Victoria Socha

DocwireNews

Researchers recently reported studies on autosomal-dominant polycystic disease (ADPKD). ADPKD is among the most common genetic diseases that lead to chronic kidney disease and end-stage renal disease (ESRD).The three recent studies examined: (1) the potential long-term effect of tolvaptan in slowing progression to ESRD; (2) the unexpected potential of a new treatment approach using a class of agents not currently used in ADPKD; and (3) an effective treatment for ADPKD-related hepatomegaly.<h2>Long-term Benefits of Tolvaptan</h2>The tolvaptan study was reported by Hayley Bennett, PhD, and colleagues in BMC Nephrology. The researchers sought to examine the efficacy and safety of the selective vasopressin V2 antagonist over time. Using the ADPKD Outcomes Model, a validated construct that can stimulate disease progression &ldquo;over a lifetime horizon&rdquo; and estimate the incidence of long-term clinical outcomes, the study found that tolvaptan would be predicted to delay the mean age of ESRD onset by 5 years compared with the natural course of disease progression. The estimated delay was highest in patients with CKD stage 1 (6.6 years) compared with the CKD 2 subgroup (4.7 years) and the CKD 3 subgroup (2.7 years).Dr. Bennett said, &ldquo;Despite limitations with regards to the generalization of the results to all ADPKD patients, the data from this study highlight the potential value of early intervention and long-term treatment with tolvaptan, which may alleviate the economic and societal costs of providing care to ADPKD patients who progress to ESRD.&rdquo;<a href="https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-019-1290-5">https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-019-1290-5&nbsp;</a><h2>Unexpected Role of Dopamine Receptor Antagonists</h2>Researchers, led by Parama Paul, PhD, screened an FDA-approved compound library for drugs that promote nuclear export of histone deacetylase 5 (HDAC5) they believed would indicate therapeutic potential for treating ADPKD. Unexpectedly, domperidone and loxapine succinate, dopamine receptor antagonists, were potent promoters of HDAC5 export in renal cells. Further, domperidone slowed growth of cysts, reduced the number of cysts, and increased body weight and activity in a mouse model of ADPKD. The findings were reported in PlosOne.The researchers said, &ldquo;These results suggest that HDAC5 nucleocytoplasmic shuttling may be modulated to impede disease progression in ADPKD, and uncovers an unexpected role for a class of dopamine receptors in renal epithelial morphogenesis.&rdquo;<a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216220">https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216220</a><h2>Lanreotide Reduces Liver Volume Growth</h2>In addition to the kidney, ADPKD affects the liver; more than 80% of patients develop hepatic cysts. While many patients remain asymptomatic, there are no available treatments to ameliorate hepatomegaly-related pain, shortness of breath, and other symptoms. Researchers in The Netherlands, led by Ren&eacute; M M van Aerts, MD, published results of a study showing that, compared with standard care, patients with ADPKD with large livers had significantly reduced liver volume growth after 120 weeks of treatment with lanreotide; the benefit persisted at least 4 months following treatment cessation. Study results were reported in Gastroenterology.The researchers said, &ldquo;Lanreotide not only reduces liver volume by 5.9%, but it also attenuates&nbsp; growth in kidney volume, resulting in a 7.2% reduction of combined liver and kidney volume compared with the standard of care.&rdquo;<a href="https://www.gastrojournal.org/article/S0016-5085(19)36711-3/abstract">https://www.gastrojournal.org/article/S0016-5085(19)36711-3/abstract</a>

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ADPKD: Three Studies Provide New Insights

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Researchers recently reported studies on autosomal-dominant polycystic disease (ADPKD). ADPKD is among the most common genetic diseases 

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