Department Affliation: Primary: Pharmacology and Molecular Sciences; Secondary: Medicine
Degree: M.D., Columbia University
Rank: Professor
E-Mail: mwalser@bs.jhmi.edu
Nitrogen metabolism in protein-intolerant states: amino acid analogues in nutrition
This laboratory is involved in studies of amino acid metabolism and in vivo protein turnover, in both man and laboratory animals. We are also evaluating the therapeutic potential of N-free analogues of the essential amino acids in treatment of disorders of N metabolism, including chronic renal failure and protein-wasting disorders, in which these ketoacids favorably influence turnover.
Progression of chronic renal failure. For many years, we have been exploring the hypothesis that a common mechanism underlies the progressive deterioration that is characteristic of renal failure from any cause, and that this process can be attenuated by diet and/or drugs. Our aim is to arrest chronic renal failure before it becomes symptomatic, thereby obviating dialysis and/or transplantation. One approach that offers promise is a very low protein diet supplemented by keto-analogues of the essential amino acids or by essential amino acids themselves. Protein restriction appears to slow progression in experimental models and in patients. Another approach is to partially suppress glucocorticoid production, which seems to play a role in mediating progression. Since ketoacid administration and glucocorticoid suppression both reduce protein breakdown, these effects may be related. In some patients, we have been successful in arresting progression.
Representative Publications:
- Walser, M. and Hill, S. Effect of ketoconazole plus low-dose prednisone on progression of chronic renal failure, Am. J. Kidney Dis. 29:503-513, 1997. Pub Med Reference
- Walser, M. Effects of a supplemented very low protein diet in pre-dialysis patients on serum albumin level, proteinuria, and subsequent survival on dialysis, Mineral Electrolyte Metab. 24:64-71, 1998. Pub Med Reference
- Walser, M. and Hill, S. Can renal replacement be deferred by a supplemented very-low-protein diet? J. Am. Soc. Nephrol. 10:110-116, 1999. Pub Med Reference
- Walser, M., Mitch, W.E., Maroni, B.J., and Kopple, J.D. Should protein intake be restricted in pre-dialysis patients? Kidney Internat., 55:771-777, 1999. Pub Med Reference
- Eustace, J.A., Coresh, J., Kutchey, C., Te, P.L., Gimenez, L.F., Scheel, P.J. Jr., and Walser, M. Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia, Kidney Internat., 55:2527-2538, 2000. Pub Med Reference
- Walser, M. Is there a role for protein restriction in the treatment of chronic renal failure? Blood Purif., 18:304-312, 2000. Pub Med Reference
- Mitch, W.E. and Walser, M. Nutritional therapy in renal disease. In: The Kidney,Volume II, 7th edition, BM Brenner, Editor, WB Saunders, in press.
