The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study.

University of Wisconsin (UW) solution is not optimal for preservation of marginal organs. Polyethylene glycol (PEG) could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on kidney endothelial cells, ex vivo on preserved kidneys, and in vivo in a pig kidney autograft model. In vitro, all PEGs provided superior preservation than UW in terms of cell survival, adenosine triphosphate (ATP) production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L).

Role of warm ischemia on innate and adaptive responses in a preclinical renal auto-transplanted porcine model.

BACKGROUND: Deceased after cardiac arrest donor are an additional source of kidney graft to overcome graft shortage. Deciphering the respective role of renal warm and cold ischemia is of pivotal interest in the transplantation process. METHODS: Using a preclinical pig model of renal auto-transplantation, we investigated the consequences of warm and cold ischemia on early innate and adaptive responses as well as graft outcome. Kidneys were subjected to either 60 min-warm ischemia (WI) or auto-transplanted after cold storage for 24 h at 4°C (CS), or both conditions combined (WI+CS). Renal function, immune response and cytokine expression, oxidative stress and cell death were investigated at 3 h, 3 and 7 days (H3, D3 and D7) after reperfusion. At 3 months, we focused on cell infiltration and tissue remodelling. RESULTS: WI + CS induced a delayed graft function linked to higher tubular damage. Innate response occurred at D3 associated to a pro-oxidative milieu with a level dependent on the severity of ischemic injury whereas adaptive immune response occurred only at D7 mainly due to CS injuries and aggravated by WI. Graft cellular death was an early event detected at H3 and seems to be one of the first ischemia reperfusion injuries. These early injuries affect graft outcome on renal function, cells infiltration and fibrosis development. CONCLUSIONS: The results indicate that the severe ischemic insult found in kidneys from deceased after cardiac arrest donor affects kidney outcome and promotes an uncontrolled deleterious innate and adaptive response not inhibited 3 months after reperfusion.

Chronic renoprotective effect of pulsatile perfusion machine RM3 and IGL-1 solution in a preclinical kidney transplantation model.

BACKGROUND: Machine perfusion (MP) of kidney graft provides benefits against preservation injury, however decreased graft quality requires optimization of the method. We examined the chronic benefits of MP on kidney grafts and the potential improvements provided by IGL-1 solution. METHOD: We used an established autotransplantation pig kidney model to study the effects of MP against the deleterious effects of warm ischemia (WI: 60 minutes) followed by 22 hours of cold ischemia in MP or static cold storage (CS) followed by autotransplantation. MPS and IGL-1 solutions were compared. RESULTS: Animal survival was higher in MPS-MP and both IGL groups. Creatinine measurement did not discriminate between the groups, however MPS-MP and both IGL groups showed decreased proteinuria. Chronic fibrosis level was equivalent between the groups. RTqPCR and immunohistofluorescent evaluation showed that MP and IGL-1 provided some protection against epithelial to mesenchymal transition and chronic lesions. IGL-1 was protective with both MP and CS, particularly against chronic inflammation, with only small differences between the groups. CONCLUSION: IGL-1 used in either machine or static preservation offers similar levels of protection than standard MP. The compatibility of IGL-1 with both machine perfusion and static storage could represent an advantage for clinical teams when choosing the correct solution to use for multi-organ collection. The path towards improving machine perfusion, and organ quality, may involve the optimization of the solution and the correct use of colloids.

Total laparoscopic renal artery bypass for restenosis after failed percutaneous transluminal renal stenting.

OBJECTIVE: The purpose of this article was to report our experience of the repair of renal artery restenosis after percutaneous transluminal renal angioplasty (PTRA) using a total laparoscopic technique without robotic assistance. METHODS: Between February 2005 and October 2009, we performed six total laparoscopic aortorenal artery bypasses for restenosis after failed PTRA. All these patients had recurrent hypertension with renal insufficiency. RESULTS: The mean operative time was 246 minutes (range, 200-310 minutes). The mean warm renal ischemic time was 28 minutes (range, 22-35 minutes). All patients received a prosthetic graft interposition. The estimated surgical blood loss was 980 mL (range, 500-1400 mL). No conversion was observed and no in-hospital deaths occurred. There was no severe postoperative morbidity. Postoperative serum creatinine levels raised in all patients but all returned to baseline before discharge. Median length of postoperative hospital stay was 6 days (range, 4-8 days). Median follow-up was 13 months (range, 7-19 months). Color Doppler ultrasound scan examination and computed tomography (CT) with injection of contrast media showed patency of all bypasses. Hypertension was improved in all patients but renal insufficiency remained unchanged. CONCLUSION: Total laparoscopic renal artery bypass is feasible and safe in patients after failed PTRA. This approach may reduce the morbidity of open repair but is technically demanding and necessitates a large previous experience in total laparoscopic aortic surgery.

Does the risk of compressive hematoma after thyroidectomy authorize 1-day surgery?

BACKGROUND: Compressive hematoma after thyroidectomy is a rare complication (1%) but can potentially be severe. The aim of this study was to search for risk factors, in particular the use of anticoagulants or antiplatelet medication, and to see if the delay of hematoma formation would require 1-day surgery performed in a careful manner. MATERIALS AND METHODS: Retrospective review of 6,830 patients undergoing thyroidectomy in a single institution (1991 to 2006) identified 70 patients with hematomas requiring reoperation. Case controls (210 patients) were matched for age, gender, year of operation, type of thyroid disease, and type of operation. The notion of anticoagulant or antiplatelet medication was particularly studied. The delay of hematoma formation and the cause of bleeding were studied in univariate analysis by a chi-squared test and a Fischer's test. RESULTS: In univariate analysis, the formation of hematoma is not related to age, gender, type of thyroid disease, or type of bleeding. The pre or intraoperatory administration of anticoagulant or antiplatelet medication did not influence hematoma formation. Thirty-seven hematomas (53%) presented within 6 h postoperatively, 26 (37%) between 7 and 24 h and seven (10%) beyond 24 h. CONCLUSION: Patients undergoing anticoagulant or antiplatelet treatment are not a high-risk population for hematoma formation. Forty-seven percent of the patients presented postoperative hematomas beyond 6 h postoperatively, leading to the conclusion that 1-day surgery is not safe.