Michael Bewick

Transplant renal artery stenosis in 77 patients--does it have an immunological cause?

Transplant renal artery stenosis (TRAS) is a common complication after transplantation and is an important cause of graft dysfunction. Damage from graft rejection, trauma, and atherosclerosis have been implicated as possible causes. We reviewed all 917 patients transplanted in our unit since 1978 to study the prevalence, clinical features, and possible causes of TRAS. Seventy-seven patients with TRAS were identified. The detected incidence was 2.4% before the introduction of color doppler ultrasonography (CDU) and rose to 12.4% after CDU was introduced in 1985, giving an overall incidence of 8.4% during a mean follow-up period of 6.9 years. The TRAS group was compared with a control group of 77 transplanted patients matched for age, year of transplant, sex, and number of previous grafts. Mean ages for the study and control groups were 43.6 +/- 15 and 44.8 +/- 13.7 yr. A total of 25% of cases of TRAS were diagnosed within the first 8 wk of transplantation and in 60% within the first 30 wk (median = 23 wk). All patients were treated with angioplasty, 28 patients had recurrence of TRAS requiring multiple angioplasties (maximum 5) and 1 went on to have surgery. Angioplasty resulted in a significant fall in plasma creatinine. Patient and graft survival were significantly worse in the TRAS group: 69% vs. 83% (P < 0.05) and 56% vs. 74% (P < 0.05) (TRAS vs. Control), respectively. There was a significantly higher incidence of rejection, especially cellular rejection in the TRAS group, 0.67 vs. 0.35 episodes per patient (P < 0.01) (TRAS vs. Control). Recurrence but not occurrence of TRAS was associated with the use of cyclosporine.

Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation

BACKGROUND Many patients with circulating antibodies to human leucocyte antigens (anti-HLA) are highly sensitised against renal transplantation and are liable to immediate graft loss through hyperacute rejection. Our aim was to find out whether removal of anti-HLA immediately before renal transplantation prevented hyperacute graft rejection. METHODS 13 highly sensitised patients underwent cadaveric renal transplants immediately after immunoadsorption (IA) treatment to remove anti-HLA. Before IA, 12 patients had a positive crossmatch against donor cells either by cytotoxic or flow-cytometric assay; results for one patient were equivocal. FINDINGS Renal biopsy samples were obtained 20 min after removal of the vascular clamps in nine patients. There was no evidence of hyperacute rejection in six of the nine patients; the other three patients showed glomerular thrombosis but no other evidence of hyperacute rejection. Two of these three grafts were functioning at 31 months of follow-up. Six episodes of acute rejection occurred in five patients during the first month after transplantation and overall there were 13 rejection episodes in nine patients. At latest follow-up (median 26 months, range 9-42), 12 of 13 patients were alive and seven of 13 grafts were surviving with a median plasma creatinine concentration of 185 mumol/L (range 106-296) in the functioning grafts. No graft was lost as a result of classic hyperacute rejection. INTERPRETATION Immediate pretransplant IA can prevent hyperacute rejection and provide an opportunity for successful transplantation in highly sensitised patients.

Survival on home haemodialysis: its relationship with physical symptomatology, psychosocial background and psychiatric morbidity.

An entire group of 32 home dialysis patients from one hospital renal unit was assessed for psychiatric morbidity on a standardized interview of proven reliability. A rating of physical symptomatology and an enquiry into the childhood and psychosocial background were made at the same time. Psychiatric morbidity, physical symptomatology and a history of good relationships with both natural parents in childhood were inter-related. They were all related to survival on haemodialysis 3 1/2 years later. Survival was also associated with a coping spouse and full-time employment or housework by the patient. These findings are discussed in the light of current concepts of the psychosocial setting for physical illness.

5-Year Follow-Up of Patients Successfully Transplanted after Immunoadsorption to Remove Anti-HLA Antibodies

The function of renal allografts in patients who had received pretransplant immunoadsorption in order to remove cytotoxic anti-HLA antibodies was studied. We reviewed 6 patients who received a graft which functioned beyond 3 months; the mean follow-up period was 76 (range 62-89) months. Two grafts have been lost from chronic rejection, at 12 and 62 months, respectively. The mean plasma creatinine levels at 1 and 5 years were 169 (range 143-211) mumol/l and 155 (range 92-235) mumol/l, respectively (1.91, range 1.62-2.39, mg/dl and 1.75, range 1.04-2.66 mg/dl, respectively). The major source of morbidity during long-term follow-up has been the occurrence of renal artery stenosis in 5 patient and renal vein stenosis in 1. In conclusion, the 5-year graft survival and function was good in patients who received immunoadsorption and whose grafts survived beyond the first 3 months after transplantation.

Canine pancreatic endocrine function after interruption of pancreatic exocrine drainage.

Pancreatic endocrine function was studied in forty dogs after ligation or free i.p. drainage of the pancreatic duct, with or without simultaneous partial pancreatectomy. Shrinkage and fibrosis of the pancreas occurred in all dogs, with equal severity in the open duct and duct-tied groups. Fasting blood sugars remained within the normal range but fasting levels of plasma insulin and glucagon were reduced. Dynamic tests of endocrine function indicated that partial pancreatectomy reduced the insulin response to i.v. injection of dextrose or glucagon and delayed the reestablishment of glucose homeostasis. Glucose tolerance was normal in dogs with intact pancreases, but duct ligation was associated with deteriorating recovery after glucagon injection. The precise coordination of circulating glucose, insulin, and glucagon levels seen in normal dogs was lost in both partial and intact pancreas groups and these disturbances were attributed to the fibrotic changes arising from interference with the ductal drainage. Both ligation and free i.p. drainage of the pancreatic duct therefore resulted in abnormalities of islet function. When combined with partial pancreatectomy, both techniques were associated with significant pancreatic endocrine insufficiency.

Progressive, predominantly motor, uraemic neuropathy

ABSTRACT – A severe rapidly progressive neuropathy is described in 4 young male adults with end‐stage renal failure, 3 of whom had accelerated hypertension. The onset of symptoms developed after regular haemodialysis had been started and in all 4 patients was closely associated with a septicaemic illness. In 2 patients, renal transplantation led to considerable clinical improvement, and in a third patient charcoal haemoperfusion halted further clinical progression of the neuropathy. This improvement was not reflected by the nerve conduction studies which remained grossly impaired. A possible ischaemic aetiology related to accelerated hypertension and septicaemia is suggested for this unusual variant of uraemic neuropathy.