Background/Aims: Early onset of hypertension and its consequences account for the great majority of deaths in patients with autosomal dominant polycystic kidney disease (ADPKD). Renin-angiotensin system (RAS) components have been shown in ADPKD kidneys independent of systemic RAS. Thus, we examined the urinary angiotensinogen (UAGT) levels as a biomarker of intrarenal RAS status in ADPKD patients with/without hypertension and healthy subjects. Methods: Eighty-four ADPKD patients (43 with hypertension and 41 without hypertension) and 40 healthy controls were studied cross-sectionally. Patients with glomerular filtration rate <60 ml/min were excluded from the study. Hypertension was diagnosed with ambulatory blood pressure monitoring. Urinary and plasma concentration of angiotensinogen, spot urine microprotein and creatinine (UCre) levels were recorded for each participant. Results: UAGT/UCre levels were higher in hypertensive ADPKD patients (23.7 ± 8.4) compared with normotensive ADPKD patients (16.6 ± 5.2) and healthy controls (6.9 ± 3.3; p < 0.001). In univariate analysis, UAGT correlated with systolic blood pressure, diastolic blood pressure (DBP) and proteinuria. The independence of these correlations was analyzed in a regression model, and UAGT was shown to be significantly predicted by proteinuria and DBP. Conclusion: Intrarenal RAS activation which is monitored by UAGT levels clinically may be a harbinger of hypertension and kidney disease in ADPKD patients.

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD. Eighty ADPKD patients (44.6 ± 12.7 years, 40% female, 65% hypertensive) and 50 healthy subjects (HS; 45.4 ± 12.7, 44% female) were enrolled in the study. Serum levels of 384 miRs were determined by Biomark Real Time PCR. Groups were compared using the limma method with multiple-testing correction as proposed by Smyth (corrected p < 0.01 considered significant). Comparing ADPKD to HS, we found significant differences in blood levels of 18 miRs (3 more and 15 less abundant). Of these, miR-3907, miR-92a-3p, miR-25-3p and miR-21-5p all rose while miR-1587 and miR-3911 decreased as renal function declined in both cross-sectional and longitudinal analysis. Using ROC analysis, an increased baseline miR-3907 in the circulation predicted a > 10% loss of GFR over the following 12 months (cut-off >2.2 AU, sensitivity 83%, specificity 78%, area 0.872 [95% CI: 0.790–0.953, p < 0.001]). Adjusting for age and starting CKD stage using multiple binary logistic regression analysis did not abrogate the predictive value. Increased copy numbers of miR-3907 in the circulation may predict ADPKD progression and suggest pathophysiological pathways worthy of further study.

Cardiovascular disease (CVD) is the main cause of mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Prior to hypertension early vascular changes and inflammation have been reported. We aimed to investigate long pentraxin 3 (PTX-3), which has been recently described as a biomarker of inflammation, and its relation with endothelial dysfunction in early ADPKD patients. Twenty-five ADPKD patients without hypertension and 25 healthy controls were studied cross-sectionally. Hypertension was diagnosed with ambulatory blood pressure monitoring. Plasma concentrations of PTX-3 and proteinuria levels were obtained from each participant. Endothelial dysfunction was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). PTX-3 levels were higher in ADPKD patients compared to healthy controls (4.2 [1.2–10.1] vs. 1.4 [0.4–3.1] ng/ml, p < 0.001). Additionally, C-reactive protein (CRP) and proteinuria levels were higher in ADPKD patients than in healthy subjects. In the whole cohort, PTX-3 correlated negatively with FMD (r: −0.58, p < 0.001) and positively with proteinuria (r: 0.56, p < 0.001) and uric acid (r: 0.57, p < 0.001). In all subjects, FMD was independently predicted by PTX-3, but not by uric acid, CRP or proteinuria. PTX-3 may be a better biomarker of inflammation than CRP to predict endothelial dysfunction in normotensive ADPKD patients with well-preserved kidney function. Hence, inflammation which is demonstrated by PTX-3 may potentially be used to predict future CVD in this population.

Background/Aims: Early occurrence of hypertension is the prominent feature of autosomal dominant polycystic kidney disease (ADPKD). The role of angiotensin-converting enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism in the clinical course of ADPKD is not well understood. However, data about the expression of these genes are lacking. Thus, we aimed to investigate the polymorphisms and expressions of both the ACE and eNOS genes that affect hypertension in ADPKD. Methods: Whole blood samples were obtained from all participants. ACE and eNOS gene polymorphisms and their expressions were analyzed in 78 ADPKD patients and 30 controls. Gene expressions were assessed by quantitative real-time PCR. Twenty-four-hour blood pressure monitoring was performed for the diagnosis of hypertension in all study participants. Results:eNOS expression and the estimated glomerular filtration rate were found to be significantly higher in ADPKD patients without hypertension than in those with hypertension. Each unit of increase in eNOS expression led to a 0.88-fold decrease (95% CI: 0.80-0.96) in the risk of hypertension in multiple logistic regression analysis. Conclusions:eNOS gene expression is independently predictive of hypertension in the ADPKD population. This study showed, for the first time, a novel link between eNOS gene expression and hypertension in ADPKD.