Renal transplant in a patient with major donor-recipient blood group incompatibility: reversal of acute rejection by the use of modified plasmapheresis.

A 47-year-old patient with blood group O inadvertently received a mismatched kidney from a donor of blood group A. Two days after transplantation, the clinical, biochemical manifestation of an intrarenal, intravascular coagulation was seen. This was treated by plasma exchange with the rapid reversal of all parameters, and reduction of both the IgG and IgM component of the circulating anti-A antibody. The patient, 20 months after transplantation, has normal renal function. Subsequent repeated biopsies have shown no recurrence or manifestation of the effects of the intravascular coagulopathy. This case report documents, for the first time, the reversal of the known deleterious effects of major blood group incompatibility on renal transplantation by the use of a new technique, modified plasmapheresis. Furthermore, it implies that the limitation of transplantation of kidneys on the basis of major ABO blood groups may not be justifiable in all instances.

The role of plasmapheresis in renal transplantation.

Plasmapheresis has been studied in ten patients who received cadaveric renal allografts. In six patients (group A), plasma was carried out on the first post-operative day and then on alternate days until six treatments had been completed. No beneficial effect was observed but treatment was well tolerated and there were no complications. One patient retains a functioning graft. Plasma exchange was carried out on six consecutive days in five patients (group B) who were actively rejecting their grafts and in whom conventional methods of treatment had failed. All five patients showed improvement in graft function. Rejection was reversed in four patients and was contained in one patient. Subsequently rapid recrudescence of graft rejection occurred in one patient, extended graft survival was seen in two patients, and the other two patients have retained life supporting grafts. Plasmapheresis may have a part to play in the treatment of renal allograft rejection and further evaluation of this treatment is indicated.

Nutritional blood flow to the limbs after access procedures.

We have measured the blood flow to skin and muscle in normal subjects, asymptomatic dialysis patients, and dialysis patients, and dialysis patients who complained of cold hands (symptomatic patients) in whom a radiocephalic fistula had been constructed. Mean skin blood flow in asymptomatic dialysis patients was identical to that in normal subjects. Skin blood flow in the fistula hand of symptomatic dialysis patients was greatly reduced but it was normal in the contralateral hand. Muscle blood flow at rest was lower in dialysis patients than in normal subjects, but was reduced still further in the fistula hand of symptomatic patients. Muscle hyperaemia in response to exercise was greatly impaired in the fistula hands of all patients, irrespective of symptoms. The haemodynamic consequences of arteriovenous fistulae may be a cause of pain, paraesthesiae, muscle wasting or claudication in dialysis patients.

Acute proliferative glomerulonephritis with crescents and renal failure in pregnancy successfully managed by intermittent haemodialysis. Case report.

A 26-year-old patient with no previous history of renal disease developed acute non-streptococcal crescentile glomerulonephritis with severe renal failure in the 17th week of her second pregnancy. It became necessary to treat her with haemodialysis to maintain the blood urea around 25 mmol/l. The haemoglobin was maintained above 9 g/dl with regular blood transfusion and the blood pressure was controlled with hypotensive drugs. Measurement of fetal biparietal diameter and human placental lactogen indicated normal fetal growth and placental function. The patient spontaneously delivered a healthy infant at 32 weeks. Haemodialysis requirements decreased post partum and the patient even managed without dialysis for 12 weeks. Renal function, however, remained severely impaired and maintenance haemodilysis was again necessary at nine months post partum. Glomerulonephritis complicating pregnancy is reviewed and the management of acute and chronic renal failure in pregnancy is discussed.

Comparative study of alkaline phosphatase isoenzymes, bone histology, and skeletal radiography in dialysis bone disease.

Liver, intestinal, and bone alkaline phosphatase isoenzymes were measured using heat stability and L-phenylalanine inhibition techniques in 78 patients on intermittent haemodialysis. Fifty-five patients had abnormalities in one or more of the isoenzymes. Changes in bone and intestinal alkaline phosphatase activities seemed to be related and raised liver isoenzyme activity was associated with the development of liver disease. Abnormal histological and radiological findings were better correlated with bone alkaline phosphatase levels than with total alkaline phosphatase, and serial estimations of bone isoenzyme activity were useful in assessing the response of renal osteodystrophy to treatment with a vitamin D analogue. Serum alkaline phosphatase isoenzyme measurement provides another useful and non-invasive index for monitoring metabolic bone disease in patients with chronic renal failure.

Inappropriate renin secretion and abnormal cardiovascular reflexes in coarctation of the aorta.

The response of the renin-angiotensin system to high and low sodium diets, to standing, and to saralasin infusion was assessed before and after surgical correction of aortic coarctation in a 27-year-old man. The cardiovascular responses to tests of autonomic function were measured. The heart rate responses to the Valsalva manoeuvre and standing were abnormal before operation, and plasma renin levels were high and renin secretion responded poorly to changes in dietary sodium, to standing, and to saralasin. Renin responsiveness and cardiovascular reflexes returned to normal after operation. The results are consistent with the hypothesis that there is a high level of sympathetic efferent activity in coarctation of the aorta and that factors other than increased activity of the renin-angiotensin system may cause high blood pressure.

Effects of vitamin D metabolites and analogues on renal function.

The long-term effects of vitamin D analogues and metabolites on renal function were assessed in 24 patients with and without chronic renal failure. Treatment for periods of 5-45 months did not adversely affect renal function in 10 of 11 patients with stable renal function, although transient hypercalcaemia did cause transient rises in plasma creatinine. Of 13 patients with progressive renal failure before treatment, vitamin D-like compounds or the vehicle used for their administration may have accelerated renal failure in 3 patients independently of changes in plasma calcium or phosphate. Particular difficulties in assessing the effects of vitamin D-like compounds in progressive renal disease are discussed.

Ingestion of formic acid-containing agents--report of three fatal cases.

Three patients were treated after they had deliberately ingested domestic agents containing formic acid. The major complications included the local effects on the oropharynx, oesophagus and stomach, metabolic acidosis, derangement of clotting mechanisms with haemorrhage and shock, widespread intravascular haemolysis, disseminated intravascular coagulation and the acute onset of respiratory and renal failure. All 3 patients died between 2 and 14 days after admission. It is the authors' belief that intensive therapy from the outset to include exchange transfusion, infusion of clotting factors, high dose steroids, ventilatory support and peritoneal or haemodialysis with parenteral nutrition may perhaps offer a better chance for survival.

Serious renal transplant rejection and adrenal hypofunction after gradual withdrawal of prednisolone two years after transplantation.

Ten patients with stable renal function two years after transplantation had their sole immunosuppressive treatment (oral prednisolone 10 mg daily) withdrawn by reducing the daily dose by 1 mg at monthly intervals. Plasma prednisolone concentration, cortisol concentration, creatinine clearance, and serum creatinine concentration were measured in all patients, and the adrenal response to corticotrophin was determined in five by measuring plasma cortisol concentrations before and after tetracosactrin injection. No episodes of rejection occurred in patients taking over 7 mg prednisolone daily. Although three patients apparently required only minimal immunosuppressive treatment (less than 5 mg daily) the remainder suffered episodes of rejection at daily doses below 7 mg. There was a tenuous association between rejection and low plasma cortisol concentration, but neither the pattern of plasma prednisolone concentrations nor the response to tetracosactrin were related to episodes of rejection. Reducing the daily dose of oral prednisolone to under 7 mg should not be attempted in patients with renal transplants unless there are extenuating circumstances.

Familial gout and renal failure.

Clinical gout and renal failure was seen in a 9-year-old girl. The family tree showed that 9 out of 11 young females in three generations suffered from hyperuricaemia and normal (n = 1), or impaired (n = 8), renal function. One set of twins occurred in each generation and there is only one living male subject. In members with renal failure there was no improvement in renal function after treatment of hyperuricaemia, and in 2 sisters oral contraceptives appeared to precipitate hypertension. This clinical picture may be more common than is generally realised because of failure to compare blood uric acid values with suitable age- and sex-matched controls. The evidence from this family suggests that hyperuricaemia preceded the development of renal failure.

Effect of haemodialysis on the control of the circulation in patients with chronic renal failure.

The mechanisms of hypotension during haemodialysis were investigated by studying cardiovascular reflexes, body fluid volumes, and osmolality in 11 patients with renal failure before and after haemodialysis and in 17 normal subjects before and after furosemide diuresis. Blood pressure and heart rate responses to tests of autonomic nervous function were unaffected in either group except that in the patients, head-up tilt after haemodialysis caused a fall in blood pressure. This was associated with a greater fall in cardiac output than before haemodialysis but with a similar rise in peripheral vascular resistance. Resting plasma noradrenaline levels were higher than normal, and the rise in plasma noradrenaline levels in response to tilt was unaffected by haemodialysis. Plasma renin activity rose in response to head-up tilt in normal subjects, but not in patients either before or after haemodialysis. Our studies indicate that changes in plasma potassium and osmolality or the possible peripheral circulatory effects of acetate do not impair the regulation of the circulation in response to haemodialysis. Haemodialysis does not reduce plasma noradrenaline levels. Impaired myocardial function in response to fluid depletion or unresponsiveness of the renin-angiotensin system may contribute to haemodialysis hypotension.

Changes in protein-bound calcium during haemodialysis in relation to bone disease.

29 patients receiving haemodialysis treatment for chronic renal failure were divided into two groups on the basis of the presence or absence of bone disease as defined by radiology and bone alkaline phosphatase. The group of patient with bone disease showed a significantly greater increase in protein-bound calcium during dialysis compared with the control group. There were no significant differences in the changes in total calcium, albumin or hydrogen ion concentration during dialysis between each group. The data suggest that there is a relationship between the increase in protein-bound calcium during dialysis and the incidence of bone disease.

Spinal calcium changes with 1alpha-hydroxyvitamin D3.

During treatment of renal osteodystrophy with 1alpha-hydroxyvitamin D3 in eleven patients, regional changes in the skeleton have been compared with long-term calcium balance as assessed by whole-body calcium. Radial bone changes did not correlated well with calcium balance, but spinal calcium changes were of a similar magnitude when changes were large. Bone alkaline phosphatase changes correlated well with changes in spinal calcium, but less well with changes in radial bone density.

Agranulocytosis during malaria prophylaxis with Maloprim (pyrimethamine and dapsone).

A case of agranulocytosis during malaria prophylaxis with Maloprim (pyrimethamine and dapsone) is described. At the recommended dose of one tablet weekly this is apparently a rare occurrence but highlights one of the hazards in a changing climate of malarial prophylaxis in which the use of Maloprim is increasing.

Hypokalaemic hyperchloraemic metabolic acidosis and vesical stone complicating appendicovesical fistulae.

Two patients with appendicovesical fistulae are described. Both presented with gastrointestinal and urinary symptoms. Biochemical examination showed hypokalaemic hyperchloraemic metabolic acidosis; radiographic investigations showed a vesical stone and a communication between the bladder and the bowel. The findings at operation suggested that the fistulae may have arisen as complications of previous appendicitis. The diagnosis of appendicovesical fistulae may be difficult but should be considered in the presence of hypokalaemic hyperchloraemic metabolic acidosis and vesical stones.