There is little clinical data of how hypertension may influence individuals with nephron deficiency in the context of being born with a single kidney. We recently developed a new rat model (the HSRA rat) that is born with a single kidney and exhibits progressive kidney injury and decline in kidney function with age. We hypothesized that deoxycorticosterone acetate (DOCA)-salt would induce a greater increase in blood pressure and therefore accelerate progression of kidney injury in rats born with a solitary kidney compared to rats that have undergone unilateral nephrectomy. Time course evaluation of blood pressure, kidney injury, and renal hemodynamics was performed in 6 groups of animals from week 13 -18: (1-2) DOCA+S or Placebo+S (solitary kidney); (3-4) DOCA+C or Placebo+C (two-kidney control); and (5-6) DOCA+UNX8 or Placebo+UNX8 (two-kidney control that have undergone uninephrectomy). DOCA+S treated rats demonstrated a significant (p<0.05) rise in blood pressure (192±4 mmHg), proteinuria (205±31 mg/24hr) and decline in GFR (600+42 µl/min/gKW) relative to DOCA+UNX8 (173±3 mmHg, 76±26 mg/24hr, 963+36 µl/min/gKW) and DOCA+C (154±2 mmHg, 7±1 mg/24hr, 1484+121 µl/min/gKW). Placebo groups showed no significant change among the three groups. An assessment of renal injury markers via real-time PCR/western analysis and histological analysis was concordant with the measured physiological parameters. In summary, congenital solitary kidney rats are highly susceptible to the induction of hypertension compared to uninephrectomized rats, suggesting that low nephron endowment is an important driver of elevated blood pressure, hastening nephron injury through transmission of elevated systemic blood pressure, and thereby accelerating decline in kidney function.
- unilateral renal agenesis
- high blood pressure
- Copyright © 2015, American Journal of Physiology - Renal Physiology