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2018 ; 19
(1
): 180
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Rehydration with fructose worsens dehydration-induced renal damage
#MMPMID30005632
Milagres T
; García-Arroyo FE
; Lanaspa MA
; Garcia G
; Ishimoto T
; Andres-Hernando A
; Kuwabara M
; Jensen T
; Sato Y
; Glaser J
; Sánchez-Lozada LG
; Johnson RJ
; Roncal-Jimenez C
BMC Nephrol
2018[Jul]; 19
(1
): 180
PMID30005632
show ga
BACKGROUND: Increasing evidence suggests heat stress induced chronic kidney
disease (CKD) may be mediated by endogenous fructose generation and may be
exacerbated by rehydration by fructose-containing solutions. We have recently
reported a model of CKD induced by heat stress. Here we test the hypothesis that
rehydration with fructose may induce worse kidney injury than rehydration with
equal amounts of water, and we also test if this fructose-induced injury is
associated with activation of inflammasomes in the kidney. METHODS: Mice were
recurrently exposed to heat (39.5 C(0) for 30 min/h, 5 times daily for 5 wks)
with rehydration consisting of 6 ml each night of water (Heat, n?=?7) or fructose
(Heat+F, 10%, n?=?7), and were compared to control mice on water (Control, n?=?7)
or fructose (Fructose, n?=?7). Various markers of renal injury were assessed.
RESULTS: Compared to control animals, there was a progressive worsening of renal
injury (inflammation and fibrosis) with fructose alone, heat stress alone, and
heat stress with fructose rehydration (P?0.01 by ANOVA). The combination of
heat stress with rehydration with fructose was associated with increased
intrarenal expression of the inflammasome markers, NLRP3 and IL-18, compared to
heat stress alone. In addition, heat stress with or without fructose was
associated with increased expression of caspase -?3 and monocyte chemoattractant
protein-1 levels. Fructose administration was also associated with an increase in
serum copeptin levels (a biomarker of vasopressin) and elevated copeptin was also
observed in mice undergoing heat stress alone. CONCLUSIONS: These studies suggest
that heat stress may activate intrarenal inflammasomes leading to inflammation
and renal injury, and provide evidence that rehydration with fructose may
accelerate the renal injury and inflammatory response.