The osmotic effectiveness of a large molecular weight glucose polymer fraction (Icodextrin) as a novel "colloid" osmotic agent in peritoneal dialysis was established, but the long-term safety remained undetermined. A randomized, controlled multicenter investigation of Icodextrin in ambulatory peritoneal dialysis (MIDAS) was undertaken to evaluate the long-term safety and efficacy by comparing daily overnight (8 to 12 hr dwell) use of isosmolar Icodextrin (282 mOsm/kg) with conventional 1.36% (346 mOsm/kg) and 3.86% (484 mOsm/kg) glucose exchanges over six months. Two hundred and nine patients were randomized from 11 centers, with 106 allocated to receive Icodextrin (D) and 103 to remain on glucose (control group; C); 138 patients completed the six month study (71 C, 67 D). All patients were divided into weak (1.36%) or strong (3.86%) subgroups based on their use of glucose solutions overnight during the pretreatment baseline period. The mean (+/- SEM) overnight ultrafiltration (UF) with D was 3.5 times greater than 1.36% glucose at eight hours [527 +/- 36 vs. 150 +/- 47 ml; 95% confidence interval (CI) for the difference +257 to +497 ml; P < 0.0001] and 5.5 times greater at 12 hours (561 +/- 44 vs. 101 +/- 48 ml, 95% CI for the difference +329 to +590; P < 0.0001) and no different from that of 3.86% glucose at eight hours (510 +/- 48 vs. 448 +/- 60 ml, 95% CI for the difference -102 to +226 ml; P = 0.44) and at 12 hours (552 +/- 44 vs. 414 +/- 78 ml, 95% CI for the difference -47 to +325 ml; P = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

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Objective-To determine the age related incidence of advanced chronic renal failure in two areas of England. Design-Prospective study of patients newly identified as having advanced chronic renal failure within a two year period; subsequent monitoring of patients' clinical course for a further 26 months. patients Setting-Devon and Blackburn. tion) accepted Subjects-Those patients in a population of ir in 708 997 who developed advanced chronic renal failure (serum creatinine concentration >500 [tmol/l) 1982 1988 for the first time during a two year period. Main outcome measures and results-210 Patients 38-1 957 (148 per million population per year) developed 5382 850 advanced chronic renal failure, 117 (51%) of whom were over 70. The age related incidence rose from 58 44 0 77°per million per year in those aged 20-49 to 588 per 27-4 65-3 pemilo 41-3 64-3 million per year in those aged 80 or over. Only 54% 4485 61 8 (113) of patients were referred to a nephrologist; 120 18-8 59-2 32-7 57.1 patients (57%) needed dialysis or died within three 30 9 56-3 months of presenting without receiving dialysis, and 3318 5457 187 (89%) died or needed dialysis within three years. 37-3 52-7 After those unsuitable for further treatment had 26-9 52-5 been excluded, 78 patients per million population per year aged under 80 needed to start long term renal replacement treatment. Conclusions-Many patients suitable for renal replacement treatment are still not referred for nephrological opinion and are denied treatment. If the treatment rate in the United Kingdom rose from the 1988 rate of 55-1 per million per year to 78 per million per year then the number ofpatients receiving treatment would rise to about 800 per million. This is double the present number and has considerable but predictable resource implications for the NHS.

Objective To investigate the biocompatibility profile of a new peritoneal dialysis fluid containing glucose polymer (GPF). Design Viability and function of peripheral neutrophils (PMN) from healthy donors and cultured human peritoneal mesothelial cells were assessed in vitro after exposure to dialysis fluids. Phagocytosis, leukotriene B4 synthesis, and respiratory burst activation were measured following stimulation with serum-treated zymosan (STZ) or opsonized Staphylococcus epidermidis (S. epidermidis). Bacterial growth in the fluids was also investigated. In vivo pH equilibration of GPF and subsequent respiratory burst activation following incubation in spent dialysate were studied. Results For all the host defense parameters measured, commercial dialysis fluids (Dianeal; 1.36% and 3.86% glucose) and GPF (pH 5.2) were significantly more inhibitory than the control buffer (pH 7.3). Mesothelial cell viability was reduced by all the fluids tested irrespective of pH. Glucose polymer fluid was significantly more inhibitory than DianeaI 1.36% for STZ phagocytosis and respiratory burst activation. In contrast, it was less suppressive than DianeaI3.86% for L TB4 synthesis. For all parameters tested, except LTB4 generation, there was a marked effect of pH, with GPF being significantly more inhibitory at pH 5.2 than at pH 7.3. None of the fluids tested supported the growth of S. epidermidis, although the viable counts in GPF were significantly higher than in Dianeal. Fluid inhibition of PMN respiratory burst activation and cytotoxicity were reduced in a time-dependent manner following increasing dwell time in vivo. Conclusions GPF does not appear to be significantly different from Dianeal as far as host defense parameters are concerned. However, the cell viability and bacterial survival data suggest some possibly negative aspects of this fluid formation.

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Objective To compare peritonitis occurrence and outcome in a large U.K. study Multicentre Investigation of Icodextrin in Ambulatory Dialysis (MIDAS). Design Prospective, randomized, controlled 6-month comparison of icodextrin with glucose for the long dwell in continuous ambulatory peritoneal dialysis (CAPD) patients. Setting Eleven CAPD units in U.K. teaching hospitals. Patients A total of 209 patients established on CAPD for at least 3 months (103 control, 106 icodextrin). Twentythree control (C) and 22 icodextrin (I) patients experienced peritonitis during the study. Intervention Patients who had peritonitis remained on treatment (unless CAPD was withdrawn, temporarily or permanently). Main Outcome Measures The main outcome measures were the rate of peritonitis and duration of CAPD treatment prestudy; the rate of peritonitis episodes and their outcome during study; the effect of peritonitis on laboratory variables, serum icodextrin metabolites, and ultrafiltration efficacy. Results Prestudy: Nine (39%) of C but 14 (64%) of I patients had suffered previous peritonitis episode(s), with overall rates of 0.58 and 0.78 episodes per patient year, respectively. During study There were 31 C episodes and 35 I episodes, with overall rates of 0.76 and 0.93 per patient year, respectively. The increase in the C and I groups was 31% and 19%, respectively. Serum osmolality and sodium levels were unaffected by peritonitis, and there was no increase in serum icodextrin metabolites during peritonitis. Overnight ultrafiltration volume during peritonitis (mean±SD) declined slightly from 218±354 mL to 185±299 mL (NS) in the control group, but increased in the icodextrin group from 570±146 mL to 723±218 mL (p < 0.01). Conclusions Using icodextrin for the long dwell in CAPD does not increase the rate of peritonitis, nor does it alter the outcome of peritonitis. Peritonitis does not affect uptake of icodextrin from the peritoneum.

A risk of beta 2-microglobulin (beta 2-M)-associated amyloidosis in long-term CAPD patients has been recognised. We examined the kinetics of beta 2-M and potential clinical manifestations of amyloidosis in patients well-established on CAPD for 1-76 months (mean +/- SEM; 16.4 +/- 14 months). In 57 patients, serum beta 2-M concentration was elevated to 30 +/- 1.8 (mean +/- SEM, mg/l) and correlated positively with the duration on CAPD. In 18 patients studied with variable degrees of residual renal function, serum beta 2-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 +/- 1.3 mOsm/kg) containing 5% glucose polymer (9.4 mmol/l; MW 16,800), the transperitoneal elimination of beta 2-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 beta 2-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.

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