Glomerular endothelial cell-podocyte stresses and crosstalk in structurally normal kidney transplants.

Increased podocyte detachment begins immediately after kidney transplantation and is associated with long-term allograft failure. We hypothesized that cell-specific transcriptional changes in podocytes and glomerular endothelial cells after transplantation would offer mechanistic insights into the podocyte detachment process. To test this, we evaluated cell-specific transcriptional profiles of glomerular endothelial cells and podocytes from 14 patients of their first-year surveillance biopsies with normal histology from low immune risk recipients with no post-transplant complications and compared these to biopsies of 20 healthy living donor controls. Glomerular endothelial cells from these surveillance biopsies were enriched for genes related to fluid shear stress, angiogenesis, and interferon signaling. In podocytes, pathways were enriched for genes in response to growth factor signaling and actin cytoskeletal reorganization but also showed evidence of podocyte stress as indicated by reduced nephrin (adhesion protein) gene expression. In parallel, transcripts coding for proteins required to maintain podocyte adherence to the underlying glomerular basement membrane were downregulated, including the major glomerular podocyte integrin α3 and the actin cytoskeleton-related gene synaptopodin. The reduction in integrin α3 protein expression in surveillance biopsies was confirmed by immunoperoxidase staining. The combined growth and stress response of patient allografts post-transplantation paralleled similar changes in a rodent model of nephrectomy-induced glomerular hypertrophic stress that progress to develop proteinuria and glomerulosclerosis with shortened kidney life span. Thus, even among patients with apparently healthy allografts with no detectable histologic abnormality including alloimmune injury, transcriptomic changes reflecting cell stresses are already set in motion that could drive hypertrophy-associated glomerular disease progression.

Histidine-Tryptophan-Ketoglutarate Solution for Donor Heart Preservation Is Safe for Transplantation.

BACKGROUND: Various solutions are used for donor heart preservation. We examined the outcomes in our heart transplant population where histidine-tryptophan-ketoglutarate (HTK) solution has been used for heart preservation since 2004. METHODS: This was a retrospective review of the United Network for Organ Sharing (UNOS) database (2004-2016) comparing our heart transplant outcomes with other national centers. Propensity matching in a 1:3 ratio was performed to adjust for preoperative recipient variables. RESULTS: After propensity matching comparing UNOS outcomes (n = 1080) with our institutional data (n = 360), there was no difference in matched preoperative variables. Donor hearts were similar for donor age, sex, donor-to-recipient size ratio, LVEF, and ischemic time. Our HTK cohort had a larger proportion with donor cardiac arrest (26.3% vs 6.1%, P < .001) and longer cardiac arrest duration (22.1 ± 16.0 vs 17.2 ± 14.0 minutes, P = .052). Our primary graft dysfunction (PGD) rate requiring mechanical support was 4.2% (n = 1). Postoperative mechanical support use for PGD included extracorporeal membrane oxygenation in 9 (60.0%), intraaortic balloon pump in 4 (26.7%), right ventricular assist device in 3 (20%), and biventricular assist device in 3 (20%). Overall survival at our institution was similar to the national average (P = .649). Survival at 1, 5, and 10 years with HTK was 92.2%, 81.3%, and 70.8%, and for the UNOS population was 91.6%, 80.3%, and 62.0%, respectively. CONCLUSIONS: Use of HTK solution for donor hearts was associated with a low rate of severe PGD. Overall survival was not significantly different from other institutions using a variety of preservation solutions in the UNOS database during the same period. HTK solution is efficacious for preservation of donor hearts.