A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease

Kipp, Kevin R.; Rezaei, Mina; Lin, Louis M.; Dewey, Elyse C.; Weimbs, Thomas

doi:10.1152/ajprenal.00551.2015

Cited by 89 publications

(83 citation statements)

References 26 publications

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“…Because water intake remained higher in the TD treatment group compared to the other groups and responded to titration steps, a lower food intake and consequently, possibly a lower dose of the V2RA is not a concern. Nevertheless, recent studies in mice revealed that a lower food intake can also be protective in ADPKD [29,30]. Although food intake (adjusted for body weight) in the TD treatment group was similar after 6 weeks of study in comparison to the FD treatment group, body weight was markedly different between these study groups at the end of our experiment.…”

Section: Discussioncontrasting

confidence: 58%

Dose-Titrated Vasopressin V2 Receptor Antagonist Improves Renoprotection in a Mouse Model for Autosomal Dominant Polycystic Kidney Disease

Zittema¹,

Versteeg²,

Gansevoort³

et al. 2016

Am J Nephrol

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Background: In autosomal dominant polycystic kidney disease, renoprotective treatment with a vasopressin V2 receptor antagonist (V2RA) is given in a fixed dose (FD). Disease progression and drug habituation could diminish treatment efficacy. We investigated whether the renoprotective effect of the V2RA can be improved by dose titration of the V2RA aiming to maintain aquaresis at a high level. Methods: The V2RA OPC-31260 was administered to Pkd1-deletion mice in an FD (0.1%) or in a titrated dose (TD, up to 0.8% when drinking volume dropped). Total kidney weight (TKW) and cyst ratio were investigated and compared to non-treated Pkd1-deletion mice. Treatment was started early or late (21 or 42 days postnatal). Results: Water intake was significantly higher throughout the experiment in the TD compared to the FD group. FD treatment that was initiated early reduced TKW and cyst ratio but lost its renoprotective effect later during the experiment. In contrast, TD treatment was able to maintain the renoprotective effect. TD treatment, however, was also associated with a higher early termination rate in comparison with FD treatment. Late start of treatment (FD or TD) did not show a renoprotective effect. Conclusions: Titration of a V2RA aimed to maintain aquaresis at a high level showed a better renoprotective effect compared to FD administration. However, this treatment regimen was poorly tolerated and did not overcome treatment unresponsiveness when started later in the disease.

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Section: Discussioncontrasting

confidence: 58%

Dose-Titrated Vasopressin V2 Receptor Antagonist Improves Renoprotection in a Mouse Model for Autosomal Dominant Polycystic Kidney Disease

Zittema¹,

Versteeg²,

Gansevoort³

et al. 2016

Am J Nephrol

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“…Consistent with this hypothesis, mild-to-moderate food restriction was recently shown to slow progression in multiple mouse models of ADPKD, concomitant with suppressed mTOR signaling and AMPK activation. 12,13 Obesity is a well established independent risk factor for incident CKD, 6,34,35 ESRD,7,8 and decline in eGFR in the general population. 36 In individuals with prevalent CKD, obesity is associated with a decline in eGFR in some 8,37 but not in other studies.…”

Section: Discussionmentioning

confidence: 99%

“…have suggested that ADPKD is a state of defective glucose metabolism and metabolic reprogramming. 10,11 Furthermore, mild-tomoderate food restriction slows disease progression in multiple mouse models of ADPKD, 12,13 suggesting that changes in energy status may have a profound effect on ADPKD progression.…”

mentioning

confidence: 99%

Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease

Nowak

You

Gitomer

et al. 2017

JASN

126

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The association of overweight/obesity with disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) remains untested. We hypothesized that overweight/obesity associates with faster progression in early-stage ADPKD. Overall, 441 nondiabetic participants with ADPKD and an eGFR>60 ml/min per 1.73 m who participated in the Halt Progression of Polycystic Kidney Disease Study A were categorized on the basis of body mass index (BMI; calculated using nonkidney and nonliver weight) as normal weight (18.5-24.9 kg/m; reference; =192), overweight (25.0-29.9 kg/m; =168), or obese (≥30 kg/m; =81). We evaluated the longitudinal (5-year) association of overweight/obesity with change in total kidney volume (TKV) by magnetic resonance imaging using linear regression and multinomial logistic regression models. Among participants, mean±SD age was 37±8 years, annual percent change in TKV was 7.4%±5.1%, and BMI was 26.3±4.9 kg/m The annual percent change in TKV increased with increasing BMI category (normal weight: 6.1%±4.7%, overweight: 7.9%±4.8%, obese: 9.4%±6.2%; <0.001). In the fully adjusted model, higher BMI associated with greater annual percent change in TKV (=0.79; 95% confidence interval [95% CI], 0.18 to 1.39, per 5-unit increase in BMI). Overweight and obesity associated with increased odds of annual percent change in TKV ≥7% compared with <5% (overweight: odds ratio, 2.02; 95% CI, 1.15 to 3.56; obese: odds ratio, 3.76; 95% CI, 1.81 to 7.80). Obesity also independently associated with greater eGFR decline (slope) versus normal weight (fully adjusted =-0.08; 95% CI, -0.15 to -0.02). In conclusion, overweight and, particularly, obesity are strongly and independently associated with rate of progression in early-stage ADPKD.

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“…and metabolic reprogramming are effective approaches for slowing cyst expansion and disease progression in murine models of ADPKD (7,18). In particular, we and others have demonstrated the protective effects of mild to moderate calorie/food restriction (FR) (10%-40% decrease in total caloric intake) in multiple murine models of ADPKD (18,19). In addition to that, a recent study reported that time-restricted feeding and ketosis led to protective effects against ADPKD in rat, mouse, and feline models of ADPKD (20).…”

Section: Introductionmentioning

confidence: 99%

“…FR without malnutrition extends lifespan and increases resistance to age-related diseases in rodents and monkeys, improves the health of overweight humans, and has recently been reported to delay the progression of ADPKD (8,9,18,19,21,22). Interestingly, the beneficial effects of FR in aging and life span appear to be mediated in large part by suppression of the IGF pathway (8,9,21,22).…”

Section: Introductionmentioning

confidence: 99%

Metalloproteinase PAPP-A regulation of IGF-1 contributes to polycystic kidney disease pathogenesis

Kashyap¹,

Hein²,

Chini³

et al. 2020

JCI Insight

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A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease

Abstract: Kipp KR, Rezaei M, Lin L, Dewey EC, Weimbs T. A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease.

Cited by 89 publications

References 26 publications

Dose-Titrated Vasopressin V2 Receptor Antagonist Improves Renoprotection in a Mouse Model for Autosomal Dominant Polycystic Kidney Disease

Dose-Titrated Vasopressin V2 Receptor Antagonist Improves Renoprotection in a Mouse Model for Autosomal Dominant Polycystic Kidney Disease

Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease

Metalloproteinase PAPP-A regulation of IGF-1 contributes to polycystic kidney disease pathogenesis

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