Tubuloglomerular Feedback Response in the Contralateral Kidney after 24-hour Unilateral Ureteral Obstruction

Abstract

Reduction of the functioning renal mass by unilateral nephrectomy or unilateral ureteral occlusion (UUO) leads to increased function of the remaining nephrons, an important factor being the glomerular filtration rate (GFR). GFR can be modified via the tubuloglomerular feedback control (TGF), which senses the distal delivery of fluid and alters the tonus of the glomerular arterioles. The aim of the present study was to investigate the TGF sensitivity in the intact left kidney of rats after 24 hours of right ureteral occlusion. Using a micropuncture technique, proximal tubular stop-flow pressure (Psf), as a relative index of glomerular capillary pressure, was measured upstream to the block, while late proximal segments were perfused with Ringer solution (rates 0-40 nl/min). The maximal drop in Psf and the tubular flow rate at which 50% of this response was achieved, the turning point (TP), were determined. Considerable decrease in the sensitivity of the TGF system in the contralateral kidney during UUO was indicated by a significantly higher TP as compared with control rats (sham operation), viz. 29 v. 19 nl/min. Maximal Psf drop after UUO was significantly less than in the controls (6 v. 12 mm Hg). Reduced TGF sensitivity in the contralateral kidney after protracted UUO is a prerequisite for that kidney's increased excretion of salt and water to compensate for the loss of functioning renal mass.

FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts

“…That renal disease is not a prominent feature of patients with hereditary or acquired primary hypophosphataemic disorders, nor seen in transgenic animals over-expressing FGF23 40 , seems consistent with these observations and the requirement for a priming step. While this study elaborates strong mechanistic parallels between the effects of FGF23 excess on the kidney and heart, there is a clear distinction in the requirement for a priming signal, as FGF23 appears sufficient to drive cardiac hypertrophy in wild-type healthy animals without pre-existing injury 21 .…”

“…Since functionality is compromised in the obstructed kidney of the UUO model, the C/L undergoes various haemodynamic, structural and functional adaptations to persevere clearance and maintain homeostasis 40, 45, 46 . Accordingly, the circulating concentrations of phosphate, calcium, as well as calcitriol, PTH and intact FGF23 were unchanged by UUO.…”

Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction

“…It is known that cytokines such as TGF-␤ 1 have a key role to play in both the apoptotic and fibrotic responses. the single-nephron filtration rate of the contralateral nonobstructed kidney (5). In the absence of recovery of the obstructed rat kidney, the contralateral kidney undergoes a compensatory hypertrophy (21) and, in the case of congenital obstruction, both hypertrophy and hyperplasia also occur (80).…”