Kidney - Outcomes 2

Wednesday September 14, 2022 from 12:00 to 13:00

Room: C3

412.2 High intrapatient variability tacrolimus´s levels is associated with post-transplant diabetes mellitus in kidney transplant, a Mexican cohort

Award Winner

Lucino Bahena Carrera, Mexico has been granted the Emerging Economy Congress Scientific Award

Lucino Bahena Carrera, Mexico

nephrology consultant
Nephrology and trasplant deparment
Central Military Hospital

Abstract

High intrapatient variability tacrolimus's levels is associated with post-transplant diabetes mellitus in kidney transplant, a mexican cohort

Lucino Bahena Carrera1, Héctor Faustino Noyola Villalobos1, Ricardo Mendiola Fernández1, Miguel Eduardo López Chico1, Alexis Aguilar Marcial1.

1Nephrology and Trasplant, Central Military Hospital, Mexico city, , Mexico

Introduction: Porrini E showed that tacrolimus represents a risk factor for post-transplant Diabetes Mellitus (PTDM) development, increasing prediabetes incidence by 33% 1 year post-transplantation. Several mechanisms have been implicated in the association of calcineurin inhibitor and PTDM: decreased insulin secretion, glucose intolerance, reduced pancreatic beta cell mass and decreased insulin gene expression. DIRECT study (Diabetes Incidence after Renal Transplantation) showed the incidence in 73 CsA patients (26%) and 96 Tac patients (33.6%, p = 0.046). By the other side, Malik RF et al mention that FK levels isn´t a risk factor for the development of PTDM.

Method: A retrospective study was performed.  All patients who received living or deceased-donor kidney transplant in the study period 2002 to 2020 was included and measured Tac/CsA and glucose level at months 0,3,6,9, and 12. Hb1Ac was also determined at 6 and 12 months. Patients who did not have at least 12 months post-transplant follow-up were excluded. PTDM diagnosis was made according the American Diabetes Association (ADA). Intrapatient Variability (IPV) coeficient was estimated by calculating the CV according to the following equation: CV (%) = (SD/mean Tac trough concentration) ×100. Mean concentrations were calculated using all outpatient Tac concentrations between 1 and 12 months. Recipients were separated into 2 groups, low IPV and high IPV, according to the CV cutoff= 37.31% (which is CV median value in the whole cohort).

Results: 640 patients were included; 69.4% were transplanted from living related donors; most frequent CKD etiologies were ND and CNG with 33.3%, 30.3% respectively. 64.4% of the transplant recipients were induced with Basiliximab and 1-year postransplant time, 463 patients (72.3%) were on tacrolimus as maintenance immunosuppression and 27.7% on CsA. The mean age recipients was 38.32 (±13.66) years old. Cr mean 1-year postransplant time was 1.39 (±1.19) mg/dL. There were no statistical differences in mean oral steroid dose between groups. Mean levels FK and CsA were 12.41 (±5.31) and 234.34 (±87.80) ng/mL and 9.13 (±5.3) and 194.38 (±92.44) ng/mL in the PTDM and whitout PTDM groups, respectively (p >0.05). 116 patients did met PTDM criteria (18.1%) within first year after transplantation; 55.1% patients were treated with metformin and 33.6% patient with basal insulin. Patients who had tacrolimus high IPV coefficient developed higher PTDM than those with low variability with statistically significant difference (43.22% vs 29.99%, p<0.05). The student's t test value to compare the IPV ​​was 0.03; ANOVA p= 0.00. Our PTDM incidence was lower than other hispanic multicenter cohort.

Conclusion: High IPV tacrolimus´s levels proved to be another risk factor for the development of PTDM. The use of prolonged-release medications can be a measures to maintain stable serum values and reduces this complication. Other prospective studies should be carried out to verify the results found.



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