Physiological Reviews, Vol 59, 137-164, Copyright © 1979 by American Physiological Society

JOURNAL ARTICLE

Functional adaptation to reduction in renal mass

J. P. Hayslett

As the population of nephrons diminishes, while the dietary intake and/or endogenous production of water and solutes is unchanged, there is a proportional increase in the excretion of water and solute by individual residual nephrons. This adaptive change, which preserves zero net balance in the early phase of renal insufficiency, involves a reduction in the fractional reabsorption of substances derived from the initial glomerular ultrafiltrate and an increase in the rate of secretion of solutes that are extracted by tubular epithelial cells from peritubular blood. These compensatory changes are adequate to maintain electrolyte and water homeostasis until severe renal failure ensures (GFR less than 20% of normal). After a moderate reduction in nephron population there is no evidence that the factors that modulate ion transport are qualitatively different from those that regulate renal function in the intact subject, when the excretory load of solute is varied by changes in intake or endogenous production. In severe renal insufficiency, however, it seems likely that several factors, not present in the subject with intact renal function, also play an important role in modifying the excretion of water and electrolytes. For example, an osmotic diuresis in severe renal failure apparently decreases the tubular reabsorption of sodium and divalent cations and that of water. Moreover, elaboration of a partially identified "natriuretic" substance may participate in the regulation of electrolyte excretion in severe renal insufficiency. The appearance of these factors in severe renal insufficiency probably complements mechanisms that normally regulate the transfer of water and ions across tubular epithelium, since even after a marked reduction in GFR the urinary excretion of solutes and water changes proportionally with intake, although within narrower limits than exist in normal subjects. Studies in experimental animals and in man with acquired renal disease demonstrate the important role of other factors in compensatory adaptation, in addition to changes in tubular transport. The marked increases in glomerular filtration rate and nephron blood flow, which occur at least in some conditions, increase the absolute amount of water and solute delivered to the various nephron segments in ultrafiltrate and peritubular blood. Moreover, the expansion of extracellular fluid in severe renal failure inhibits tubular reabsorption of filtered water and solute in the same qualitative way that has been demonstrated in subjects with intact renal function. Quantitatively the response to acute volume expansion is exaggerated compared with control. Concomitant changes in renal hypertrophy and hyperplasia probably play an important role in functional adaptation. The apparent marked capacity for compensatory growth in all nephron segments and even in portions of tubular segments in parenchymal renal disease increases the area for transport by tubular epithelia in residual nephrons, as the overall number of nephrons diminishes...

This article has been cited by other articles:

				H.-Y. Kim, C. Baylis, J. W. Verlander, K.-H. Han, S. Reungjui, M. E. Handlogten, and I. D. Weiner Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1238 - F1247. [Abstract] [Full Text] [PDF]

				R. M. Chamberlain and D. G. Shirley Renal: Time course of the renal functional response to partial nephrectomy: measurements in conscious rats Exp Physiol, January 1, 2007; 92(1): 251 - 262. [Abstract] [Full Text] [PDF]

				E. Joly, R. Seqqat, B. Flamion, N. Caron, A. Michel, J. D. Imig, and R. Kramp Increased renal vascular reactivity to ANG II after unilateral nephrectomy in the rat involves 20-HETE Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R977 - R986. [Abstract] [Full Text] [PDF]

				S. A. Bahous, A. Stephan, J. Blacher, and M. E. Safar Aortic Stiffness, Living Donors, and Renal Transplantation Hypertension, February 1, 2006; 47(2): 216 - 221. [Abstract] [Full Text] [PDF]

				A. Tendron-Franzin, J.-B. Gouyon, J.-P. Guignard, S. Decramer, E. Justrabo, T. Gilbert, and D. Salomon Semama Long-Term Effects of In Utero Exposure to Cyclosporin A on Renal Function in the Rabbit J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2687 - 2693. [Abstract] [Full Text] [PDF]

				A. R. R. Goncalves, C. K. Fujihara, A. L. Mattar, D. M. A. C. Malheiros, I. L. Noronha, G. de Nucci, and R. Zatz Renal expression of COX-2, ANG II, and AT1 receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory Am J Physiol Renal Physiol, May 1, 2004; 286(5): F945 - F954. [Abstract] [Full Text] [PDF]

				A. C. C. Girardi, R. O. Rocha, L. R. G. Britto, and N. A. Reboucas Upregulation of NHE3 is associated with compensatory cell growth response in young uninephrectomized rats Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1296 - F1303. [Abstract] [Full Text] [PDF]

				K. Takahashi, S. Masuda, N. Nakamura, H. Saito, T. Futami, T. Doi, and K.-I. Inui Upregulation of H+-peptide cotransporter PEPT2 in rat remnant kidney Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1109 - F1116. [Abstract] [Full Text] [PDF]

				N. H. Garcia, S. T. Baigorria, and L. I. Juncos Hyperkalemia, Renal Failure, and Converting-Enzyme Inhibition: An Overrated Connection Hypertension, September 1, 2001; 38(3): 639 - 644. [Abstract] [Full Text] [PDF]

				S. Muto Potassium Transport in the Mammalian Collecting Duct Physiol Rev, January 1, 2001; 81(1): 85 - 116. [Abstract] [Full Text] [PDF]

				T.-H. Kwon, J. Frokiaer, P. Fernandez-Llama, A. B. Maunsbach, M. A. Knepper, and S. Nielsen Altered expression of Na transporters NHE-3, NaPi-II, Na-K-ATPase, BSC-1, and TSC in CRF rat kidneys Am J Physiol Renal Physiol, August 1, 1999; 277(2): F257 - F270. [Abstract] [Full Text] [PDF]

				G. Remuzzi and T. Bertani Pathophysiology of Progressive Nephropathies N. Engl. J. Med., November 12, 1998; 339(20): 1448 - 1456. [Full Text] [PDF]

				T.-H. Kwon, J. Frokiaer, M. A. Knepper, and S. Nielsen Reduced AQP1, -2, and -3 levels in kidneys of rats with CRF induced by surgical reduction in renal mass Am J Physiol Renal Physiol, November 1, 1998; 275(5): F724 - F741. [Abstract] [Full Text] [PDF]

				A. Aviv and H. Aviv Reflections on Telomeres, Growth, Aging, and Essential Hypertension Hypertension, May 1, 1997; 29(5): 1067 - 1072. [Abstract] [Full Text]