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

Abstract

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.

Safety Profile of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease

“…In addition, ADPKD is linked to several extrarenal manifestations, especially liver cysts and intracranial aneurysms. 4 Importantly, the majority of patients develop hypertension and endothelial dysfunction, 5 leading to high rates of cardiovascular morbidity and mortality. 6 …”

miRNA-16 as a predictive factor for intracranial aneurysms in autosomal dominant polycystic kidney disease

“…miR-16 is expressed by vascular endothelial cells and is involved in angiogenesis [8]. While the function of endothelial cells is disturbed in ADPKD [10], it seemed desirable to verify the results of Li et al [8] in ADPKD patients.…”

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes

“…In ADPKD, the uncontrolled growth of renal cysts increases renal volume and the destruction of the parenchyma progressively, resulting in renal failure in most patients [ 41 ]. In addition, endothelial dysfunction which occurs very early in the course of the disease appears to be involved in increased oxidative stress and inflammation [ 42 , 43 ]. Then, the progression of ADPKD is highly variable, in part because of the gene affected [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ], as well as the presence of other variants modifying its effect.…”