Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Lai, Silvia; Mastroluca, Daniela; Matino, Silvia; Panebianco, Valeria; Vitarelli, Antonio; Capotosto, Lidia; Turinese, Irene; Marinelli, Paolo; Rossetti, M.; Galani, Alessandro; Baiocchi, P; D’Angelo, Anna; Palange, Paolo

doi:10.1159/000486011

Cited by 19 publications

(13 citation statements)

References 59 publications

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“…Pathologic rates of ABI values were lower in patients with ADPKD than in CKDoe, and similar to controls without CKD. A previous study showed a normal ABI value in patients with ADPKD with an eGFR > 60 mL/min [30].…”

Section: Discussionmentioning

confidence: 87%

Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease

et al. 2021

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Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease. There is an increased rate of cardiovascular disease (CVD) in ADPKD. In this study, we evaluate the prevalence of cardiovascular risk factors, the achievement rates for treatment goals and cardiovascular events (CVE) in ADPKD and their relations with asymptomatic CVD in CKD from other etiologies (CKDoe) and controls. Methods We evaluated 2445 CKD patients (2010–2012). The information collected was: clinical, anthropometric and analytical parameters, treatments and CVD evaluation (intima-media thickness (IMT), atheromatous plaque presence and ankle-brachial index (ABI)). Laboratory, vital status, CVE and hospitalizations were collected for 4 years. Results ADPKD patients had a worse renal function and worst achievement of blood pressure, higher parathormone levels but lower proteinuria compared to CKDoe. ADPKD patients presented lower IMT values than other groups, however, an intermediate rate of pathologic ABI and atheromatous plaque was present. More than half of the patients received statins, achieving LDL-c levels < 100 only in 50 and 39.8% of them (ADPKD and CKDoe respectively). The number of CVE during the follow-up period was low. In adjusted Cox regression model, ADPDK had the lowest occurrence of CVE of all three groups (HR:0.422, 95%CI 0.221–0.808, p = 0.009). Conclusion ADPKD patients show intermediate control rates of CVD. A better control of CVD risk seems to be related with a lower load of CVD compared to other groups, which may lead in the long term to a better prognosis. Further investigation is necessary to determine cardiovascular prognosis in ADPKD.

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Section: Discussionmentioning

confidence: 87%

Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease

et al. 2021

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“…Subsequently, five studies were excluded as two of them did not contain a control group, 29,30 two studies used different procedures for the evaluation of vascular stiffness 31,32 (ie nitroglycerin‐induced dilatation, hand skin heating test) while one article 33 represented a partial duplicate of a study that was already included in the present review. As a result, a total of 27 studies 34‐60 were included, comprising 1967 individuals (1141 ADPKD patients and 826 healthy controls).…”

Section: Resultsmentioning

confidence: 99%

Markers of endothelial dysfunction and arterial stiffness in patients with early‐stage autosomal dominant polycystic kidney disease: A meta‐analysis

2020

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Objectives Autosomal dominant polycystic kidney disease (ADPKD) is characterised by increased rates of cardiovascular complications leading to significant morbidity and mortality. This meta‐analysis aims to evaluate whether the disease is linked to endothelial dysfunction and arterial stiffness during its early stages. Methods Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov and Google Scholar databases comparing ADPKD patients with preserved renal function to healthy controls were included. The outcomes of interest were brachial flow‐mediated dilatation, carotid‐femoral pulse wave velocity, augmentation index, carotid intima‐media thickness and central systolic blood pressure, plasma ADMA or homocysteine levels. Standardised mean differences (SMDs) were estimated by a random‐effects model in R‐3.6.3. Results A total of 27 studies were included, comprising 1967 individuals. ADPKD was linked to significantly lower flow‐mediated dilatation (SMD: −1.44, 95% CI: [−2.35, −0.53]) and higher pulse wave velocity (SMD: 1.44, 95% CI: [0.22, 2.66]) and carotid intima‐media thickness (SMD: 1.02, 95% CI: [0.57, 1.47]). No significant associations were noted regarding augmentation index (SMD: 0.62, 95% CI: [−0.19, 1.43]) and central systolic blood pressure (SMD: 1.84, 95% CI: [−0.12, 3.80]). Plasma homocysteine was significantly higher in ADPKD (SMD: 0.81, 95% CI: [0.16, 1.45]), while no difference was calculated for ADMA levels (SMD: 1.14, 95% CI: [−0.25, 2.53]). Conclusions Early‐stage ADPKD patients present increased vascular stiffness and endothelial dysfunction, as reflected by low flow‐mediated dilatation and elevated values of pulse wave velocity, carotid intima‐media thickness and plasma homocysteine. The exact effects of early arterial stiffness on long‐term outcomes remain to be elucidated.

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“…Higher baseline serum uric acid in ADPKD patients has also been retrospectively associated with a high risk of ESRD [40] and uric acid is increased in the urine of a juvenile cystic mouse model [37]. One study found an association between increased serum uric acid and decreased creatinine clearance rate in ADPKD, without any evidence of increased uric acid production [41], a second study found ADPKD patients had a higher incidence of hyperuricemia than patients with CKD or normal renal function despite all groups having normal rates of uric acid excretion [29] and a third study found ADPKD patients with normal renal function had elevated serum uric acid [42]. Neither study found evidence of increased uric acid synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…A comparison between ADPKD with normal kidney function and healthy patients found only 3 components of metabolic syndrome were increased in ADPKD patients, namely hypertension, fasting glycemia and abdominal obesity [47]. A different study of young ADPKD patients with normal renal function found increased insulin resistance, inflammation and low density lipoprotein (LDL) in ADPKD [42]. A study in Southern India found ADPKD patients of a wide variety of ages had moderately increased plasma triglycerides, LDL and very low density lipoprotein (VLDL), and a ~ 50% reduction in high density lipoprotein (HDL) compared to healthy controls [48].…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course

et al. 2019

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Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by gradual cyst growth and expansion, increase in kidney volume with an ultimate decline in kidney function leading to end stage renal disease (ESRD). Given the decades long period of stable kidney function while cyst growth occurs, it is important to identify those patients who will progress to ESRD. Recent data from our and other laboratories have demonstrated that metabolic reprogramming may play a key role in cystic epithelial proliferation resulting in cyst growth in ADPKD. Height corrected total kidney volume (ht-TKV) accurately reflects cyst burden and predicts future loss of kidney function. We hypothesize that specific plasma metabolites will correlate with eGFR and ht-TKV early in ADPKD, both predictors of disease progression, potentially indicative of early physiologic derangements of renal disease severity. Methods To investigate the predictive role of plasma metabolites on eGFR and/or ht-TKV, we used a non-targeted GC-TOF/MS-based metabolomics approach on hypertensive ADPKD patients in the early course of their disease. Patient data was obtained from the HALT-A randomized clinical trial at baseline including estimated glomerular filtration rate (eGFR) and measured ht-TKV. To identify individual metabolites whose intensities are significantly correlated with eGFR and ht-TKV, association analyses were performed using linear regression with each metabolite signal level as the primary predictor variable and baseline eGFR and ht-TKV as the continuous outcomes of interest, while adjusting for covariates. Significance was determined by Storey’s false discovery rate (FDR) q-values to correct for multiple testing. Results Twelve metabolites significantly correlated with eGFR and two triglycerides significantly correlated with baseline ht-TKV at FDR q-value < 0.05. Specific significant metabolites, including pseudo-uridine, indole-3-lactate, uric acid, isothreonic acid, and creatinine, have been previously shown to accumulate in plasma and/or urine in both diabetic and cystic renal diseases with advanced renal insufficiency. Conclusions This study identifies metabolic derangements in early ADPKD which may be prognostic for ADPKD disease progression. Clinical trial HALT Progression of Polycystic Kidney Disease (HALT PKD) Study A; Clinical www.clinicaltrials.gov identifier: NCT00283686; first posted January 30, 2006, last update posted March 19, 2015. Electronic supplementary material The online version of this article (10.1186/s12882-019-1249-6) contains supplementary material, which is available to authorized users.

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Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Cited by 19 publications

References 59 publications

Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease

Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease

Markers of endothelial dysfunction and arterial stiffness in patients with early‐stage autosomal dominant polycystic kidney disease: A meta‐analysis

Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course

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