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Tubular sodium handling and tubuloglomerular feedback in compensatory renal hypertrophy

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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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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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