In this article, four European transplant centers, analyzed the molecular alterations in peripheral blood samples (pbs) taken at the time of a protocol kidney allograft biopsy (between June 2011 and August 2016). They used RNA-sequencing of a set of pbs selected for rejection and polyomavirus nephropathy (PVAN), and compared it with transcriptomics of control samples without these pathologies. In a case control study design, 384 pbs from 365 kidney recipients (~85% europeans, >90% on CNI plus steroids) were analyzed: 136 with rejection (86 ABMR and 68 TCMR, of which 18 had concomitant ABMR), 21 PVAN cases; and 227 heterogeneous control biopsies (no rejection nor PVAN). In pbs from any type of rejection, the differentially expressed genes (DEGs) showed up regulation of genes that reflect immune activation pathways (the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway was the most up-regulated). For ABMR cases, Interferon-regulatory factors were the most activated upstream regulators whereas in TCMR cases were less specific. Interestingly, no DEG showed a significant difference between clinical (n=78) vs. subclinical (n=58) rejection. It was also compared DEGs from pbs with DEGs from 224 biopsies, and they found a consistently upregulated genes per phenotype in both, blood and biopsy. Authors conclude that peripheral blood RNASeq data in the peripheral blood reveals immune activation pathways in peripheral blood leukocytes, reflecting renal allograft pathology.

In this research letter, a group from Edinburg explore the hypothesis that living kidney donors, without CKD or overt CVD, would have retinal microvascular changes similar to patients with CKD after kidney donation. For that, they used optical coherence tomography angiography (OCT-A) from one eye of 30 patients with CKD, 30 age and sex-matched healthy volunteers, and 30 kidney donors at the same time of day. eGFR were 96±11, 35±29, 63±16 ml/min for Control, CKD and Donor group respectively. Proteinuria and systolic blood pressure was significantly present in CKD group. They had identified two clusters of retinal features that differentiate CKD from healthy volunteers. Pre donation, Donors spanned in both clusters with most of them falling into the CKD cluster. Then they investigated how the retinal features identified changed over time in healthy controls and in kidney donors before, and following, kidney donation. Donors showed significant temporal changes in 6 of the phenotypes that were stable in controls. Interestingly, from the 6 phenotypes only one of them (increase in Foveal Avascular Zone area) showed a moderate correlation (R=0.54; P<0.03), with eGFR changes after donation. This study represents a step forward in characterizing the renal and cardiovascular consequences of living kidney donation and that these findings may contribute to asses outcomes in these population.