Dichloroacetate treatment accelerates the development of pathology in rodent autosomal recessive polycystic kidney disease

Gattone, Vincent H.; Bacallao, Robert L.

doi:10.1152/ajprenal.00009.2014

Cited by 8 publications

(3 citation statements)

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“…Genic and allelic heterogeneity [3], possible modifying genetic factors [24], and environmental factors, such as treatment of hypertension [25], salt intake [26], and possible toxic water [27], are associated with phenotypic variability (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

Imaging Identification of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease: Simple Eligibility Criterion for Tolvaptan

et al. 2020

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Background: Tolvaptan was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, the official indication of “rapidly progressive disease” is described differently in the clinical guidelines. We aim to define “rapidly progressive disease” by risk of ESRD, which is evaluated using estimated height-adjusted total kidney volume (HtTKV) growth rate. Methods: The risk of ESRD was retrospectively analyzed in 617 initially non-ESRD adults with ADPKD and observed with standard of care between 2007 and 2018. The estimated annual growth rate of the HtTKV, termed as eHTKV-α (%/year), is derived from the following equation: [HtTKV at age t] = K(1 + eHTKV-α/100)t, where K = 150 mL/m is used in Mayo Imaging Classification and K = 130 mL/m is proposed for individually stable eHTKV-α value from baseline. The accuracy of eHTKV-α to predict ESRD for censored ages was analyzed using time-dependent receiver-operating characteristic curves (ROC). The cutoff point of initially measured eHTKV-α to predict ESRD was assessed using Kaplan-Meier and Cox’s proportional hazards models. Performance characteristics of the cutoff point for censored ages were calculated using time-dependent ROC and validated by the bootstrap method. Results: The area under the time-dependent ROC of eHTKV-α to predict ESRD at age 65 was 0.89 ± 0.04 (K = 130). The mean renal survival was less than 70 years at eHTKV-α ≥4.0%/year (K = 130). Mean renal survival was approximately 12 years shorter, and hazard ratio of ESRD was more than 5-time higher at this cutoff point than at lower point. Time-dependent sensitivity for age 65 and cutoff point of 4.0%/year (K = 130) was 93.4 ± 0.3%. Between cutoff points ≥4.0%/year (K = 130) and ≥3.5%/year (K = 150), there was no significant difference in performance characteristics and accuracy to predict ESRD. Conclusion: eHTKV-α well predicts ESRD. Initially, measured eHTKV-α ≥4.0%/year (K = 130) defines high-risk ESRD. Without additional conditions, a single eHTKV-α cutoff point identifies subjects that are most likely to benefit from tolvaptan.

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Section: Discussionmentioning

confidence: 99%

Imaging Identification of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease: Simple Eligibility Criterion for Tolvaptan

et al. 2020

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“…For instance, the use of the glycolysis inhibitor 2-deoxyglucose (2-DG) has been shown to reduce renal injury and inflammation in animal models of kidney disease [ 171 , 209 , 210 ]. Additionally, several other inhibitors of glycolysis, such as dichloroacetate (DCA) and lonidamine, are currently under investigation as potential therapies for kidney disease [ 211 , 212 ].…”

Section: Potential Therapeutic Interventions Targeting Immunometaboli...mentioning

confidence: 99%

The Interplay between Immune and Metabolic Pathways in Kidney Disease

Jiao

2023

Cells

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Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways, such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

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“…Bromodichloromethane was found to result in renal tubular degeneration and necrosis 7 . Dichloroacetate exposure accelerated the pathological development of autosomal recessive polycystic kidney disease in rodents 8 . Long‐term exposure to KBrO 3 caused renal cell tumors in mice and thyroid and testicular mesothelioma in rats 9 .…”

Section: Introductionmentioning

confidence: 99%

Bromoacetic acid causes oxidative stress and uric acid metabolism dysfunction via disturbing mitochondrial function and Nrf2 pathway in chicken kidney

Liu

et al. 2022

Environmental Toxicology

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Since the outbreak of COVID‐19, widespread utilization of disinfectants has led to a tremendous increase in the generation of disinfection byproducts worldwide. Bromoacetic acid (BAA), one of the common disinfection byproducts in the environment, has triggered public concern because of its adverse effects on urinary system in mammals. Nevertheless, the BAA‐induced nephrotoxicity and potential mechanism in birds still remains obscure. According to the detected content in the Taihu Lake Basin, the model of BAA exposure in chicken was established at doses of 0, 3, 300, 3000 μg/L for 4 weeks. Our results indicated that BAA exposure caused kidney swelling and structural disarrangement. BAA led to disorder in renal function (CRE, BUN, UA) and increased apoptosis (Bax, Bcl‐2, caspase3). BAA suppressed the expression of mitochondrial biogenesis genes (PGC‐1α, Nrf1, TFAM) and OXPHOS complex I genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6). Subsequently, BAA destroyed the expression of Nrf2 antioxidant reaction genes (Nrf2, Keap1, HO‐1, NQO1, GCLM, GCLC). Furthermore, renal oxidative damage led to disorder in uric acid metabolism genes (Mrp2, Mrp4, Bcrp, OAT1, OAT2, OAT3) and exacerbated destruction in renal function. Overall, our study provided insights into the potential mechanism of BAA‐induced nephrotoxicity, which were important for the clinical monitoring and prevention of BAA.

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Dichloroacetate treatment accelerates the development of pathology in rodent autosomal recessive polycystic kidney disease

Abstract: Gattone VH II, Bacallao RL. Dichloroacetate treatment accelerates the development of pathology in rodent autosomal recessive polycystic kidney disease.

Cited by 8 publications

References 40 publications

Imaging Identification of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease: Simple Eligibility Criterion for Tolvaptan

Imaging Identification of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease: Simple Eligibility Criterion for Tolvaptan

The Interplay between Immune and Metabolic Pathways in Kidney Disease

Bromoacetic acid causes oxidative stress and uric acid metabolism dysfunction via disturbing mitochondrial function and Nrf2 pathway in chicken kidney

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