Yves Caumartin

Carbon monoxide-releasing molecules protect against ischemia–reperfusion injury during kidney transplantation

Carbon monoxide (CO) can provide beneficial antiapoptotic and anti-inflammatory effects in the context of ischemia-reperfusion injury (IRI). Here we tested the ability of pretreating the kidney donor with carbon monoxide-releasing molecules (CORM) to prevent IRI in a transplant model. Isogeneic Brown Norway donor rats were pretreated with CORM-2 18 h before kidney retrieval. The kidneys were then cold-preserved for 26 h and transplanted into Lewis rat recipients that had undergone bilateral nephrectomy. Allografts from Brown Norway to Lewis rats were also performed after 6 h of cold ischemic time with low-dose tacrolimus treatment. All recipients receiving CORM-2-treated isografts survived the transplant process and had near-normal serum creatinine levels, whereas all control animals died of uremia by the third post-operative day. This beneficial effect was also seen in isografted Lewis recipients receiving kidneys perfused with CORM-3, indicating that CORMs have direct effects on the kidney. Pretreatment of human umbilical vein endothelial cells in culture with CORM-2 for 1 h significantly reduced cytokine-induced nicotinamide adenine dinucleotide phosphate-dependent production of superoxide, activation of the inflammation-relevant transcription factor nuclear factor-κB, upregulated expression of E-selectin and intercellular adhesion molecule-1 adhesion proteins, and leukocyte adhesion to the endothelial cells. Thus, CORM-2-derived CO protects renal transplants from IRI by modulating inflammation.

Acute Page Kidney Following Renal Allograft Biopsy: A Complication Requiring Early Recognition and Treatment

The acute Page kidney phenomenon occurs as a consequence of external compression of the renal parenchyma leading to renal ischemia and hypertension. Between January 2000 and September 2007, 550 kidney transplants and 518 ultrasound‐guided kidney biopsies were performed. During that time, four recipients developed acute oligo‐anuria following ultrasound‐guided allograft biopsy. Emergent doppler‐ultrasounds were performed demonstrating absence of diastolic flow as well as a sub‐capsular hematoma of the kidney. Prompt surgical exploration with allograft capsulotomy was performed in all cases. Immediately after capsulotomy, intraoperative Doppler study demonstrated robust return of diastolic flow. Three patients maintained good graft function, and one kidney was lost due to acute antibody‐mediated rejection. We conclude that postbiopsy anuria associated with a subcapsular hematoma and acute absence of diastolic flow on doppler ultrasound should be considered pathognomonic of APK. All renal transplant specialists should be able to recognize this complication, because immediate surgical decompression can salvage the allograft.

Dual-kidney transplants as an alternative for very marginal donors: long-term follow-up in 63 patients.

Background. Organ shortage has led to the use of dual-kidney transplant (DKT) of very marginal donors into a single recipient to increase the use of marginal organs. To date, few data are available about the long-term outcome of DKT and its usefulness to increase the pool of available organ. Methods. We conducted a single-center cohort study of DKTs with longitudinal follow-up over an 8-year period. Between 1999 and 2007, 63 DKTs were performed. All kidneys from donors younger than 75 years refused by all centers for single transplantation, and kidneys from donors aged 75 years or older were routinely evaluated based on preimplantation glomerulosclerosis. Renal function, patient or graft survival, and perioperative complications were compared with 66 single kidneys from expanded criteria donors (ECD) and 63 ideal kidney donors. Results. After a median follow-up of 56 months, patient or graft survival was similar between the three groups. Twelve-, 36-, and 84-month creatinine clearance were similar for DKT and ECD (12 months: 58 and 59 mL/min; 36 months: 54 and 60 mL/min; and 84 months: 62 and 51 mL/min, respectively). For the study period, the routine evaluation of very marginal kidneys for DKT in our center has led to an increase of 47% in the transplants from donors aged 50 years or older, which represent 12% at the level of our organ procurement organization. Conclusions. DKT patients can expect long-term results comparable with single kidney ECD. The implementation of a DKT program in our unit safely increased the pool of organs from marginal donors.

Chylous ascites as a complication of laparoscopic donor nephrectomy.

Laparoscopic living donor nephrectomy (LLDN) is a minimally invasive technique for kidney procurement and was developed with the hope of reducing the disincentives associated with live renal donation. Compared with open donor nephrectomy (ODN), this alternative has many advantages including less postoperative pain and earlier return to work. Unfortunately, these benefits are sometimes negated by postoperative complications. Among these, chylous ascites (CA) is a rare but serious problem that is usually managed conservatively. We report the case of a living donor who developed CA refractory to initial conservative management and surgical treatment. We also discuss the role of surgery in the treatment of CA following LLDN.

Donor-specific antibodies, C4d and their relationship with the prognosis of transplant glomerulopathy.

Background Transplant glomerulopathy (TG) is a diagnostic criterion for chronic active antibody-mediated rejection (CAABMR), with C4d, donor-specific antibodies (DSA) and other lesions of chronic tissue injury. However, TG often presents without C4d or DSA. Until recently, such cases were termed suspicious for CAABMR, and their prognosis remains unclear. Methods To better understand the contribution of TG, C4d, and DSA on outcomes, we retrospectively studied 61 patients with late TG for the composite endpoint of death-censored graft failure or doubling of serum creatinine. Cases were matched to controls based on age, year and number of transplant, type of donor, and the availability of an indication biopsy during the same time after transplantation. Analyses were performed using proportional hazards models. Results Compared to matched controls, patients with TG had a more than fivefold increased risk of reaching the endpoint (adjusted hazard ratio (aHR), 5.3; 95% confidence interval (95% CI), 1.5-18.4). The proportion of patients with isolated TG, TG suspicious for CAABMR (C4+/DSA− or C4d−/DSA+) and TG with definite CAABMR (C4d+/DSA+) were 63%, 20%, and 17%, respectively. Suspicious and definite CAABMR showed a similar prognosis, significantly worse than isolated TG (aHR, 4.5; 95% CI, 1.1-18.9 and aHR, 5.9, 95% CI, 1.1-31.3 respectively). Conclusion Transplant glomerulopathy is associated with poor prognosis, independent of the level of graft dysfunction and other chronic histologic changes. This prognosis is similar whether there is evidence of tissue or peripheral alloantibody reactivity. These findings are relevant to the development of clinically meaningful criteria for CAABMR, for its clinical management, and in the future selection of population for clinical trials.

Extracapsular versus intracapsular allograft nephrectomy: impact on allosensitization and surgical outcomes

INTRODUCTION Our objective was to compare the impact of extra-capsular (ECAN) versus intracapsular allograft nephrectomy (ICAN) on allosensitization and surgical outcomes. METHODS Between 1990 and 2004, 96 allograft nephrectomies were performed at our institution. Of these, 29 procedures were performed within 1 month of the transplant and were therefore omitted from analysis. Overall, the results of 44 ECAN and 23 ICAN were reviewed. RESULTS The mean operative times were 110.9 versus 130.4 min for ICAN versus ECAN (p = 0.02) and the estimated blood loss was 226 mL for ICAN versus 483 mL for ECAN (p = 0.004). Intraoperative and postoperative complications were low using either technique and differences were not statistically significant. Overall, the preoperative to postoperative change in the percentage of panel reactive antibody was +2.1% for ICAN versus +1.2% for ECAN (NS) at 3 to 12 months postoperatively, respectively (NS). The percentage of patients relisted was 33.3% versus 54.3% (NS), and the percentage of patients re-transplanted once relisted was also very similar: 63.2% for ECAN versus 66.7% for ICAN (NS), after a mean follow-up of 4.5 and 8.4 years, respectively. CONCLUSIONS ICAN can be performed with shorter operative times and less blood loss versus the extracapsular approach. As well, this operative approach does not appear to affect allosensitization and the ability to re-transplant patients.

Robot-Assisted Pyeloplasty: Follow-Up of First Canadian Experience with Comparison of Outcomes Between Experienced and Trainee Surgeons

BACKGROUND AND PURPOSE Robot-assisted pyeloplasty (RAP) has been established recently as an option in the management of ureteropelvic junction obstruction (UPJO). We present the first Canadian experience with RAP with respect to operative results and outcomes. We compare the surgical outcomes between experienced and trainee surgeons, with respect to operating room times and success rates. PATIENTS AND METHODS Eighty-eight patients underwent transperitoneal RAP for UPJO using the da Vinci robotic platform. Two surgeons performed Anderson-Hynes dismembered pyeloplasty in 85 cases and YV-plasty in 5 cases. Five patients had RAP for secondary UPJO after failure of other treatments. Diuretic renography was performed at 6 weeks, and 6, 12, 18, 24, and 36 months postpyeloplasty. The mean follow-up was 14.1 ± 8.5 months. RESULTS The mean operative time was 167.7 ± 43.2 minutes, and the mean anastomotic time was 41.9 ± 14.1 minutes. The mean operative duration significantly decreased with time (P < 0.05). Ten patients needed simultaneous nephroscopic stone management via the pyelotomy incision. The mean blood loss was 56.6 ± 55.4 mL, and the mean hospital stay was 2.5 ± 0.5 days. There were five major postoperative (stent migration, urinoma) and three minor complications that were associated with the RAP procedures. Postoperative renal scintigraphy demonstrated only four cases with persistent obstruction. Eighty-three (94.3%) patients experienced improvement of symptoms whereas 5 continued to be symptomatic. Two patients needed secondary procedures to relieve persisting obstruction. There were no statistical differences in outcomes between the experienced surgeons and trainees (P = 0.28). CONCLUSIONS In the first large case series of RAP from Canada, we demonstrate that RAP can be performed with relatively short operative times and is safe and effective, achieving similar long-term results with standard open repair. We show that robot-assisted surgery can be safely transitioned to surgical trainees. With its cost and availability, its role in the Canadian system needs further study.

Preoperative Cylex assay predicts rejection risk in patients with kidney transplant.

The ImmuKnow assay measures cell‐mediated immunity by quantifying ATP release from CD4+ T‐cells in peripheral blood. Herein, we hypothesized that this assay could predict complications associated with over‐/under‐immunosuppression in patients with kidney transplant (KT).

Perfusion of Renal Allografts with Verapamil Improves Graft Function

The effect of adding a calcium channel antagonist to kidney allograft perfusate solution was assessed. All renal transplants in which both kidneys from the same donor used for transplantation were studied between November, 2003 and August, 2005 (n=46). The first renal allograft was perfused on the backtable with 1 L of histidine-tryptophan-ketoglurate solution and the second with 1 L of histidine-tryptophan-ketoglurate with 5 mg/L of verapamil. Both organs were transplanted in the usual manner. Baseline demographic parameters were similar between first and second kidney recipients other than BMI and cold ischemic time. At 6 and 12 months, renal function was significantly improved in the verapamil versus control cohort (creatinine clearance 73.8±23.5 mL/min vs. 55.8±17.0 mL/min, P<0.05 and 87.5±28.4 mL/min vs. 59.7±21.3 mL/min, P<0.05 respectively). Additionally, rates of hypotension during graft reperfusion and other adverse reactions were similar in both groups. In conclusion, verapamil supplemented perfusate significantly improved renal function posttransplantion.

Outcome of third renal allograft retransplants versus primary transplants from paired donors.

Background. Third kidney retransplants have technical and immunologic hurdles that may preclude success, which is of particular importance in the contemporary context of discrepancy between organ supply and demand. Methods. The outcomes of third renal transplant recipients (TRTR) were compared with those receiving a first transplant from paired donor kidneys to assess transplant success and complication rates. The Ontario-based Trillium Gift of Life Network database was used to identify deceased donors (n=28) who donated one kidney to a TRTR and the mate kidney to a primary renal transplant recipient (PRTR) from June 1977 to August 2006. Results. As anticipated, TRTR were sensitized versus PRTR based on % panel reactive antibodies (24%±34% vs. 7%±14%, P=0.03). Delayed graft function (46% vs. 22%, P=0.05) and biopsy-proven rejection episodes (50% vs. 29%, P=0.01) occurred more frequently with TRTR despite greater frequency of induction therapy (74% vs. 35%, P=0.004). However, 1- and 5-year patient survival were similar at 93%, 83% and 96%, 87% for TRTR and PRTR, respectively. Accordingly, 1- and 5-year allograft survival censored for mortality, were comparable at 78%, 66% and 78%, 75%. Renal function was similar in both groups. Bacterial infections (43% vs. 18%, P=0.001) and wound problems (28% vs. 11%, P=0.09) were the only postoperative complications to occur more frequently in the TRTR. Conclusion. We conclude that third renal transplantation should not be discouraged based on functional outcomes alone.