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The results of 88 cadaver-donor renal first transplants from the Newcastle Transplantation Centre have been reviewed after a minimum period of 6 months post transplant. They show the significant benefit of two antigen identity at the second HL-A locus between kidney donor and recipient. Pretransplant blood transfusion showed a beneficial effect on kidney survival. Cases with preformed cytotoxic antibodies showed a favourable outcome compared to cases without antibody, provided the crossmatch was negative. Rh(D) positive recipients showed a significant association with satisfactory outcome when compared to the Rh(D) negative recipients.

To determine whether skeletal muscle function testing (SMF) provides an index of nutritional status in patients with chronic renal failure (CRF), two groups with comparable CRF were studied. In 48 well-nourished (WN) and 17 malnourished (MN) patients with stable CRF, and in 33 WN nonazotemic controls, adductor pollicis function was assessed. The force at 10 Hz was expressed as a % of force at 100 Hz (F10/F100), and maximal relaxation rate (MRR) as % force loss/10 ms. Standard nutritional assessment was also performed. The WN group was not significantly different from controls for either F10/F100 or MRR. The F10/F100 of the MN group was significantly greater than either the WN group or controls (p less than 0.001), while MRR was less (p less than 0.001). Significant malnutrition by conventional parameters was shown in patients with abnormal F10/F100, and also in patients with abnormal MRR. Hence, SMF as described is unaffected by azotemia, and provides a functional measure of nutritional status in CRF.

A double-blind controlled trial has been undertaken to assess the value of a preparation containing polyunsaturated fatty acids (PUFA) in human cadaveric renal transplantation. Eighty-nine patients were studied and followed for 6 months after transplantation. Forty-four took the PUFA preparation and 45 the placebo (oleic acid). Other immunosuppression was standardised. Functional graft survival was significantly better in the PUFA group than in those taking the placebo during the first 3 to 4 months post-transplant. At 6 months, however, although the difference between the groups persisted, it was no longer statistically significant. Complications were equally distributed between the groups.

Summary Lowering of lipids in patients with chronic renal failure is advantageous but cannot be done by calorie restriction. In a controlled study the anabolic steroid norethandrolone (Nilevar) was found to lower triglycerides by 50%, while D-thyroxine (Choloxin) lowered the cholesterol by 25%. Both drugs increased the activity of lipoprotein lipase in spite of uraemic inhibition. Norethandrolone also reduced basal serum insulin levels. Norethandrolone seems appropriate for underweight patients and D-thyroxine for overweight patients, but side effects are more frequent than in non-uraemic patients.

The investigation, management and clinical course of 12 patients developing stenosis of the renal artery following transplantation are described. The possible aetiology of the three arteriographic patterns of stenosis is discussed. Surgical correction of graft arterial stenosis is difficult and may lead to graft loss, whereas the outcome with antihypertensive drug treatment with or without anticoagulants is good. Surgery should only be contemplated if medical treatment is failing or if renal function is deteriorating.

Studies of serum proteins, platelets, and fibrinolysis in patients after renal allografting show that a fall in plasma fibrinogen in the postoperative period can be associated with early rejection and that a rise in serum fibrin degradation products when accompanied by a fall in platelets is associated with rejection. Fibrinolysis is depressed in these patients until two months after transplantation and marked depression of fibrinolysis may precede rejection. The late coincidence of fibrinolytic depression with a rise in fibrin degradation products suggests chronic insidious rejection.

SUMMARY Experiments are described which show the effect of cold on the kidneys of rats and dogs. In attempts to preserve these in a viable state problems have been revealed caused by the prolonged perfusion with physiological solutions and the use of di–methylsulfoxide. The adverse effects have been partially solved, but further study is necessary.

Two to six years after they had donated a kidney the 24-hour creatinine clearances of five women and four men had recovered to 85% and 87% respectively of prenephrectomy performance. The male donors had a lower 24-hour creatinine clearance than age-matched controls, but during dextrose and inulin infusion they had similar values for inulin clearance, creatinine clearance, and glucose reabsorption. By contrast, the female donors had significantly reduced clearances both over 24 hours and during infusion, as well as impaired ability to reabsorb glucose. This suggests that potential female donors should be more vigorously investigated before nephrectomy.

The phagocytic capacity of the reticuloendothelial system (R.E.S.) was assessed in patients with chronic renal failure and in renal transplant recipients. R.E.S. phagocytosis was increased in the former group. Soon after transplantation R.E.S. phagocytosis was moderately reduced (through levels were comparable with those of normal controls) but was particularly reduced after high-dose corticosteroid treatment for rejection. In long-term allograft recipients R.E.S. phagocytosis was also depressed though steroid maintenance doses were small.

In an analysis of a series of 186 consecutive first cadaver renal transplants in Newcastle upon Tyne, the most significant finding was the improved graft survival in patients who received pre-transplant blood-transfusion. This apparent benefit was not dependent on the number of units of blood received nor on the interval between transfusion and transplantation. A significant advantage was also shown when there was identity between donor and recipient at the HLA-B locus. This advantage outweighs any disadvantage resulting from the extra time required to transfer kidneys from one centre to another and indeed cold-ischaemia times up to 18 hours did not adversely affect graft survival. It is suggested that the present national distribution of cadaver kidneys in the U.K. is fully justified, but preference should be given to B-locus identity in determining selection.

A case study demonstrating a scheme for the management of a renal tr ansplant recipient prior to conception and during gestation delivery and the puerperium is presented. During pregnancy the physiological changes in homeostasis of normal pregnancy were present. The monitoring of maternal fetal and renal health is described and discussed. The woman delivered a live preterm male child. The postpartum period was uneventful. Careful evaluation of the patient indicated that the pregnancy did not impair renal function.

The clinical and histopathological features of 37 patients with idiopathic membranous nephropathy are presented. Males were four times as commonly affected as females and the age at presentation ranged from nine to 70 years. The period of observation varied from three months to 23 years. Twenty-eight patients (76 percent) presented with the nephrotic syndrome and nine patients (24 per cent) presented with non-nephrotic proteinuria. At the end of the study, of the patients presenting with the nephrotic syndrome, seven (25 per cent) were in remission, seven (25 per cent) remained nephrotic, nine (32 per cent) showed only proteinuria and five (18 per cent) were dead or on dialysis. Altogether eight patients (28 per cent) developed renal failure. The nine patients who presented with non-nephrotic proteinuria appeared to do better, and none developed renal failure. The occurrence of spontaneous remission makes assessment of benefit from immunosuppressivet herapy difficult. However, analysis of our data and a review of the literature suggest that in this condition oral prednisone, cyclophosphamide and azathioprine have no significant therapeutic properties. Histological assessment confirmed the occurrence of mild (Grade 1) changes in patients biopsied soon after presentation, and tubular atrophy increased with the duration of illness. Immunofluorescence confirmed deposition of mainly IgG and complement. Repeat biopsies in 14 patients showed no histological improvement and remission was not accompanied by resolution of histological abnormalities.

Among 39 patients treated by regular haemodialysis for four years or more pathological fractures and histological evidence of osteomalacia were significantly more common in those taking barbiturates. Out of 58 transplant recipients surveyed after one year, seven had osteomalacia; four of these had been taking phenobarbitone and phenytoin and one had taken barbiturates alone. Sedatives and other drugs such as phenobarbitone and phenytoin that induce hepatic microsomal enzymes should probably be avoided when possible in patients with chronic renal failure and after transplantation.

This study included patients, all relatives with the haemolytic uraemic syndrome, and 18 family members. The diagnosis was uncertain in one patient, probable in one other and definite in four patients. Three of these four comprised a father and two of his children. Data are presented to emphasize the widespread nature of the disease. Other than hypertension, predisposing factors, and red cell and HL-A genetic markers, although sought, have not been found. Management is discussed with special reference to the one surviving patient. Early bilateral nephrectomy may be life-saving.

Assessment of 78 successful renal transplants carried out in Newcastle upon Tyne between October 1967 and March 1973, revealed avascular necrosis of bone (A.N.) in 11 patients (14 percent). Pain and restriction of movement were the cardinal symptoms, while the onset was from five to 35 months after transplantation. In some patients one joint only was affected but in seven patients (64 per cent) A.N. developed in other joints too in an additive and progressive fashion. A time lag was usually noted between the onset of symptoms and radiological proof. These 11 patients with A.N. were compared with two control groups of unaffected renal transplant patients. Taking into account the patients' body weight, the cumulative dose of prednisone received by affected patients during the first three post-transplant months was found to be significantly higher than that for both control groups (P less than 0.05). Patients with A.N. were found to have had an unusually high incidence of early post-transplant surgical complications and the length of their initial stay in hospital was significantly prolonged (P less than 0.02) when compared to both control groups. It is possible that excessive corticosteroid therapy is more deleterious in transplant patients weakened by peri-renal haematomas, urinary extravasations and stormy prolonged post-operative periods. Having emphasized the detrimental effects of excessive anti-rejection corticosteroid therapy it must be mentioned that occasionally patients develop avascular necrosis even after low doses of steroid therapy, while others, receiving high doses of steroid therapy and undergoing a stormy post-operative course, do not develop this complaint. It is suggested that although excessive steroid therapy is positively harmful, avascular necrosis is not an invariable complication and that ofther factors including possibly a genetic predisposition operate to produce avascular necrosis of bone in renal transplant patients.

The effect of short-term administration of heparin has been studied in seven patients with oliguric glomerulonephritis, five with accelerated hypertension, and three with transplant rejection. Measurements were made of the glomerular filtration rate, radiofibrinogen catabolism, and complement inhibition. Beneficial effects on fibrinogen catabolism were found in some cases of accelerated hypertension and transplant rejection, but heparin alone had no dramatic effect in glomerulonephritis. Heparin produced an increase of glomerular filtration rate, but in-vivo inhibition of complement by heparin was small.

Uldall, P. R., Khan, H. A., Ennis, J. E., McCallum, R. I., and Grimson, T. A. (1970). Brit. J. industr. Med., 27, 372-377. Renal damage from industrial arsine poisoning. An incident is reported in which three men were accidentally poisoned by arsine (A s H 3 ) in an industrial chemical plant. Two mildly affected individuals recovered quickly-without treatment but the third, who was severely poisoned, developed oliguric renal failure. Though this patient recovered after repeated peritoneal dialysis he was left with a legacy of chronic renal insufficiency and hypertension. This severe case drew attention to a previous incident in the same factory involving three other men, the cause of which had not hitherto been suspected. The previous reports of arsine-induced renal failure treated by dialysis have been reviewed and certain common features are apparent. Dangerous uraemia may persist long after the onset of the diuretic phase. Dialysis provides a high chance for recovery in what was previously a universally fatal condition, but permanent renal interstitial damage is a likely sequel. There are strong reasons for the prompt use of exchange transfusion in the severely affected patient with oliguria. Mild arsine poisoning unaccompanied by oliguria may remain unrecognized and should therefore be considered in the differential diagnosis of any patient presenting with haematuria or jaundice, particularly if his occupation brings him in contact with acids and metals.

Ten adults with minimal-change nephrotic syndrome, eight of whom had failed to respond satisfactorily to steroid therapy, have been treated with cyclophosphamide. Eight patients are now in remission with protein-free urine 2-46 months after withdrawal of all treatment. The remaining two patients have had a partial remission. The only serious side-effect was permanent secondary amenorrhoœa in a 31-year-old woman treated with cyclophosphamide for 20 months. It is suggested that cyclophosphamide should be tried in any adult with minimal-change nephrotic syndrome who does not respond to prednisone within 2 months.

• Using the clearance of microaggregated iodinated human serum albumin reticuloendothialial system (RES) phagocytic function was tested in 48 long-term renal allograft recipients and was found to be defective at the time of testing in 70%. Depression of RES phagocytosis could be related to total steroid dosage in the previous year and to the patients liability to bacterial infections. Evidence from this test does not suggest an immunosuppressive effect of cytomegalovirus. However, three patients are discussed who have developed chronic active hepatitis that is not due to type B virus. ( Arch Surg 111:1368-1371, 1976)