Effects of exogenous desmopressin on a model of heat stress nephropathy in mice

Roncal-Jiménez, Carlos A.; Milagres, Tamara; Andrés-Hernando, Ana; Kuwabara, Masanari; Song, Zilong; Bjornstad, Petter; García, Gabriela; Sato, Yuka; Sánchez-Lozada, Laura G.; Lanaspa, Miguel A.; Johnson, Richard J.

doi:10.1152/ajprenal.00495.2016

Cited by 34 publications

(29 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The heat stress and dehydration protocol consist of placing mice in a heated environment (Isotemp-Fisher Scientific Incubator, Dubuque, IA) at 39.5°C for 30 min each hour for a total of 7 h, 5 days/week for a total duration of 5 wk (31,33). This procedure resulted in the animal sweating (on its paws) with an acute loss of 10 -13% of body weight by the end of the heating period each day, in the absence of hydration.…”

Section: Methodsmentioning

confidence: 99%

“…The etiology remains unknown, although some believe it may relate to exposure of toxins, heavy metals, or subacute infections (18,42). Our group has postulated that it may be the consequence of recurrent heat stress, resulting in renal injury driven by effects of hyperosmolarity (via activation of the polyol pathway), heat, vasopressin, and/or hyperuricemia (9,15,30), and we have established experimental models in which some of these pathways can be shown to induce chronic tubulointerstitial damage (11,12,31,33).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Experimental heat stress nephropathy and liver injury are improved by allopurinol

Roncal-Jiménez

Sato

Milagres

et al. 2018

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

An epidemic of chronic kidney disease (CKD) has been observed in Central America among workers in the sugarcane fields. One hypothesis is that the CKD may be caused by recurrent heat stress and dehydration, and potentially by hyperuricemia. Accordingly, we developed a murine model of kidney injury associated with recurrent heat stress. In the current experiment, we tested whether treatment with allopurinol (a xanthine oxidase inhibitor that reduces serum urate) provides renal protection against recurrent heat stress and dehydration. Eight-week-old male C57BL/6 mice were subjected to recurrent heat stress (39.5°C for 30 min, 7 times daily, for 5 wk) with or without allopurinol treatment and were compared with control animals with or without allopurinol treatment. Mice were allowed ad libitum access to normal laboratory chow (Harlan Teklad). Kidney histology, liver histology, and renal function were examined. Heat stress conferred both kidney and liver injury. Kidneys showed loss of proximal tubules, infiltration of monocyte/macrophages, and interstitial collagen deposition, while livers of heat-stressed mice displayed an increase in macrophages, collagen deposition, and myofibroblasts. Allopurinol provided significant protection and improved renal function in the heat-stressed mice. The renal protection was associated with reduction in intrarenal uric acid concentration and heat shock protein 70 expression. Heat stress-induced renal and liver injury can be protected with allopurinol treatment. We recommend a clinical trial of allopurinol for individuals developing renal injury in rural areas of Central America where the epidemic of chronic kidney disease is occurring.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Experimental heat stress nephropathy and liver injury are improved by allopurinol

Roncal-Jiménez

Sato

Milagres

et al. 2018

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…30,31 We did not study whether the effect of tolvaptan on the estimated GFR was mediated or paralleled by an effect on kidney volume; renal hemodynamic or other mechanisms could have also played a role. 27,28,35 The patients in the trial were asked to maintain good hydration. By increasing hydration and suppressing vasopressin release in the patients in the placebo group, the benefit that was associated with the administration of tolvaptan may have been underestimated.…”

mentioning

confidence: 99%

Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

et al. 2017

View full text Add to dashboard Cite

BACKGROUNDIn a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V 2 -receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODSWe conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m 2 of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m 2 were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTSThe change from baseline in the estimated GFR was −2.34 ml per minute per 1.73 m 2 (95% confidence interval [CI], −2.81 to −1.87) in the tolvaptan group, as compared with −3.61 ml per minute per 1.73 m 2 (95% CI, −4.08 to −3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m 2 ; 95% CI, 0.86 to 1.68; P<0.001). Elevations in the alanine aminotransferase level (to >3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONSTolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145.)

show abstract

“…Vasopressin may act in part by increasing glomerular hydrostatic pressure, and vasopressin has been shown to increases albumin excretion in humans [16]. Experimental studies of heat stress-induced kidney injury have also provided evidence that exogenous desmopressin can induce further kidney damage [17], while blocking vasopressin action via the V1a and V2 receptors may ameliorate renal injury [4], especially in the setting where the hydration fluids contain sugar-based solutions containing fructose. Potential mechanisms of injury include elevation in oxidative stress and the concurrent over-activation of the intra-renal polyol (aldose reductase-fructokinase) pathway [4].…”

Section: Discussionmentioning

confidence: 99%

Association of Copeptin, a Surrogate Marker of Arginine Vasopressin, with Decreased Kidney Function in Sugarcane Workers in Guatemala

et al. 2020

View full text Add to dashboard Cite

Background: Vasopressin is elevated in response to heat and dehydration and has been postulated to have a role in the chronic kidney disease of unknown origin being observed in Central America. The aims of this study were to examine whether the vasopressin pathway, as measured by copeptin, is associated with the presence of kidney dysfunction, and to examine whether higher fluid intake is associated with lower circulating copeptin and thereby preserves kidney health among sugarcane workers exposed to hot conditions. Methods: Utilizing a longitudinal study of 105 workers in Guatemala, we examined relationships between hydration indices, plasma copeptin concentrations, and kidney function markers at 3 times during the 6-month harvest. We also examined whether baseline copeptin concentrations increased the odds of developing an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 . Results:Copeptin concentrations were positively associated with serum creatinine (β 1.41, 95% CI 0.88-2.03) and negatively associated with eGFR (β -1.07, 95% CI -1.43 to -0.70). In addition, as workers improved their hydration (measured by increases in fluid balance), copeptin concentrations were reduced, and this reduction was associated with an improvement in kidney function. Conclusions: Results suggest that copeptin should be studied as a potential prognostic biomarker.

show abstract

Effects of exogenous desmopressin on a model of heat stress nephropathy in mice

Cited by 34 publications

References 38 publications

Experimental heat stress nephropathy and liver injury are improved by allopurinol

Experimental heat stress nephropathy and liver injury are improved by allopurinol

Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

Association of Copeptin, a Surrogate Marker of Arginine Vasopressin, with Decreased Kidney Function in Sugarcane Workers in Guatemala

Contact Info

Product

Resources

About