Retarding Progression of Chronic Kidney Disease in Autosomal Dominant Polycystic Kidney Disease with Metformin and Other Therapies: An Update of New Insights

Carullo, Nazareno; Zicarelli, Maria Teresa; Casarella, Alessandro; Nicotera, Ramona; Castagna, Alberto; Urso, Alessandra; Presta, Pierangela; Andreucci, Michele; Russo, Emilio; Bolignano, Davide; Coppolino, Giuseppe

doi:10.2147/ijgm.s305491

Cited by 3 publications

(3 citation statements)

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“…Metformin is a novel and attractive therapeutic candidate for ADPKD. Metformin inhibits the mTOR and CFTR pathways and activates AMPK, which has been associated with reduced renal cyst growth in an ADPKD mouse model ( Takiar et al, 2011 ; Carullo et al, 2021 ; Pastor-Soler et al, 2022 ). In the present analysis, metformin also showed a favorable trend, but it was not significant, possibly because of a small sample size.…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy of Pharmacological Treatments for Adults With Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

et al. 2022

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Background: Tolvaptan is the gold standard treatment for autosomal dominant polycystic kidney disease (ADPKD), while several other drugs have the potential to inhibit the progression of ADPKD. However, individual clinical trials may not show sufficient differences in clinical efficacy due to small sample sizes. Furthermore, the differences in therapeutic efficacy among drugs are unclear. Herein, we investigated the effect of the ADPKD treatments.Methods: We systematically searched PubMed, Medline, EMBASE, and the Cochrane Library through January 2022 to identify randomized controlled trials in ADPKD patients that compared the effects of treatments with placebo or conventional therapy. A network meta-analysis was performed to compare the treatments indirectly. The primary outcomes were changes in kidney function and the rate of total kidney volume (TKV) growth.Results: Sixteen studies were selected with a total of 4,391 patients. Tolvaptan significantly preserved kidney function and inhibited TKV growth compared to the placebo {standardized mean difference (SMD) [95% confidence interval (CI)]: 0.24 (0.16; 0.31) and MD: −2.70 (−3.10; −2.30), respectively}. Tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors inhibited TKV growth compared to the placebo; somatostatin analogs significantly inhibited TKV growth compared to the placebo and tolvaptan [MD: −5.69 (−7.34; −4.03) and MD: −2.99 (−4.69; −1.29), respectively]. Metformin tended to preserve renal function, although it was not significant [SMD: 0.28 (−0.05; 0.61), p = 0.09].Conclusion: The therapeutic effect of tolvaptan was reasonable as the gold standard for ADPKD treatment, while somatostatin analogs also showed notable efficacy in inhibiting TKV growth.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022300814.

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Section: Discussionmentioning

confidence: 99%

Comparative Efficacy of Pharmacological Treatments for Adults With Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

et al. 2022

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“…Another drug that can enhance autophagic flux is metformin. This agent is mainly used to treat type 2 diabetes mellitus, but it can also activate AMPK, the master inducer of autophagy [100,101]. Experimental studies showed that metformin may prevent the progression of cysts and protect kidney function [102].…”

Section: Autophagy Regulators In Adpkdmentioning

confidence: 99%

Autosomal Dominant Polycystic Kidney Disease: Is There a Role for Autophagy?

Ponticelli,

Moroni,

Reggiani

2023

IJMS

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Autosomal-Dominant Polycystic Kidney Disease (ADPKD) is a monogenic disorder initiated by mutations in either PKD1 or PKD2 genes, responsible for encoding polycystin 1 and polycystin 2, respectively. These proteins are primarily located within the primary cilia. The disease follows an inexorable progression, leading most patients to severe renal failure around the age of 50, and extra-renal complications are frequent. A cure for ADPKD remains elusive, but some measures can be employed to manage symptoms and slow cyst growth. Tolvaptan, a vasopressin V2 receptor antagonist, is the only drug that has been proven to attenuate ADPKD progression. Recently, autophagy, a cellular recycling system that facilitates the breakdown and reuse of aged or damaged cellular components, has emerged as a potential contributor to the pathogenesis of ADPKD. However, the precise role of autophagy in ADPKD remains a subject of investigation, displaying a potentially twofold impact. On the one hand, impaired autophagy may promote cyst formation by inducing apoptosis, while on the other hand, excessive autophagy may lead to fibrosis through epithelial to mesenchymal transition. Promising results of autophagy inducers have been observed in preclinical studies. Clinical trials are warranted to thoroughly assess the long-term safety and efficacy of a combination of autophagy inducers with metabolic and/or aquaferetic drugs. This research aims to shed light on the complex involvement of autophagy in ADPKD, explore the regulation of autophagy in disease progression, and highlight the potential of combination therapies as a promising avenue for future investigations.

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“…Su indicación debe acompañarse del conjunto de medidas no específicas dirigidas a enlentecer la progresión de la ERC (20) . Junto con la búsqueda de estrategias para minimizar los efectos adversos del tratamiento con tolvaptán (21) , un conjunto de nuevos fármacos se encuentran en desarrollo y evaluación con el fin de constituirse en tratamientos específicos dirigidos a enlentecer la progresión de la ERC en pacientes con PQRAD (22)(23)(24)(25)(26)(27) .…”

Section: Conclusiones Y Perspectivasunclassified

Poliquistosis renal autosómica dominante: ¿quiénes se benefician del tratamiento con tolvaptán? Estado del arte

2022

RMU

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Retarding Progression of Chronic Kidney Disease in Autosomal Dominant Polycystic Kidney Disease with Metformin and Other Therapies: An Update of New Insights

Cited by 3 publications

References 80 publications

Comparative Efficacy of Pharmacological Treatments for Adults With Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Comparative Efficacy of Pharmacological Treatments for Adults With Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Autosomal Dominant Polycystic Kidney Disease: Is There a Role for Autophagy?

Poliquistosis renal autosómica dominante: ¿quiénes se benefician del tratamiento con tolvaptán? Estado del arte

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