Abstract
Tubular sodium handling and tubuloglomerular feedback (TGF) activity were assessed in established compensatory renal hypertophy in Sprague Dawleys rats. Hyperfiltration at the level of the single nephron was confirmed 4–6 weeks following a reduction in renal mass. TGF activity, determined as the difference between late proximal and early distal measurements of single-nephron glomerular filtration rate (SNGFR), was significantly increased in compensatory renal hypertrophy, being 7.8±1.0 vs 23.3±1.9 vs 25.5±2.6 nl/min (P for analysis of variance <0.05) following sham operation, unilateral nephrectomy, and 1 1/3 nephrectomy, respectively. Enhanced net tubular Na transport was also observed, with total Na reabsorption up to the late proximal site being 1.8±0.2 vs 2.7±0.1 vs 3.1±0.3 nmol/min (P<0.05), and to the early distal site being 3.4±0.5 vs 5.8±0.6 vs 7.9±0.8 nmol/min (P<0.05) in the three animal groups respectively. Comparison of proximal tubular length demonstrated a 71.9±8.1% increase in uninephrectomised vs sham-operated animals. This increase was proportionately greater than the increase in proximal Na reabsorption (50.0±4.0%) observed in the corresponding animal groups. Concurrent electron microprobe experiments in uninephrectomised and sham-operated animals demonstrated that the proximal tubular intracellular Na concentration was significantly lower following uninephrectomy (16.8±0.6 vs 18.9±0.5 mmol/kg wet weight, P<0.01), in association with evidence of reduced basolateral Na/K-ATPase activity. In summary, these data indicate that total Na transport in individual nephrons is increased in the proximal tubule and in the loop of Henle in compensatory renal hypertrophy, although the net amount of Na reabsorbed per unit proximal tubular length is actually reduced. The cell composition data suggest that the site of inhibition of transcellular transport is at the apical cell membrane. The elevated SNGFR is under the regulatory influence of an appropriately activated TGF system, which serves to limit the hyperfiltration.
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References
Allison MEM, Lipham EM, Lassiter WE, Gottschalk CW (1973) The acutely reduced kidney. Kidney Int 3:354–363
Beck F, Bauer R, Bauer U, Mason J, Dorge A, Rick R, Thurau K (1980) Electron microprobe analysis of intracellular elements in the rat kidney. Kidney Int 17:756–763
Beck FX, Dorge A, Blumner E, Giebisch G, Thurau K (1988) Cell rubidium uptake: a method for studying functional heterogeneity in the nephron. Kidney Int 33:642–651
Beck FX, Dorge A, Giebisch G, Thurau K (1990) Effects of diuretics on cell potassium transport: an electron microprobe study. Kidney Int 37:1423–1428
Bengel HH, Evan A, McNamara ER, Alexander EA (1978) Tubular sites of potassium regulation in the normal and uninephrectomised rat. Am J Physiol 3:F146–153
Blantz RC, Peterson OW (1989) Effect of acute nephrectomy (Nx) on tubuloglomerular feedback activity (TGF) in the rat (abstract). Kidney Int 35:467
Boberg U, Persson AEG (1986) Increased tubuloglomerular feedback activity in Milan hypertensive rats. Am J Physiol 250:F967–974
Bradley SE, Coelho JB (1979) Glomerulotubular dimensional read-justments during compensatory renal hypertrophy in the hypertrophied rat. In: Peters G, Diezi J, Guignard JP (eds) Renal adaptation to nephron loss. Karger, Basel, pp 83–86
Bricker NS, Shapiro MS, Levine MM, Makoff RK (1985) Physiology and pathology of electrolyte metabolism in chronic renal disease. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology. Raven, New York, pp 1837–1862
Cheval L, Doucet A (1990) Measurement of Na-K ATPase mediated rubidium influx in single segments of rat nephron. Am J Physiol 259:F111-F121
Diezi J, Michoud P, Arslan Y (1973) Micropuncture studies of compensatory adaptation in rats (abstract). Kidney Int 3:274
Dirks JH, Wong NLM, Evanson RL (1973) Reduction in proximal tubular fluid reabsorption after clamping the contralateral kidney in the dog. Clin Res 19:528
Fine LG, Trizna W, Bourgoignie JJ, Bricker NS (1978) Functional profile of the isolated uremic nephron. Role of compensatory hypertrophy in the control of fluid reabsorption by the proximal straight tubule. J Clin Invest 60:1508–1518
Guignard JP, Dirks JH (1976) Compensatory adaptation of sodium and bicarbonate excretion: effect of diuretics. Am J Physiol 230:F1225-F1230
Guignard JP, Filloux B (1979) Studies on compensatory adaptation of renal function. In: Peters G, Diezi J, Guignard JP (eds) Renal adaptation to nephron loss. Karger, Basel, pp 12–18
Hayslett JP (1979) Functional adaptation to reduction in renal mass. Physiol Rev 59:137–164
Hayslett JP, Kashgarian M, Epstein FH (1968) Functional correlates of compensatory renal hypertrophy. J Clin Invest 47:774–782
Hayslett JP, Kashgarian M, Epstein FH (1969) Mechanisms of change in the excretion of sodium per nephron when renal mass is reduced. J Clin Invest 48:1002–1006
Katz AI, Epstein FH (1967) Relation of glomerular filtration rate and sodium reabsorption to kidney size in compensatory renal hypertrophy. Yale J Biol Med 4O:222–230
Kaufman JM, Siegel NJ, Hayslett JP (1975) Functional and hemodynamic adaptation to progressive renal ablation. Circ Res 36:286–293
Manno C, D'Elia F, Mingarelli M, Stella M, Cervellati M, Fornarelli G, Schena FP (1991) Effects of an acute protein load on urinary albumin excretion in kidney donors. Clin Nephrol 35:59–65
Miskell CA, Simpson DP (1990) Hyperplasia precedes increased glomerular filtration rate in rat remnant kidney. Kidney Int 37:758–766
Moller JC (1988) Proximal tubules in long term compensatory renal growth. Quantitative light- and electron-microscopic analyses. APMIS [Suppl 4]:82–86
Morsing P, Stenberg A, Muller-Suur C, Persson AEG (1987) Tubuloglomerular feedback in animals with unilateral partial ureteral occlusion. Kidney Int 32:212–218
Muller-Suur R, Gutsche HU, Samwer KF, Oelkers W, Hierholzer K (1975) Tubuloglomerular feedback in rat kidneys of different renin contents. Pflügers Arch 359:33–56
Muller-Suur R, Norlen B-J, Persson AEG (1980) Resetting of tubuloglomerular feedback in rat kidneys after unilateral nephrectomy. Kidney Int 18:48–57
O'Donnell MP, Kasiske BL, Raij L, Keane WF (1985) Age is a determinant of the glomerular morphologic and functional responses to chronic nephron loss. J Lab Clin Med 106:308–313
Peters G (1963) Compensatory adaptation of renal function in the unanesthetised rat. Am J Physiol 205:1042–1048
Pollock CA, Field MJ, Bostrom TE, Dyne M, Gyory AZ, Cockayne DJH (1991) Proximal tubular cell sodium concentration in early diabetic nephropathy assessed by electrom microprobe analysis. Pflügers Arch 418:14–17
Pollock CA, Lawrence JR, Field MJ (1991) Tubular Na handling and tubuloglomerular feedback in experimental diabetes mellitus. Am J Physiol 260:F946-F952
Pollock DM, Arendshorst WJ (1990) Native tubular fluid attenuates ANF-induced inhibition of tubuloglomerular feedback. Am J Physiol 258:F189–198
Potter DE, Leumann EP, Sakai T, Holliday MA (1974) Early response of glomerular filtration rate to unilateral nephrectomy. Kidney Int 5:131–136
Rick R, Dorge A, Thurau K (1982) Quantitative analysis for electrolytes in frozen-dried sections. J Micros 125:239–247
Salmond R, Seney FD jr (1991) Reset tubuloglomerular feedback permits and sustains glomerular hyperfunction after extensive renal ablation. Am J Physiol 260:F395-F401
Schnermann J, Briggs J (1982) Concentration dependent sodium chloride transport as the signal in feedback control of glomerular filtration. Kidney Int 22 [Suppl 12]:S 82-S 89
Schnermann J, Briggs J (1985) Function of the juxtaglomerular apparatus: local control of glomerular hemodynamics. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology. Raven, New York, pp 669–697
Selen G, Muller-Suur R, Persson AEG (1983) Activation of the tubuloglomerular feedback mechanism in dehydrated rats. Acta Physiol Scand 117:83–89
Seney FD, Salmond R (1988) Tubuloglomerular feedback in diabetic rats (abstract). Kidney Int 33:412
Seney FD, Persson AEG, Wright FS (1987) Modification of tubuloglomerular feedback signal by dietary protein. Am J Physiol 252:F83-F90
Snedecor GW, Cochran WG (1980) Statistical methods (7th edn). Iowa State University Press, Ames, Iowa
Tabei K, Levenson DJ, Brenner BM (1983) Early enhancement of fluid transport in rabbit proximal straight tubules after loss of contralateral renal excretory function. J Clin Invest 72:871–881
Tapson JS, Mansy H, Marshall SM, Tisdall SR, Wilkonson R (1986) Renal functional reserve in kidney donors. Q J Med 60:725–732
Toback FG, Lowenstein LM (1974) Thymidine metabolism during normal and compensatory renal growth. Growth 38:38–44
Trizna W, Yanagawa N, Bar-Bhayim Y, Houston B, Fine LG (1981) Functional profile of the uremic nephron. Evidence of proximal tubular “memory” in experimental renal disease. J Clin Invest 68:760–767
Weber H, Lin KY, Bricker NS (1975) Effect of sodium intake on single nephron glomerular filtration rate and sodium reabsorption in experimental uremia. Kidney Int 8:14–20
Wen SF, Wong NLM, Evanson RL, Lockhart EA, Dirks JH (1973) Micropuncture studies of sodium transport in the remnant kidney of the dog. J Clin Invest 52:386–397
Wen SF, Wong NLM, Evanson RL, Lockhart EA, Dirks JH (1976) Electrolyte transport in the remnant kidney of the dog: Effect of fruosemide. Am J Physiol 230:F1231-F1238
Wong NLM, Wen SF, Evanson RL, Dirks JH (1979) Chronic reduction in renal mass: Micropuncture studies of response to volume expansion and furosemide. In: Peters G, Diezi J, Guignard JP (eds) Renal adaptation to nephron loss. Karger, Basel, pp 51–57
Yoshida Y, Fogo A, Shiraga H, Glick AD, Ichikawa I (1988) Serial micropuncture analysis of single nephron function in subotal renal ablation. Kidney Int 654–660
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Pollock, C.A., Bostrom, T.E., Dyne, M. et al. Tubular sodium handling and tubuloglomerular feedback in compensatory renal hypertrophy. Pflügers Arch. 420, 159–166 (1992). https://doi.org/10.1007/BF00374985
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DOI: https://doi.org/10.1007/BF00374985