Effect of a Vasopressin V2 Receptor Antagonist on Polycystic Kidney Disease Development in a Rat Model

Wang, Xiaofang; Constans, Megan; Chebib, Fouad T.; Torres, Vicente E.; Pellegrini, Lorenzo

doi:10.1159/000500667

Cited by 21 publications

(21 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, kidney weight/body weight and microalbuminuria indicated the severity of kidney disease. 17,18 In our study, kidney weight/body weight and microalbuminuria of mice analysis indicated that the kidney weight/body weight and microalbuminuria in HFDinduced mice were significantly increased compared with control group, which was markedly reduced by valsartan or silibinin ( Figure 5B and C). Moreover, combination treatment exhibited better anti-fibrosis effect compared with valsartan or silibinin ( Figure 5B and C).…”

Section: Silibinin In Combination With Valsartan Exhibited Significanmentioning

confidence: 48%

<p>Silibinin Augments the Antifibrotic Effect of Valsartan Through Inactivation of TGF-β1 Signaling in Kidney</p>

Liu

Wang

Ding

et al. 2020

DDDT

View full text Add to dashboard Cite

Background: Chronic kidney disease (CKD) has become a major public health issue. Meanwhile, renal fibrosis caused by diabetic nephropathy can lead to CKD, regardless of the initial injury. It has been previously reported that silibinin or valsartan could relieve the severity of renal fibrosis. However, the effect of silibinin in combination with valsartan on renal fibrosis remains unclear. Material and Methods: Proximal tubular cells (HK-2) were treated with TGF-β1 (5 ng/mL) to mimic in vitro model of fibrosis. The proliferation of HK-2 cells was tested by CCK-8. Epithelial-mesenchymal transition (EMT) and inflammation-related gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of TNF-αNF-A. Additionally, HFD-induced renal fibrosis mice model was established to investigate the effect of silibinin in combination with valsartan on renal fibrosis in vivo. Results: Silibinin significantly increased the anti-fibrosis effect of valsartan in TGF-β1-treated HK-2 cells via inhibition of TGF-β1 signaling pathway. Furthermore, silibinin significantly enhanced the anti-fibrosis effect of valsartan on HFD-induced renal fibrosis in vivo through inactivation of TGF-β1 signaling pathway. Conclusion: These data indicated that silibinin markedly increased anti-fibrosis effect of valsartan in vitro and in vivo. Thus, silibinin in combination with valsartan may act as a potential novel strategy to treat renal fibrosis caused by diabetic nephropathy.

show abstract

Section: Silibinin In Combination With Valsartan Exhibited Significanmentioning

confidence: 48%

<p>Silibinin Augments the Antifibrotic Effect of Valsartan Through Inactivation of TGF-β1 Signaling in Kidney</p>

Liu

Wang

Ding

et al. 2020

DDDT

View full text Add to dashboard Cite

show abstract

“… 51 Regarding the role of metformin, the outcomes of the TAME-PKD trial 52 are awaited to shed light on its efficacy and the frequency of its adverse effects, especially gastrointestinal ones. Interestingly, lixivaptan has been shown to effectively reduce kidney volume in a rat model of the disease, 53 while a toxicology modeling study has suggested its beneficial safety profile; 54 however, its clinical utility remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Safety Profile of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease

Bellos¹

2021

TCRM

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease constitutes the most prevalent hereditary kidney disease, associated with high rates of morbidity leading eventually to end-stage renal disease. Tolvaptan is a selective vasopressin antagonist and has emerged as a promising therapeutic option for patients with autosomal dominant polycystic kidney disease. The present review summarized current evidence regarding the safety profile of tolvaptan in patients with the disease. Consistent with its pharmacological action, aquaretic adverse events represent the most common side effects of tolvaptan, consisting of polyuria, pollakiuria and polydipsia. Gradual dose titration based on urinary osmolality, as well as dietary interventions aiming to reduce solute excretion, have been proposed as potential strategies to mitigate polyuria. In addition, tolvaptan administration may be complicated by liver injury, characterized by alanine aminotransferase and bilirubin elevations. Hepatotoxicity has been suggested to be triggered by impaired biliary clearance, activation of innate immunity and increased oxidative stress. Frequent monitoring of liver function tests has been shown to be effective in preventing Hy’s Law and liver failure cases. Uric acid elevation due to reduced renal excretion may lead to hyperuricemia and gout, although no drug discontinuations have been linked to these events. Future studies should confirm the safety profile of tolvaptan in large-scale real-world studies, clarify the pathogenetic pathways leading to hepatotoxicity and define its role in special populations, especially pediatric patients.

show abstract

“…Tolvaptan slows ADPKD progression by blocking vasopressin-stimulated pathways, lowering intracellular cAMP, and inhibiting fluid secretion. In rodent models, treatment with vasopressin aggravated the development of ADPKD, while antagonism of its receptor helped preserve renal function ( Hopp et al, 2015 ; Wang et al, 2019a ). Blocking the V2R with tolvaptan can affect the extracellular signal-regulated kinase (ERK) pathway, cAMP production, and Cl − secretion ( Reif et al, 2011 ; Aihara et al, 2014 ; Kanhai et al, 2020 ).…”

Section: Available Adpkd Treatment and The Mechanisms Behind Itmentioning

confidence: 99%

Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases

et al. 2021

View full text Add to dashboard Cite

Autosomal dominant (AD) and autosomal recessive (AR) polycystic kidney diseases (PKD) are severe multisystem genetic disorders characterized with formation and uncontrolled growth of fluid-filled cysts in the kidney, the spread of which eventually leads to the loss of renal function. Currently, there are no treatments for ARPKD, and tolvaptan is the only FDA-approved drug that alleviates the symptoms of ADPKD. However, tolvaptan has only a modest effect on disease progression, and its long-term use is associated with many side effects. Therefore, there is still a pressing need to better understand the fundamental mechanisms behind PKD development. This review highlights current knowledge about the fundamental aspects of PKD development (with a focus on ADPKD) including the PC1/PC2 pathways and cilia-associated mechanisms, major molecular cascades related to metabolism, mitochondrial bioenergetics, and systemic responses (hormonal status, levels of growth factors, immune system, and microbiome) that affect its progression. In addition, we discuss new information regarding non-pharmacological therapies, such as dietary restrictions, which can potentially alleviate PKD.

show abstract

Effect of a Vasopressin V2 Receptor Antagonist on Polycystic Kidney Disease Development in a Rat Model

Cited by 21 publications

References 14 publications

<p>Silibinin Augments the Antifibrotic Effect of Valsartan Through Inactivation of TGF-β1 Signaling in Kidney</p>

<p>Silibinin Augments the Antifibrotic Effect of Valsartan Through Inactivation of TGF-β1 Signaling in Kidney</p>

Safety Profile of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease

Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases

Contact Info

Product

Resources

About