Varsseveld, O.C. van (Otis) (2019) Tacrolimus reduces renal injury: the effects of tacrolimus and partial ischemia in an ex vivo normothermic machine perfusion model with porcine kidneys. thesis, Medicine.
Full text available on request.Abstract
Background. Presently, kidney transplantation is the best treatment for end stage renal failure. Donation after circulatory death (DCD) is increasingly common to expand the donor pool, emphasizing the need for objective renal graft quality assessment. Ex vivo normothermic machine perfusion (NMP) provides a platform for organ preservation and simultaneous organ quality and function assessment. This study aimed to obtain more understanding of the effects of tacrolimus and partial ischemia on renal function in NMP. Methods. We compared three groups in an ex vivo NMP model with porcine kidneys. After 20 minutes of warm ischemia kidneys were procured from domestic landrace pigs and hypothermically perfused for 2-3 hours followed by 6 hours of NMP. The Tacrolimus (Tac) group (n=3) received tacrolimus (60 µg/L) at the start of NMP and in the partial ischemia (PI) group (n=3) the artery branch of one kidney pole was occluded for 60 minutes at one hour of NMP to be compared to controls (n=3). Results. After 6 hours NMP, significantly lower lactate dehydrogenase production (Tac, 0 U vs. control, 101.0 ± 30.7 U, P = 0.02) and lactate concentration (Tac, 2.5 ± 0.6 mmol/L vs. control, 5.0 ± 0.7 mmol/L, P = 0.01) were found in the Tac group compared to controls. Renal flow and cumulative diuresis did not differ significantly between the three groups, but a trend of lower values was seen in PI kidneys compared to Tac and control. Area under the curve for creatinine clearance was 816.2 ± 336.3 mL (control), 2531.7 ± 2075.2 mL (Tac) and 386.3 ± 487.8 mL (PI), with no statistically significant difference between the three groups (P = 0.177). Conclusions. Tacrolimus administration during NMP may have beneficial effects on kidney viability. Renal flow is possibly an interesting target for quality assessment in PI kidneys.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Leuvenink, Prof. Dr. H.G.D. and Moers, Dr. C. and Chirurgisch Onderzoekslab UMCG |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:39 |
| Last Modified: | 25 Jun 2020 10:39 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/93 |
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