Abstract 220: Nephron Deficient Rats are Highly Susceptible to Hypertension Induced Kidney Injury
It is well known that hypertension can promote decline in renal function, but there is a paucity of information on how hypertension influences single kidney individuals. The HSRA model exhibits a high incidence of congenital single kidney (50-75% offspring) that is characterized by low nephron number (~20% less in solitary kidney vs. control kidney), glomerular and kidney hypertrophy, elevated single nephron glomerular filtration rate (GFR), which culminates in kidney injury and decline in kidney function. We hypothesized that renal hemodynamic stressors, such as DOCA induced hypertension, would accelerate onset and progression of kidney injury in rats born with a solitary kidney (HSRA-S) compared to two-kidney littermates (HSRA-C) or rats that have undergone unilateral nephrectomy (HSRA-UNX). Time course evaluation of blood pressure, renal hemodynamics, and kidney injury was performed in 6 animal groups: (1-2) HSRA-S+DOCA or placebo; (3-4) HSRA-C+DOCA or placebo; and (5-6) HSRA-UNX+DOCA or placebo. At the conclusion of the study (5 weeks), HSRA-S+DOCA treated rats demonstrated a significant (ANOVA; 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 HSRA-UNX+DOCA (173±3 mmHg, 76±26 mg/24hr, 963+36 μl/min/gKW) and HSRA-C+DOCA (154±2 mmHg, 7±1 mg/24hr, 1484+121 μl/min/gKW). Animals in placebo groups showed no significant change in blood pressure, proteinuria or GFR from week 13-18 between all three groups. To elucidate the molecular mechanism of nephron deficiency in the HSRA model and better understand how elevated blood pressure promotes rapid decline in renal function, whole transcriptome analysis (RNA sequencing) of embryonic kidney isolated at key stages in nephrogenesis (E14.5, 15.5, and 16.5) was performed which identified a number of novel genes involved in nephrogenesis and kidney development. We are currently working to understand the functional role of these genes and pathways using an in vitro whole organ kidney culture system. In summary, nephron deficient rats are highly susceptible to hypertension induced kidney injury and several novel genes/pathways involved in nephrogenesis likely program the model to develop significant kidney disease with age.
Author Disclosures: X. Wang: None. A.C. Johnson: None. Z. Guo: None. F. Chen: None. L. Solberg-Woods: None. M.R. Garrett: None.
- © 2014 by American Heart Association, Inc.