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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.

We describe the long term use for haemodialysis of the PermCath (Quinton, Seattle, Washington) dual lumen, jugular venous catheter (DLJVC) in 21 patients who had no apparent alternative means of access. The nineteen patients maintained in this manner for periods of 30 to 600 days (mean 233.2) included 6 patients dialyzed for over 12 months. Blood flows exceeded 250 mls/min and recirculation rates averaged 5.9%. Infection and insufficiency due to thrombosis were the major problems. In 8 patients (38.1%) infection required DLJVC removal; in three the catheter was immediately replaced over a guidewire along the same track under antibiotic cover and infection has not recurred. Insufficiency occurred in 10 patients (47.6%) and was successfully managed with oral anticoagulants, local instillation of urokinase (4 cases), systemic streptokinase (2 cases) or by changing the DLJVC over a guidewire (2 cases). We believe that the DLJVC is the long term access method of choice for patients in whom conventional access cannot be constructed.

CVVHD is an effective treatment of choice applicable to all critically ill unstable patients with CARF. It is a technique that offers clinical advantages. It is easily initiated. It offers good clearance. Its closed dialysate circuit offers accurate control of UF that is adaptable to the patient's needs. The use of a blood pump reduces the risks of heparin-induced bleeding and arterial cannulation. In all patients, the blood flow rate was maintained at 100 ml/min. or more regardless of systemic BP. The UF removed per hour was between 100-200 mls/hour. Fluid removal on overloaded patients was easily accomplished with stable hemodynamic status. Adequate parenteral nutrition was able to be maintained to meet the requirement of the patients. The accuracy of the UF pump, no large volume fluid replacement and the safeguard of a closed system facilitates the work of the ICU nurses who have few or no adjustments to perform. Experience with CVVHD has proven that nurses working in the ICU are willing to be trained to take responsibility for this mode of treatment.

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.

The mixed lymphocyte reaction (MLR) between donor and recipient lymphocytes has been measured by the macrophage electrophoretic mobility (MEM) test and the modified (MOD-MEM) test. Its value as a measure of compatibility has been assessed by comparison with conventional HL-A serotyping and with the outcome of renal transplantation. Thirty-six living donor/recipient pairs and 59 cadaver donor/recipient pairs for transplantation have been studied. Whilst uniovular twins gave lymphocyte interactions, measured as macrophage slowings of about 1%, the slowing produced by paired allogeneic lymphocytes ranged from 2% to 26% depending on the number of HL-A matches. The test measurement of lymphocytic interaction was significantly correlated with histocompatibility measured by HL-A serotyping, in both living and cadaver donors. One way MEM-MLR showed the dominant role of the second HL-A sublocus in mixed lymphocyte reactivity. The long term success of the renal graft correlated with the pre-transplant initial reaction between donor and recipient lymphocytes. The test has advantages in the field of human histocompatibility assessment since no particular reference to individual antigens is made and it may be performed in a matter of hours.

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.

The blood pressure of 18 patients with refractory hypertension was controlled by treatment with Minoxidil in combination with Propranolol and diuretics. Ten of these patients were studied prospectively and were found not to have deterioration of carbohydrate tolerance while on Minoxidil therapy. Pericardial effusions occurred in 40% of the patients, including 2 with normal renal function. This untoward effect of prolonged use Minoxidil warrants further study.

This is an analysis of the outcome of 35 patients with end-stage autosomal dominant polycystic kidney disease (ADPKD) at Toronto Western Hospital (TWH) during a 10-year period. The primary treatment in each case was hemodialysis. In the 15 patients managed exclusively with hemodialysis the one- and five-year actuarial survival was 93% and 77% respectively. Twenty patients ultimately received a total of 26 cadaveric renal allografts. Graft survival at one year was 76%. One- and five-year patient survival was 92% and 73% respectively. Beyond 5 years a trend towards increased survival in the transplant group was seen, compared with the exclusively hemodialyzed group. Bilateral nephrectomy prior to transplantation was associated with high morbidity and mortality, and did not change either graft or patient survival. In view of the similar survival and because it is accepted that transplantation offers the highest quality of life amongst the modalities of treatment for end-stage renal failure, transplantation should be considered the treatment of choice for end-stage ADPKD. There is no justification for routine bilateral nephrectomy before renal transplantation.

Sixty patients have been entered into a controlled trial evaluating the use of intensive plasma exchange (IPE) in renal transplant recipients. During the first three months post-transplant, patients receive either conventional anti-rejection therapy alone (control group) or conventional anti-rejection therapy and IPE (IPE group) for all rejection episodes. Twenty percent of the grafts in the control group versus 10% in the IPE group have been lost to rejection (p = NS). The actual three month patient and graft survival in the control group (97% and 70%), respectively, is similar to the IPE group (94% and 80%), as is the one year actuarial graft and patient survival in the two groups. No statistically significant benefit of IPE has yet been demonstrated but the trend is encouraging and the complication rate sufficiently low so as to justify continuing the study.

A controlled, cross-over trial of bicarbonate versus acetate hemodialysis over a 24 wk period in 16 patients with end-stage renal failure has shown a significantly lower incidence of dialysis-related symptoms during dialysis with bicarbonate. The level of well-being in the intervals between dialysis was not appreciably affected by the dialysis mode. It is suggested that bicarbonate dialysis should be made available to all patients receiving regular hemodialysis for end-stage renal failure provided that this can be done reliably and safely.

A new silastic and teflon cannula has been developed for temporary hemodialysis access. It is introduced through the subclavian vein by the Seldinger technique. The cannula which is quick and easy to insert, can be used repeatedly for weeks or months without limiting the patient's mobility and without the need for repeated vessel punctures. Complications are few and largely preventable. Since introduction of the subclavian hemodialysis cannula at the Toronto Western Hospital in September 1977 no patient with end-stage renal failure has required insertion of a silastic-teflon shunt or temporary peritoneal dialysis, nor has hemodialysis had to be postponed because of lack of an arteriovenous fistula.

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 immunosuppressive therapy 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.

In two patients right atrial ball thrombi developed following prolonged subclavian cannulation for hemodialysis. One patient died, the other had the ball thrombus removed by open heart surgery. It appears that repeated friction of the catheter tip may have damaged the endothelium of the right atrial wall. This hitherto unrecognised complication might be prevented by ensuring that subclavian hemodialysis catheters are never allowed to reach as far as the right atrium.

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.

The effect of recurrent early homograft rejection on subsequent patient and renal graft survival. Two hundred renal transplants performed in Newcastle between 1968 and 1974 and followed up for at least 6 months are reviewed. There was a significant fall ingraft survival at 1 year in those patients who suffered a rejection episode during the first two months post-transplant and this fall became greater with each successive rejection episode. The rise in patient mortality with increasing numbers of rejections showed a similar trend but was less (40-50% at 1 year in those suffering 3 or 4 rejection episodes) and did not reach statistical significance beyond the first episode. We, therefore, conclude that in patients not suitable for home dialysis and in whom, because of uncommon tissue type, a second transplant is not likely to be offered under prevailing conditions of kidney donor shortage, it is justifiable to treat third and fourth rejections occurring during the first two months.

Serial histological studies in patients after successful renal transplantation indicate that with restoration of adequate renal function osteomalacia invariably improves with symptomatic relief in bone pain. Histological changes of osteitis fibrosa resolve more slowly and radiological changes may persist longer, occasionally in the absence of confirmatory histological evidence of secondary hyperparathyroidism. For accurate and sensitive follow-up a combination of biochemistry, histology and radiology is desirable.

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.

Intensive plasma exchange (IPE) was used to treat 13 rejection episodes in eight renal transplant recipients with biopsy evidence of humoral rejection. Prior to IPE, each patients had several rejection episodes treated with high dose steroids. The IPE-treated rejections had not responded to conventional anti-rejection therapy and all patients appeared likely to lose their grafts. IPE reversed 7 of the 13 rejections (5 of 8 patients responded). Two of the 8 grafts continue to have adequate function 6 and 8 months after IPE. IPE temporarily reverses rejection but not increase long term graft survival.

This paper describes a simple system for the performance of slow continuous hemodialysis (SCHD) as a means of treating difficult and complicated cases of oliguric acute renal failure. The method, which employs access to the circulation via a double-lumen central venous catheter and a BSM 22 blood systems module, can be performed safely in the intensive care unit of a general hospital if closely supervised by a trained nephrologist. The results of treating 16 consecutive cases of complicated acute renal failure in a large general hospital without a hemodialysis unit are described. The method, whose simplicity makes it suitable for intensive care unit nurses without previous hemodialysis training, was not associated with any serious accidents or complications, and was tolerated well by even the most critically ill and hemodynamically unstable patients. The advantages of this approach over more traditional continuous arteriovenous hemofiltration (CAVH) are discussed.

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.

This study included patients, all relatives with the haemolytic uraemic syndrome, and 18 family members. The diagnosis was uncertain 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.

Between January 1968 and June 1974 at Newcastle upon Tyne, 63 patients underwent splenectomy in association with transplantation; 45 of these had splenectomy with bilateral nephrectomy before (20) or at the time of (25) transplantation; 18 had post-transplant splenectomy for leucopenia. Mortality was significantly higher in splenectomized patients than in 136 non-splenectomized controls. Of the 63 splenectomized patients, 25 died within 1 year of transplantation, 12 of severe infection associated with leucopenia. Although splenectomy produced a temporary rise in white cell count, leucopenia during the first year of immunosuppressive therapy was not significantly less frequent in splenectomized patients than in controls. There was no significant difference in graft loss between the splenectomy and control groups. It is concluded that splenectomy is contra-indicated in patients who are to undergo renal transplantation and confers no benefit when carried out because of leucopenia developing after renal transplantation.

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.

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.

Single-lumen silastic catheters were placed in the jugular veins of 12 patients to provide vascular access for hemodialysis. In all cases construction of arteriovenous fistulas had been difficult or impossible. The catheters have provided adequate dialysis with a single needle system for periods up to 32 months. Only one case of blood stream infection occurred, in a confused patient who damaged his catheter. There has been no evidence of venous thrombosis or other complications. Jugular vein catheters should be considered as long-term alternatives when A-V fistula construction is not possible.

Vascular access with an indwelling subclavian cannula is now being widely used as an alternative to silastic-teflon shunts or femoral cannulation in patients with end-stage renal failure who are temporarily lacking an arteriovenous fistula. Advantages are the preservation of blood vessels and the avoidance of repeated vein puncture for each dialysis. The only disadvantage of the standard single-lumen subclavian cannula is the need to use a single needle machine. This is an encumbrance especially in the management of acute renal failure. We have developed a double-lumen subclavian cannula which, having 2 blood pathways, does not require the use of a single needle machine. This device function well for temporary vascular access in patients with terminal renal failure who are awaiting AV fistula construction or repair. It is also especially convenient in the management of acute renal failure when there are difficulties in the construction of a shunt.

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.