PhD defence H. (Hui) Lin

Below is a brief summary of the dissertation:

The shortage of donor organs remains a major challenge in kidney transplantation, increasing the need to use kidneys from older donors or donors with comorbidities. Reliable methods to assess the quality of these kidneys before transplantation are therefore essential. This thesis investigated whether the endocrine function of human donor kidneys during ex vivo normothermic machine perfusion (NMP) could help predict kidney function after transplantation. Donor kidneys remained capable of secreting several hormones during NMP, and the secretion of urodilatin, erythropoietin and, to a lesser extent, active vitamin D showed potential as biomarkers for predicting early post-transplant outcomes.

This thesis also investigated the role of the (pro)renin receptor [(P)RR] in human kidney development using kidney organoids derived from induced pluripotent stem cells. Reducing (P)RR expression at different stages of organoid development revealed stage-specific effects and demonstrated an important role for (P)RR in proximal tubule formation.

Finally, the roles of two V-ATPase subunits, ATP6V0d1 and ATP6V1H, in adipose tissue development were investigated in mice. Loss of either subunit reduced fat mass but resulted in distinct phenotypes. Loss of ATP6V0d1 caused severe lipodystrophy and spontaneous cardiomyopathy, whereas loss of ATP6V1H reduced fat mass and protected against high-fat diet-induced obesity and insulin resistance. Together, these findings provide new insights into donor kidney assessment, human kidney development, and the molecular regulation of adipose tissue.