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In spite of the reduction in peritonitis and catheter-related infection rates in patients undergoing peritoneal dialysis, these infections remain major sources of morbidity and transfer to haemodialysis. Touch contamination at the time of doing the exchanges is still a major cause of peritonitis and leads to Gram-positive organisms (coagulation-negative staphylococcus) being the most common pathogens. Newer exchange techniques have reduced this incidence but the more serious pathogens (Staphylococcal aureus, pseudomonas and fungi) remain a major problem. Treatment has to be immediate, and hence empirical, giving adequate cover for both Gram-positive and Gram-negative organisms. The use of vancomycin as an initial antibacterial has been discontinued because of the problem of vancomycin-resistant enterococcus. Recent guidelines advocate the use of a first generation cephalosporin combined with ceftazidime (if the urine output is >100 ml/day) or an aminoglycoside in anuric patients. Subsequent therapy changes are made upon bacterial isolation and sensitivities. Vancomycin is reserved for methicillin-resistant staphylococcus. Peritoneal catheter-related infections (exit site and tunnel) are predominantly caused by S. aureus and pseudomonal organisms and can be difficult to eradicate. Tunnel infections invariably involve the catheter dacron cuffs and therefore are more likely to lead to peritonitis; in this situation catheter removal is the treatment of choice. Treatment of exit-site infections is with oral antibacterials (penicillinase-resistant penicillins, cefalexin). Vancomycin is avoided if possible. The identification that nasal carriage of S. aureus predisposes to exit-site and tunnel infections has led to prophylactic regimens to combat this problem. Mupirocin applied at the exit site leads to a reduction in catheter-related infections and peritonitis. [ABSTRACT FROM AUTHOR]

Fertility is restored following renal transplantation, and the potential for motherhood can be realised. This retrospective study reviews the outcome of 53 pregnancies, in 24 patients, between 1988 and 1995. All patients underwent transplant surgery, and received antenatal care at a single centre. The mean age at first conception was 27·6 years, and graft function, as assessed by serum creatinine at the time of antenatal booking, was good. Patients were referred early, seen regularly, and had both obstetrician and nephrologist involved in management. The main maternal complication was hypertension, affecting 50% of patients. Seven patients had a worsening of pre-existing hypertension, whilst four patients developed hypertension for the first time during pregnancy. Graft function was, for the most part, well maintained. Four patients required delivery because of declining renal function, two of these went on to develop frank rejection, necessitating a return to dialysis within 3 months of delivery. These figures however are not higher than have been reported in the non-pregnant population. The overall pregnancy loss was 26%. There were a total of 39 live births. Premature birth was higher than that of the general population, with 57% of infants in the study delivering before 37 weeks' gestation (average 34 weeks' gestation) Of the 39 infants born alive 27% were growth retarded. Congenital abnormalities were, reassuringly, no higher than that in the general population, despite the need to take immunosuppressive drugs. Delivery was by caesarean section in 64% of cases, which may reflect a high degree of clinical caution in this group of patients. The study concludes that, whilst risks are recognised, for both the mother and infant, with a careful, multidisciplinary approach, the outcome is generally good. [ABSTRACT FROM AUTHOR]

Background.The combination of a low pH and a high concentration of lactate which is present in most dialysis fluids is found to be cytotoxic in vitro. For these reasons it would seem logical to use a bicarbonate-containing solution and thus automatically provide a solution with a neutral pH. [ABSTRACT FROM PUBLISHER]

Background. A recent survey puts the global dialysis population at 535 100; of those on peritoneal dialysis, 85% are on continuous ambulatory peritoneal dialysis. Current hyperosmolar dialysis fluids are toxic to peritoneal cells and inhibit certain host-defence functions. An alternative preparation, glucose polymer, has recently been developed. Methods. Mesothelial cell viability, interleukin-6 and prostacyclin synthesis, after exposure to 7.5% glucose polymer, 1.36% glucose or 3.86% glucose peritoneal dialysis effluent solution was assessed. Results. In its neat form, at an original pH of 5.4, glucose polymer was as toxic as hyperosmolar solutions (P <0.01). Synthesis of interleukin-6 and prostacyclin were significantly inhibited by neat dialysis fluid, (P <0.01). However, after an in vivo intraperitoneal incubation of only 15 min the toxicity of all solutions tested in vitro was lost. Conclusfons. Despite rapid in situ neutralization of dialysis fluid toxicity, mesothelial injury and inhibition of host-defence function, early in the dialysis cycle, may affect peritoneal physiology given the complex network of pathways to which these cells contribute. Although recent trials indicate improved ultrafiltration is achievable with glucose polymer, it is not a biocompatible dialysis fluid in its current manufactured form. [ABSTRACT FROM PUBLISHER]

Based on correlation analysis with 24-h dialysis collections the peritoneal equilibration test (PET) has been promoted as an aid to prescribe and monitor dialysis dose. However correlation is an incorrect statistical technique to demonstrate the similarity of one measure to another. The closeness (or limits) of agreement should be measured using the technique of Bland and Altman. One hundred and nineteen patients underwent a 24-h dialysate collection and a PET. D/P ratios for urea and creatinine, dialysate volume, urea and creatinine clearance and KT/V (urea) were calculated using both methods and compared using correlation analysis. In addition the limits of agreement, reflecting the potential margins of difference between the two methods, were determined. When used to calculate a daily dialysate volume required to achieve adequacy targets, the PET was found to result in a prescription error range of −0.6 to +1.5 l/day for creatinine clearance and −0.9 to +0.6 l/day for urea clearance. The tendency of the PET to exaggerate clearance resulted in 14% of patients incorrectly achieving a target creatinine clearance of 50 l/week and 17% incorrectly reaching a target KT/V of 1.7. The PET cannot be used in place of 24-h dialysis collections to prescribe or monitor dialysis therapy. [ABSTRACT FROM PUBLISHER]

Patients with chronic renal failure show an excess mortality from cardiovascular disease (CVD). Over a 4-year period (1983–1986) we have prospectively studied 305 patients (177 men, 128 women) from a geographically constrained population entering a renal replacement therapy (RRT) programme. The development of new cardiovascular events and patient survival have been documented up to the end of 1990. We have determined the incidence of CVD amongst the patients compared to the general population of the region and assessed the predictive value for future cardiovascular events of risk factors present at the start of RRT. One hundred and fourteen patients experienced a new cardiovascular event. One hundred and fifteen patients died, 89 from CVD. Stratification by age and sex identified diabetes, previous coronary heart disease, and cardiomegaly to be significantly associated with an increased risk of a cardiovascular event, and diabetes, previous coronary heart disease, and accelerated hypertension to be significantly associated with an increased risk of cardiovascular death. Mortality from CVD was 10.1 times that of the corresponding general population, and was increased 44 times for patients with diabetes. Duration of RRT did not influence mortality rates. This excessive early mortality has significant implica tions for RRT programmes and further research is necessary to identify individuals at risk and the modi fiable risk factors that could receive targeted interven tional therapy. [ABSTRACT FROM PUBLISHER]

We studied 38 patients (9 haemodialysis, 18 peritoneal dialysis, 11 advanced renal failure) over the first 12 weeks of erythropoietin therapy. In 14 iron-overloaded patients (ferritin >500 μg/l) the haemoglobin (±SEM) increased from 6.74±0.27 to 9.85±0.36 g/dl (<0.0001) entirely by mobilizing iron reserves (reduced from 1,220±73 to 739±111 mg, <0.0001). In the 24 non-overloaded patients (ferritin<500 μg/l) the haemoglobin rose similarly from 7.04±0.18 to 10.70±0.36 g/dl (<0.0001), partly from iron reserves (depleted from 200±74 to −44±77mg, =0.016) and partly from oral iron supplements (305±110 mg). In the overloaded patients the ferritin declined from 1057 μg/l (geometric mean, range 504–3699) to 317 μg/l (42–1505, <0.0001). In the non-overloaded patients it declined from 82 μg/l (8–461) to 45 μg/l (5–379, =0.016). The transferrin saturation (TS) in the overloaded patients appeared to decline from 38.3±7.2% to 24.0±3.7% but this was not statistically significant. In the non-overloaded the TS was unchanged (23.3±2.4 before and 28.1±3.6% after treatment). Considering all 38 patients together, the haemoglobin correlated negatively with the ferritin (=0.3731, <0.001) but not with the TS. The TS correlated with the serum ferritin initially (=0.75, <0.001) but not after the first 4 weeks. At 12 weeks, eight of 15 patients with iron deficiency (ferritin<50 μg/l) had a TS >20%, whereas two of five patients with persistent iron overload (ferritin >500 μg/l) had a TS <20%. We conclude that (a) in patients with iron overload, stored iron is utilizable for erythropoiesis; (b) oral iron supplements are necessary and sufficient for most patients without iron overload; (c) the serum ferritin is a better indicator of iron status than the TS for renal patients on erythropoietin. [ABSTRACT FROM PUBLISHER]

Twenty-seven patients with renal failure (16 on CAPD and 11 predialysis) were treated with erythropoietin. At 12 weeks, the mean haemoglobin concentration (±SEM) in the CAPD patients had increased from 7.07 ± 0.20 to 10.88 ± 0.45 g/dl (two-tailed paired test, <0.0001) and in the predialysis patients from 6.90 ±0.35 to 10.05 ± 0.47 g/dl (P< 0.0001). Predialysis patients were taking more antihypertensive medication at baseline. No increase was required in either group after erythropoietin; there was no change in blood pressure in the CAPD patients, though in the predialysis patients the systolic blood pressure rose slightly from 132 to 146 mmHg (=0.029) and the mean blood pressure from 95 to 103 mmHg (=0.028). In 12 patients (6 on CAPD and 6 predialysis) the red cell volume, plasma volume, and total blood volume were measured before and after treatment. In the CAPD patients there was a marked expansion of the red cell volume from 912±127 to 1471±222 ml (=0.004) and a concomitant contraction of the plasma volume from 3932 ±250 to 3178 ±326 ml (=0.005), leaving the blood volume unchanged from 4843 ± 352 to 4649 ±503 ml. Predialysis patients had a similar expansion of the red cell volume from 733 ± 59 to 1304± 161 ml (=0.017) but no contraction of the plasma volume (from 3417 ±354 to 3314 ±260 ml), so that the blood volume tended to expand from 4149 ±347 to 4618 ±414 ml (= 0.053). The mean contraction of the plasma volume in the predialysis group was trivial (− 102 ±214 ml), whereas in the CAPD group it was large (−754 ±158 ml, P=0.034, two-tailed unpaired test). Thereby the predialysis group experienced an expansion of the total blood volume of 469±186ml, whereas the CAPD group experienced a contraction of the blood volume of −195±189 ml(=0.031). We conclude that (a) increased blood volume may contribute to the exacerbation of hypertension induced by erythropoietin therapy; (b) gradual reduction of plasma volume, aiming for a stable total blood volume, is an important strategy for the prevention and control of erythropoietin-induced hypertension; (c) as reduction of plasma volume may be more problematic in predialysis patients, adequate blood pressure control may consequently be slightly more difficult, placing more reliance on antihypertensive medication. [ABSTRACT FROM PUBLISHER]

The osmotic effectiveness of an isosmolar glucose polymer (GP) solution during long-dwell (8–12 h) peritoneal dialysis has been demonstrated. The absorption of GP, though only a fraction of currently used glucose, is usually accompanied by the systemic accumulation of its breakdown product, maltose. The long-term consequences of maltose accumulation remain unknown. We studied the accumulation pattern of GP fractions, changes in serum electrolytes, osmolality, and adverse reaction profile over a 3-month period, using a daily regime of an overnight exchange of 7.5% GP±0.35% glucose solution with three daytime exchanges of 1.36% glucose in five non-diabetic CAPD patients. The GP solution (299 ±0.7 mOsm/kg) produced mean daily overnight UF of 589 ml and maintained stable serum biochemistry. The mean serum maltose level increased from a preanalysis value of 0.03 ±008 g/1 to a steady-state level of 1.1 ±0.14 g/1 within 2 weeks and remained stable throughout the study. This did not influence serum osmolality or sodium and produced no significant adverse effects. Once-daily overnight use of an isosmolar GP solution is safe and effective. The accumulation of maltose reaches steady-state levels quickly and produces no adverse toxic effects in the short term. Further long-term studies are planned. [ABSTRACT FROM PUBLISHER]

Chronic renal failure is associated with an increased rate of premature death from cardiovascular disease. Non-invasive identification of asymptomatic cardiac disease should be valuable in the management of such patients, and in selection for transplantation. One hundred and three high-risk patients (66 male, 37 female) with chronic renal failure who were without cardiovascular symptoms were assessed by exercise-graded thallium myocardial perfusion imaging and followed prospectively for 4 years. The development of a cardiovascular event, or death, and the interval to event or death were recorded. Cardiovascular events were documented in 50 patients; in 44 of the 60 patients with a positive thallium test and in only six of the 43 patients with a negative thallium test (test sensitivity 88%, specificity 70%, predictive value of a positive test 73%). Forty patients died, 28 from cardiovascular causes, during the study period. Thallium myocardial perfusion imaging is of value in the prediction of future cardiovascular events in patients with chronic renal failure, and is a useful non-invasive screening technique in patients with end-stage renal failure being considered for transplantation. [ABSTRACT FROM PUBLISHER]

Lipoprotein (a) is a subspecies of low-density lipoprotein which possesses as part of its protein moiety a mutant form of plasminogen termed apolipo-protein (a), and which may be closely related to the risk of ischaemic heart disease and cerebral infarction. We have investigated the serum concentrations of lipoprotein (a) and other lipoproteins in 24 male patients on CAPD and compared them to healthy men (= 100) and to age-matched healthy controls (=38). The most striking finding was a substantial elevation of serum lipoprotein (a) in CAPD patients in whom it was 46.9 (2.2–168) mg/dl (median and range) compared to 9.0 (<0.6–87.4) mg/dl in healthy control group and 6.7 (< 0.6–84.2) mg/dl in age-matched controls (both <0.001). Patients, when compared to healthy men, also had significantly increased serum triglycerides (median and range, 1.94 (0.55–8.00) versus 1.24 (0.36–4.40) mmol/1; < 0.001), very-low-density lipoprotein cholesterol (median and range, 0.98 (0.10–3.71) versus 0.46 (0.10–1.17) mmol/l; <0.001), and lower-high-density lipoprotein cholesterol (mean±1 sd, 1.26±0.29 versus 1.35±0.31 mmol/l). Of these, however, only the difference in very-low-density lipoprotein cholesterol remained statistically significant (< 0.001) in comparison to age-matched controls. The marked elevation of serum lipoprotein (a) in patients on CAPD may be due to increased hepatic synthesis as a consequence of the substantial amounts of plasma proteins lost in the dialysate. Elevated serum lipoprotein (a) concentrations in CAPD patients may contribute to their risk of coronary artery disease. [ABSTRACT FROM PUBLISHER]

TOral calcium carbonate is an effective phosphate binder in dialysis patients. Its use minimizes aluminium intake, and by maintaining a high-normal serum ionized calcium, suppresses serum parathyroid hormone levels. However, the dose required to control hyperphosphataemia may cause hypercalcaemia. We performed prospective studies in 50 previously undialysed patients starting CAPD (28 study group, 22 control group). Calcium carbonate was the only phosphate binder used in the study group which utilized a low calcium PD fluid (calcium 1.25 mmol/1), whilst the control group used standard PD solution (calcium 1.75 mmol/1) with calcium carbonate plus aluminium hydroxide phosphate binders as clinically indicated. The study group was able to take larger doses of oral calcium carbonate with no increase in episodes of hypercalcaemia compared to the control group. There were no instances of hypocalcaemia in any patient using the low-calcium dialysis fluid. Phosphate control was better in the study group, despite the additional use of aluminium-containing phosphate binders by some patients in the control group. Serum aluminium levels in the study group were maintained at <11.5μmol/l, but increased significantly in the control group from 3 months onward. Mean serum parathyroid hormone in the study group declined significantly from baseline values over the first 6 months, and remained at the lower level. Bonehistology showed a tendency towards improvement over the 12 months, in terms of osteoclast numbers and activity. We conclude that using dialysis fluid with a reduced calcium concentration in compliant, well-monitored patients is safe. It allows administration of large doses of calcium carbonate to obtain good control of serum phosphate and maintain serum ionized calcium near the upper end of the normal range. Parathyroid hormone is suppressed in the majority of patients and bone histology improves. By utilizing this more physiological dialysis fluid, aluminium-containing phosphate binders may be completely avoided in most CAPD patients [ABSTRACT FROM PUBLISHER]

A risk of β2microglobulin (β2-M)-associated amyloidosis in long-term CAPD patients has been recognised. We examined the kinetics of β2-M and potential clinical manifestations of amyloidosis in patients wellestablished on CAPD for 1–76 months (mean±SEM; 16.4±14 months). In 57 patients, serum β2-M concentration was elevated to 30±1.8 (mean±SEM, mg\1) and correlated positively with the duration on CAPD. In 18 patients studied with variable degrees of residual renal function, serum β2-M concentration increased with declining renal function; this was most marked when the creatinine clearance was less than 1 ml\min. Using an isosmolar solution (302±1.3mOsm\kg) containing 5% glucose polymer (9.4 mmol\1; MW 16 800), the transperitoneal elimination of β2-M was significantly enhanced (1.6 times) compared to conventional 1.36% glucose solution, but without a detectable change in serum concentrations during a 6-h study. No significant difference was found between the estimated minimum volume of distribution of β2-M in CAPD and haemodialysis patients. Symptomatic. amyloid-associated disease was absent in patients in this study, and may be attributed to the short duration of dialysis. [ABSTRACT FROM PUBLISHER]

In a multi-centre study by seven large renal units in the United Kingdom, the morbidity and mortality of all patients starting CAPD and haemodialysis during a 2-year period (1983–1984) has been monitored prospectively and related to reasons for choice of therapy and potential risk factors. Over this period 338 new patients (mean age 48; range 3–77 years) started CAPD; 17% had diabetes mellitus and 25% had cerebro/cardiovascular disease. One hundred and seventy-five patients (mean age 45; range 5–73 years) started haemodialysis; 6% had diabetes mellitus and 14% had cerebro/cardiovascular disease. The Kaplan-Meier actuarial patient survival estimates at 2 years were haemodialysis 84% and CAPD 83%, whilst technique survival figures for the same period were haemodialysis 92% and CAPD .80%. Cox's regression analysis showed that cerebro/cardiovascular disease and age >60 years were most important predictors for survival in CAPD patients, in whom smoking appeared to be a significant risk factor, for permanent change of therapy to haemodialysis. The major cause of ‘drop out’ in both groups was transplantation, whilst hospitalisation was 14.9 days per patient year for CAPD and 12.8 for haemodialysis patients. Within the CAPD group a temporary change to haemodialysis (<2 months) occurred on 106 occasions (each of mean of 19 days duration), amounting to 10 days per patient year of therapy. CAPD was used twice as often as haemodialysis for managing new patients. After 2 years hospitalisation technique and patient survival were comparable in the two groups, with cerebro/cardiovascular disease, age, and smoking being significant predictors of outcome. [ABSTRACT FROM PUBLISHER]

Ten children in end-stage renal failure were treated by continuous ambulatory peritoneal dialysis (CAPD). This represents a total of 3.4 patient years. Biochemical control was good, and parent and patient acceptability high. Peritonitis was the chief complication, but after the institution of a specific CAPD education and training programme the incidence declined 10-fold. We regard CAPD as an effective short- and medium-term treatment for children with end-stage renal failure as part of an integrated dialysis and transplant programme, but it requires a devoted and enthusiastic trained staff to ensure success. [ABSTRACT FROM AUTHOR]

1. The oral pharmacokinetics of fluconazole were studied in three groups of volunteers (n = 5) with various degrees of renal function (GFR greater than 70 ml min-1; 20-70 ml min-1; less than 20 ml min-1) and in a group of patients with chronic end-stage renal failure requiring regular haemodialysis. 2. The pharmacokinetics of fluconazole were markedly affected by impaired renal function with the elimination of half-life in Group III (GFR less than 20 ml min-1) being approximately three times that observed in normal volunteers (Group I). 3. Fluconazole renal clearance was positively correlated with GFR. 4. Non-renal clearance of fluconazole decreased with decreasing renal function. 5. Approximately 38% of the 50 mg dose of fluconazole was removed by haemodialysis extending over a 3 h period. [ABSTRACT FROM AUTHOR]

AIMS: To determine the effect of concomitant azathioprine treatment on the response of patients with renal failure to treatment with subcutaneous recombinant human erythropoietin (r-HuEPO). METHODS: Two groups of patients with renal failure not receiving haemodialysis were studied. One comprised seven patients receiving erythropoietin alone, the second consisted of nine patients who were also treated with azathioprine. The haematological changes were monitored, and the functional erythropoietic response was studied by two different ferrokinetic models. One analysed the initial, the other the extended plasma iron clearance. Studies were performed before r-HuEPO treatment on all 16 patients, and repeated on 11 of these when the target haemoglobin (10-11 g/dl) was achieved and stabilised. Total erythropoiesis was determined using both techniques. Analysis of the extended plasma iron clearance also permitted calculation of both effective and ineffective erythroid activity. RESULTS: The haematological response to r-HuEPO was the same for both patient groups. Measurement of total erythropoiesis by both ferrokinetic methods showed good correlation. For those receiving long term azathioprine, the percentage ineffective erythropoiesis was high compared with that of the other patients, and remained so for as long as they continued with azathioprine. For those uncomplicated by azathioprine treatment, r-HuEPO increased levels of both effective and ineffective erythropoiesis by the same degree. A substantial reduction in ineffective erythropoiesis was shown only by those patients who either discontinued or reduced their azathioprine once they started r-HuEPO treatment. CONCLUSIONS: Azathioprine increases ineffective erythropoiesis. In this study, the r-HuEPO dose was sufficient to overcome this effect and promoted effective erythropoiesis so that the anaemia lessened. Measurement of total erythropoiesis provided limited information on the functional changes involved, differentiation of effective from ineffective erythropoiesis being necessary to define the changes after azathioprine reduction or withdrawal. [ABSTRACT FROM PUBLISHER]