Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not major renal ischaemic injury.

BACKGROUND: CD11/CD18 beta(2) integrins are involved in leukocyte adhesion to the activated endothelium, and therefore represent a possible therapeutic target in the prevention of ischaemic acute renal failure (ARF). METHODS: To assess the effect of an anti-CD11b monoclonal antibody (mAb) in ischaemic ARF, uninephrectomized Fischer rats were subjected to 45 or 60 min of warm renal ischaemia, then received 1 mg of anti-CD11b mAb 5 min before reperfusion. RESULTS: After 45 min of ischaemia, renal function tests at 24 and 48 h were less altered in mAb-treated than in control rats, but after 60 min of ischaemia the same level of renal insufficiency was observed in the two groups. In parallel, milder tubular necrosis and less leukocyte infiltration were observed in the treated group after 45 min of ischaemia, but no difference was seen after 60 min compared to the control group. The mAb was detected on blood neutrophils up to 48 h after infusion and a marked down-regulation of CD11b expression on neutrophil surfaces was documented by flow cytometry. CONCLUSION: These results indicate that anti-CD11b mAb administered prior to reperfusion decreases moderate ischaemic ARF but fails to prevent renal injury secondary to prolonged ischaemia in this model.

Effects of portal versus systemic venous drainage in kidney-pancreas recipients.

A randomized study of combined kidney-pancreas transplantation was performed on 30 insulin-dependent diabetic patients with end-stage renal disease to compare the consequences of pancreas transplantation with portal venous (PV) and systemic venous (SV) drainage. Fourteen patients (SV) group) received systemically drained and sixteen (PV group) portally drained pancreas allografts. Enteric drainage was performed in both groups. The routine follow-up included documentation of the clinical course and detailed endocrine studies. At 1 year after transplantation, the patient survival rate was 92% for the SV group and 96% for the PV group; the graft survival rate was 78% and 82%, respectively. Endocrine studies indicated no difference in fasting and stimulated glucose or in glycosylated hemoglobin between the two groups. In addition, no hyperinsulinemia and lipidic abnormalities were evidenced in either group Long-term studies are required to conclude whether PV and SV drainage in pancreas transplantation are equivalent in terms of patient and graft survival as well as metabolic consequences.

In vivo effects of monoclonal antibodies against rat beta(2) integrins on kidney ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR) involves adhesion of leukocytes to the activated endothelium, leading to tissue damage. CD11/CD18 beta(2) integrins interact with their ligands on endothelial cells and may therefore represent a therapeutic target for the prevention of IR. We investigated the effects of three monoclonal antibodies (mAbs) that recognize epitopes of heavy or light chain of the beta(2) integrins on IR in kidneys. METHODS: Uninephrectomized Fischer rats were subjected to 45 or 60 min of renal ischemia, treated with intravenously anti-beta(2) integrin monoclonal antibodies (anti-CD11a, anti-CD11b, and anti-CD18) 5 min prior to reperfusion, and compared to a nontreated group. Serum creatinine, blood urea nitrogen (BUN), and kidney histopathological damages were assessed at 1, 2, and 7 days after ischemia. RESULTS: After 45 and 60 min of ischemia, serum creatinine and BUN were significantly higher in the control than in animals treated with anti-CD11a and anti-CD18 at 24 and 48 h. Administration of anti-CD11b had a beneficial effect on renal function after 45 min but not after 60 min of ischemia. Histologic and immunostaining studies demonstrated mild tubular necrosis and less leukocyte infiltration in the anti-CD11a- and anti-CD18-treated groups compared to the control group. CONCLUSION: These results indicate that selected antibodies to CD11a/CD18 may decrease kidney IR injury when administered prior to reperfusion.

Effect of the surgical technique on long-term outcome of pancreas transplantation.

To date there is no general consensus as to the best surgical technique for pancreas transplantation. Patients with a pancreas transplant functioning for 3 years or more were retrospectively investigated to compare three surgical techniques: segmental graft with duct obstruction (DO), whole graft with bladder drainage (BD), and whole graft with enteric drainage (ED). Several parameters were studied: patient and graft survival, rejection, long-term surgical and medical complications, and endocrine function. The best results in terms of graft survival and quality of metabolic control were obtained in the group that underwent whole graft transplantation with ED. At 3 years, overall pancreas graft survival was 65% for ED, 60% for BD, and 47% for DO. This surgical method has become the preferred technique in our unit.

[Hazards of lumbar ureteroscopy: apropos of 4 cases of avulsion of the ureter]. / Des dangers de l'urétéroscopie à l'étage lombaire: à propos de 4 cas d'avulsion de l'uretère.

Ureteroscopy is frequently indicated in the treatment of stones of the pelvic ureter. Access to the lumbar ureter is associated with a higher complication rate: wounds, ureteric rupture, haemorrhage, or more serious lesions such as avulsions of the ureter. We present 4 cases of avulsion of the ureter seen in our department, corresponding to 4 men with stones of the lumbar ureter treated by ureteroscopy, 2 of them after failure of in situ extracorporeal lithotripsy (ESWL) and an attempt to "flush" the stone and the other two because ESWL was not available. The ureteric lesion was related to a Dormia catheter in 2 cases and the ureteroscope in 2 cases. The lesion was diagnosed and treated immediately in 2 patients and after a delay in the other 2 cases. Repair consisted of ureteric reimplantation on a Boari flap (1 case), implantation onto a psoas bladder (1 case), ureteroileoplasty (1 case) and autologous transplantation (1 case). Ureteric lesions prevented uretero-ureterostomy. Ureteric reimplantation on psoas bladder and/or Boari flap appears to be the simplest method, but it cannot always be performed. In the case of avulsion of the ureteropelvic junction with a large defect, autologous transplantation is a method of choice in young subjects. Ureteroileoplasty appears to be reserved for elderly patients.

Pancreas transplantation: results and indications.

Pancreatic transplantation is the best method of replacing the endocrine function of the gland in Type 1 insulin-dependent diabetic patients. At the end of 1996, 9,000 pancreas transplants had been reported to the international Pancreas Transplant Registry. For 1994-1996, one-year pancreas survival rates were 81% for simultaneous pancreas and kidney transplantation (n = 1,516), 71% for pancreas after kidney (n = 141) and 64% for pancreas alone (n = 64). In patients with a functional graft, glycosylated haemoglobin, fasting blood sugar, and 24-h metabolic profiles are normal. The effect of pancreatic transplantation on secondary complications often appears after several years of normal pancreatic function. Successful transplantation is associated with an improvement in different aspects of the quality of life. The decision to perform pancreatic transplantation depends on the balance between the risks of transplantation, mainly surgical or related to immunosuppression, and those of diabetes development. The advantages and drawbacks of pancreatic transplantation and insulin therapy need to be honestly and carefully analysed for specific populations of diabetic patients as well as for each individual. At present, simultaneous pancreaticorenal transplantation is the best treatment for diabetic patients with chronic renal failure. Transplantation of the pancreas alone in non-uraemic patients may also be considered in carefully selected subjects.

[Simultaneous allotransplantation of the adrenal gland and the kidney]. / Allotransplantation simultanée de la surrénale et du rein.

Thirteen months after a bilateral nephrectomy for a synchronous bilateral renal cell carcinoma involving both adrenal glands, a 46 years-old man underwent a simultaneous adrenal and kidney allotransplantation. The left renal allograft was harvested together with a ipsilateral adrenal gland using a common aortic patch. Maintenance immunosuppression was based on azathioprine, antilymphocyte globulin cyclosporine and prednisolone. Kidney allograft function remained stable for 5 years until the patient died from multifocal pancreatic metastases. Clinical, biochemical, radiological and histological arguments demonstrated the function of adrenal allograft. To our knowledge, it is the first report of a simultaneous kidney and adrenal gland allotransplantation in a therapeutic intent. An adrenal gland allotransplantation is only justified when the adrenal insufficiency exists with an end stage organ failure requiring transplantation and therefore immunosuppressive drugs.