Molecular Pathways Underlying Adaptive Repair of the Injured Kidney: Novel Donation After Cardiac Death and Acute Kidney Injury Platforms

International audienceObjective: To test the hypothesis that gene expression profiling in peripheral blood from patients who have undergone kidney transplantation (KT) will provide mechanistic insights regarding graft repair and regeneration.Background: Renal grafts obtained from living donors (LD) typically function immediately, whereas organs from donation after cardiac death (DCD) or acute kidney injury (AKI) donors may experience delayed function with eventual recovery. Thus, recipients of LD, DCD, and AKI kidneys were studied to provide a more complete understanding of the molecular basis for renal recovery.Methods: Peripheral blood was collected from LD and DCD/AKI recipients before transplant and throughout the first 30 days thereafter. Total RNA was isolated and assayed on whole genome microarrays.Results: Comparison of longitudinal gene expression between LD and AKI/DCD revealed 2 clusters, representing 141 differentially expressed transcripts. A subset of 11 transcripts was found to be differentially expressed in AKI/DCD versus LD. In all recipients, the most robust gene expression changes were observed in the first day after transplantation. After day 1, gene expression profiles differed depending upon the source of the graft. In patients receiving LD grafts, the expression of most genes did not remain markedly elevated beyond the first day post-KT. In the AKI/DCD groups, elevations in gene expression were maintained for at least 5 days post-KT. In all recipients, the pattern of coordinate gene overexpression subsided by 28 to 30 days.Conclusions: Gene expression in peripheral blood of AKI/DCD recipients offers a novel platform to understand the potential mechanisms and timing of kidney repair and regeneration after transplantation

Laparoscopic versus open donor nephrectomy: Comparing ureteral complications in the recipients and improving the laparoscopic technique

Background. Laparoscopic live donor nephrectomy (LDN) is a recently developed procedure, the performance of which needs to be studied. Given the reported advantages in the donors, this study looks at graft outcome and ureteral complications in recipients of kidneys procured by open donor nephrectomy (ODN) versus LDN. Methods. The LDN recipients consisted of 193 patients since 3/27/96. A total of 168 ODN recipients from 1991 to 1998 served as controls. Immunosuppression protocols were similar for both groups. Results. Two-year graft survival for LDN and ODN was 98% and 96%, respectively. Two-year patient survival for LDN and ODN was 98% and 97%, respectively. The incidence of delayed graft function and mean serum creatinine at 3 and 12 months was similar in both groups. However, the number of ureteral complications that required operative repair was significantly higher for LDN recipients compared to ODN recipients, 7.7% (n = 15) vs. 0.6% (n = 1) respectively (P = 0.03). Ureteral stenting was required in an additional 3.1% (n = 6) of LDN and 2.4% (n = 4) of ODN (P = NS). There was, however, a learning curve with time. For the first 130 LDN patients, a total of 20 ureteral complications were recorded, whereas only one occurred in the more recent 63 patients (P = 0.03). Conclusions. The higher ureteral complication rate in LDN recipients has improved over time as technical causes have been identified. We have noted significant improvement in ureteral viability by using the endogastrointestinal anastomosis instrument on the ureter and peri-ureteral tissue. LDN is therefore an excellent alternative to ODN. Identification of hazards unique to this technique is critical before its broader application