Lowering Perfusate Temperature From 37°C to 32°C Diminishes Function in a Porcine Model of Ex Vivo Kidney Perfusion

Abstract

BackgroundEx vivo perfusion (EVP) is a novel method of preservation. However, optimal perfusion conditions remain undetermined. Reducing the temperature of the perfusate to subnormothermia may be beneficial during EVP and improve early graft function. The aim of this study was to investigate whether subnormothermia would influence the conditioning effect of EVP when compared with normothermic perfusion, and standard cold static storage (CS).MethodsPorcine kidneys underwent static CS for 23 hours followed by 1 hour of EVP using leukocyte-depleted blood at a mean temperature of 32°C or 37°C. After this, kidneys were reperfused with whole autologous blood at 37°C for 3 hours to assess renal function and injury. These were compared with a control group that underwent 24 hours CS.ResultsDuring EVP, kidneys perfused at 37°C had a higher level of renal blood flow and oxygen consumption compared with EVP at 32°C (P = 0.001, 0.002). During reperfusion, 32°C EVP kidneys had lower creatinine clearance and urine output than control (P = 0.023, 0.011) and a higher fractional excretion of sodium, serum potassium, and serum aspartate transaminase than 37°C EVP kidneys (P = 0.01, 0.023, 0.009).ConclusionsTubular and renal functions were better preserved by a near-physiological temperature of 37°C during 1 hour of EVP, when compared to EVP at 32°C or cold storage.

Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform

“…PRBCs (230 ml) were added to a reservoir (with integrated oxygenator, heat exchanger, and arterial filter) (Terumo Capiox FX05, Tokyo, Japan), along with 150 ml Hartmann's solution, 250 ml Gelofusine (B. Braun Australia Pty Ltd, Bella Vista, Australia), 18 ml sodium bicarbonate 8.4%, 50 ml mannitol 10%, 2000 IU of unfractionated heparin, 5 ml calcium gluconate 0.22 mmol/ml, and 25 ml water for injection. Creatinine (Merck, Darmstadt, Germany) was added to achieve a concentration of 1000 μmol/L to allow for subsequent creatinine clearance (CrCl) calculation 42 .…”

“…Urine output (UO) was measured at the end of NMP. CrCl, fractional excretion of sodium (FeNa), and renal oxygen consumption were calculated as described elsewhere 42 . (2020) 10:6930 | https://doi.org/10.1038/s41598-020-63687-0…”

The future of marginal kidney repair in the context of normothermic machine perfusion

“…However, these clinical trials did not replicate the same successful outcomes previously demonstrated in rodent models. All the studies in question have faced similar challenges associated with systemic drug delivery and have been discontinued 23, 24, 25, 26. Traditionally, treatments for IRI (as well as for most other renal diseases) are delivered systemically following transplantation 27, 28.…”

“…Leading centers in the UK, Canada, The Netherlands, and the United States have all begun to move NMP technology forward8, 24, 25, 26 (Table 1). Normothermic perfusion technologies have begun to make their way into the clinic in an attempt to recondition marginal organs and reverse aspects of IRI.…”

“…Oxygen consumption is maximized at normothermic temperatures, making NMP an ideal system for reconditioning 25. Nevertheless, there are other gases that, when delivered at low doses, have shown some evidence of having protective effects in the kidney.…”