Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat

Abstract

This study tests the possible influence of the urinary concentrating process and/or of vasopressin (AVP) on the progression of early chronic renal failure (CRF). Male Sprague-Dawley rats were submitted to 5/6 nephrectomy and were offered water ad libitum throughout the study. In addition, half of the rats (high water intake, HWI) received their food mixed with a water-rich agar gel. The other rats (normal water intake, NWI) ate the same amount of food plus agar in the usual dry powder form. This resulted in doubling the daily water ingestion in HWI. Renal function was studied for 10 wk and kidney morphology assessed thereafter. Increased water intake in HWI reduced solute-free water reabsorption and urine osmolality about threefold to 12 +/- 1 ml/day and 390 +/- 9 mosmol/kgH2O, respectively (week 5 as example). Hematocrit, plasma sodium, and plasma creatinine concentration were unchanged. The progressive increases in urinary protein excretion and in systolic blood pressure observed in this model of CRF were significantly slowed in HWI compared with NWI (at week 5, 8.6 +/- 1.8 vs. 23.1 +/- 6.2 mg protein/day and 142 +/- 8 vs. 167 +/- 10 mmHg, respectively). Remnant kidney weight per unit body weight was 21% lower in HWI than in NWI (P less than 0.02). Incidence of glomerulosclerosis was also reduced and was correlated with kidney weight (P less than 0.01). AVP plasma level (PAVP) and plasma renin activity (PRA) were measured in additional rats. PAVP was about twofold higher (P less than 0.05) and PRA twofold lower (P less than 0.001) in rats with 5/6 nephrectomy than in control rats with two kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Antagonism of vasopressin V2 receptor improves albuminuria at the early stage of diabetic nephropathy in a mouse model of type 2 diabetes

“…Similar to our findings, Levine et al found no difference between db/db and wild type mice three weeks after uninephrectomy (Levine et al, 2008). However, we observed that the V2R antagonist treatment slightly attenuated kidney hypertrophy in the uninephrectomized db/db mice, consistent with its other renal effects and in agreement with previous studies in rats (Bouby et al, 1990;Bardoux et al, 2003b).…”

“…This effect of dDAVP does not occur in subjects with loss of function mutations in V2R (Bardoux et al, 2003a). In renal diseases, activation of V2R was shown to participate in the progression of renal failure in rats with five-sixth reduction in renal mass (Bouby et al, 1990). In a rat model of type 1 diabetes, vasopressin was shown to contribute to microalbuminuria through its V2R activation (Bardoux et al, 2003b).…”

“…V2R is active in the collecting duct. Our previous studies in non-diabetic rats suggest that the deleterious effect of vasopressin in the kidney is mainly secondary to the V2R-mediated urine concentrating action of the hormone (Bouby et al, 1990;Bankir et al, 1993). It has been suggested that the activation of V2R in the tubule inhibits the tubuloglomerular feedback as a result of reduction in salt concentration at the macula densa, triggering elevation of intraglomerular capillary pressure, hyperfiltration and glomerular injury .…”

Mild dehydration, vasopressin and the kidney: animal and human studies

“…In the second experiment, we studied the effect of restoring urine concentrating activity by chronic infusion of a V2 agonist in 5/6 nephrectomized Brattleboro rats (which are devoid of endogenous vasopressin). Both these experiments showed that rats with the lowest urine concentrating activity displayed the slowest progression of chronic renal failure as assessed by the reduction in proteinuria, kidney hypertrophy, incidence of glomerulosclerosis and mortality (Bouby et al, 1990 (Figure 6). In another study, it has been shown that Brattleboro rats, unlike normal rats, do not present any increase in the single-nephron glomerular hyperfiltration rate after 5/6 nephrectomy (Bregman et al, 1990).…”

“…Left: Sprague-Dawley rats with 5/6 nephrectomy were given an increased water intake for 10 weeks by mixing a water-rich agar gel with their feed (open dots) and were compared to rats with similar initial renal impairement but normal water intake (closed dots). Mean7SEM, n¼9 rats per group at the beginning of the experiment, three rats in each group died or were killed during weeks 6-7, adapted from Bouby et al (1990). Right: Brattleboro rats with 5/6 nephrectomy were given an i.p.…”