Tubuloglomerular feedback response in the prenatal and postnatal ovine kidney

Brown, Russell D.; Turner, Anita J.; Carlström, Mattias; Persson, A. Erik G.; Gibson, Karen J.

doi:10.1152/ajprenal.00019.2011

Cited by 10 publications

(20 citation statements)

References 35 publications

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“…However, it has also been shown that due to this resetting, the reactivity of the TGF is attenuated following nephrectomy (22). However, we believe we have to be cautious when extrapolating findings from adult nephrectomy models to that of the fetus as regulation of renal function is distinct in the fetus compared with the adult (8).…”

Section: Discussionmentioning

confidence: 98%

Renal responses to furosemide are significantly attenuated in male sheep at 6 months of age following fetal uninephrectomy

Singh

Bertram²,

Denton

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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We have previously shown that fetal uninephrectomy (uni-x) at 100 days of gestation (term = 150 days) in male sheep results in a 30% nephron deficit, reduction in glomerular filtration rate (GFR) and renal blood flow, and elevation in arterial pressure at 6 mo of age. Furthermore, in response to an acute 0.9% saline load, sodium excretion was significantly delayed in uni-x animals leading us to speculate that tubuloglomerular feedback (TGF) activity was reset in uni-x animals. In the present study, we induced TGF blockade by furosemide administration (1.5 mg/kg iv over 90 min) and determined GFR, effective renal plasma flow, and urine and sodium excretion responses in 6-mo-old male sheep. In response to furosemide, a significant diuresis and natriuresis was observed in the sham group; however, the response was significantly delayed and reduced in uni-x animals (both, P(treatment×time) < 0.001). Cummulative urinary and sodium output was significantly less in the uni-x compared with the sham sheep (both, P(treatment×time) < 0.001). GFR was increased in the sham but not the uni-x sheep (P(treatment×time) < 0.0001). In conclusion, the excretory response to furosemide was attenuated in the uni-x sheep, and this suggests a rightward resetting of the TGF operating point. The TGF mechanism is important in the fine tuning of sodium homeostasis and is likely a contributing factor for the dysfunction in sodium regulation we have previously observed in the uni-x animals.

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Section: Discussionmentioning

confidence: 98%

Renal responses to furosemide are significantly attenuated in male sheep at 6 months of age following fetal uninephrectomy

Singh

Bertram²,

Denton

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…For GFR to rise following uni-x, when flow to the distal segments of the nephron concurrently increases, temporal adaptations in tubuloglomerular feedback (TGF) are likely to occur (12). Indeed, resetting of TGF has been demonstrated in lambs at birth, facilitating the postnatal increase in GFR and excretion by the kidney (16). Similarly, nephrectomy in adult rats also resets TGF operating point, to function at a higher single nephron GFR and solute delivery to the distal tubules (20,57).…”

Section: A Solitary Functioning Kidney: Mechanisms Underlying the Renmentioning

confidence: 99%

Loss of a kidney during fetal life: long-term consequences and lessons learned

Lankadeva

Singh

Tare

et al. 2014

American Journal of Physiology-Renal Physiology

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Epidemiological studies reveal that children born with a solitary functioning kidney (SFK) have a greater predisposition to develop renal insufficiency and hypertension in early adulthood. A congenital SFK is present in patients with unilateral renal agenesis or unilateral multicystic kidney dysplasia, leading to both structural and functional adaptations in the remaining kidney, which act to mitigate the reductions in glomerular filtration rate and sodium excretion that would otherwise ensue. To understand the mechanisms underlying the early development of renal insufficiency in children born with a SFK, we established a model of fetal uninephrectomy (uni-x) in sheep, a species that similar to humans complete nephrogenesis before birth. This model results in a 30% reduction in nephron number rather than 50%, due to compensatory nephrogenesis in the remaining kidney. Similar to children with a congenital SFK, uni-x sheep demonstrate a progressive increase in arterial pressure and a loss of renal function with aging. This review summarizes the compensatory changes in renal hemodynamics and tubular sodium handling that drive impairments in renal function and highlights the existence of sex differences in the functional adaptations following the loss of a kidney during fetal life.

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“…In adult animals, a sensitized TGF results in lower SNGFR . Therefore, the observations of Brown and colleagues suggest that a sensitized TGF may contribute to the suppression of GFR in the fetus . Furthermore, the lesser sensitivity of TGF observed in the lamb compared with the fetus suggests that this rightward shift in TGF facilitates the increase in GFR after birth.…”

Section: Glomerular Adaptations During the Postnatal Periodmentioning

confidence: 99%

“…Brown et al demonstrated that TGF is active in the sheep fetus and is more sensitive compared with the young lambs at 2 weeks of age. 30 In adult animals, a sensitized TGF results in lower SNGFR. 31 Therefore, the observations of Brown and colleagues suggest that a sensitized TGF may contribute to the suppression of GFR in the fetus.…”

Section: Glomerular Adaptations During the Postnatal Periodmentioning

confidence: 99%

“…31 Therefore, the observations of Brown and colleagues suggest that a sensitized TGF may contribute to the suppression of GFR in the fetus. 30 Furthermore, the lesser sensitivity of TGF observed in the lamb compared with the fetus 30 suggests that this rightward shift in TGF facilitates the increase in GFR after birth. Although a direct association between NO and TGF has not been established during postnatal development of renal haemodynamics, the ontogeny of expression of NO synthase (NOS) activity in the preglomerular resistance vasculature of the newborn compared with the adult suggests a critical role for NO in modulating TGF activity in the newborn.…”

Section: Glomerular Adaptations During the Postnatal Periodmentioning

confidence: 99%

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Compensatory responses to nephron deficiency: Adaptive or maladaptive?

et al. 2014

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This is a comprehensive review on our current understanding of postnatal functional and structural maturation of a kidney. We further explore how these adaptations in the setting of abnormal kidney development or loss of a kidney which result in low nephron number can lead to maladaptive phenotypes such as renal failure and hypertension later in life. ABSTRACT:Compensatory renal growth is a characteristic adaptation to reduced renal mass that appears to recapitulate the normal pattern of maturation of the kidney during the postnatal period. Hypertrophy of tubules (predominantly the proximal tubule) and glomeruli is accompanied by increased single nephron glomerular filtration rate and tubular reabsorption of sodium. We propose that the very factors, which contribute to the increase in growth and function of the renal tubular system, are, in the long term, the precursors to the development of hypertension in those with a nephron deficit. The increase in single nephron glomerular filtration rate is dependent on multiple factors, including reduced renal vascular resistance associated with an increased influence of nitric oxide, and a rightward shift in the tubuloglomerular feedback curve, both of which contribute to the normal maturation of renal function. The increased influence of nitric oxide appears to contribute to the reduction in tubuloglomerular feedback sensitivity and facilitate the initial increase in glomerular filtration rate. The increased single-nephron filtered load associated with nephron deficiency may promote hypertrophy of the proximal tubule and so increased reabsorption of sodium, and thus a rightward shift in the pressure natriuresis relationship. Normalization of sodium balance can then only occur at the expense of chronically increased arterial pressure. Therefore, alterations/adaptations in tubules and glomeruli in response to nephron deficiency may increase the risk of hypertension and renal disease in the long-term.

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Tubuloglomerular feedback response in the prenatal and postnatal ovine kidney

Cited by 10 publications

References 35 publications

Renal responses to furosemide are significantly attenuated in male sheep at 6 months of age following fetal uninephrectomy

Renal responses to furosemide are significantly attenuated in male sheep at 6 months of age following fetal uninephrectomy

Loss of a kidney during fetal life: long-term consequences and lessons learned

Compensatory responses to nephron deficiency: Adaptive or maladaptive?

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