Metabolic abnormalities in autosomal dominant polycystic kidney disease

Mao, Zhiguo; Xie, Guoqiang; Ong, Albert

doi:10.1093/ndt/gfu044

Cited by 41 publications

(26 citation statements)

References 67 publications

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“…Currently, the link between polycystin function and insulin resistance, in ADPKD patients with preserved renal function, is still poorly known [41], even if recently Mao et al . [42] showed that polycystin proteins could regulate insulin secretion, being expressed in pancreatic islet beta cells. Other significant metabolic alterations were observed in ADPKD patients in our study, like higher Hcy and SUA respect to control group.…”

Section: Discussionmentioning

confidence: 99%

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Lai

Mastroluca

Matino

et al. 2017

Kidney Blood Press Res

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Background/Aims: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. Methods: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O₂ uptake (V’O₂max), and O₂ uptake at lactic acid threshold (V’O₂@LT). Results: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V’O₂max, V’O₂max/Kg and V’O₂max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V’O₂@LT, V’O₂ @LT%, V’O₂@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). Conclusion: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

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Section: Discussionmentioning

confidence: 99%

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Lai

Mastroluca

Matino

et al. 2017

Kidney Blood Press Res

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“…Hence, it was of extreme interest to the field of ADPKD when a similar high rate of aerobic glycolysis and glucose dependence was identified in ADPKD kidney tissue and relevant mouse models [56, 103, 104]. Mechanistic analyses indicated that the defect represented inhibition of LKB1/AMPK signalling, coupled with strongly elevated levels of mTORC1.…”

Section: Adpkd and The Hallmarks Of Cancermentioning

confidence: 99%

The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease

et al. 2015

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Autosomal dominant polycystic kidney disease (ADPKD) is a progressive inherited disorder in which renal tissue is gradually replaced with fluid-filled cysts, giving rise to chronic kidney disease (CKD) and progressive loss of renal function. ADPKD is also associated with liver ductal cysts, hypertension, chronic pain and extrarenal problems such as cerebral aneurysms. Intriguingly, improved understanding of the signalling and pathological derangements characteristic of ADPKD has revealed marked similarities to those of solid tumours, even though the gross presentation of tumours and the greater morbidity and mortality associated with tumour invasion and metastasis would initially suggest an entirely different disease processes. The commonalities between ADPKD and cancer are provocative, particularly in the context of recent preclinical and clinical studies of ADPKD that have shown promise with drugs that were originally developed for cancer. The potential therapeutic benefit of such repurposing has led us to review in detail the pathological features of ADPKD through the lens of the defined, classic hallmarks of cancer. In addition, we have evaluated features typical of ADPKD, and determined whether evidence supports the presence of such features in cancer cells. This analysis, which places pathological processes in the context of defined signalling pathways and approved signalling inhibitors, highlights potential avenues for further research and therapeutic exploitation in both diseases.

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“…The later cyst expansion is caused by enhanced epithelial cell proliferation, fluid secretion, detachment from the original tubular structure, abnormal extracellular matrix, altered gene expression and cell polarity, inflammation, increased apoptosis and environmental factors [4,6,7]. Cyst formation also occurs in the liver, pancreas and spleen; intracranial aneurysms and cardiac valve defects may be present as well [8].…”

Section: Introductionmentioning

confidence: 99%

An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease

Santoro

Pellicanò

Visconti

et al. 2015

Expert Opinion on Investigational Drugs

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Among the drugs currently being explored, mammalian target of rapamycin inhibitors reduce kidney volume enlargement but their role remains uncertain. The most promising drug is the V2 receptor antagonist tolvaptan, which reduces the increased rate of total kidney volume and slows down glomerular filtration rate decline. The main candidates for the treatment of cysts growth, both in the kidney and in the liver whenever present, are the somatostatin analogues, such as lanreotide and octreotide and more recently pasireotide. As for other therapies, some favorable results have been achieved but data are still not sufficient to establish if these approaches may be beneficial in slowing ADPKD progression in the future.

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Metabolic abnormalities in autosomal dominant polycystic kidney disease

Cited by 41 publications

References 67 publications

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease

An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease

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