Low salt diet does not protect kidney function in normotensive rat model of chronic kidney disease

Abstract

Intrarenal hypoxia has been shown to cause renal damage. Na+‐restriction in normotensive rats reverses the normal cortical‐medullary oxygen gradient, an alteration that may compromise long‐term kidney function. Indeed, two weeks of low salt (LS) diet to rats induces both glomerular and tubulointerstial fibrosis. We hypothesized that chronic LS diet may also aggravate kidney damage in chronic kidney disease (CKD).Male Sprague Dawley rats were subjected to a two‐step surgery with right nephrectomy and surgical ablation of the upper and lower poles of the left kidney (5/6Nx). This produces a normotensive salt‐sensitive animal model of CKD. After one week recovery, animals where fed normal (NS, 0.4%) or low (LS, 0.01%) salt diet during the following four weeks. Thereafter, catheters were placed in the carotid artery and femoral vein for blood pressure measurement and infusion of saline containing 3H‐inulin, respectively, in thiobutabarbital anesthetized animals. Oxygen consumption (QO2) was estimated from the arterio‐venous difference in O2 content multiplied by renal blood flow (RBF, transonic flow probe). Renal cortical and medullary partial pressures of oxygen (PO2) were measured using Clark‐type electrodes. At the end of the experiment, a bolus injection of angiotensin II AT1 receptor blocker candesartan (1 mg/kg) was given intravenously in order to determine the degree of renin‐angiotensin system (RAS) activation.Mean arterial blood pressure, glomerular filtration rate and RBF were similar in healthy control and 5/6Nx. RAS activation was confirmed by the more pronounced decrease in MAP following systemic angiotensin II AT1 receptor blockade in LS. 5/6Nx on both diets had incerased QO2 and lower Na+ transport efficiency when compared with controls. Reduced cortical PO2 was also observed in 5/6Nx animals on both diets, whereas medullary PO2 was increased only in 5/6Nx on LS. Increased TBARS were not improved and total protein excretion was further increased in 5/6Nx animals by LSTaken together, these results indicate that LS diet does not normalize renal QO2, prevents cortical hypoxia or TBARS in the 5/6Nx model of CKD. Actually, LS diet to 5/6Nx magnified the already existing proteinuria, which may imply that LS and subsequent RAS activation may have detrimental effect on long term kidney function in CKD.Support or Funding InformationThis work was supported by the Swedish Heart and Lung Foundation and the Swedish Research Council.