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Glomeruli and blood pressure. Less of one, more the other?
B M Brenner1, D L Garcia, S Anderson
1Renal Division, Brigham and Women's Hospital, Boston, MA 02115.
Insights
A reduced number of nephrons may cause salt-sensitive hypertension by limiting the kidney's ability to excrete sodium. This renal abnormality could explain essential hypertension and susceptibility to kidney disease in certain populations.
Area of Science:
- Nephrology
- Hypertension Pathophysiology
- Renal Medicine
Background:
- The kidney's role in hypertension is established, but underlying mechanisms involving renal hemodynamics, hormones, genetics, and sodium intake are unclear.
- Reduced renal filtration surface area, from disease or surgery, causes hypertension and renal insufficiency, worsened by high sodium intake.
- Congenital kidney abnormalities like solitary kidneys or oligomeganephronia are linked to hypertension and progressive renal disease.
Purpose of the Study:
- To investigate the hypothesis that a reduced nephron number is a key factor in essential hypertension.
- To explore the link between nephron deficiency, impaired sodium excretion, and salt-sensitive hypertension.
- To understand how congenital variability in filtration surface area influences susceptibility to chronic kidney disease and diabetic glomerulopathy.
Main Methods:
- Review of existing evidence on renal function, hypertension, and congenital renal anomalies.
- Analysis of data from intrinsic renal disease, surgical renal ablation, and inbred rat models.
- Correlation of filtration surface area with hypertension and renal insufficiency progression.
Main Results:
- Reduced filtration surface area, whether acquired or congenital, leads to systemic hypertension and renal insufficiency.
- Hypertension is observed in conditions with congenitally deficient filtration surface area, such as inbred rat strains.
- A reduced nephron count is postulated as a cause of salt-sensitive hypertension due to impaired sodium excretion.
Conclusions:
- A reduced number of nephrons is a potential contributing factor to essential hypertension in the general population.
- Congenital variability in nephron number influences susceptibility to salt-sensitive hypertension and chronic nephropathy.
- This nephron hypothesis may also explain differential susceptibility to glomerulopathy in diabetic patients.
Abstract:
A primary role for the kidney in the initiation and maintenance of hypertension has long been recognized, but the pathogenetic interactions among renal hemodynamics, hormonal and hereditary factors, and dietary sodium intake remain enigmatic. Reduction in filtration surface area, whether acquired in the course of intrinsic renal disease or after surgical renal ablation, leads to systemic hypertension as well as to progressive renal insufficiency, sequellae made even more severe by dietary sodium excess. Moreover, hypertension and progressive renal disease eventuate in some individuals born with a solitary kidney, as well as in those with more severe degrees of dysgenesis (ie, oligomeganephronia). Hypertension is also commonly observed in certain inbred rat strains in which filtration surface area is congenitally deficient. Based on these and other lines of evidence reviewed herein, we postulate that a renal abnormality that contributes to essential hypertension in the general population is a reduced number of nephrons. The consequences of this abnormality are limitations in the ability to excrete sodium and thus, salt-sensitive hypertension. Finally, congenital variability in filtration surface area may explain why only some, but not all, patients exposed to potentially injurious renal stimuli eventually manifest chronic nephropathy. This may also account for the susceptibility of subsets of Type I and Type II diabetics to develop overt glomerulopathy.