CHRONIC RENAL FAILURE © 2003 The Medicine Publishing Company Ltd 66 MEDICINE being investigated as means of stimulating erythropoiesis. These include the following. Erythropoietin-mimetic peptides have functional properties similar to those of erythropoietin, inducing the proliferation of erythroid progenitor cells. They are not orally active, but may form the template for the design of a non-peptide, orally active erythropoietin-mimetic in the future. Haematopoietic cell phosphatase (HCP) inhibitors – HCP is an intracellular molecule that negatively regulates the action of erythropoietin. Theoretically, inhibitors of HCP should allow cells to become more responsive to erythropoietin; this is currently being tested. Erythropoietin gene therapy has been tested in animals, which show an erythropoietic response, but it will be some time (if ever) before it is used in humans. u FURTHER READING Adamson J W, Eschbach J W. Erythropoietin for End-stage Renal Disease. N Engl J Med 1998; 339: 625–7. Macdougall I C, Eckardt K-U. Haematological Disorders. In: Davison A M, Cameron J S, Grünfeld J-P et al., eds. Oxford Textbook of Clinical Nephrology. 2nd ed. Oxford: Oxford University Press, 1998: 1935–54. VaIderrabano F. Recombinant Erythropoietin: 10 Years of Clinical Experience. Nephrol Dial Transplant 1997; 12: (Suppl. 1): 2–9. Practice points • The anaemia of renal failure is usually normochromic and normocytic • Renal anaemia develops and progresses when GFR declines below 30 ml/minute (approximately corresponding to serum creatinine > 300 μmol/litre); in patients who appear to have anaemia disproportionate to the degree of renal impairment, other causes (e.g. myeloma) should be sought • Erythropoietin therapy corrects the anaemia of renal failure in 90–95% of patients • Many patients treated with erythropoietin require intravenous iron • There are few adverse effects of erythropoietin therapy; the most common is hypertension (20–30% of patients) • Since 1998, there has been an increase in the incidence of pure red cell aplasia with anti-erythropoietin antibodies in patients receiving erythropoietin therapy; the cause of this remains unclear • Darbepoetin alfa is a second-generation erythropoietic agent with a longer half-life in vivo than conventional erythropoietin therapy Haemodialysis is a highly successful renal replacement therapy; with its complementary treatments peritoneal dialysis and renal transplantation, it has revolutionized the outlook for patients with end-stage renal failure (ESRF) over the last 40 years. Worldwide, hundreds of thousands of patients are currently maintained on haemodialysis, which can be regarded as the default therapy usable in the increasing numbers of patients unsuitable for other modalities because of age, dependency and coexistent disease. However, dialysis only partially replaces some aspects of renal function. Many facets of the uraemic syndrome (e.g. accelerated cardiovascular disease) are not improved, which contributes to the high mortality on dialysis. Dialysis is expensive, and access to the treatment and its quality are under constant economic scrutiny. Principles of haemodialysis Diffusive and convective mass transfer occur across a semi- permeable membrane, allowing changes in the composition of body fluids. Priyada Pandya was Research Fellow in Nephrology at Lister Hospital, Stevenage, UK. She qualified in Cardiff, and trained in general medicine in South Wales and London. Ken Farrington is Consultant Nephrologist at Lister Hospital, Stevenage, UK. He qualified in chemistry from the University of Manchester and in medicine in Cardiff, and trained in nephrology at the Royal Free Hospital, London. His main interest is metabolic aspects of chronic renal failure and dialysis. Haemodialysis Priyada Pandya Ken Farrington What’s new ? • The haemodialysis population is increasing rapidly in developed countries; elderly and dependent patients with coexistent disease is the most rapidly increasing group • Haemodiafiltration combines diffusive and convective clearance and has theoretical advantages, enabling solute removal over a wide range of molecular weights • The HEMO study has recently provided support for current adequacy targets for three-times-weekly treatments • Despite recent advances, mortality on dialysis remains high