Nutritional therapy of the nephrotic syndrome - We have found that a very low protein diet, supplemented by essential amino acids, may induce long- term remission of the nephrotic syndrome, even when it is caused by diabetes or by focal segmental glomerulosclerosis (disorders in which the nephrotic syndrome rarely remits spontaneously), provided that treatment is started before renal function has deteriorated severely. The mechanism of this surprising result remains to be determined by study of additional patients. Use of ketoconazole to slow progression of chronic renal failure - A randomized cross-over study of ketoconazole (to suppress cortisol production) plus low-dose prednisone (to prevent anterior pituitary escape) in patients with progressive chronic renal failure of various types has been completed. In diabetic nephropathy, glomerular disease, and interstitial nephritis, rate of decline of glomerular filtration rate slowed significantly; in polycystic kidney disease, rate of decline accelerated. Side effects or toxicity caused drug withdrawal in 20% of patients. Survival on dialysis of patients treated with a supplemented very low protein diet before dialysis - Extending our previously published finding that patients so treated generally enter dialysis with normal serum albumin levels, in contrast to the national experience, we determined the survival on dialysis of 46 such patients. During the first two years, survival on dialysis was markedly improved, compared with the national experience, correcting for age, sex, and diagnosis. Whether this was because these patients had higher serum albumin levels during dialysis could not be determined. Use of dehydroepiandrosterone to slow progression of chronic renal failure - Based on our unpublished finding that progression is negatively correlated with serum DHEA-S concentration, we hypothesized that DHEA supplementation may slow progression. Accordingly, a randomized, double- blind crossover study of sequential glomerular filtration rates in patients with all types of chronic renal failure given either a placebo or enough DHEA to raise serum DHEA-S level to about 12 ug/ml has been started. Renal production of nitric oxide as a determinant of progression - We have reported in abstract form that progression is positively correlated with the 24 excretion rate of nitrate (the stable end-product of nitric oxide). We have developed a method to determine renal (as opposed to systemic) production of nitrate, based on measuring nitrate and chloride clearances and glomerular filtration rate before and after an oral load of NaNO 3. We plan to extend these measurements and to determine whether the source of renal NO production is inducible to nitric oxide synthase (as opposed to constitutive NOS) by repeating these measurements after giving a nearly specific inhibitor of iNOS (aminoguanidine).
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