Abstract: SA-PO514

High Calcineurin Inhibitor (CNI) Intra Patient Variability (IPV) Is Associated with Early Renal Allograft Inflammation, Chronicity, and Loss

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Sharma, Akhil, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, United States
  • Cherukuri, Aravind, UNIVERSITY OF PITTSBURGH, Pittsburgh, Pennsylvania, United States
  • Mehta, Rajil B., UNIVERSITY OF PITTSBURGH, Pittsburgh, Pennsylvania, United States
  • Sood, Puneet, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
  • Hariharan, Sundaram, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
Background

High CNI IPV has been associated with poor kidney allograft outcomes, albeit in small limited studies.

Methods

We evaluated effect of CNI IPV (the degree of fluctuation of CNI levels in all patients over 2-12M post-transplant) on early allograft inflammation, subsequent chronicity, graft loss (GL) and a composite end-point (CEP) of GL and impending GL (GLi defined as eGFR<30ml/min & 30% decline). 286 patients transplanted between 01/13-11/14 were enrolled with 2 Protocol Bx and any For-Cause Bx. The mean CNI values tested per patient was 37±15. The trough level < 6 ng/ml was considered as sub-therapeutic.

Results

CNI-IPV: The mean CNI-IPV was 28.5% and 1/4 of them had IPV≥35% (High IPV). High IPV was associated with more sub-therapeutic CNI levels (29% vs.11%, p<0.0001). Baseline demographic differences between those with high IPV and acceptable IPV were similar with a trend towards more non-Caucasian patients in the high IPV group. Allograft Histology: High IPV was associated with a higher incidence of subclinical & clinical acute rejection (AR) at 3mos (40.9% vs. 19.5%, p<0.0001), more persistent/recurrent AR at 1yr (18.2% vs 6.2%, p 0.002) and high-grade AR (≥Banff 1B, 27.5% vs 7.3%, p < 0.0001). Patients with denovo DSA & high IPV had more AR (24.6% vs. 9.1%, p=0.001). High IPV was associated with worse IFTA (p= 0.005) and IF+’i’ (p < 0.0001) on 1yr protocol Bx. Graft Outcomes: High CNI-IPV was associated with increased GL (Fig1A) and GLi (Fig1B). Sub-analysis of patients with DGF and denovo DSA revealed that high IPV was associated with worse GLi. In a multivariate Cox Proportional Hazards Model, high CNI IPV was independently associated with GLi (HR 3.1, p=0.0005).

Conclusion

High CNI-IPV within 1 year post-transplant is associated with worse allograft outcomes including more severe acute rejection, allograft chronicity, GL, and GLi. Thus, this represents an early simple modifiable risk factor for allograft loss.