Sirolimus Produced S-Shaped Effect on Adult Polycystic Kidneys After 2-Year Treatment

Soliman, Amin R.; Zamil, S.; Lotfy, A.; Ismail, Eman I.

doi:10.1016/j.transproceed.2012.06.073

Cited by 17 publications

(19 citation statements)

References 17 publications

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“…While everolimus slowed cyst growth in ADPKD patients, this inhibition did not translate into an improvement of renal function. However, other pilot studies yielded more promising results, 101 leaving open the role of mTOR inhibition as an ADPKD target. 102,103 To determine the involvement of mTORC1 in cyst growth and ADPKD disease progression, we abrogated ciliogenesis in the thick ascending limb of Henle and distal tubular segments, generating Kif3a fl/fl*KspCre mice.…”

Section: Gerd Walzmentioning

confidence: 99%

The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees

Antignac

Calvet

Germino

et al. 2015

Journal of the American Society of Nephrology

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Polycystic kidney disease (PKD) is one of the most common life-threatening genetic diseases. Jared J. Grantham, M.D., has done more than any other individual to promote PKD research around the world. However, despite decades of investigation there is still no approved therapy for PKD in the United States. In May 2014, the University of Kansas Medical Center hosted a symposium in Kansas City honoring the occasion of Dr. Grantham's retirement and invited all the awardees of the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease to participate in a forward-thinking and interactive forum focused on future directions and innovations in PKD research. This article summarizes the contributions of the 12 Kaplan awardees and their vision for the future of PKD research.

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Section: Gerd Walzmentioning

confidence: 99%

The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees

Antignac

Calvet

Germino

et al. 2015

Journal of the American Society of Nephrology

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“…Several studies have reported that many promising drugs showed potential therapeutic effects for ADP-KD in a large number of preclinical and clinical trials (1,7,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). However, some of those in clinical trials -these promising drugs included mTOR inhibitors (55,56), somatostatin analogs (57,58), ACEI/ ARB (59,60), and tyrosine kinase inhibitor (61) -did not prevent the decline of EGFR in ADPKD patients.…”

Section: Introductionmentioning

confidence: 99%

Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD

Li¹,

Xu²,

Fan³

et al. 2018

JCI Insight

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“…Five RCTs were included in this meta-analysis [9,10,11,12,13]. These 5 studies included 619 patients with ADPKD, 314 of whom were treated with TORIs.…”

Section: Resultsmentioning

confidence: 99%

“…These 5 studies included 619 patients with ADPKD, 314 of whom were treated with TORIs. The other 303 patients were treated with placebos or conventional therapies [9,10,11,12,13]. The characteristics of the 5 included studies are listed in table 1.…”

Section: Resultsmentioning

confidence: 99%

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Long-Term Treatment with Mammalian Target of Rapamycin Inhibitor Does Not Benefit Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-Analysis

2013

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Background: The role of the mammalian target of rapamycin (mTOR) inhibition in the treatment of autosomal dominant polycystic kidney disease (ADPKD) remains unclear. This meta-analysis included all randomized controlled trials (RCTs) that used mTOR inhibitors (TORIs) to halt the progression of ADPKD. Methods: Databases including MEDLINE, EMBASE, and the Cochrane Library were searched to find relevant trials. RCTs of TORI treatment in patients with ADPKD were included. Effects on the primary outcome [total kidney volume (TKV)] and secondary outcomes [changes in cyst volume (CV) and parenchymal volume (PV), glomerular filtration rate (GFR), proteinuria, and adverse events] were analyzed. Results: The results of 5 RCTs, which included 619 patients, were analyzed. TORIs did not significantly reduce TKV [mean difference (WMD) -90.01 ml, 95% CI -235.49 to 55.47, p = 0.23; I² = 0%; p for heterogeneity = 0.67]. CV decreased after TORI treatment (WMD -15.08 ml, 95% CI -17.82 to -12.34, p < 0.00001), and PV did not change (WMD -0.55 ml, 95% CI -64.55 to 63.45, p = 0.99). There was no significant difference in GFR between the TORI-treated and control groups (WMD 4.94 ml/min, 95% CI -0.81 to 10.68, p = 0.09). Proteinuria was significantly higher in the TORI-treated group than in the control group (standard mean difference 0.27, 95% CI 0.09-0.44, p = 0.002). Conclusion: Long-term treatment with TORIs does not benefit patients with ADPKD.

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Sirolimus Produced S-Shaped Effect on Adult Polycystic Kidneys After 2-Year Treatment

Cited by 17 publications

References 17 publications

The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees

The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees

Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD

Long-Term Treatment with Mammalian Target of Rapamycin Inhibitor Does Not Benefit Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-Analysis

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