A United Kingdom Multicenter Study of Icodextrin in Continuous Ambulatory Peritoneal Dialysis

Abstract

While glucose remains the only osmotic agent used universally for peritoneal dialysis, its various shortcomings for the long dwell equilibration continuous ambulatory peritoneal dialysis (CAPD) has led to a search for alternative agents. The large molecular weight group has been of interest, because these agents theoretically would lead to greater ultrafiltration and a better metabolic profile. Mostsubstances (dextrans, charged macromolecules) have been found unsuitable for reasons of insolubility, allergenicity, and peritoneal toxicity. Short-chain polypeptides have been studied in humans, but the experience is limited, and there is the potential for allergenicity with long-term use. The only large molecular weight agent that has been studied in some detail but hitherto in one center only and in a limited number of patients is glucose polymer (generic name, icodextrin). Because of the promise shown by these initial studies, a randomized controlled multicenter investigation of icodextrin in CAPD (MIDAS Study Group) was undertaken to evaluate the long-term safety and efficacy by comparing daily overnight (8 12 hours) use of a slightly hypo-osmolar solution (282 mOsm/ kg) with 1.36% (346 mOsm/kg) and 3.86% (484 mOsm/kg) glucose exchanges. Over a 6-month period 209 patients from 11 centers in the United Kingdom were randomized, with 106 allocated to receive icodextrin (study group) and 103 to remain on glucose (control group). One hundred and thirty-eight patients completed the 6-month study (71 control, 67 study). The mean net ultrafiltration overnight with icodextrin was 3.5 times greater than 1.36% at 8 hours and 5.5 times greater at 12 hours (p<0.0001), but no different from that of 3.86% glucose at 8 and 12 hours (although for the latter dwell the net mean ultrafiltration volume was greater by about 140 mL). Biochemical profiles were no different except for a small fall in serum sodium and chloride in the icodextrin group. The mean serum maltose rose to a steady-state level of 1.2 g/L within 2 weeks and remained stable. The mean carbohydrate absorbed for icodextrin (29±5 g) was lower than with 3.86% glucose (62±5 g). The use of icodextrin did not increase the incidence of peritonitis, nor did it alter its outcome, affect uptake of icodextrin from the peritoneum, alter serum osmolality or sodium levels. There were no adverse effects associated with the use of icodextrin, and the overall CAPD-related symptom score was significantly better for icodextrin than control subjects. This study and subsequent extensive use and clinical experience has demonstrated that the daily use of an iso-osmolar icodextrin solution is generally well tolerated, effective, and could replace the overnight use of hyperosmotic glucose solution. Its use was of equal efficacy in peritonitis and in diabetic patients. The elevated levels of maltose did not appear to have any clinical side effects.