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Biomedical subjects

R S Rodger

Publications and source records attributed to R S Rodger.

At least 19 recordsLinked to original sources
PubMed2000

Endothelial dysfunction in renal transplant recipients maintained on cyclosporine.

BACKGROUND: Hypertension is almost universal following renal transplantation and may contribute to the already poor cardiovascular prognosis of this group. Cyclosporine-induced hypertension is a particular problem and has variously been attributed to increased sympathetic nerve activity, salt and water retention, and increased circulating endothelin levels. However, the effects of cyclosporine on the L-arginine/nitric oxide (NO) system in vivo in humans are unknown. In this present study, we examined basal and stimulated NO production from the vascular endothelium in cyclosporine-treated renal transplant recipients using the technique of forearm venous plethysmography. METHODS: In study 1, stimulated NO production was assessed in 9 cyclosporine-treated renal transplant recipients (CsA), 7 azathioprine-treated renal transplant recipients (AZA), and 12 controls, using carbachol (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator). In study 2, basal NO production was assessed in 9 cyclosporine-treated patients and 11 controls using L-NMMA (inhibits NO synthase), with norepinephrine as a control vasoconstrictor. Drugs were infused into the nondominant forearm through a sterile 27-gauge needle, and changes in forearm blood flow (FBF) were measured using venous occlusion plethysmography. RESULTS: In study 1, sodium nitroprusside caused a similar dose-dependent increase in FBF in all groups. However, the median (range) percentage increase FBF to carbachol (3 micrograms/min) was markedly reduced in the CsA patients (188.8; 72.5 to 385.1) compared with AZA patients (378.1; 124.0 to 548.9; P = 0.042) and to controls (303.8; 124.8 to 813.3; P = 0.028). In study 2, the maximum percentage reduction in FBF to L-NMMA (4 mumol/min) was less pronounced in CsA patients (-19.5; -4.7 to -63.1) compared with controls (-39.5; -15.7 to -52.8; P = 0.056), and while controls vasoconstricted to the maximum dose of norepinephrine (240 pmol/min) as expected (-26.9; -1.4 to -38.6), CsA patients as a group tended to vasodilate (7.9; -36.8 to 92.6; P = 0.02). CONCLUSION: These data demonstrate impaired stimulated and basal NO production in CsA patients, indicating endothelial dysfunction. This may predispose patients to atherosclerosis and may be involved in the etiology of post-transplant hypertension.

Adult↗
PubMed2000

Early echocardiographic changes and survival following renal transplantation.

BACKGROUND: Left ventricular hypertrophy, ventricular dilatation and poor systolic function prior to renal transplantation are associated with increased mortality. However, whether the improvement in these echocardiographic indices that is reported to follow renal transplantation improves patient survival has not been investigated. METHODS: We studied 67 patients who underwent renal transplantation in our unit between 1988 and 1990 and in whom echocardiography was performed immediately prior to transplant surgery and 4 months later. Pre- and post-transplantation echocardiographic parameters were compared between the 20 patients who have since died and surviving patients and a descriptive survival analysis was performed. RESULTS: Following transplantation there was no significant change in left ventricular mass index (LVMI) or end diastolic diameter (EDD). End systolic diameter (ESD) improved in 60% of patients (median 3.3 vs 3. 7 cm; P=0.031) as did fractional shortening in 67% (0.33 vs 0.29; P=0.001). However, improvement was not associated with survival benefits. We also found that prior to transplantation, fractional shortening, ESD and EDD were strongly associated with outcome; this was no longer the case following transplantation. In contrast, LVMI provided a stronger association with adverse outcome (albeit of limited statistical significance) following transplantation. CONCLUSIONS: In this Preliminary Report, we conclude that echocardiographic parameters are associated with adverse outcome in patients receiving renal replacement therapy (RRT). Different echocardiographic parameters are associated with adverse outcome before and after renal transplantation and improvement of pre-transplant abnormalities (e.g. poor LV systolic function) following transplantation does not necessarily confer survival benefits. Whether this is a genuine observation or a reflection of the interpretation of echocardiographic measurements in dialysis patients requires further investigation.

Adolescent↗
PubMed2000

Impaired endothelium-dependent vasodilatation in uraemia.

BACKGROUND: Patients with chronic renal failure (CRF) have a substantially increased risk of cardiovascular death, the proposed mechanisms being arrhythmias (left ventricular hypertrophy) and accelerated atherosclerosis. The vascular endothelium protects against the development of atherosclerosis principally by releasing vasoactive substances such as nitric oxide (NO) and endothelium-derived hyperpolarizing factor. In CRF there is accumulation of endogenous inhibitors of NO synthesis. In this present study we assessed endothelium-dependent vasodilatation in patients with advanced uraemia. METHODS: Sixteen uraemic patients (pre-dialysis and continuous ambulatory peritoneal dialysis) and 18 controls were studied. Forearm plethysmography was used to measure forearm blood flow and the changes induced by carbachol (endothelium-dependent vasodilator) and sodium nitroprusside (SNP; endothelium-independent vasodilator). The order of drugs infused was randomized between subjects. Dose response curves were constructed for each agent and area under the curve (AUC) calculated (arbitrary units). RESULTS: Overall, vasodilatation to SNP and carbachol was similar between uraemic patients and controls. However, it became apparent that there was a marked order effect for the drugs infused, such that infusion of SNP as the first agent blunted the subsequent response to carbachol. When only those patients and controls who received carbachol followed by SNP were studied (10 in each group), the response to carbachol in uraemic patients was attenuated compared to controls: AUC (median(range)) for uraemic patients 529.0 (150.9-834.7) compared to AUC for controls 703.9 (583.5-1576.6); P=0. 028. Vasodilatation to SNP was, however, similar between groups: AUC for uraemic patients 1475.0 (857.8-4717.1) compared to AUC for controls 1328.1 (216.6-3311.4); P=0.545. CONCLUSIONS: This study has demonstrated a marked drug order effect not previously described for forearm plethysmography. When the order effect was taken into account, this study demonstrated reduced vasodilatation to carbachol in uraemic patients with a preserved response to SNP. This pattern indicates impaired endothelium-dependent vasodilatation in uraemic patients, a defect that may predispose this group to accelerated atherosclerosis.

Adult↗
PubMed1999

Early graft function and patient survival following cadaveric renal transplantation.

BACKGROUND: The influence of events that occur early following renal transplantation such as delayed graft function (DGF) and acute rejection on long-term graft survival has been widely reported, but its association with patient survival has received less attention. METHODS: We studied 589 patients who received their first cadaveric transplants between 1984 and 1993, all of whom received cyclosporine-based immunosuppression and who had a median follow-up of seven years. The following factors were identified, and both univariate and multivariate analyses were used to determine their association with long-term patient and graft survival: age, sex, duration of pretransplant dialysis, primary renal disease, immediate graft function (IGF), DGF, primary nonfunction (PNF), acute rejection, and serum creatinine at 3, 6, and 12 months. RESULTS: Patients with PNF had a poorer survival than those with DGF and IGF (P = 0.01), but there was no difference in survival between DGF and IGF (P = 0.54). Good graft function (serum creatinine of less than 200 mumol/liter) at three months was predictive of better long-term patient survival (P = 0.03). Other factors associated with poor patient outcome were older age, diabetes, adult polycystic kidney disease, male gender, and acute rejection. Cardiovascular disease was the most common cause of death (51.8%). Good graft function at three months (P < 0.001) and an absence of rejection episodes (P = 0.01) were associated with better graft survival. CONCLUSION: Patients with poor levels of early graft function (but not DGF) and those with either acute rejection episodes or early graft loss are at an increased risk of early death. These high-risk groups should be targeted for interventional studies in an attempt to improve patient survival.

Adolescent↗
PubMed1999

Echocardiography overestimates left ventricular mass in hemodialysis patients relative to magnetic resonance imaging.

UNLABELLED: Echocardiography overestimates left ventricular mass in hemodialysis patients relative to magnetic resonance imaging. BACKGROUND: Left ventricular hypertrophy (LVH) is a common finding and a strong adverse prognostic factor in patients with chronic renal failure. An accurate method of measuring left ventricular mass (LV mass) is therefore a prerequisite in the management of these patients. Recent evidence has suggested that echocardiography overestimates LV mass in patients with essential hypertension, and this error increases with increasing LV mass. METHODS: We studied 35 patients on maintenance hemodialysis within 24 hours of their last dialysis. LV mass was measured by both echocardiography and magnetic resonance imaging (MRI) performed less than three hours apart. Clinic and ambulatory blood pressure (ABPM), resting echocardiogram, and blood sampling were performed at the same visit. RESULTS: Thirty-two patients had results from both methods. Clinic blood pressure, ABPM, and QT dispersion all correlated with LV mass, with a stronger correlation observed for MRI values. Intraobserver and interobserver variability were significantly greater for echocardiography (although similar to other published data). Comparing the two methods, the difference in LV mass values (echo minus magnetic resonance) increased in a linear fashion with an increasing mean mass and chamber diameter. CONCLUSIONS: Echocardiography significantly overestimates LV mass relative to MRI in the presence of LVH and dilation. This overestimation is the result of assumptions made in the calculation of mass from echocardiography M-mode images, which are invalid when LV geometry is abnormal. This error is therefore amplified in dialysis patients, the majority of whom have LVH and in whom intravascular volume is constantly changing.

Adult↗
PubMed1999

QT dispersion before and after hemodialysis.

Sudden cardiac death is common in patients on hemodialysis, and may occur in the immediate postdialysis period, when ventricular premature complexes are common. Elevated QT dispersion (Maximum - Minimum QT interval on standard 12-lead electrocardiogram) is associated with increased risk of ventricular arrhythmias following myocardial infarction, but has not previously been assessed in patients with chronic renal failure. We studied electrocardiograms recorded in 50 patients before and after a single hemodialysis session, and in 20 control subjects. QT dispersion was significantly higher in patients (63.1 +/- 20.6 ms) compared with control subjects (36.0 +/- 13.7 ms; P < 0.001) and rose significantly after hemodialysis to levels comparable to those seen following myocardial infarction (76.6 +/- 27.0 ms; P < 0.01). Because QT dispersion reflects nonhomogeneous recovery of ventricular excitability, hemodialysis patients may be at significantly greater risk of reentrant arrhythmias and sudden death in the postdialysis period.

Electrocardiography↗
PubMed1998

Long-term outcome of a prospective randomized trial of conversion from cyclosporine to azathioprine treatment one year after renal transplantation.

BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about the long-term adverse effects of CsA, especially with respect to renal function and blood pressure. This randomized controlled trial was set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS: Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine of less than 300 micromol/L and who had not had acute rejection within the last 6 months were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone. Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS: There was no significant difference in actuarial 10-year patient or graft survival (Kaplan-Meier), despite an increased incidence of acute rejection within the first few months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119 micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients required antihypertensive treatment at the start of the study, decreasing to 55% from 1 year after randomization in the Aza group and increasing to >80% in the CsA group (55% (Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion from CsA to Aza at 1 year after renal transplantation results in improvement in both blood pressure control and renal allograft function, and is not associated with significant adverse effects on long-term patient or graft survival.

Acute Disease↗
PubMed1998

Pre-operative echocardiographic abnormalities and adverse outcome following renal transplantation.

BACKGROUND: Premature cardiovascular disease is now the leading cause of death in renal transplant recipients. Although patients with progressive renal disease have many of the conventional risk factors for cardiovascular disease these do not have the same predictive power as they do in the general population. Echocardiographic abnormalities, notably left ventricular hypertrophy, have been shown to be associated with adverse outcome in patients on dialysis. METHODS: The echocardiograms were studied from 141 patients who were examined on the eve of renal transplantation between 1988 and 1990 to try to identify factors predicting outcome. Thirty-four patients have since died, 22 of cardiovascular disease. Ninety-three of the survivors and 27 of the dead patients had echocardiographic traces suitable for analysis. RESULTS: Left ventricular mass index was increased in those patients who died (median 167 vs 134 g/m2; P=0.03), as were end-systolic (4.3 vs 3.4 cm; P<0.01) and end-diastolic (5.8 vs 5.2 cm; P<0.01) diameters. Systolic function was also more severely impaired (fractional shortening, 27 vs 33%; P<0.01). Apart from age, only systolic function and end systolic diameter were independent predictors of outcome in multivariate analysis. CONCLUSIONS: This pattern of echocardiographic abnormality is similar to that reported in long-term dialysis populations, despite the adverse effects on survival. Moreover, despite potential benefits of transplantation on cardiac function, left ventricular hypertrophy, ventricular dilatation and systolic dysfunction were all associated with adverse outcome following transplantation. We conclude that echocardiography identifies markers for premature death following transplantation and provides targets for therapeutic intervention.

Adolescent↗
PubMed1997

Effect of renal-artery stenting on progression of renovascular renal failure.

BACKGROUND: Placement of renal-artery stents has a high technical success rate in atherosclerotic renovascular disease, but little is known about the clinical benefits of the procedure. We monitored renal function serially before and after stent insertion in patients with renovascular renal failure. METHODS: Renal function was assessed before and after stent placement by means of serial serum creatinine values in 32 patients with atherosclerotic renal-artery stenosis. The effect on the progression of renal failure was analysed in 23 patients by comparison of the reciprocal slopes of serum creatinine versus time plots before and after stent placement. FINDINGS: 33 transluminal stents were placed in 32 patients with atherosclerotic renovascular disease. Immediate patency was achieved in all cases: the angiographic restenosis rate at 6 months was 12% (n = 24). One patient died after a procedure-related haemorrhage. Median diastolic blood pressure was significantly lower after stenting than before (95 [IQR 86-103] vs 87 [81-90] mm Hg; p > 0.01) but the requirement for antihypertensive drugs was unchanged. Renal function improved or stabilised in 22 (69%) of the 32 patients. Progression of renal failure was significantly slowed after the procedure; the mean (SE) of the slopes of reciprocal serum creatinine values was -4.34 (0.85) L mumol-1 day-1 before stent placement, and -0.55 (1.0) L mumol-1 day-1 after stent placement (p < 0.01, two-sample t test). INTERPRETATION: Renal-stent placement in selected patients slows the progression of renovascular renal failure and may delay the need for renal replacement therapy.

Aged↗
PubMed1997

Renal replacement therapy in the elderly.

Before 1980 few patients over the age of 65 started chronic dialysis, despite the fact that the incidence of advanced chronic renal failure was approximately ten times greater in this group compared to young and middle aged adults. Since that time the number of elderly patients starting renal replacement has increased markedly and accounted for 38% of new dialysis patients in Scotland in 1995. (Data supplied by the Scottish Renal Registry). In order to meet the needs of older patients with chronic renal failure there has been considerable expansion in renal services and it has been predicted that this will continue to increase in Scotland until 2010.

Adolescent↗
PubMed1996

Ranitidine reduces phosphate binding in dialysis patients receiving calcium carbonate.

BACKGROUND: In a previous controlled study we showed that ranitidine significantly reduced the phosphate binding of aluminium hydroxide in patients with renal failure, probably increasing intragastric pH. METHODS: In this study we have investigated the effect of ranitidine on the phosphate binding of calcium carbonate in fifteen dialysis patients. Ranitidine 300 mg or a placebo tablet was taken before breakfast for two 4-week periods in a double-blind crossover trial with no washout period. The mean daily dose of calcium carbonate was 2 g and neither the dose nor the patient's diet was changed during the study period. Blood was taken at 2-weekly intervals for serum phosphate, calcium, albumin, and alkaline phosphatase measurements, and at the end of each treatment period for parathyroid hormone (PTH) level. RESULTS: Serum phosphate concentrations were significantly higher during the ranitidine than the placebo phase, 1. 78 (+/-0.43 SD) versus 1.59 (+/-0.49 SD) mmol/l (P<0.001). Serum calcium, albumin, PTH, and alkaline phosphatase concentrations did not differ between the two treatment periods. CONCLUSION: This study shows that ranitidine has a significant adverse effect on the phosphate binding of calcium carbonate in patients with renal failure.

Adult↗
PubMed1996

Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors.

Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 +/- 1.6 g dl-1 (range - 0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31%) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) - complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytosis.

Adult↗
PubMed1995

Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy.

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.

Adult↗