Perfusate Biomarker Comparison during Renal Hypothermic and Normothermic Machine Perfusion: Do These Techniques Provide Similar Insights?

Background: Hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) are increasingly used in renal transplantation. Both techniques enable pretransplant organ viability assessment through biomarker measurements in the perfusion solution. This study examines similarities and differences in biomarker release during HMP and NMP, focusing on well-established biomarkers alongside functional markers in porcine and discarded human donor kidneys. 

Methods: Discarded human donor kidneys (n=25) underwent 4 h of oxygenated hypothermic machine perfusion (HMPO2) and subsequently 4 h of NMP. Porcine kidneys were exposed to either minimal warm ischemia or 75 min of warm ischemia (n=30 per group). Hereafter, kidneys were placed on HMPO2 for 6 h followed by 6 h of NMP. Flow dynamics were recorded, and the biomarkers aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), N-Acetyl-β-glucosaminidase, tissue inhibitor of metalloproteinases-2 (TIMP-2), and heart-Type fatty acid-binding protein were measured longitudinally in the perfusates. 

Results: For human kidneys, we found moderate to strong correlations between ASAT, LDH, TIMP-2, and heart-Type fatty acid-binding protein content measured during HMPO2 and the same biomarkers during NMP. In porcine kidneys, clear distinctions between ischemically damaged and healthy kidneys were observed in flow dynamics and content of ASAT, LDH, and TIMP-2 during both HMPO2 and NMP. 

Conclusions: Our findings suggest that biomarker release during HMPO2 and NMP have similarities, indicating that some biomarkers might already be assessed during HMPO2. However, the predictive value of biomarkers in both techniques remains elusive. Additionally, NMP could provide important benefits over HMPO2, including functional assessment and reconditioning.