and donor [15 (37%) males; mean age 47±13 years] pairs for LIMS1 rs893403 variant by Sanger sequencing in order to assess their impact on rejection and graft failure. The recipients homozygous for LIMS1 rs893403 GG genotype which tags a common 1.5-kb deletion (CNVR915.1) received a transplant from a nonhomozygous donor were defined as risk mismatched. CNVR915.1 deletion is confirmed by PCR in recipients with rs893043-AG and GG genotypes. Rejections were defined as T-cell mediated (TCMR) or antibody mediated rejection (ABMR) defined by Banff 2013 criteria. Outcomes were abstracted by review of medical records.

Results

There were no differences between recipients with risk LIMS1 mismatching (n=5) and recipients without risk LIMS1 mismatching (n=36) regarding demographic factors, duration of dialysis, pretransplant PRA, HLA mismatching, immunosuppressive protocols and follow up time. After a median post-KTx follow up of 10.5 (IQR 8.7-12.6) years recipients with risk LIMS1 mismatching had significantly higher risk of allograft rejection (60%; median 1 month) compared to recipients without risk LIMS1 mismatching (13.9%; median 72 months) (HR=4.32, 95CI% 1.46-12.76, p=0.015). TCMR was higher in recipients with risk LIMS1 mismatching (40%) compared to recipients without risk LIMS1 mismatching (11.1%) (p=0.087). There were no significant differences found between patients with and without risk LIMS1 mismatching regarding risk of post-KTx DSA, ABMR and allograft failure. The mean eGFR levels at last follow up were also similar among recipients with and without risk LIMS1 mismatching.

Conclusion

Genomic mismatching at LIMS1 gene appears to impact risk of TCMR. LIMS1 may be a potential minor histocompatibility antigen and pre-transplant genetic testing may have clinical implications for the prediction and clinical management of KTx rejection.

Funding

  • Private Foundation Support