- Email: [email protected]
The Aging Kidney
Symposium on The Aging Process
The Aging Kidney George A. Kaysen, M.D., Ph.D.,* and Bryan D. Myers, M .D .t
Aging of biologic systems, and especially aging of the human organism, is a very complex phenomenon. Despite all efforts and recent progress, this complexity and ambiguity form the major reason for the fact that modern biology and gerontology are still unable to provide a complete understanding of the nature of aging. The human kidney in the adult weighs 130 to 170 gm (approximately 0. 25 per cent of body weight) and contains about 2,000,000 nephrons. The main functions of the kidney include the maintenance of volume and ionic composition of body fluids (homeostasis); the elimination of fixed waste products of metabolism; the elimination of exogenous chemicals and their metabolites; the metabolism of certain hormones (parathyroid hormone, calcitonin, antidiuretic hormone, angiotensin, insulin); and the catabolism of other small-molecular-weight proteins (light chains, beta-2 microglobulin). A host of metabolic interconversions (for example, conversion of lactic and alpha-ketoglutaric acid to glucose) occur within the kidney. The kidney influences the red blood cell mass by the production of erythropoietin and exercises control over the extracellular fluid volume and blood pressure through the renin-angiotensin and the renal kallikreinkinin systems and by the formation of renal prostaglandins. It controls the intestinal absorption of calcium through regulation of the hydroxylation of vitamin D. With advancing age, changes occur in both the structure and function of the human kidney. Because the aging kidney is part of the aging organism as a whole, it is subject to other key organ systems, such as the endocrine glands, the nervous system, and the cardiovascular system. In this review, we will examine the relatively scanty data available concerning the structural and functional changes that occur in the kidney with advancing age and will attempt to assess their possible clinical consequences. Furthermore, the possible adaptive , involutional, pathophys-
*Associate Professor of Medicine, University of California School of Medicine, Davis; Chief, Division of Nephrology, VA Medical Center, Martinez, California tAssociate Professor of Medicine and Acting Chief, Division ofNephrology, Stanford University School of Medicine, Stanford, California
Clinics in Geriatric Medicine-Vol. 1, No. 1, February 1985
207
222
GEORGE
A. KAYSEN AND BRYAND. MYERS
90. Smalley, J. W.: Age-related changes in hydroxylysylglycosides in human glomerular basement membrane. Exp. Gerontol., 15:65-66, 1980. 91. Spitzer, A., and Brandis, M.: Functional and morphologic maturation of the superficial nephrons. Relationship to total kidney function. J. Clin. Invest., 53:27\f--287, 1974. 92. Sunderam, S. G., and Mankikar, G. D.: Hyponatremia in the elderly. Age Ageing, 12:77-80, 1983. 93. Taki, M., Goldsmith, D. I. , and Spitzer, A. : Impact of age on effects of ureteral obstruction on renal function. Kidney Int. , 24:602--609, 1983. 94. Taylor, S. A., and Price, R. G.: Age-related changes in rat glomerular basement membrane. Int. J. Biochem., 14:201-206, 1982. 95. Tores, V. E., Velosa, J. A., Holley, D. E ., et al.: The progression of vesicoureteral reflux nephropathy. Ann. Int. Med., 92:776-784, 1980. 96. Tucker, S. M., Mason, R. L. , and Beauchene, R. E.: Influence of diet and feed restriction on kidney function of aging male rats. J. Gerontol., 31:264-270, 1976. 97. Tucker, B. J., and Blantz, R. C.: Factors determining superficial neprhon filtration in the mature growing rat. Am. J. Physiol., 232:F97-Fl04, 1977. 98. Viberti, G. C., Belous, R. W., Mackintosh, D., et al.: Monitoring glomerular function in diabetic nephropathy. Am. J. Med., 74:256-264, 1983. 99. Vincenti, F., Amend, W. J. C., Kaysen, G., et al.: Long-term renal function in kidney donors. Transplantation, 36:626-629, 1983. 100. Weidmann, P. , De Myttenaere-Bursztein, S., Maxwell, M. H ., et al.: Effect of aging on plasma renin and aldosterone in normal man. Kidney Int., 8:325-333, 1975. 101. Zbuzek, V. K., and Wu, W.: Age-related vasopressin changes in rat plasma and the hypothalamo-hypophyseal system. Exp. Gerontol., 17:133-138, 1982. 102. Zbuzek, V. K., Zbuzek, V., and Wu, W.: The effect of aging on vasopressin system in Fisher 344 rats. Exp. Gerontol., 18:305-311, 1983. School of Medicine University of California Davis, California 95616
The Aging Kidney George A. Kaysen, M.D., Ph.D.,* and Bryan D. Myers, M .D .t
Aging of biologic systems, and especially aging of the human organism, is a very complex phenomenon. Despite all efforts and recent progress, this complexity and ambiguity form the major reason for the fact that modern biology and gerontology are still unable to provide a complete understanding of the nature of aging. The human kidney in the adult weighs 130 to 170 gm (approximately 0. 25 per cent of body weight) and contains about 2,000,000 nephrons. The main functions of the kidney include the maintenance of volume and ionic composition of body fluids (homeostasis); the elimination of fixed waste products of metabolism; the elimination of exogenous chemicals and their metabolites; the metabolism of certain hormones (parathyroid hormone, calcitonin, antidiuretic hormone, angiotensin, insulin); and the catabolism of other small-molecular-weight proteins (light chains, beta-2 microglobulin). A host of metabolic interconversions (for example, conversion of lactic and alpha-ketoglutaric acid to glucose) occur within the kidney. The kidney influences the red blood cell mass by the production of erythropoietin and exercises control over the extracellular fluid volume and blood pressure through the renin-angiotensin and the renal kallikreinkinin systems and by the formation of renal prostaglandins. It controls the intestinal absorption of calcium through regulation of the hydroxylation of vitamin D. With advancing age, changes occur in both the structure and function of the human kidney. Because the aging kidney is part of the aging organism as a whole, it is subject to other key organ systems, such as the endocrine glands, the nervous system, and the cardiovascular system. In this review, we will examine the relatively scanty data available concerning the structural and functional changes that occur in the kidney with advancing age and will attempt to assess their possible clinical consequences. Furthermore, the possible adaptive , involutional, pathophys-
*Associate Professor of Medicine, University of California School of Medicine, Davis; Chief, Division of Nephrology, VA Medical Center, Martinez, California tAssociate Professor of Medicine and Acting Chief, Division ofNephrology, Stanford University School of Medicine, Stanford, California
Clinics in Geriatric Medicine-Vol. 1, No. 1, February 1985
207
222
GEORGE
A. KAYSEN AND BRYAND. MYERS
90. Smalley, J. W.: Age-related changes in hydroxylysylglycosides in human glomerular basement membrane. Exp. Gerontol., 15:65-66, 1980. 91. Spitzer, A., and Brandis, M.: Functional and morphologic maturation of the superficial nephrons. Relationship to total kidney function. J. Clin. Invest., 53:27\f--287, 1974. 92. Sunderam, S. G., and Mankikar, G. D.: Hyponatremia in the elderly. Age Ageing, 12:77-80, 1983. 93. Taki, M., Goldsmith, D. I. , and Spitzer, A. : Impact of age on effects of ureteral obstruction on renal function. Kidney Int. , 24:602--609, 1983. 94. Taylor, S. A., and Price, R. G.: Age-related changes in rat glomerular basement membrane. Int. J. Biochem., 14:201-206, 1982. 95. Tores, V. E., Velosa, J. A., Holley, D. E ., et al.: The progression of vesicoureteral reflux nephropathy. Ann. Int. Med., 92:776-784, 1980. 96. Tucker, S. M., Mason, R. L. , and Beauchene, R. E.: Influence of diet and feed restriction on kidney function of aging male rats. J. Gerontol., 31:264-270, 1976. 97. Tucker, B. J., and Blantz, R. C.: Factors determining superficial neprhon filtration in the mature growing rat. Am. J. Physiol., 232:F97-Fl04, 1977. 98. Viberti, G. C., Belous, R. W., Mackintosh, D., et al.: Monitoring glomerular function in diabetic nephropathy. Am. J. Med., 74:256-264, 1983. 99. Vincenti, F., Amend, W. J. C., Kaysen, G., et al.: Long-term renal function in kidney donors. Transplantation, 36:626-629, 1983. 100. Weidmann, P. , De Myttenaere-Bursztein, S., Maxwell, M. H ., et al.: Effect of aging on plasma renin and aldosterone in normal man. Kidney Int., 8:325-333, 1975. 101. Zbuzek, V. K., and Wu, W.: Age-related vasopressin changes in rat plasma and the hypothalamo-hypophyseal system. Exp. Gerontol., 17:133-138, 1982. 102. Zbuzek, V. K., Zbuzek, V., and Wu, W.: The effect of aging on vasopressin system in Fisher 344 rats. Exp. Gerontol., 18:305-311, 1983. School of Medicine University of California Davis, California 95616