Furosemide attenuates tubulointerstitial injury and allows functional testing of porcine kidneys during normothermic machine perfusion

Artif Organs. 2024 Jun;48(6):595-605. doi: 10.1111/aor.14705. Epub 2024 Jan 1.

Abstract

Background: Normothermic machine perfusion (NMP) is a promising pretransplant kidney quality assessment platform, but it remains crucial to increase its diagnostic potential while ensuring minimal additional injury to the already damaged kidney. Interventions that alter tubular transport can influence renal function and injury during perfusion. This study aimed to determine whether furosemide and desmopressin affect renal function and injury during NMP.

Methods: Eighteen porcine kidneys (n = 6 per group) were subjected to 30 min of warm ischemia and 4 h of oxygenated hypothermic perfusion before being subjected to 6 h of NMP. Each organ was randomized to receive no drug, furosemide (750 mg), or desmopressin (16 μg) during NMP.

Results: Compared with the other groups, the addition of furosemide resulted in significantly increased urine output, fractional excretion of sodium and potassium, and urea clearance during NMP. Urinary neutrophil gelatinase-associated lipocalin levels decreased significantly with furosemide supplementation compared with the other groups. The addition of desmopressin did not result in any significantly different outcome measurements compared with the control group.

Conclusions: This study showed that the addition of furosemide affected renal function while attenuating tubulointerstitial injury during NMP. Therefore, furosemide supplementation may provide renal protection and serve as a functional test for pretransplant kidney viability assessment during NMP.

Keywords: V2‐specific vasopressin agonist; kidney transplantation; loop diuretics; normothermic machine perfusion; organ preservation.

MeSH terms

  • Animals
  • Deamino Arginine Vasopressin / pharmacology
  • Furosemide* / pharmacology
  • Kidney Transplantation
  • Kidney* / drug effects
  • Kidney* / pathology
  • Organ Preservation* / methods
  • Perfusion* / methods
  • Swine
  • Warm Ischemia / adverse effects