Ciaran C. Doherty

Oxidative stress and erythrocyte membrane fluidity in patients undergoing regular dialysis.

Oxidative damage due to free radical production is increased in uraemic patients and has been suggested as a possible factor contributing to the anaemia of chronic renal failure (CRF) and the pathogenesis of atherosclerosis. Oxidative stress was assessed in 40 patients with CRF maintained by either haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) and in 18 healthy controls. Lipid peroxidation (assessed as malondialdehyde, MDA), total glutathione (TG), antioxidant enzyme (glutathione reductase (GSHRx), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD)) activity and antioxidant associated trace metal (selenium, copper, zinc) levels were studied. Erythrocyte membrane fluidity was examined using the fluorescent probe 1,6 diphenyl-1,3,5-hexatriene (DPH). The results indicate increased levels of oxidative stress and altered erythrocyte membrane fluidity in patients treated with CAPD compared with controls and patients treated with HD. Only minor changes were observed in patients treated with HD. Altered free radical activity, oxidative stress and altered erythrocyte membrane fluidity observed in patients with CRF may contribute to the increase in vascular disease in such patients and to the anaemia of CRF.

Influence of immunosuppressive therapy on lipoprotein(a) and other lipoproteins following renal transplantation

Coronary heart disease (CHD) is more common in patients with chronic renal failure and is a major cause of death after renal transplantation. Elevated serum levels of lipoprotein(a) (Lp(a)) are a known risk factor for CHD in the general population and levels have been reported to be increased in renal transplant recipients. It has been suggested that cyclosporin may elevate Lp(a) levels. We therefore measured the serum concentration of Lp(a) in 50 renal transplant recipients who were receiving cyclosporin alone as immunosuppressive therapy and 50 who were treated with azathioprine and prednisolone, but not cyclosporin. The patients attended two renal transplant centres, one where cyclosporin alone was used as immunosuppressive treatment when possible and another where many patients commenced on azathioprine and prednisolone remain on this medication rather than cyclosporin. Patients in each group were matched for age and sex, but the time since transplantation was greater in those not receiving cyclosporin. Transplant function, obesity and the underlying cause of renal disease were similar in both groups of patients. Median Lp(a) concentration in the cyclosporin monotherapy group was 32.0 (range <0.8-140.3) mg/dl and was significantly (p < 0.05) greater than that of the azathioprine and prednisolone group which was 18.3 (range <0.8-167.7) mg/dl. The serum high-density lipoprotein (HDL) cholesterol concentration, which was 1.24 +/- 0.39 mmol/l (mean +/- SD) in patients receiving cyclosporin, was significantly (p < 0.05) less than that of those treated with azathioprine and prednisolone in whom it was 1.41 +/- 0.40 mmol/l. The lower level in those on cyclosporin was due to a decrease in the HDL2 subfraction. Serum lipid and lipoprotein concentrations were otherwise similar in the two groups of patients. The serum level of Lp(a) after renal transplantation may be influenced by the choice of immunosuppressive therapy.

Objective testing for vasospasm in the hand-arm vibration syndrome.

Since vibration white finger (VWF) became a prescribed industrial disease in 1985, objective testing for the diagnosis and grading of the severity of the condition has become desirable. Measurements have been made of finger blood flow and finger systolic pressure before and after cold challenge in 22 healthy control subjects and 34 men presenting for medical examination in connection with compensation claims for VWF. This type of testing has previously produced one false negative result in 35 patients with an established clinical diagnosis of Raynauds syndrome and no false positives in 40 control subjects. Finger blood flow was not significantly different in the claimants and controls in either warm or cool environments at local finger temperatures from 32 degrees C down to 20 degrees C. Finger systolic pressure in the claimants was not significantly different from that in the controls when the fingers were warm at 32 degrees C. After five minutes middle phalangeal cooling to 15 or 10 degrees C, finger systolic pressure was 0 mm Hg in 22 of the claimants indicating that vasospasm had occurred. No vasospasm occurred in the remaining 12 claimants or in any of the 22 control subjects. By clinical assessment alone, 26 of the 34 claimants had been thought to have VWF and 21 (81%) of these exhibited vasospasm in the laboratory. Of the eight considered not to have VWF, only one exhibited vasospasm in the laboratory.

Renal replacement therapy in multiple myeloma and systemic amyloidosis

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis.Overall one year and two year survival rates were 66 % and 57 % respectively. The median duration on RRT was 7.5 months (range 1–96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality.We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful asssessment and selection of patients is necessary prior to renal transplantation.

Acute polymyositis following renal transplantation.

Myositis is a rare complication following renal transplantation and is most commonly the result of drug‐mediated myotoxicity. Other causative disorders include viral infection, electrolyte imbalance and myositis of autoimmune origin. We describe a 60‐year‐old patient who developed acute polymyositis 4 weeks after a 000 human leukocyte antigen (HLA) mismatch cadaveric renal transplant. Following an uncomplicated transplant course with maintenance triple immunosuppression (prednisolone, mycophenolate mofetil and cyclosporine), the patient presented with severe symmetrical proximal muscle weakness associated with a rise in serum creatine kinase to 46 800 U/L. Electromyography confirmed myopathic changes and muscle biopsy demonstrated extensive muscle‐fiber necrosis with an inflammatory infiltrate. There were no obviously culpable drugs and viral studies were negative. Prompt initiation of high‐dose steroid therapy led to clinical and biochemical recovery. Acute polymyositis may occur following renal transplantation. Potential mechanisms include viral antigen transmission or a localized form of graft vs. host disease.

Gastric secretion in chronic uraemia and after renal transplantation

SummaryAn association has been reported between chronic renal failure and peptic ulcer. In this study, gastric acid secretion was measured in 106 patients undergoing treatment for chronic renal failure and in 24 normal subjects. Compared with controls, 32 undialysed uraemic patients had no significant difference in basal or peak acid output, although 7 of the 32 (22%) showed hyposecretion. In contrast, 36 patients undergoing regular dialysis had significant elevations of basal and peak acid output. In 38 renal transplant patients, basal and peak acid outputs were also significantly elevated, but peak acid output tended to fall with time after transplantation.While these results are in keeping with the traditional concept of uraemic hypoacidity, they show that in uraemic patients treated by regular dialysis, gastric acid secretion is in fact greater than in normal subjects, and it falls again towards normal following renal transplantation.

Live donor renal transplantation — the experience of the belfast renal unit

SummaryLive donor renal transplants are often preferred to cadaver grafts because of better graft survival. In a retrospective study of 41 live donor transplants performed in the Belfast Renal Unit from 1971 until November 1988, actual graft survival at 2 and 5 years was 84% and 69% respectively. Corresponding patient survival rates were 87% and 81%. These results are no better than those of cadaver grafts. A subdivision of patients considered to be relatively poor risk for transplantation showed less favourable results than those who were good risk. 15% of the donors suffered post-operative complications, which occurred more often in older donors.Live donor transplantation is not necessarily preferable to cadaver organ graft, and is not recommended for poor risk recipients or donors aged over 50 years.