Fig. 3: Reduced renin-angiotensin-aldosterone system activity after kidney xenotransplantation.

a Schematic of renin-angiotensin-aldosterone pathway (created with Biorender.com). b Plasma renin activity (measured by Angiotensin I generated) was measured in pre- and post-transplant samples from NHP recipients. c As in (b) but for aldosterone. d Pathway analysis of tissue biopsy RNA-seq as compared to CUK demonstrates significantly enriched differential expression in RAAS-related pathways. e Gene network mapping differentially expressed genes across gene sets of interest. ^&Denotes animal with a single native NHP kidney in situ at time this sample was taken, subsequent samples demonstrated consistently low values. For box and whisker plots, the central line in each box represents the median of the distribution, i.e., the value that separates the lower 50% of observations from the upper 50%. The box itself represents the interquartile range (IQR), which spans from the 25th to the 75th percentile of the distribution. The lower bound of the box is the first quartile (Q1), while the upper bound is the third quartile (Q3). The whiskers of the box and whisker plot extend from the box to the minimum and maximum observations within 1.5 times the IQR of the lower and upper quartile, respectively (panels b and c). Statistical testing for panels b and c was performed using generalized linear models with xenotransplantation bin (pre vs post) and recipient IDs as factor variables. Statistical testing for panels d and e was performed by pathfindR using the hypergeometric test on results from DESeq2 which were FDR-adjusted for multiple comparisons. n = 7 biologically independent transplants for panel b and n = 6 biologically independent transplants for panel c. ACE angiotensin converting enzyme, ADH antidiuretic hormone, IQR inter-quartile range (25th–75th percentiles).