Effect of alfacalcidol on renal bone disease in mild to moderate renal failure. Monitoring the calcium-phosphate product is important.
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Biomedical subjects
Publications and source records attributed to B J Junor.
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We have investigated the influence of the functional insertion (I) and deletion (D) polymorphism in intron 16 of the gene for angiotensin-converting enzyme (ACE) in a retrospective study of 100 patients with IgA nephropathy. There was no difference in genotype frequency compared with normal subjects. However, patients homozygous for the D allele tended to present at an earlier age (medians: DD, 33; ID, 34; II, 42 years) and to require renal replacement therapy at a younger age (medians 37, 42, and 48 years, respectively). The rate of progression was significantly worse in patients homozygous for the D allele. The DD genotype is associated with increased severity of disease in patients with IgA nephropathy.
A prospective study comparing colour Doppler ultrasound (US) with the 'gold standard' of intra-arterial digital subtraction angiography in the evaluation of renal transplant artery stenosis was performed. Both the intrarenal vessels and the transplant renal artery were examined by Doppler US. Diagnostic arteriography was performed only if, on Doppler, the peak systolic velocity in the transplant renal artery exceeded 1.5 ms-1. Of 109 patients, the transplant artery could not be visualized using colour Doppler US in three, and these were omitted from statistical analysis. Of the remaining 106 patients, 31 had a peak systolic velocity greater than 1.5 ms-1 in the transplant renal artery and were referred for DSA. Of the multiple renal Doppler indices recorded, the peak systolic velocity in the transplant artery was the best discriminating measurement for the detection of renal artery stenosis. A peak systolic velocity of > or = 2.5 ms-1 in the transplant renal artery had a sensitivity of 100% and a specificity of 95% for the detection of renal artery stenosis ( > 50% diameter reduction). Although a significant difference in Pulsatility Index, Resistive Index, Acceleration Index and Acceleration Time was recorded from the intrarenal vessels in the angiographically normal and stenosed groups with Doppler, these measurements were less useful as discriminating diagnostic tests. In conclusion, the peak systolic velocity in the transplant renal artery is the most sensitive Doppler criterion for renal artery stenosis and is sensitive and specific enough to be used as a screening test. The intrarenal acceleration time and index should not be used in isolation.
OKT3 was used to treat steroid-resistant acute renal allograft rejection in 30 of 496 adult patients transplanted over a 6-year period. Rejection was reversed (defined as a fall in serum creatinine by 50% or more within 30 days of treatment with OKT3) in 40% of cases. Successful reversal was significantly more likely when rejection occurred shortly after transplantation (t ratio -2.53; P = 0.019). The long-term outcome was disappointing; the actuarial graft survival at 1 year from the start of treatment with OKT3 was 42%, and no grafts have thus far survived longer than 3 years. Graft survival was shorter in older patients (coefficient/standard error 2.226; P < 0.05), and no other predictor of long-term outcome was identified. Patient survival at 3 years was 88%. Serious infection occurred in 33% of patients, with two deaths. Our experience suggests that treatment with OKT3 is unlikely to reverse acute renal allograft rejection in more than half of patients where rejection is resistant to steroids. Although long-term graft survival occurred in a few cases, the overall long-term outcome was disappointing, particularly in older patients. Finally, our analysis indicates the difficulty of predicting which patients will derive long-term benefit when OKT3 is used to treat steroid-resistant rejection.
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Sclerosing peritonitis (ScP) is a rare but fatal complication of continuous ambulatory peritoneal dialysis (CAPD), presenting as small bowel obstruction. We have observed that only patients receiving a renal transplant survived more than a few months after the diagnosis of ScP. We now report prolonged survival of patients given immunosuppressive therapy with or without a functioning transplant. ScP was found at laparotomy in 17 Glasgow patients, 15 of whom had been exposed to chlorhexidine in alcohol. All patients discontinued CAPD after diagnosis. Within a year 12 died with recurrent bowel obstruction; none received immunosuppressive therapy. The remaining 5 patients received immunosuppressive therapy; 4 are alive between 1 and 9 years later, and one patient with widespread vascular disease died after 3 years with mesenteric ischemia. Four of the 5 received a renal transplant. One patient rejected his transplant; when immunosuppression was stopped he developed symptoms suggestive of recurrent ScP. Immunosuppressive therapy was restarted and he remains well 3 years later. The fifth patient, who did not receive a transplant, was immunosuppressed after ScP was diagnosed. She remains well 18 months later. Our experience suggests that immunosuppression is beneficial in ScP.
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AIMS: To determine a possible mechanism to explain the presence of aluminium lines within fully calcified bone in aluminium-related osteomalacia. METHODS: Fifty five bone cases shown by bone biopsy to be aluminium-related osteomalacia were studied. In 38 specimens aluminium lines were identified within calcified bone by means of the Aluminon stain and a characteristic form of patchy mineralisation was seen within thickened osteoid seams. Five representative examples were analysed quantitatively by histomorphometry and electronprobe X-ray microanalysis and compared with five cases of vitamin D deficiency-related osteomalacia which also had patchy mineralisation. RESULTS: The patchy calcification occupied 40 +/- 8% (mean +/- SEM) of the osteoid and consisted of small focal deposits (less than 40 microns diameter), often (52%) around osteoid osteocytes (probably an underestimate of the association), and larger areas that extended to the aluminium lines at the underlying mineralisation front. Small and large mineralisation nuclei were seen ultrastructurally in the patchy calcification. Quantitative electronprobe X-ray microanalysis showed that calcium concentrations and calcium:phosphorus ratios in the mineralisation nuclei and in the superficial layer of the fully calcified bone of the aluminium-related osteomalacia cases were significantly less than values measured at similar sites in the vitamin D deficiency-related osteomalacia cases. Furthermore, aluminium could not be detected by means of this technique at the mineralisation front or along cement lines in these specimens. CONCLUSIONS: Calcification can occur in thickened osteoid seams in osteomalacia. It can begin around osteoid osteocytes as small deposits that enlarge within the osteoid and extend to the underlying mineralisation front or cement line where aluminium lines may become trapped. Complete calcification of osteoid could account for the presence of aluminium lines within fully calcified bone. The Aluminon stain appears to be a more sensitive method for the detection of aluminium in bone than electronprobe X-ray microanalysis.
Crescentic glomerulonephritis is a well defined pathological lesion occurring in a range of renal and systemic diseases. We have retrospectively reviewed the aetiology, clinical features and outcome in 60 patients presenting over a five and a half year period. Most patients were elderly (median age 61 years, range 16-84 years). The majority presented with severe renal impairment, 32 requiring dialysis at admission. The degree of glomerular crescent formation on biopsy was closely related both to initial dialysis dependence and the ensuing response to immunosuppression. Forty-three patients received immunosuppressive treatment. A beneficial response was seen in 40% of patients requiring dialysis, and in 88% of those with less severe renal impairment. A high early mortality was apparent (30% within three months), exclusively affecting elderly patients (all > 60 years), with advanced renal failure (all dialysis dependent), the majority of whom (15 out of 18) had been immunosuppressed. The results suggest that the benefits of immunosuppression in this group may be outweighed by the complications of treatment.
OBJECTIVE: To audit the outcome of patients treated at home by hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective comparison of nondiabetic hemodialysis patients with age- and sex-matched nondiabetic patients treated by CAPD. SETTING: Renal Units, Stobhill General Hospital and Western Infirmary, Glasgow, providing the home dialysis service for the West of Scotland. PATIENTS: Between 1982 and 1988, 139 hemodialysis patients starting treatment at home, compared with 139 matched patients starting CAPD over the same time period. MAIN OUTCOME MEASURES: Patient characteristics and cardiovascular risk factors at the start of home treatment. Patient and technique survival with both forms of dialysis. RESULTS: Patients selected for home hemodialysis were less likely to be smokers (p < 0.02) and to have electrocardiographic evidence of ischemia or left ventricular hypertrophy (p < 0.05) than patients treated by CAPD. Patient survival and technique survival (excluding death and renal transplantation) at 3 years were 93.8% versus 86.2% (p < 0.05) and 94.2% versus 80.8% (p < 0.04) for hemodialysis and CAPD, respectively. Cardiovascular events were responsible for the majority of deaths in both groups, but there was a greater proportion of deaths from other causes in patients treated by CAPD. There was no significant difference in the transplantation rate between the two treatment groups. CONCLUSIONS: Home dialysis is an effective method of renal replacement treatment for patients with end-stage renal disease. The results of hemodialysis are superior to CAPD, but this may be partly due to selection bias.
Chronic liver disease has been reported to be an important cause of late morbidity and mortality in renal transplant recipients. We have examined the prevalence and nature of chronic liver disease among 538 patients with functioning renal allografts managed at the Western Infirmary, Glasgow, between 1980 and 1989. Thirty-seven patients (7 per cent) satisfied biochemical criteria for chronic liver dysfunction. Liver biopsies were obtained from 24 of these, and autopsy tissue was available from three other patients. Chronic hepatitis of variable severity was present in 15 patients, haemosiderosis in 12 patients and nodular regenerative hyperplasia in five patients. Nineteen patients (51 per cent) had serological evidence of infection with the hepatitis C virus, and one of these developed chronic hepatitis B and D infection as well. Although a variety of chronic liver diseases occurred in our transplant population, the frequency of serious sequelae from liver dysfunction was much lower than that reported from transplant centres in other countries.
A single 6-g dose of aluminum hydroxide was given to eight patients on regular hemodialysis before and 3 days after parathyroidectomy (PTX). Serum aluminum levels were measured before and after 5 h after ingestion of aluminum hydroxide to examine indirectly the effects on absorption of aluminum from the gastrointestinal tract of both high and low parathyroid hormone (PTH). Plasma PTH levels fell significantly from 2,724 +/- 1,830 ng/l (mean +/- 1 SD) before PTX to 352 +/- 63 ng/l after PTX. However, no significant change was detected in serum aluminum levels before or after PTX (1.45 +/- 0.96 to 1.92 +/- 0.88 mumol/l before PTX; 2.02 +/- 1.41 to 2.89 +/- 1.19 mol/l after). These findings indicate that in patients with chronic renal failure, high plasma levels of PTH are not associated with significant increases in serum aluminum concentrations after ingestion of a large quantity of aluminum hydroxide. Parathyroid hormone may not enhance intestinal absorption of aluminum in humans.
Aluminium-transferrin (Al-Tf) and gallium-transferrin caused a dose-dependent decrease in proliferation of human peripheral blood lymphocytes cultured for 3 days with phytohaemagglutinin (PHA). Addition of apotransferrin reduced the inhibitory effect. Al added as AlCl3 or aluminium citrate had no effect, and there was no significant difference in the response of cells from renal failure patients with or without high serum Al levels or controls. Lymphocytes cultured in the presence of Al-Tf showed a dose-dependent uptake of Al, whereas uptake from aluminium citrate was low and not dose-dependent. Uptake from AlCl3 was very high but probably involved a nonspecific uptake mechanism. Levels of Al in freshly isolated lymphocytes were approximately 1.6 ng/10(6) cells, there being no difference between cells from patients and controls. It is concluded that Al, when bound to transferrin, may have a detrimental effect on lymphocyte function and might contribute to the decreased immune responsiveness of renal failure patients on haemodialysis. However, lymphocyte Al levels are probably not useful as a marker of Al overload in such patients.
Sclerosis of the peritoneum, with encapsulation of the small bowel is one of the most serious complications of continuous ambulatory peritoneal dialysis (CAPD), and carries a high mortality. The abnormalities seen on ultrasound are described for 14 patients and comprise increased small bowel peristalsis, tethering of the bowel to the posterior abdominal wall, intraperitoneal echogenic strands and, in the late stages of the disease, membrane formation. Optimal visualization of these features in the early stages of the disease was obtained by examining the patients with dialysis fluid present in the abdomen. Sclerosing peritonitis should be suspected in patients being treated by CAPD who develop abdominal pain and progressive loss of ultrafiltration and subsequent investigation should include the use of ultrasound.
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Renal biopsies were examined from 17 renal transplant recipients before and after conversion from cyclosporin to azathioprine, and in 17 patients who remained on cyclosporin. All patients had stable renal function. We used an immunoperoxidase technique with an antiserum to human renin to identify renin-containing cells. We demonstrated hyperplasia of renin-containing cells in patients treated with cyclosporin. Numbers of renin-containing cells decreased after conversion to azathioprine. We suggest that local activation of the intrarenal renin-angiotensin system could mediate the effects of cyclosporin on renal haemodynamics. This could play a role in the pathogenesis of cyclosporin nephrotoxicity and cyclosporin hypertension.
Approximately 20% of monocytes and peritoneal macrophages from renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were transferrin-receptor (TfR) positive by immunofluorescence, whereas cells from normal controls were generally TfR negative, as were monocytes from rheumatoid arthritis patients and from renal failure patients treated by haemodialysis. There was a significant correlation between the length of time on CAPD and the proportion of TfR-positive blood monocytes. CAPD peritoneal macrophages possessed 6.7-37.1 x 10(3) transferrin binding sites per cell, with a Ka of 3-25 x 10(7) mol l-1. In culture, monocytes from CAPD patients showed a progressive decrease in TfR expression, while in contrast about 20% of monocytes from normal controls which were originally 100% TfR negative expressed TfR after 3 days in culture. These findings indicate that regulation of TfR in monocytes/macrophages is complex, and that frequent removal of peritoneal cells during dialysate exchange may place a strain on the bone marrow, resulting in the release of an increasingly immature population of TfR positive monocytes to the circulation in CAPD patients.