Human Transplant Kidneys on Normothermic Machine Perfusion Display Endocrine Activity

Abstract

Normothermic machine perfusion (NMP) is an alternative to hypothermic machine perfusion (HMP) for donor kidney preservation before transplantation. Contrary to HMP, NMP allows for functional assessment of donor kidneys because normothermic conditions allow for metabolic activity. The kidneys are key producers of hormones. Yet, it remains unknown whether donor kidneys during NMP display endocrine functions.

Methods: Fifteen donor kidneys were subjected to HMP followed by 2 h of NMP before transplantation. NMP perfusate was collected at 3 time points (0, 1, 2 h) for the measurements of prorenin/renin, erythropoietin (EPO), and vitamin D, and urine samples were collected at 1 h and 2 h for urodilatin measurement. Fifteen HMP perfusate samples were collected for the same measurements.

Results: Kidneys on NMP secreted significantly more prorenin, renin, EPO, and active vitamin D than during HMP. EPO and vitamin D secretion remained stable during 2 h of NMP, whereas the prorenin release rate increased and renin release rate decreased after 1 h. Donation after brain death kidneys secreted more vitamin D and less EPO during NMP than donation after circulatory death kidneys. Twelve donor kidneys produced urine during NMP and released detectable levels of urodilatin. Kidneys exhibited a large variation in hormone release rates. No significant differences were found in hormone release capacity between delayed graft function (DGF) and non-DGF kidneys, and no significant correlations were found between hormone release rates and the duration of DGF or 1-mo posttransplant serum creatinine levels.

Conclusions: Human transplant kidneys display endocrine activity during NMP. To explore whether correlations exist between hormone release rates and posttransplant kidney function, large numbers of kidneys are required.

Graphical abstract

FIGURE 1.

Hormone release from human donor kidneys during NMP. Prorenin (A) and renin (B) levels measured by IRMA; prorenin (C) and renin (D) activities measured by EKA; EPO (E) and 1,25(OH)₂D (F) levels measured in perfusate from 15 donor kidneys at t = 0, 1, and 2 h of NMP. The above data are corrected by the levels measured at t = 0 h. Urodilatin levels (G) measured in urine from 12 donor kidneys after 1 or 2 h of NMP. No urine was available for urodilatin measurements in patients no. 1, 4, and 5. EKA, enzyme-kinetic assay; EPO, erythropoietin; IRMA, immunoradiometric assay; NMP, normothermic machine perfusion; 1,25(OH)2D, 1,25-dihydroxy vitamin D.

FIGURE 2.

Comparison of hormone release rates of kidneys between HMP and NMP. Prorenin (A), renin (B), EPO (C), and 1,25(OH)₂D (D) release rates in 15 kidneys during HMP and 15 kidneys during 2 h of NMP. Data are presented as median with IQR. *P < 0.05, ***P < 0.001. EPO, erythropoietin; HMP, hypothermic machine perfusion; IQR, interquartile range; NMP, normothermic machine perfusion; 1,25(OH)2D, 1,25-dihydroxy vitamin D.

FIGURE 3.

Effects of donor type on hormone release capacity of human donor kidneys. Comparison of prorenin (A), renin (B), EPO (C), and 1,25(OH)₂D (D) release rates during 2 h of NMP between DBD and DCD donor kidneys (DBD: n = 3, DCD: n = 12). Urodilatin release rates during the first (E) and second (F) h of NMP were compared between DBD and DCD donor kidneys (DBD: n = 2, DCD: n = 10). Data are presented as median with IQR. ns, *P < 0.05, **P < 0.01. DBD, donation after brain death; DCD, donation after circulatory death; EPO, erythropoietin; IQR, interquartile range; NMP, normothermic machine perfusion; ns, not significant; 1,25(OH)2D, 1,25-dihydroxy vitamin D.