Successful treatment of fulminant encapsulating peritoneal sclerosis following fungal peritonitis with tamoxifen.

Encapsulating peritoneal sclerosis remains a serious complication of peritoneal dialysis. Prolonged duration on dialysis and severe episodes of peritonitis are the two most important risk factors for developing the condition. Here we describe a patient who developed a fulminant form of encapsulating peritoneal sclerosis soon after suffering from an episode of fungal peritonitis. There was clinical evidence of ongoing inflammation and gross malnutrition. Signs of chronic intestinal stasis were present on radiological imaging. There was concern in this situation that symptoms could partly relate to ongoing peritoneal sepsis, which could be worsened by immunosuppressives such as steroids. Tamoxifen was used without steroids in our patient with prompt resolution of stasis symptoms and withdrawal of artificial nutrition support. To our knowledge tamoxifen has never been previously used alone, in this scenario. We propose that tamoxifen might be a safer alternative to use in this clinical setting where there is concern about presence of ongoing sepsis, than corticosteroids and immunosuppressive agents.

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.

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant.

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.

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.

Comparison of icodextrin and glucose solutions for the daytime dwell in automated peritoneal dialysis.

BACKGROUND: The sustained ultrafiltration achieved by icodextrin is more suited for the daytime dwell in automated peritoneal dialysis (APD) than glucose solutions. METHODS: Seventeen patients receiving APD underwent assessment using three different solutions for the daytime dwell: 2.27% glucose, 3.86% glucose and 7.5% icodextrin. Patients were then observed on icodextrin for a 6 month period. RESULTS: Daytime ultrafiltration was greater for 3.86% glucose (median 0.10, IQR 0.01 to 0.321) P<0.01 and icodextrin (median 0.26, IQR 0.14 to 0.361) P<0.001 than 2.27% glucose (median -0.19, IQR -0.54 to -0.081), with 3.86% glucose and icodextrin not being significantly different. Positive ultrafiltration occurred in 3/17 patients with 2.27% glucose, 13/17 patients with 3.86% glucose and 16/17 patients with icodextrin (chi2 P<0.0001). The difference in ultrafiltration of icodextrin and 3.86% glucose correlated with the 4 h dialysate/plasma creatinine ratio in a PET test (r = 0.51, P<0.05). Daytime Kt/V urea was greater for 3.86% glucose (median 0.27, IQR 0.20 to 0.48 per week, P<0.01) and icodextrin (median 0.31, IQR 0.27 to 0.49 per week, P<0.0001) than for 2.27% glucose (median 0.22, IQR 0.15 to 0.38 per week), with the difference between 3.86% glucose and icodextrin not reaching statistical significance (P = 0.06). Daytime creatinine clearance was greater for 3.86% glucose (median 10.2, IQR 6.9 to 13.61/week/1.73 m2, P<0.02) and icodextrin (median 12.1, IQR 9.3 to 15.71/week/1.73 m2, P<0.005) than for 2.27% glucose (median 8.8, IQR 4.9 to 11.91/week/1.73 m2). Daytime creatinine clearance was greater for icodextrin than for 3.86% glucose (P<0.005). The effects of icodextrin were sustained for the 6 month observation period. CONCLUSIONS: Icodextrin produced enhanced ultrafiltration and clearances compared with 2.27% glucose, without the exposure of the peritoneum to hypertonic glucose solutions.

Comparison of in-vivo body composition using two Lunar dual-energy X-ray absorptiometers.

OBJECTIVE: To compare in-vivo composition analysis between two dual energy X-ray absorptiometers, a DPX and a DPX/L, from the same manufacturer (LUNAR), pre(Study A) and post(Study B) hardware changes on both absorptiometers. DESIGN: Comparison of (1) quality assurance (QA) data: air-counts low (38 keV), air-counts high (70 keV), air-counts ratio, percent spillover, R-delrin; and (2) total body compartments: total body tissue (TBTISS), total body fat (TBF), percent total body fat (%TBF), total body lean (TBLEAN), total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD), between the two absorptiometers. SETTING: Centre for Bone and Body Composition Research, University of Leeds. SUBJECTS: Study A, 14 normal subjects and Study B, a different cohort of 19 normal subjects, were scanned on both machines on the same day. RESULTS: In Study A, large significant differences were observed in the QA parameters between the two machines. The DPX, air-counts low and air-counts high, being 25% and 22% lower than the DPX/L. The Bland Altman method of analysis indicated that the DPX was significantly higher for TBTISS (0.3 kg), %TBF (2%) and TBF ( 1.4 kg) and correspondingly lower for TBLEAN (-1.0 kg). No significant difference was observed in TBBMC. After the hardware changes (Study B) a marked reduction in the differences in QA air-counts was observed. The DPX air-counts low was now 1% higher and air-counts high 8% lower than the DPX/L. The DPX had now only small significant negative differences for %TBF (-0.6%) and TBF (-0.4 kg) and a small significant positive difference for TBLEAN (0.4 kg), compared to the DPX/L. TBBMC difference although slightly increased, was still non-significant. CONCLUSIONS: The closer agreement observed in the QA parameters after the hardware changes was associated with a reduction in the mean differences, 95%CI of the mean differences and limits of agreement of the comparison of body composition analysis from the Lunar machines using the Bland-Altman method. The study indicates that the QA limits set for bone mineral analysis may require more stringent limits for body composition.

Increased plasma leptin/fat ratio in patients with chronic renal failure: a cause of malnutrition?

BACKGROUND: Protein-energy malnutrition occurs in patients with chronic renal failure primarily due to loss of appetite. The ob gene protein, leptin, which is secreted by adipocytes, regulates body composition by lowering food intake. We have measured plasma leptin in undialysed and dialysed patients and in controls and the concentrations have been related to body composition, dietary intake, and biochemistry. METHODS: Plasma leptin was measured by radioimmunoassay in 93 individuals in groups of undialysed, peritoneal dialysed, and haemodialysed patients and controls. Body composition was determined by DEXA. RESULTS: Protein-energy malnutrition was evident in non-dialysed and dialysed patients from low lean or fat tissues, plasma albumin and transferrin. A third of the dialysis patients were eating less than prescribed intakes. Leptin relative to total fat mass (ng/ml/kg) was significantly greater for patients than for controls, particularly the dialysed patients. Leptin was highly correlated with total, arm, leg, and all other fat measurements, e.g. r for leptin vsm % total fat was: undialysed 0.88, PD 0.81, HD 0.93, and controls 0.83 (P < 0.0001 for all). Dialysis patients with the highest leptin/fat mass ratio had low protein intakes and significantly lower lean tissue mass. Leptin/fat ratio correlated inversely with dietary intake e.g. with protein intake in g/day and marginally in g/kg of ideal weight/day. Leptin concentration was unrelated to plasma creatinine or residual renal function or to the protein 'nutritional indices', albumin and transferrin. CONCLUSIONS: Our data suggests that leptin is markedly increased in some patients with chronic renal failure. The association of increased leptin with low protein intake and loss of lean tissue is consistent with leptin contributing to malnutrition but a definitive role cannot be substantiated by this study.

Technique failure in peritoneal dialysis and its impact on patient survival.

OBJECTIVE: To determine the frequency and causes of continuous ambulatory peritoneal dialysis (CAPD) technique failure and its effect on patient outcome. DESIGN: Retrospective study of CAPD technique and patient outcome. SETTING: Teaching hospital renal unit. PATIENTS: All 221 patients commencing CAPD over a 14-year period. OUTCOME MEASURES: Outcomes assessed included patient survival and technique survival (with change to hemodialysis being considered as technique failure). RESULTS: CAPD failure occurred in 46 patients, with a CAPD technique survival of 93%, 73%, and 63% at 1, 3, and 5 years after start of treatment. Peritonitis was the major cause of technique failure. CAPD system had no effect on technique survival, despite the lower peritonitis rate in patients using Y-connection systems. Overall patient survival was 91%, 72%, and 53% at 1, 3, and 5 years after start of treatment, with increasing age and diabetes being associated with a worse outcome. There was a high early mortality after CAPD failure, with an actuarial survival of only 61% 1 year later. CONCLUSION: Failure of CAPD is an important problem, with peritonitis being the major cause, either directly, or indirectly by the later effects of damage to the peritoneal membrane with loss of dialysis adequacy. The high mortality in the period following CAPD failure warrants careful monitoring of patients during this phase, along with efforts to optimize correctable factors such as nutrition, adequacy of the new form of dialysis, and treatment of residual sepsis.