Chronic kidney disease (CKD) is an increasingly prevalent and disproportionately costly condition. The majority of patients are treated by haemodialysis (HD) which primarily removes small water soluble molecules. However, most protein bound and larger molecular weight azotaemic toxins remain within the body and accumulate, impairing cardiovascular function and contributing to the morbidity and mortality of HD. Adsorbent therapies with the capacity to remove key protein bound and larger azotaemic toxins not removed by HD may solve this and also delay the need to start HD. Recent advances in synthetic carbon technology using multi-modal, highly adsorbent carbons may provide an effective sorbent adjunct to augment HD.
As an important source of these toxins is the intestine, where azotaemic compounds are introduced into the body either via the diet or via in situ generation, our hypothesis is that orally administered mesoporous carbon adsorbents may be of clinical benefit in CKD via their ability to remove azotaemic toxins within the gut. Our preliminary data has shown that adsorbents are efficacious and capable of removing albumin-bound molecules and azotaemic toxins from physiological solutions in vitro.
This project began in 2008 and is ongoing.
The aims of this pilot study are to investigate the effects of oral administration of mesoporous carbon on (i) the accumulation of specific azotaemic toxins in the plasma of animals suffering CKD and (ii) the progression of CKD in these animals.
It is hoped that our findings will support the role of adsorptive therapy in the treatment of CKD and facilitate further research. Ultimately, the removal of currently 'difficult to remove' azotaemic toxins could diminish clinical complications thereby extending and greatly improving patient quality of life.
Administration of MAST carbon to animals with CKD may reduce the development of the disease based on urinary protein excretion although effects on biochemical parameters remain to be determined and further studies are certainly required. In the future, administration of oral carbon absorbents to patients at in the early stages of CKD may reduce the development of the disease and associated cardiovascular disease, however the full effects of MAST carbon on humans will need to be determined.
Dr PK (Charley) Chatterjee (Principal Investigator)
Dr Susan Sandeman
Dr Carol Howell
Dr Andrew Davenport (Royal Free Hospital)
Professor Sergei Mikhalovsky