EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis.

OBJECTIVE: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE). METHODS: A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing. RESULTS: 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group. CONCLUSIONS: There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.

The provision and practice of renal replacement therapy on adult intensive care units in the United Kingdom.

This study surveyed the availability and current practice of renal replacement therapy on adult general intensive care units in the United Kingdom. Questionnaires were returned from 236 units (89%). Renal replacement therapy was provided by 212 (90%) of responding units, treating 9442 patients per year. Renal physicians were involved in the initiation and prescription of treatment in 22 (11%) units. Ninety-one units (43%) had no step down facility on-site for those patients still requiring renal replacement therapy but no longer requiring intensive care. Continuous techniques are used by the majority of units, most commonly, continuous veno-venous haemofiltration, with an ultrafiltration rate of 2000 ml.h-1. Fifty-eight units (28%) use haemofiltration as adjuvant treatment in septic shock. The provision and practice of renal replacement therapy is now an integral part of intensive care medicine in the United Kingdom.

A novel technique to demonstrate disturbed appetite profiles in haemodialysis patients.

BACKGROUND: Malnutrition is common among dialysis patients and is associated with an adverse outcome. One cause of this is a persistent reduction in nutrient intake, suggesting an abnormality of appetite regulation. METHODS: We used a novel technique to describe the appetite profile in 46 haemodialysis (HD) patients and 40 healthy controls. The Electronic Appetite Rating System (EARS) employs a palmtop computer to collect hourly ratings of motivation to eat and mood. We collected data on hunger, desire to eat, fullness, and tiredness. HD subjects were monitored on the dialysis day and the interdialytic day. Controls were monitored for 1 or 2 days. RESULTS: Temporal profiles of motivation to eat for the controls were similar on both days. Temporal profiles of motivation to eat for the HD group were lower on the dialysis day. Mean HD scores were not significantly different from controls. Dietary records indicated that dialysis patients consumed less food than controls. CONCLUSIONS: Our data indicate that the EARS can be used to monitor subjective appetite states continuously in a group of HD patients. A HD session reduces hunger and desire to eat. Patients feel more tired after dialysis. This does not correlate with their hunger score, but does correlate with their fullness rating. Nutrient intake is reduced, suggesting a resetting of appetite control for the HD group. The EARS may be useful for intervention studies.

The measurement of total body potassium in patients on peritoneal dialysis.

OBJECTIVES: To assess the validity of measuring total body potassium (TBK) to estimate fat-free mass (FFM) and body cell mass (BCM) in patients on peritoneal dialysis (PD). METHODS: We studied 29 patients on PD (14 men, 15 women) and 30 controls (15 men, 15 women). We calculated TBK by using a whole-body counter to measure 1.46 MeV gamma-ray emissions from naturally occurring 40K. We measured total body water (TBW) by deuterium oxide dilution, and extracellular water (ECW) from bromide dilution. These measurements allowed us to estimate intracellular water (ICW), fat-free mass dilution (FFM(Dilution)), and body cell mass dilution (BCM(Dilution)). RESULTS: The FFM(TBK) in male PD patients (55.7 +/- 7.0 kg) did not differ from that in male controls (57.0 +/- 10.9 kg). The FFM(TBK) in female PD patients (38.4 +/- 6.8 kg) was less than that in female controls (44.7 +/- 4.5, p < 0.01). The FFM(Dilution) did not differ from the FFM(TBK). Correlation of FFM(TBK) and FFM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.90, p < 0.0001 for PD patients; and r = 0.90, p < 0.0001 for controls. Bland-Altman comparison of FFM(Dilution) with FFM(TBK) in individuals showed bias 0.6 kg, range -8.5 kg to 9.7 kg for the whole group; bias 1.4 kg, range -7.9 kg to 10.7 kg for PD patients; and bias -0.2 kg, range -9.0 kg to 8.6 kg for controls. The BCM(TBK) in male PD patients (30.1 +/- 4.5 kg) did not differ from that in male controls (31.9 +/- 6.2 kg). The BCM(TBK) in female PD patients (19.0 +/- 4.4 kg) was less than that in female controls (23.1 +/- 2.9 kg, p < 0.01). The BCM(Dilution) results did not differ from those for the BCM(TBK). Correlation of BCM(TBK) and BCM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.87, p < 0.0001 for PD patients; and r = 0.93, p < 0.0001 for controls. Bland-Altman comparison of BCM(Dilution) with BCM(TBK) in individuals showed bias 0.1 kg, range -5.9 kg to 6.1 kg for the whole group; bias 0.0 kg, range -6.9 kg to 6.9 kg for PD patients; and bias 0.1 kg, range -5.0 kg to 5.2 kg for controls. The [K+]ICW did not differ between PD patients and controls (148.0 +/- 25.1 mmol/L vs 148.1 +/- 14.3 mmol/L, p = nonsignificant). CONCLUSIONS: Total body potassium is a valid, noninvasive technique for measuring FFM and BCM in PD patients. In our PD patient group, depletion of FFM and BCM as compared with controls was identified in the women but not in the men.

Effects of icodextrin in automated peritoneal dialysis on blood pressure and bioelectrical impedance analysis.

BACKGROUND: Glucose absorption from glucose-based dialysis fluids limits ultrafiltration from the daytime dwell in automated peritoneal dialysis (APD). Icodextrin may allow greater ultrafiltration during the daytime period in APD, enhancing fluid control. METHODS: A 7.5% icodextrin dialysate was compared with a 2. 27% glucose dialysate for the daytime dwell in 14 subjects on APD. Blood pressure, weight and body water compartments estimated by multifrequency bioelectrical impedance (MFBIA) were determined in subjects using 2.27% glucose as the daytime dwell and then repeated 1 month after switching to icodextrin. RESULTS: Icodextrin resulted in symptomatic hypotension requiring reduction of antihypertensive medication in six of the 14 patients. Despite this reduction in treatment, systolic blood pressure fell from 142.4 (23.9) mmHg to 122.9 (17.7) mmHg, P<0.005, and diastolic blood pressure tended to fall from 82.8 (9.8) mmHg to 76.8 (10.1) mmHg, P=0.075. Change in systolic blood pressure significantly correlated with changes in weight (r=0.62, P<0.05) and MFBIA estimates of total body water (TBW) (r=0.56, P<0.05), extracellular water (ECW) (r=0.79, P<0.002), extra/intracellular water ratio (ECW/ICW) (r=0.72, P<0.01) and derived resistances R(ecf) of ECW (r=-0.69, P<0.01) and R(inf) of TBW (r=-0.66, P<0.02). Changes in diastolic blood pressure significantly correlated with changes in ECW (r=0.64, P<0.02) and ECW/ICW ratio (r=0.58, P<0.05), and almost significantly with R(ecf) (r=-0.51, P=0.08) and R(inf) (r=-0.52, P=0.07) estimated by MFBIA, but not with changes in weight or TBW. CONCLUSIONS: Use of icodextrin for the daytime dwell in APD results in improved fluid balance and blood pressure control compared with 2.27% glucose. MFBIA detected clinically important changes in fluid content in these patients.

Effect of peritoneal fluid on whole body and segmental multiple frequency bioelectrical impedance in patients on peritoneal dialysis.

OBJECTIVE: We investigated the ability of whole body and segmental multiple frequency bioelectrical impedance (MFBIA) to detect peritoneal fluid in peritoneal dialysis patients. DESIGN: Prospective study. SETTING: Teaching hospital renal unit. SUBJECTS: Patients on regular peritoneal dialysis. INTERVENTIONS: Whole body and segmental MFBIA measurements before and after drainage of peritoneal fluid. RESULTS: Changes estimated by MFBIA in total body water (-0.4 (0.8) litres) and extracellular water (-0.3 (0.3) litres) were much lower than the actual changes (2.0 (0.4) litres), P<0.0001. Derived resistances Recf and Ricf increased significantly for the trunk but not for total body measurements and changes did not correlate with volumes of fluid drained. CONCLUSIONS: MFBIA is limited in its ability to detect intraperitoneal fluid, using both whole body and segmental techniques.

Low thrombogenicity of polyethylene glycol-grafted cellulose membranes does not influence heparin requirements in hemodialysis.

Heparin is the most commonly used anticoagulant for hemodialysis despite potentially serious side effects. Polyethylene glycol-grafted cellulose (PGC) membranes produce less activation of the coagulation cascade than cuprophane membranes. Anecdotally, we found some patients required a surprisingly low level of anticoagulation using these membranes. We compared the anticoagulant requirement of the PGC membrane with that of the cuprophane membrane in this randomized, prospective, crossover study. Sixty-three patients were randomized to treatment using either membrane, and heparin administration was progressively reduced to the lowest dose that prevented visible clotting in excess of that normally encountered. Patients underwent dialysis at this dose for 1 month, after which the heparin requirement and Kt/Vurea (1.162 x ln [urea pre/urea post]) were assessed. This process was then repeated for each patient using the other membrane, and the results were compared. Heparin administration during dialysis was reduced from a mean loading dose of 29.0 +/- 9.4 to 1.5 +/- 3.2 IU/kg for both membranes and a mean maintenance infusion of 14.0 +/- 6.7 to 0.77 +/- 1.6 IU/kg/h for both membranes (both P < 0.0001 v full anticoagulation; no difference between membranes). The Kt/Vurea was not significantly altered. Forty-six patients with PGC and 45 patients with cuprophane membranes underwent dialysis successfully without heparin during dialysis, and the other patients were using considerably reduced doses. Aspirin and warfarin had no effect on the heparin requirement. These results do not support the theory that PGC membranes have a lower anticoagulant requirement than cuprophane membranes; however, they suggest that dialysis can be performed successfully with much smaller anticoagulant doses than are currently in common use.