Successful pregnancy in a renal transplant recipient with type I primary hyperoxaluria.
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Biomedical subjects
Publications and source records attributed to L R Baker.
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This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose of 0.25 to 0.5 microgram daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.
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We describe two renal transplant recipients who presented with clinical and biochemical abnormalities of liver function in whom liver scarring and silicone particles were identified in the liver by light microscopy. The presence of silicon in the particles was confirmed by x-ray energy dispersive spectroscopy. In one patient liver abnormalities were first noted more than two years after haemodialysis was discontinued and in a second patient abnormalities were still present more than four years after successful kidney transplantation. No other specific cause for the chronic liver abnormalities was determined and we consider that these may be related to the presence of silicone degradation products in the liver. Other patients haemodialysed using a siliconised peristaltic blood pump insert system may also be a risk of developing similar late complications.
Administration of recombinant erythropoietin (r-HuEPO) is an effective treatment for the anaemia of chronic renal failure, but in some patients it has been accompanied by elevated blood pressure. This study focuses on seven patients with end-stage renal failure, managed on haemodialysis, who developed probable hypertensive encephalopathy with seizures during treatment with r-HuEPO. All made a full recovery. The events were not clearly related to the haemoglobin concentrations achieved, and four patients have subsequently been restarted on r-HuEPO therapy at a reduced dose, resulting in a slower increase in haemoglobin with no recurrence of episodes of severe hypertension. Close attention needs to be paid to blood pressure in patients commencing erythropoietin therapy, and it seems prudent to aim for a gradual increase in haemoglobin concentration to allow the circulation to adapt to changes in oxygen delivery and haematocrit.
Cognitive function was assessed, and unenhanced CT head scans were carried out in 44 patients with renal failure. Thirteen had been on regular hemodialysis for 5 years or more (long-term hemodialysis group, LTHD), 12 had received hemodialysis for less than 5 years (short-term hemodialysis, STHD), 9 were on continuous ambulatory peritoneal dialysis (CAPD group) and 10 had severe chronic renal failure and were near to-but had not reached-dialysis dependence (chronic renal failure group, CRF). Employing an index of deterioration (the "discrepancy score") based on the discrepancy between current reading skills and current performance on the Wechsler Adult Intelligence Scale, 6 LTHD patients, 2 STHD patients, 2 CAPD patients and 5 CRF patients were identified as functioning below their predicted premorbid optimum level. Cerebral sulci were abnormally wide in 22 patients (8 LTHD, 2 STHD, 6 CAPD and 6 CRF) and one of the STHD group also had cerebral ventricular dilatation. Nine patients had both an abnormal scan and evidence of cognitive deterioration, 13 had an abnormal scan in the absence of such evidence and 6 had evidence of cognitive deterioration and a normal scan. Both cognitive deterioration and the CT scan finding of widening of cerebral sulci were commoner in these patients than would be expected in an age-matched sample of the general population, but no simple relationship was found between anatomical abnormality and cognitive functioning. Statistically significant correlations were found between discrepancy score and the cumulative amount of aluminum prescribed to be taken orally in both LTHD and CAPD groups.
We report renal biopsy findings in 109 patients with unexplained renal impairment (serum creatinine greater than 0.15 mmol/l) and normal-sized non-obstructed kidneys. The most common histological lesions were interstitial nephritis, rapidly progressive glomerulonephritis and a variety of other types of glomerulonephritis. The groups could not be distinguished by the presence or absence of hypertension, haematuria, proteinuria, or features of systemic disease. However interstitial nephritis was found more frequently in patients presenting with one or none of these features and rapidly progressive glomerulonephritis in patients presenting with three or more. All four patients with none of these features had interstitial lesions. Fifty-two per cent of patients with interstitial nephritis improved and 60 per cent of the patients with rapidly progressive glomerulonephritis who received immunosuppressive treatment improved or remained stable with treatment. The benefits of a biopsy diagnosis were almost wholly confined to these two groups. Complications were recorded in nine patients - prolonged macroscopic haematuria in six and symptomatic perirenal haematomata in three. Six required blood transfusion. One required nephrectomy to control haemorrhage and subsequently died. Percutaneous renal biopsy is not without risk in patients with renal impairment but the benefits of diagnosing interstitial nephritis and rapidly progressive glomerulonephritis outweigh the disadvantages.
The value of calcitriol administration in the management and prevention of renal bone disease was studied in a prospective double-blind manner in 16 patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min). They were given either calcitriol at a dose of 0.25 to 0.5 micrograms daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had biochemical or radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. Calcitriol treatment was associated with a significant fall in serum phosphorus concentrations and alkaline phosphatase levels as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of calcitriol was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.
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The pharmacokinetics of flupirtine after a single oral dose of 100mg have been studied in patients with moderate renal impairment and in healthy elderly subjects aged 66-83 years. Mean elimination half-life of flupirtine was higher in elderly patients than in younger normal subjects, and this was associated with an increased maximum serum concentration and reduced clearance. The mean half-life in patients with renal impairment was higher than in normal subjects. There was no correlation between observed elimination half-life and degree of renal impairment, but the creatinine clearance of most patients fell in a narrow range between 43 and 60 ml/min. In the light of these results and until further information is available, it would be prudent to start treatment of patients who are elderly or have evidence of renal impairment with half the dose of flupirtine recommended for younger patients with normal renal function.
Despite extensive study of the difference in the cardiovascular response to ultrafiltration in isolation and during haemodialysis, there is still disagreement in the literature as to whether or not there is a difference in the efficiency of plasma refilling between the two procedures. We believe that this results both from the use of inadequate techniques to measure change in blood volume and shortcomings in experimental design. We have employed novel methods in ten patients to study plasma refilling during isolated ultrafiltration and dialytic ultrafiltration. Measurement of blood pressure and heart rate confirmed the inferior cardiovascular tolerance to haemodialysis observed by others. However, no difference in the rate of plasma refilling could be demonstrated. Our observations suggest that the superior tolerance to isolated ultrafiltration is not explained by differences in vascular refilling.
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Blood volume (BV) change during hemodialysis is often monitored by packed cell volume (PCV). This assumes erythrocyte volume is constant. We tested this by dialyzing 5 patients for 2 hours against high (154 mmol/l), normal (140 mmol/l) and low (126 mmol/l) dialysate sodium concentrations. Erythrocyte water content, calculated from measured blood and plasma water contents, decreased with high and increased with low dialysate sodium concentrations. Erythrocyte volume, calculated from mean corpuscular hemoglobin concentration (MCHC) decreased 3.8% with high concentration dialysate and increased 2.5% when dialysate concentration was low. These changes correlated significantly (r = 0.80, p less than 0.01) with alterations in plasma sodium. Mean corpuscular volume (MCV), measured with a Coulter-S Plus Counter did not alter because of a methodological artefact. BV change can be calculated from PCV when plasma concentrations of osmotically active substances are changed only if allowance is made for altered erythrocyte volume.
Serial abdominal computed tomography (CT) scans have been performed in 15 patients with biopsy-proven idiopathic retroperitoneal fibrosis. Twelve patients had abdominal CT both before diagnosis and at a variable time later. All 12 patients showed a decrease in the size of the retroperitoneal mass at follow-up, although two had not been treated with steroids. The remaining three patients who had abdominal CT at some stage after diagnosis all showed a small residual retroperitoneal mass. Based on the findings, guidelines for the use of CT in the follow-up of retroperitoneal fibrosis are discussed.
Effect of dialysate composition on intercompartmental fluid shift and hemodynamics was studied in 12 patients during 1.5 or 2 hours of hemodialysis without net ultrafiltration, using high (H;Na 154 mmol/liter), normal (N;Na 140 mmol/liter) or low (L:Na 126 mmol/liter) concentration dialysate. H dialysate was associated with a small (0.9%) increase in blood volume, a larger increase in plasma volume and a decrease in erythrocyte volume. L dialysate resulted in a 2.3% decrease in blood volume, a larger decrease in plasma volume and an increase in erythrocyte volume. N dialysate gave results which were intermediately between the other two dialysis conditions. There was no difference in the post-dialysis mean arterial pressure between the groups, although heart rate increased more during H dialysis than during the other two conditions. Change in blood and erythrocyte volume correlated significantly with change in plasma Na concentration and osmolality, but not with change in plasma urea concentration. We conclude that dialysate composition affects the movement of water into and out of the plasma and erythrocytes in a manner that can be accounted for by altered plasma concentrations of osmotically active substances.
Sixty patients with idiopathic retroperitoneal fibrosis presenting between 1965 and 1984 are reviewed. Their mean age at presentation was 56 years and the male:female ratio was 3:1. The commonest presenting symptoms were flank and abdominal pain, weight loss, nausea and polyuria. Physical examination was usually normal, expect for the presence of hypertension. Anaemia and elevation of erythrocyte sedimentation rate were usually present. Proteinuria was found in less than a third of patients at presentation and significant bacteriuria was uncommon. The correct diagnosis was made or suspected in very few patients before referral. The cumulative actuarial survival rate was 86% at 1 year and 78% at 2 years. Seventeen patients died; they were significantly older and more uraemic at the time of referral than those who survived. A few patients did well with either corticosteroid therapy or ureterolysis alone. In the majority, both operation and steroid treatment were necessary. In bilateral obstruction with residual function in both kidneys, bilateral ureterolysis proved superior to unilateral operation (each followed by steroid therapy) in conserving renal function. Operation alone or steroid therapy alone should be considered in cases where steroids or surgery respectively present particular hazards. The less traumatic unilateral operation should be considered in poor risk patients and in those whose renal function is absent on one side. In many survivors, disease activity has persisted for many years. Life-long follow-up is recommended.