The changing face of end stage renal disease in a UK renal unit.
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Biomedical subjects
Publications and source records attributed to J Walls.
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We studied the effect of renal disease on the pharmacokinetics of flecainide after single intravenous, single oral, and multiple oral doses to patients with severe renal disease (creatinine clearances less than 12 ml/min/m2). The absorption and volume of distribution of flecainide were not altered by renal impairment. The average plasma half-life was prolonged by about twofold that of healthy subjects but most patients were within the range of values for healthy subjects. Total body clearance was reduced. With multiple oral doses of 50 mg b.i.d. or 50 mg daily, steady-state plasma levels were reached by 6 days and no further accumulation in plasma was observed. In patients with severe renal disease, therapy with flecainide should be initiated at 100 mg daily (or 50 mg b.i.d.). If necessary, dosage increases should be made cautiously at intervals of more than 4 days when plasma levels have plateaued as demonstrated by plasma level monitoring.
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Two cases of end stage renal failure occurring in association with the Laurence-Moon-Biedl syndrome are reported. Abnormalities in renal function and morphology are increasingly recognized in these patients in whom uraemia is an important cause of morbidity and early mortality. The presence of renal impairment, occurring as frequently as any of the pentad of features that characterize the syndrome, has important implications for the prognosis and long term management of these patients.
A case is reported in which a rectal villous adenoma was complicated by severe fluid and electrolyte depletion producing recurrent renal failure. The pathophysiology of the depletion syndrome and its complications are discussed. Successful management by acute haemodialysis and early surgical resection of the tumour is described.
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Evidence that glomerulosclerosis may be accelerated by high-protein diet and ameliorated by low-protein diet has led to debate concerning appropriate dietary recommendations in nephrotic syndrome. In this study, dietary protein was manipulated in a chronic, non-uraemic experimental model of nephrotic syndrome. Groups of 12 AS rats received 12, 24 or 48% protein diet after nephrotic syndrome was induced by adriamycin. Animals were sacrificed 8 weeks after change of diet when all were normotensive and none were uraemic. Animals on 24 and 48% maintained initial body weight and had persistent nephrosis. There was renal hypertrophy and histology showed tubular casts, focal tubulo-interstitial injury and glomerulosclerosis. Animals on 48% diet had more renal hypertrophy and worse histological damage but no differences in other parameters compared to 24% diet. On a 12% protein diet animals lost 15 +/- 3% of initial body weight (from 221 +/- 6 to 188 +/- 6 g; p less than 0.001). There was less proteinuria (p less than 0.0001), and lower serum cholesterol (p less than 0.0001) and triglyceride (p less than 0.01). Serum albumin was not different but total protein was lower than on 24 and 48% diet (p less than 0.01). Renal histological damage, although less severe than on 48% diet, did not differ from 24% diet. There was fatty infiltration of the liver. In view of the effects of low-protein diet in this model of nephrotic syndrome, dietary protein restriction should be applied with caution in human nephrotic syndrome.
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As many UK renal units commence more patients on CAPD than hemodialysis (HD) as the first mode of therapy a retrospective study of long-term CAPD (greater than 4 years continuous CAPD) was performed in 4 centers with substantial CAPD programs. One hundred and seventy-seven patients (103M, 74F) started CAPD before December, 1981. There was no difference in primary renal disease. Age was significantly greater in 2 units (51.9 +/- 11.7 and 53.2 +/- 12.1 vs 40.6 +/- 16.2 and 42.5 +/- 14.6 years, p less than 0.05) and correlates with pre-CAPD activity scores (Scale 3-0). After 4 years: 34 patients (19.2%) remained on CAPD: the proportion was similar in all centers. Sixty-five percent of patients were alive but 54% transferred to HD mainly due to peritonitis (overall 2.0 episodes/intercenter variation p less than 0.001). Fourty-four patients were transplanted. Significant increases occurred in hemoglobin, albumin, calcium and creatinine; a decrease in activity score (2.4 +/- 0.7 to 1.5 +/- 0.9, p less than 0.005); no change in weight, BP, urea or bone disease. Thirty-eight patients died, mainly cardiac (14) or sepsis (11). Using Cox's method of analysis significant risk multipliers were age (2.07 per decade), male sex (2.18), frequency of peritonitis (1.36), activity score less than 2 (4.45) and amyloidosis (12.45). Despite differing techniques in different centers CAPD offered a satisfactory mode of therapy for many patients; peritonitis was the main reason for transfer to HD and several significant factors were identified.
A retrospective study was performed to evaluate complications with the two most common intra-aortic balloon pump (IABP) insertion techniques. During a nine year period, 202 patients (51 women, 151 men) underwent IABP cardiac assist utilizing the arteriotomy surgical (103 balloons) and percutaneous (99 balloons) insertion techniques. Complications, including asymptomatic loss of pedal pulse, vascular-symptomatic, infection, or balloon rupture occurred in 22.8 per cent of patients. Of the 54 complications, 13 (24%) were asymptomatic loss of pedal pulse, 36 (66.7%) were vascular symptomatic, three (5.5%) were infection, and two (3.7%) were balloon malfunctions. The overall complication rates were 16/103 (15.5%) and 38/99 (38.3%) for the surgical and percutaneous methods, respectively (P = 0.007). Thirty two per cent (33/103) of the patients receiving IABP surgically and 24 per cent (24/99) of those receiving IABP percutaneously died in the hospital (P = 0.34); no death was directly attributable to IABP. The number of patients requiring surgical intervention or removal was not significantly different between the surgical and percutaneous methods (9 versus 18%, P = .06). While the method of IABP insertion did not significantly alter hospital mortality, a significantly greater complication rate was observed with percutaneous insertion (P = .007). This was particularly relevant to complications occurring at the time of removal of IABP.
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To investigate the controversy surrounding the life-expectancy of patients on continuous ambulatory peritoneal dialysis (CAPD) compared with that of patients on haemodialysis or transplantation mortality data from 389 patients accepted for renal replacement therapy in Leicester between July, 1974, and July, 1985, were retrospectively analysed with respect to a wide range of pre-treatment variables (6 scales and 115 binary variables), by a method (Cox's) that adjusts for the distorting influence of selection bias. 9 independent variables were identified as having a significant influence on survival. Adverse factors were age, amyloidosis, ischaemic heart disease, convulsions, and acute presentation. Beneficial variables were male sex, parenthood, pyelonephritis, and residence in Leicestershire. By correcting for the influence of these variables and using time-dependent treatment co-variates, the bias adjusted estimates of the relative risk of death were 1 for patients on CAPD, 1.30 for those on haemodialysis, and 1.09 for patients who received transplants. These risks do not differ significantly from one another and suggest that CAPD is at least as effective as haemodialysis or transplantation at preserving life.
Investigation into the effects of two different dietary proteins, casein and soya, fed at isonitrogenous and isocaloric levels, upon renal function, plasma amino acids and serum lipids, in normal and subtotally nephrectomized rats was undertaken. Groups 1 (24% casein, n = 10) and 2 (24% soya, n = 10) were maintained upon the diets for a 10-week period following subtotal nephrectomy, whilst groups 3 (24% casein, n = 6) and 4 (24% soya, n = 5) served as normal controls. Determination of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and histological analysis were undertaken at the end of the study. Serum lipids and plasma amino acids were determined in subtotally nephrectomized rats (group 5, 24% casein, n = 11: group 6, 24% soya, n = 12) 12 weeks following reduction in renal mass, and serum lipids determined in normal control animals (group 7, 24% casein, n = 10: group 8, 24% soya, n = 10). The glomerular filtration rate and ERPF in normal animals fed casein were significantly greater than those fed soya (P less than 0.01). Survival, proteinuria, renal histological damage and blood urea when killed were all significantly worse in subtotally nephrectomized animals fed casein. Serum cholesterol of groups 5 and 7 fed casein were significantly higher than groups 6 and 8 (P less than 0.05), whilst a significant reduction in serum triglyceride was found for group 6 (P less than 0.001). Plasma amino acids, and essential amino acid ratios of subtotally nephrectomized rats were equivalent, with the exception of plasma glycine (P less than 0.05).
Dietary protein restriction is known to be beneficial in the preservation of renal function when renal mass is reduced. This study investigates the effects of two different dietary proteins, casein and soya, upon renal function in normal rats and rats subjected to subtotal nephrectomy. The diets were isocaloric, with identical sodium, potassium and phosphorus contents. Normal rats ingesting a 24% soya protein diet demonstrate lower effective renal plasma flow rates and lower glomerular filtration rates than rats ingesting a 24% casein diet. Experimental animals were subjected to a unilateral nephrectomy and contralateral partial renal infarction and were fed either casein or soya, at 24 or 12% levels, for 3 months. Those animals ingesting the soya diets demonstrated improved survival (p less than 0.05), less proteinuria (p less than 0.02), less renal hypertrophy (p less than 0.005) and less renal histological damage. The nature of the dietary protein appears to influence both normal renal function and the progression of experimentally induced renal disease.
A 60-year-old man with rheumatoid arthritis, who developed acute reversible renal failure with nephrotic syndrome and tubulointerstitial nephritis in association with multiple-drug therapy, is described. The episode was ascribed to the nonsteroidal anti-inflammatory agent fenbufen, and the patient was reexposed to D-penicillamine within 6 months, reproducing the same renal lesion. There was no evidence of the glomerular lesions characteristically associated with D-penicillamine nephrotoxicity. D-penicillamine was the only drug therapy common to both episodes and it is concluded that it may cause tubulointerstitial nephritis with nephrotic syndrome.
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