Coronary Flow Velocity Reserve and Carotid Intima Media Thickness in Patients with Autosomal Dominant Polycystic Kidney Disease: From Impaired Tubules to Impaired Carotid and Coronary Arteries

Background and objectives: Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease. Endothelial dysfunction, an early and reversible feature in the pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening, and increased intima-media thickness. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. The aim of the study was to investigate the carotid intima-media thickness and coronary flow velocity reserve in patients with autosomal dominant polycystic kidney disease.Design, setting, participants, & measurements: Thirty normotensive patients with autosomal dominant polycystic kidney disease (10 male, 20 female) with well-preserved renal function and 30 healthy subjects (12 male, 18 female) were included in the study. Coronary flow velocity reserve was measured at baseline and after dipyridamole infusion by echocardiography. Coronary flow velocity reserve was calculated as the ratio of hyperemic to baseline diastolic peak velocities.Results: Carotid intima-media thickness was significantly higher in patients than in control subjects (0.80 ± 0.29 versus 0.54 ± 0.14 mm, respectively; P < 0.001). Moreover, coronary flow velocity reserve was significantly lower in patients than in control subjects (1.84 ± 0.39 versus 2.65 ± 0.68, respectively; P < 0.001).Conclusions: Normotensive patients with autosomal dominant polycystic kidney disease with well-preserved renal function have significantly increased carotid intima-media thickness and significantly decreased coronary flow velocity reserve compared with healthy subjects. These findings suggest that atherosclerosis starts at an early stage in the course of their disease in patients with autosomal dominant polycystic kidney disease.Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary renal disease that occurs in 1 of 400 to 1000 individuals (1,2). Cardiovascular problems are a major cause of morbidity and mortality in patients with ADPKD (3). Hypertension, a common finding in patients with ADPKD, often occurs before the onset of renal insufficiency and is associated with faster progression to ESRD and increased cardiovascular mortality (4,5). Activation of the renin-angiotensin-aldosterone system (RAAS) caused by cyst expansion and local ischemia has been proposed to play an important role in the development of hypertension in ADPKD (6). The RAAS is stimulated at an early stage of ADPKD, even before the onset of hypertension and clinical findings (7,8). Likewise, increased left ventricular mass indexes and biventricular diastolic dysfunction have been reported before the development of hypertension in patients with ADPKD with well-preserved renal function (9–16). Moreover, endothelial dysfunction (ED), which is an early manifestation of vascular injury, occurs in both normotensive and hypertensive patients with ADPKD, before the onset of renal failure (17).Coronary flow velocity reserve (CFVR) represents the capacity of the coronary circulation to dilate after an increase in myocardial metabolic demands (18). Although CFVR was measured invasively until recently, it can be evaluated noninvasively by using Doppler and vasodilator stress, such as dipyridamole or adenosine (19). By using this method, impairment of CFVR can be assessed before development of angiographically detectable stenosis in epicardial coronary arteries. The aim of this study was to investigate the CFVR in patients with ADPKD, with well-preserved renal function.     

Albuminuria as a predictor of heart failure hospitalizations in patients with type 2 diabetes

BACKGROUND: Heart failure (HF) occurs more frequently and is a significant cause of mortality in diabetic patients. The purpose of the current study is to ascertain risk factors that are predictive of HF hospitalizations in type 2 diabetic patients. METHODS: Longitudinal observational study of type 2 diabetic patients with baseline diastolic blood pressures > or =80 mm Hg and no history of New York Heart Association class III-IV HF or a serum creatinine > or =2.5 mg/dL nested within a randomized clinical trial. The outcome measure of this study was the first occurrence of HF hospitalization over a 5-year follow-up period. RESULTS: Patients with overt albuminuria at baseline had a higher and earlier occurrence of HF hospitalizations than those with micro- or normoalbuminuria (13.6% versus 3.3%, odds ratio [OR]=3.1, 95% confidence interval [CI]=2.15-4.60, P<.0001). In the multiple logistic regression analyses, the presence of overt albuminuria (OR 5.4, 95% CI=2.3-12.5, P<.001), history of myocardial infarction (OR 4.6, 95% CI=1.6-13.1, P=.004) and a history of New York Heart Association Class I or II HF (OR 8.0, 95% CI=2.2-28.6, P=.0014) at baseline were independently associated with HF hospitalizations. CONCLUSIONS: Overt albuminuria predicts the occurrence of HF hospitalizations in type 2 diabetic patients. Thus early aggressive treatment of diabetic nephropathy should be investigated as a means of preventing of HF.     

Ambulatory blood pressure and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. However, the association between ambulatory blood pressure and ED has not been investigated in these patients. Forty-one patients with ADPKD having well-preserved renal function were included in the study. Ambulatory blood pressure monitoring was performed in all patients. Patients were divided into dipper and non-dipper groups. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. The mean 24-hour systolic blood pressure was similar in both groups (125.5 +/- 10.7 mmHg in dippers and 121.2 +/- 14.3 in non-dippers, p > 0.05). There was also no significant difference between the mean 24-hour diastolic blood pressures in both groups (82.3 +/- 9.6 mmHg in dippers and 77.1 +/- 8.6 mmHg in non-dippers, p > 0.05). The nocturnal fall rate in systolic blood pressure was 11.1 +/- 1.2% in dippers and 0.98 +/- 0.9% in non-dippers (p = 0.001). The nocturnal fall rate in diastolic blood pressure was 14.0 +/- 0.9% in dippers and 3.8 +/- 0.8% in non-dippers (p = 0.001). Endothelial-dependent dilatation was significantly higher in dippers compared to non-dippers (6.22 +/- 4.14% versus 3.57 +/- 2.52%, p = 0.025). Non-dipper patients with ADPKD show significant ED, which has an important impact on cardiovascular morbidity and mortality.     

Stimulated salivary flow rate in chronic hemodialysis patients

BACKGROUND: Reduced salivary flow has been reported in patients undergoing hemodialysis (HD) treatment. Our aim was to investigate the most important factors associated with stimulated salivary flow rate (ssfr) in chronic HD patients. METHODS: Fifty HD patients (27 F, 23 M, mean age 46. 7 +/- 13.2 years) were divided into two groups according to the duration of HD treatment as those receiving HD therapy less than or equal to (group I) or those more than (group II) 24 months. Fasting blood samples were obtained to determine hepatitis B and C serology, and biochemical and hematological parameters before a HD session. After prestimulation with a standard weight paraffin wax, stimulated saliva was collected in the HD patients and control group (23 F, 25 M, mean age 45.7 +/- 19.1 years) and the flow rate was expressed as ml/min. RESULTS: Both HD groups consisted of 25 patients. There was no significant difference between the two HD groups other than serum alkaline phosphatase (ALP) levels and presence of HCV. The ssfr was decreased than controls in both groups (0.8 +/- 0.6 and 0.7 +/- 0.4, respectively, vs. 1.5 +/- 0.5 ml/min) and it did not correlate with any parameter. Smoking had a positive effect on ssfr in all groups. CONCLUSION: Although the salivary flow rate decreased significantly in chronic HD patients, the duration of therapy displayed no effect on the salivary changes in HD patients, but smoking increased ssfr.     

Acute renal failure associated with nonfulminant hepatitis A virus infection

Hepatitis A is usually a mild self-limiting infection of the liver. Nonfulminant acute renal failure very rarely complicates type A viral hepatitis. An unusual case, a 32-year-old female with serologically proven acute hepatitis A infection, was complicated by acute renal failure and the patient in this study is the first case associated with Cushing's disease. She recovered, and the laboratory tests returned normal one month after initial hospitalization. Although the mechanism responsible for renal failure in acute hepatitis A virus infection is still uncertain, possible causes are discussed with the review of literature.     

No effect of angiotensin-converting enzyme gene polymorphism on disease progression and left ventricular hypertrophy in autosomal dominant polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) shows a variable clinical course suggesting that genetic modifiers might play a role. There are conflicting results about the effect of angiotensin-converting enzyme (ACE) gene polymorphism on the progression of renal failure in ADPKD. Also, the association between ACE gene polymorphism and the occurrence of left ventricular hypertrophy (LVH) has not been investigated in patients with ADPKD. METHODS: ACE genotype analysis was performed in 409 Caucasian patients (137 male, 272 female) with ADPKD. Echocardiographic examination was done in 164 of these patients. RESULTS: There were no significant differences between different ACE genotypes regarding renal function, renal volume, urinary protein excretion, blood pressure, the rate of hypertension, the age at diagnosis of hypertension, the rate of LVH and the incidence of end-stage renal disease (ESRD). CONCLUSION: ACE gene polymorphism does not have a significant effect on the development of ESRD and the prevalence of LVH in patients with ADPKD.     

Subclinic arterial and left ventricular systolic impairment in autosomal dominant polycystic kidney disease with preserved renal functions

The International Journal of Cardiovascular Imaging - Subclinical atherosclerosis and cardiovascular events are common even in young normotensive patients with autosomal dominant polycystic kidney...