The effect of long, slow haemodialysis on patient survival.

BACKGROUND: Long, slow haemodialysis (24 h/week) has been associated with excellent patient survival and reduced cardiovascular mortality. Comparisons of patient survival have only been possible with registry data and other published series which do not control for individual patient characteristics. This retrospective study compares actuarial patient survival between a unit using long, slow haemodialysis (Tassin) and one employing 'conventional' haemodialysis (Nottingham). METHODS: All patients undergoing haemodialysis at each centre since 1980 were included (Tassin, 452 patients; Nottingham, 282 patients). Actuarial curves of patient survival were calculated by the life-table method and log rank test was used to compare data. Patients were grouped as follows: standard (SRD) and non-standard (NSRD) renal diseases; diabetics and non-diabetics; patients with and without cardiovascular antecedents; risk stratification based on age and comorbidity. RESULTS: Overall survival was significantly better in Tassin. This difference was also noted for patients with SRD and non-diabetics (both P < 0.001) and for those with (P = 0.007) and without (P < 0.001) cardiovascular antecedents. Survival did not differ significantly for NSRD and diabetics. Survival was better in Tassin in low-risk (P < 0.001) and medium-risk (P < 0.001) groups, but not for high-risk (risk stratification). CONCLUSIONS: Overall survival is increased on long, slow haemodialysis. Although the benefits are seen in the most favourable prognostic categories, they are also present in patients with comorbid illness (medium-risk group) and pre-existing cardiovascular disease.

Management of hypertension in patients developing end-stage renal failure.

The benefits of treating hypertension include preventing or delaying the progression of chronic renal failure, and reducing the cardiovascular complications of patients with renal disease. We examined how well hypertension had been managed in all 145 patients from a single health district who started dialysis during a 3-year period. Data relating to management of hypertension, including all blood pressure readings, were obtained from their general practice and hospital case notes. The anonymized data were reviewed by two independent assessors against a set of standards based on the British Hypertension Society guidelines. There was close agreement between the assessors. Complete records were obtained in 98.5% of cases. Of the 145 patients, 107 (76.4%) were hypertensive before developing end-stage renal failure. There were departures from standards in all categories of care: 24.3% in detection/diagnosis, 29% in investigation, 22.4% in referring to a nephrologist, and 17% in follow-up. The British Hypertension Society recommended standard for diastolic blood pressure of 90 mmHg was achieved in only 45%. In 32%, the assessors independently concluded that poor blood pressure control might have affected adversely the progression of renal failure. New methods of dealing with these problems are required and possible approaches are discussed.

Role of arachidonic acid and its metabolites in the priming of NADPH oxidase in human polymorphonuclear leukocytes by peritoneal dialysis effluent.

Peritoneal dialysis effluent (PDE) contains a low-molecular-weight solute that will activate and prime the NADPH oxidase of human neutrophils via a phospholipase A2 (PLA2)-dependent mechanism. Since the products of PLA2 are known to activate and prime the oxidase we have investigated their role in the dialysis effluent-mediated activation and priming of human neutrophils. NADPH oxidase activity of PDE-primed and -unprimed neutrophils was measured by lucigenin-enhanced chemiluminescence in the presence of known inhibitors of the arachidonic acid cascade. Incubation of neutrophils with the nonselective PLA2 inhibitor quinacrine (0 to 100 microM) reduced oxidase activity in both primed and unprimed cells. Furthermore, primed cells were more sensitive to the action of quinacrine than were unprimed cells. We were unable to determine the relative roles of secretory PLA2 (sPLA2) and cytosolic PLA2 (cPLA2) since the selective sPLA2 inhibitor scalaradial (0 to 100 microM) inhibited oxidase activity in both groups of cells by similar degrees, while the specific cPLA2 inhibitor AACO-CF3 (0 to 50 microM) failed to affect activity in either group. Inhibition of platelet-activating factor (PAF), cycloxygenase, and 5-lipoxygenase-activating protein by hexanolamino-PAF (0 to 25 microM), flurbiprofen (0 to 25 microM), and MK886 (0 to 5 microM), respectively, had no effect upon oxidase activity. However, the direct inhibition of 5-lipoxygenase by caffeic acid or lipoxin A4 resulted in a similar concentration-dependent attenuation of oxidase activity in both primed and unprimed cells. Leukotriene B4 (LTB4) release from primed neutrophils was comparable to that from unprimed cells with the exception of phorbol myristate acetate-stimulated cells, which released fivefold more LTB4 than control. Taken together, these results suggest that it is arachidonic acid per se, and not its metabolites, that is important in priming of the neutrophil NADPH oxidase by dialysis effluent.

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis.

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 mumol/l and Group II comprised patients with serum creatinine concentration of 600 mumol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years; (p < 0.01) patients, and the mean total creatinine clearance for Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-à-vis solute transfer are in progress.

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 umol/l and Group II comprised patients with serum creatinine concentration of 600 umol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years); (p < 0.01) patients, and the mean total creatinine clearance of Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-a-vis solute transfer are in progress.(AU)

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 umol/l and Group II comprised patients with serum creatinine concentration of 600 umol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years); (p < 0.01) patients, and the mean total creatinine clearance of Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-a-vis solute transfer are in progress.

Impaired bacterial killing and hydrogen peroxide production by polymorphonuclear neutrophils in end-stage renal failure.

Polymorphonuclear leukocytes (PMN) isolated from a sub-population of patients with end-stage renal failure (ESRF) who were identified because they demonstrated impaired intracellular bacterial killing, were assayed for hydrogen peroxide activity using two different techniques capable of distinguishing between total and intracellular hydrogen peroxide generation. In an attempt to elucidate the mechanism of impaired intracellular bacterial killing further, hydrogen peroxide activity was compared to PMN isolated from patients receiving continuous ambulatory peritoneal dialysis and a control group of healthy normal volunteers. PMN from conservatively treated ESRF patients demonstrated reduced production of intracellular hydrogen peroxide (mean 37.7 +/- 4.3 fluorescence units), compared to PMN from both ESRF patients treated with continuous ambulatory peritoneal dialysis (mean 57.9 +/- 6.6 fluorescence units) and normal controls (mean 60.4 +/- 3.5 fluorescence units). This suggests that the probable mechanism of impaired bacterial intracellular killing by the PMN of conservatively treated ESRF patients involves the production of intracellular hydrogen peroxide.

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom hospital.

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89% being less than 60 years of age compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome occurred more frequently at UHWI than at NCH but the numbers were small (p < 0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom Hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89 percent being less than 60 years of age compared to 40 percent at NCH (p<0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI than at NCH but the numbers were small (p<0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p<0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76 percent v 19 percent on haemodialysis). At UHWI, CAPD was not available and 45 percent of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available. (AU)

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom Hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89 percent being less than 60 years of age compared to 40 percent at NCH (p<0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI than at NCH but the numbers were small (p<0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p<0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76 percent v 19 percent on haemodialysis). At UHWI, CAPD was not available and 45 percent of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.

Hydrogen peroxide generation by polymorphonuclear leukocytes exposed to peritoneal dialysis effluent.

In the presence of peritoneal dialysis effluent (PDE), human polymorphonuclear leukocytes (PMN) showed reduced production of hydrogen peroxide and hypochlorous acid (H2O2 and HOCl, respectively) when at rest and when stimulated with both soluble (formylmethionyl-leucyl-phenylalanine and phorbol myristate acetate) and particulate (Staphylococcus epidermidis) agonists. This effect occurred in a concentration-dependent manner between 0 and 70%. (vol/vol) dialysis effluent. The inhibition of H2O2 and HOCl observed in resting, formy-methionylleucyphenyalanine-stimulated, and S. epidermidis-stimulated PMN was confined to a low-molecular-mass (< 10,000-Da) fraction of PDE, whereas the inhibition of the PMA response was equally dispersed throughout both low (< 10,000-Da)- and high-molecular-mass (> 10,000-Da) fractions. Human serum albumin, a major component of PDE, also inhibited H2O2 and HOCl production by PMN; however, results from cell-free systems suggested that human serum albumin was not wholly responsible for the inhibition of PMN function seen with PDE. The solute(s) responsible did not affect myloperoxidase but very rapidly scavenged H2O2 and HOCl. These data suggest that the factors capable of affecting H2O2 and HOCl production by PMN accumulate in uremia and are removed from the circulation into dialysis effluent.

Free and esterified carnitine in continuous ambulatory peritoneal dialysis patients.

Free, acetyl-, medium- and long-chain acylcarnitine and total plasma carnitine concentrations were measured in eight continuous ambulatory peritoneal dialysis (CAPD) patients and eight age- and sex-matched healthy controls. Daily loss of carnitine was also quantified in both groups, by analysis of urine and dialysis fluid. Plasma total carnitine concentration in CAPD patients was not significantly different from controls (42.8 +/- 1.6 and 43.1 +/- 2.3 mumol/liter, respectively). However, the plasma free carnitine concentration of CAPD patients was significantly lower than that of controls (28.5 +/- 1.4 and 36.2 +/- 2.5 mumol/liter, respectively; P < 0.05). No difference in the daily loss of total carnitine was found between CAPD patients and controls (269.7 +/- 30.0 and 240.5 +/-33.0 mumol/liter, respectively), but the daily loss of free carnitine was significantly greater in CAPD patients (175.8 +/- 17.3 and 105.8 +/- 16.4 mumol/liter, respectively; P < 0.05). The ratio of total acylcarnitine (acetyl-, medium- and long-chain acylcarnitine) to free carnitine was significantly greater in plasma of CAPD patients than in controls (P < 0.01) and was lower in daily fluid losses (P < 0.001). These ratio differences suggests that an alteration in acyl group metabolism is occurring in CAPD patients. This may be attributable to an accumulation of medium- and long-chain acylcarnitine in liver of CAPD patients which would be exchanged for plasma free carnitine and/or to a differential loss of free and acylcarnitine across the peritoneal cavity.

A randomized placebo-controlled study of enalapril in the treatment of erythrocytosis after renal transplantation.

BACKGROUND: Erythrocytosis is a common complication of renal transplantation with an incidence of up to 17%. It is associated with an increased risk of complications due to thromboembolic events and has traditionally been treated by intermittent venesection. More recently, angiotensin-converting enzyme inhibitors have been shown to cause a fall in haematocrit in a number of groups of subjects and some uncontrolled studies have shown these drugs to be of possible therapeutic benefit in post renal transplant erythrocytosis. METHODS: We performed a randomized double-blind placebo-controlled study in 25 patients with post-transplant erythrocytosis. Subjects received either 2.5 mg of enalapril daily or a placebo for 4 months and all patients completed the study period without any serious adverse effects. RESULTS: Haematocrit fell from 52.7 (+/- SEM 0.7) to 47.1 (+/- 1.8) at 1 month and 46.1 (+/- 1.2) after 4 months in patients receiving enalapril, with no change in the placebo group (P = 0.004). We did not demonstrate any change in serum erythropoietin in either group. CONCLUSIONS: Angiotensin-converting enzyme inhibitors are a safe and effective form of treatment for erythrocytosis developing after renal transplantation. The mechanism of action, however, is not mediated by changes in erythropoietin production and remains uncertain.

Cytomegalovirus infection in renal transplantation.

Three case reports of Cytomegalovirus (CMV) disease in seronegative renal transplant recipients of seropositive donor kidneys are presented. Clinicians need to have a high index of suspicion for CMV disease in such patients. Early diagnosis and treatment are essential to decrease morbidity and mortality. Prophylaxis with antiviral and/or CMV-hyperimmunoglobulin may decrease the incidence of serious infection.

Cytomegalovirus infection in renal transplantation

Three case reports of cytomegalovirus (CMV) disease in seronegative renal transplant recipients of seropositive donor kidneys are presented. Clinicians need to have a high index of suspicion for CMV disease in such patients. Early diagnosis and treatment are essential to decrease morbidity and mortalitiy. Prophylaxis with antiviral and/or CMV-hyperimmunoglobulin may decrease the incidence of serious infection (AU)

Cytomegalovirus infection in renal transplantation

Three case reports of cytomegalovirus (CMV) disease in seronegative renal transplant recipients of seropossitive donor kidneys are presented. Clinicians need to have a high index of suspicion for CMV disease in such patients. Early diagnosis and treatment are essential to decrease morbidity and mortalitiy. Prophylaxis with antiviral and/or CMV-hyperimmunoglobulin may decrease the incidence of serious infection