Metabolic Syndrome Components in Patients with Autosomal-Dominant Polycystic Kidney Disease

Pietrzak-Nowacka, Maria; Safranow, Krzysztof; Byra, Elżbieta; Bińczak-Kuleta, Agnieszka; Ciechanowicz, Andrzej; Ciechanowski, Kazimierz

doi:10.1159/000260042

Cited by 19 publications

(14 citation statements)

References 48 publications

(27 reference statements)

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“…ADPKD patients, like the general population, are at risk of developing diabetes due to increased body mass indexes (34). In addition, ADPKD patients have higher fasting blood glucose levels and a trend toward higher hemoglobin A1c levels than healthy controls (28). A recent study found that total renal volume was approximately doubled in ADPKD patients with type 2 diabetes compared with matched patients with ADPKD alone (31).…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage

Sas

Yin

Fitzgibbon

et al. 2015

American Journal of Physiology-Renal Physiology

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in the absence of cilia accelerates cystogenesis and induces renal damage. Am J Physiol Renal Physiol 309: F79 -F87, 2015. First published April 22, 2015 doi:10.1152/ajprenal.00652.2014.-In polycystic kidney disease (PKD), the rate of cyst formation and disease progression is highly variable. The lack of predictability in disease progression may be due to additional environmental factors or pathophysiological processes called "third hits." Diabetes is a growing epidemic, and recent studies suggest that PKD patients may be at an increased risk for this disease. We sought to determine if hyperglycemia enhances the initiation and rate of cystogenesis. Tamoxifen was administered to adult Ift88 conditional floxed allele mice to induce cilia loss in the presence of Cre. Subsequent administration of streptozotocin resulted in equivalent hyperglycemia in cilia ϩ and cilia Ϫ mice. Hyperglycemia with loss of cilia increased the rate of cyst formation and cell proliferation. Structural and functional alterations in the kidney, including focal glomerular foot process effacement, interstitial inflammation, formation of primitive renal tubules, polyuria, and increased proteinuria, were also observed in hyperglycemic cilia Ϫ mice. Gene array analysis indicated enhanced Wnt and epithelial-to-mesenchymal transition signaling in the kidney of hyperglycemic cilia Ϫ mice. These data show that hyperglycemia, in the absence of cilia, results in renal structural and functional damage and accelerates cystogenesis, suggesting that diabetes is a risk factor in the progression of PKD. polycystic kidney disease; diabetes; streptozotocin; Wnt; epithelialto-mesenchymal transition POLYCYSTIC KIDNEY DISEASE (PKD) is a relatively common inherited genetic disorder that ultimately leads to a high rate of renal failure. In human autosomal-dominant or autosomalrecessive PKD, one copy of the gene pkd1, pkd2, or pkhd1 is mutated at conception. It is thought that, over time, a second somatic mutation, referred to as the "second hit," occurs in a small number of renal epithelial cells and results in the development of renal cysts (25,39). Recently, the concept of a "third hit" has emerged; the third-hit hypothesis suggests that additional elements, such as environmental factors or pathophysiological conditions, can contribute to the rate of cyst initiation and progression (12,21,37). This hypothesis helps explain the wide variations in disease progression, especially within affected families.It is well established that PKD is a ciliopathic disorder. Nearly all the protein products of the genes involved in human cyst formation are located within the cilium-centrosome complex (36). In addition, these proteins are necessary for proper cilia function. Germline deletion of cystogenes or cilia [through inhibition of intraflagellar transport (IFT)] is usually embryonic-lethal. Establishment of the conditional floxed allele mouse, in which the cystoproteins or IFT proteins can be deleted at any time, was crucial to the advent of the third-hit theory. While de...

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage

Sas

Yin

Fitzgibbon

et al. 2015

American Journal of Physiology-Renal Physiology

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“…Beyond hypertension, other metabolic abnormalities have also been reported to occur more frequently in ADPKD patients relative to a healthy control population, resulting in coronary artery disease [22]. Several articles have reported that ADPKD patients exhibit an increased incidence of post-transplant diabetes mellitus or new-onset diabetes after transplantation [23-25], indicating that an increased diabetogenic state arises due to ADPKD itself.…”

Section: Discussionmentioning

confidence: 99%

Clinical Manifestation, Management and Prognosis of Acute Myocardial Infarction in Autosomal Dominant Polycystic Kidney Disease

Yang

Wang

et al. 2018

Kidney Blood Press Res

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Background/Aims: Cardiovascular complications are the most common cause of death in individuals with autosomal dominant polycystic kidney disease (ADPKD), yet there is no substantial data concerning the clinical characteristics of acute myocardial infarction (AMI) in this population. This study thus aimed to investigate AMI in persons with ADPKD. Methods: A retrospective analysis of ADPKD patients admitted to our hospital over a 13 year period was conducted. Age and gender-matched control patients without ADPKD were also selected at a ratio of 1: 10. Results: A total of 52 ADPKD and 520 non-ADPKD patients were enrolled in the present study, with those in the former group exhibiting significantly poorer kidney function. The distribution of AMI types differed significantly between these two groups. The incidence of ST-segment elevation myocardial infarction (STEMI) was higher (75.0%) and the incidence of non-ST segment elevation myocardial infarction (NSTEMI) was lower (25.0%) in the ADPKD group. At the onset of AMI, sudden cardiac death (SCD) was more common in ADPKD patients (11.5% vs. 4.6%). In terms of risk factors, the occurrence of hypertension was greater in ADPKD patients (78.8% vs. 39.6%). With regard to subsequent management, ADPKD patients had a higher prevalence of triple-branch coronary lesions (21.1% vs. 11.2%), undergoing more coronary artery bypass grafting (CABG) (7.7% vs. 5.4%) and fewer percutaneous coronary interventions (PCI) (73.1% vs. 84.6%). Overall, ADPKD patients had higher rates of mortality (13.5% vs. 6.2%). Conclusion: ADPKD patients with AMI suffer from more severe conditions and difficult therapies, resulting in a poorer prognosis.

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“…In a separate, small case-control study in subjects with preserved renal function, the presence of ADPKD was associated with components of metabolic syndrome such as hypertension, abdominal obesity, and higher fasting glycemia [44] . Markers of vasopressin concentration were not studied.…”

Section: Other (Lifestyle) Factorsmentioning

confidence: 93%

Polycystic Kidney Disease and the Vasopressin Pathway

Gastel

Torres

2017

Ann Nutr Metab

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Vasopressin, also known as arginine vasopressin or antidiuretic hormone, plays a pivotal role in maintaining body homeostasis. Increased vasopressin concentrations, measured by its surrogate copeptin, have been associated with disease severity as well as disease progression in polycystic kidney disease (PKD), and in experimental studies vasopressin has been shown to directly regulate cyst growth. Blocking vasopressin effects on the kidney via the vasopressin V2-receptor and lower circulating vasopressin concentration are potential treatment opportunities that have been the subject of study in PKD in recent years. Treatment with vasopressin V2-receptor antagonist tolvaptan has been shown to inhibit disease progression in experimental studies, as well as in a large randomized controlled trial involving 1,445 patients with autosomal dominant PKD, lowering total kidney volume growth from 5.5 to 2.8%, and the slope of the reciprocal of the serum creatinine level from -3.81 to -2.61 mg per mL^-1/year. Alternatively, lowering circulating vasopressin could delay disease progression. Vasopressin is secreted in response to an increased plasma osmolality, which in turn is caused by a low fluid or high osmolar intake. Other lifestyle factors, like smoking, increase vasopressin concentration. Here, we provide a comprehensive review of the physiology as well as pathophysiology of vasopressin in PKD, the promising effects of tolvaptan treatment, and potential synergistic or additive treatments in combination with tolvaptan. In this study, we also review current evidence regarding the effect of influencing disease progression in PKD by lifestyle changes, especially by fluid intake.

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Metabolic Syndrome Components in Patients with Autosomal-Dominant Polycystic Kidney Disease

Cited by 19 publications

References 48 publications

Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage

Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage

Clinical Manifestation, Management and Prognosis of Acute Myocardial Infarction in Autosomal Dominant Polycystic Kidney Disease

Polycystic Kidney Disease and the Vasopressin Pathway

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