Optimizing end-stage renal disease therapy for the patient with diabetes mellitus

Patients with diabetes represent the fastest growing segment of the end-stage renal disease (ESRD) population, which itself is growing at a rate of approximately 10% per year. The most recent report of the United States Renal Data System (USRDS) shows a prevalence of diabetes among patients with ESRD of 27.3% (59,403 of 217,479) and an incidence of 33.6% (19,013 of the 56,610). The majority of patients with ESRD secondary to diabetes (67.7%) are treated by hemodialysis, 13.2% by peritoneal dialysis, and 19.1% have functioning renal transplants. The number of patients over 60 years of age has increased steadily. Parallel with this increase, the percentage of patients with one or more comorbid conditions increased from 66% to 85% in patients with diabetes and from 57% to 66% in patients without diabetes. The relative risk of death in patients with diabetes is markedly increased and is further exacerbated in patients with poor nutritional status. Although diabetes is the most common primary disease associated with death in the ESRD population, the mortality for patients with ESRD secondary to diabetes has decreased from 46% in 1982 to 29% in 1993. Patients with ESRD from diabetes challenge the nephrologist because they have the greatest number of comorbid conditions, the highest levels of physical dysfunction, and the greatest dependency in activities of daily living. The goal of therapy is to improve quality of life, as well as reduce mortality. Patients with diabetes experience improved survival after either kidney transplant or enhanced Kt/V on dialysis. Therefore, the most important therapeutic intervention is to maximize renal replacement therapy (either by transplantation or by providing levels of dialysis adequacy higher than previously recommended). In addition, attention to several basic principles helps to guide therapy; control of hypertension, control of hyperglycemia, control of lipid abnormalities, treatment of malnutrition, and attention to the effects of erythropoietin. Advanced glycation and products (AGEs) have been proposed as new "uremic toxins", because of their pathogenetic association with a variety of vascular and morbid complications. There is sound experimental evidence to suggest that reducing the accumulation of these products to normal levels may prevent diabetic complications. Better understanding of the nature of the relationship between formation and removal is needed to direct therapeutic interventions towards adequate control of the accumulation of AGEs in patients with renal failure, with or without diabetes.