Icodextrin in Peritoneal Dialysis

The development of Icodextrin as an osmotic, non-diffusing polymer for increasing ultrafiltration in peritoneal dialysis began at Manchester Royal Infirmary (MRI).

Caloreen for the modified Giovanetti diet

At MRI in the 1960s, nephrologist Geoffrey Berlyne promoted the modified Giovanetti diet to delay dialysis in people with advanced kidney failure. The diet needed a calorie source which was not sweet. Berlyne met Gerry Milner, a scientist with a background in the food industry, who had found a suitable glucose polymer which was broken down in the intestine to glucose and maltose. It was known as Caloreen.

Caloreen for CAPD

Berlyne left Manchester, but Milner remained in contact with nephrologist Netar Mallick. CAPD was just being established, and Mallick realised that there was a need for a non-glucose osmotic agent for ultrafiltration, and that the glucose polymer Caloreen had potential.

Nephrologist Ram Gokal came to MRI in 1980 to develop a CAPD programme and took on the challenge of investigating the glucose polymer. He was soon joined by research registrar, Chandra Mistry (later a nephrologist in Merthyr Tydfil and then in Peterborough).

In early studies, Mistry identified in vitro the best molecular weight profile of the glucose polymer to promote ultrafiltration and then demonstrated its safety and efficacy in clinical pilot studies. The ideal polymer fraction was at first known as dextrin 20, and was later renamed icodextrin.

Icodextrin enters clinical practice

A partnership from 1989 with a small biotech company, ML Laboratories, supported the manufacture of icodextrin for clinical use. Working with the MRI kidney centre, ML Laboratories then funded, from 1991, the multicentre MIDAS trial (Mistry CD et al. Kidney Int 1994; 46:496-503) which confirmed the safety and efficacy of icodextrin, which thirty years later, remains a mainstay of CAPD in clinical practice worldwide.

By 1993, icodextrin had a UK product licence. It was licensed in Europe in 1994, but in the United States not until 2002 (the FDA required randomised trials conducted in the United States before it would give approval!).

A twist in the tail

This is a remarkable success story of academic-industry partnership taking a new therapy from concept right through to clinical impact. But alas, the tale does not have a completely happy ending. Mallick and Milner had agreed that the proceeds of the clinical application of icodextrin would be shared by ML Laboratories with the MRI kidney centre. But Milner’s untimely death prevented a formal agreement from being completed. ML soon ceded the exclusive worldwide licence to Baxter Healthcare, and Baxter, despite strenuous negotiation by Mallick, was unwilling to agree to ‘appropriate compensation’ reaching MRI.

Thus, an academic-industry collaboration, which started so well between MRI and ML Laboratories, turned out to undervalue the contribution of the clinicians and scientists who had done the crucial research and development work.

Read more about the icodextrin story on the UK Kidney History website Icodextrin in peritoneal dialysis – UK Kidney History