Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta‐analysis of randomized trials

Myint, Thida; Rangan, Gopi; Webster, Angela C

doi:10.1111/nep.12211

Cited by 24 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using MRI-determined increases in kidney volume as a marker of disease progression, rapamycin-based regimens showed significantly reduced cystic kidney volumes when compared to alternative treatments [190,195,196]. Clinical trials using rapamycin to treat ADPKD have however produced varied results [197,198,199], though they may have been impeded by small sample size, reliance on poor markers of clinical progression, short follow up time for such a slow-progressing disease, and insufficient rapamycin doses [200]. …”

Section: Ageing and Age-related Pathologies Amenable To Treatment mentioning

confidence: 99%

mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

Walters

Cox

2018

IJMS

View full text Add to dashboard Cite

Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing, and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR (mechanistic target of rapamycin) is a regulatory nexus that is heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

show abstract

Section: Ageing and Age-related Pathologies Amenable To Treatment mentioning

confidence: 99%

mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

Walters

Cox

2018

IJMS

View full text Add to dashboard Cite

show abstract

“…A recent meta-analysis confirmed the efficacy of SST analogues in reducing the progressive increase of TKV, on average with a reduction of 9% compared with the growth observed in patients treated with placebo or conventional therapies. However, treatment with SST analogues did not demonstrate significant effects on the eGFR (80). Based on these studies, in August 2015, European Medicines Agency (EMA) attributed to lanreotide the Orphan Drug designation for the treatment of ADPKD.…”

Section: Somatostatin Analoguesmentioning

confidence: 99%

Novel Therapeutic Strategies Targeting Molecular Pathways of Cystogenesis in Autosomal Polycystic Kidney Disease

Salvadori

Tsalouchos

2017

jrenhep

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease that results from mutations in PKD1 or PKD2. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells that destroy the architecture of the renal parenchyma and lead to kidney failure. Until recently, the causes and the molecular pathways that lead to cystogenesis remained obscure. In the last decade, enormous progress has been made in understanding the pathogenesis of ADPKD and the development of new therapies. The purpose of this review is to update on the promising therapies that are being developed and tested based on knowledge of recent advances in molecular and cellular targets involved in cystogenesis.

show abstract

“…A single trial (n ¼ 41) of eicosapentaenoic acid did not alter the progression of either total kidney volume or renal dysfunction. 49 Adverse events were significant for interventions in all trials compared to placebo. These data suggested that somatostatin analogues and AVP receptor antagonists attenuate total kidney volume increase.…”

Section: V2 Receptor Inhibitorsmentioning

confidence: 99%

“…These data suggested that somatostatin analogues and AVP receptor antagonists attenuate total kidney volume increase. 49 …”

Section: V2 Receptor Inhibitorsmentioning

confidence: 99%

“…48 Tolvaptan, as compared with placebo, slowed the increase in total kidney volume and the decline in kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events including aquaresis and hepatic adverse events unrelated to ADPKD. 48 Recently Myint et al 49 performed a meta-analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume and renal function in ADPKD. Eleven trials (2262 patients) were included.…”

Section: V2 Receptor Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

New options in the treatment of autosomal dominant polycystic kidney disease

Kazancıoğlu

Gürsu

2015

Renal Failure

View full text Add to dashboard Cite

Autosomal dominant polycystic disease (ADPKD) is one of the most common monogenic disorders, and globally is among the most common hereditary causes of end stage kidney disease. Until recently, the causes of this disease remained obscure. However, in the past decade there have been enormous advances in the understanding of the pathophysiology and genetics of this condition, and recent studies have suggested the possibility of specific treatment for slowing cyst growth. This review will focus on the new options for the control of ADPKD.

show abstract

Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta‐analysis of randomized trials

Cited by 24 publications

References 40 publications

mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

Novel Therapeutic Strategies Targeting Molecular Pathways of Cystogenesis in Autosomal Polycystic Kidney Disease

New options in the treatment of autosomal dominant polycystic kidney disease

Contact Info

Product

Resources

About