Low-protein diets in renal disease.

End-stage renal disease is a major cause of morbidity and mortality in the U.S. population and a significant contributor to national health-care expenditures. In recent years, a growing body of literature has accumulated from studies in animals and humans to suggest that dietary protein restriction can significantly retard the progression of chronic renal insufficiency. This article reviews the relevant literature and outlines the questions that remain for future investigation.

Rapid reduction of severe asymptomatic hypertension. A prospective, controlled trial.

Rapid reduction of severe asymptomatic hypertension with orally administered antihypertensive medication has become a common emergency department practice. To determine if antihypertensive loading prior to initiation of maintenance therapy improved or hastened blood pressure control, 64 asymptomatic patients with severe hypertension were randomized to treatment with (1) hourly doses of clonidine hydrochloride followed by maintenance therapy (group 1); (2) an initial dose of clonidine followed by hourly placebo and subsequent maintenance therapy (group 2); or (3) maintenance therapy without prior loading (group 3). There was no difference between groups 1 and 2 in the time required to achieve acceptable blood pressure control during loading therapy, nor was there a difference at 24 hours in pressure reduction between groups 1,2, or 3. Further follow-up in 44 of these patients at 1 week demonstrated adequate control of systemic blood pressure in all groups, but no difference between groups. In view of the small but reported risk of antihypertensive loading and the burden and expense of prolonged emergency department therapy, these results suggest that the common practice of acute oral antihypertensive loading to treat severe, asymptomatic hypertension should be reconsidered.

Reducing dietary protein intake to retard progression of diabetic nephropathy.

End-stage renal disease is a frequent complication of insulin-dependent diabetes mellitus. Recent studies have demonstrated that abnormal intrarenal hemodynamics contribute to the progression of chronic renal failure in several models of renal disease, including the diabetic rat. Restriction of dietary protein intake has been demonstrated to normalize these abnormalities and retard progression of renal failure. Limited studies in human subjects suggest a similar beneficial effect, and trials are now underway in diabetic patients with renal failure to clearly establish efficacy of this approach.

Effects of dietary protein and phosphorus restriction on the progression of chronic renal failure.

In recent years, evidence has accumulated suggesting that early dietary intervention in the form of protein restriction can dramatically alter the natural history of chronic renal insufficiency. This article reviews the literature in this area and summarizes the questions that remain for future investigators to answer. Interest in the role of protein intake in renal disease dates back to the early 1900s, when several investigators found that the progression of renal failure was accelerated in rats and rabbits fed high-protein diets. Subsequent work in animal models has demonstrated that nephron loss, resulting from a variety of disease states, is associated with elevated intraglomerular pressures and flows. Several investigators now have postulated that these abnormal hemodynamics, resulting from intrarenal vasodilation and hyperperfusion, damage the glomerulus and may produce further nephron loss independent of the initial renal insult. Dietary protein restriction appears to reduce these pressures and flows towards normal in animals, although the operative mechanism has yet to be identified. Limited studies of dietary protein restriction in human renal disease have suggested a beneficial effect, but carefully controlled prospective studies will be necessary to establish clear therapeutic efficacy.