Urinary angiotensinogen excretion is associated with blood pressure in obese young adults.

Intrarenal RAS has been suggested to be involved in the pathogenesis of hypertension. It was recently reported that urinary angiotensinogen excretion levels are associated with intrarenal RAS. However, few markers predicting intrarenal RAS have been investigated in obese young subjects. The present study evaluated the association between blood pressure and intrarenal RAS activity, inflammation and oxidative stress in obese young adults. Urinary angiotensinogen excretion and urinary monocyte chemotactic protein (MCP)-1, and urinary thiobarbituric acid reaction substance (TBARS) as markers of intrarenal RAS activity, inflammation, and oxidative stress, respectively, were determined from morning urine of 111 young male adults. Participants were divided into two groups based on the body mass index (BMI). Natural log-transformed urinary angiotensinogen excretion level was significantly associated with blood pressure, MCP-1 excretion, and TBARS excretion elevation in the obese group (BMI ≥25 kg/m(2)). Multivariable analyses showed that every 1 standard deviation increase in natural-log transformed urinary angiotensinogen and MCP-1 excretion, but not TBARS excretion level was associated with elevated blood pressure in the obese group. These results indicate that urinary angiotensinogen and MCP-1 excretion were associated with blood pressure elevation in this population of obese young adults. It suggested that inappropriate RAS activity and inflammation precedes hypertension in obese young subjects and urinary angiotensinogen could be a screening maker for hypertension in young obese subjects.

Glucose and Insulin Response to Peritoneal Dialysis Fluid in Diabetic and Nondiabetic Peritoneal Dialysis Patients.

A postprandial increase in blood glucose in peritoneal dialysis (PD) patients with diabetes was observed in our previous study using continuous blood glucose monitoring. The response was observed in diabetic but not in nondiabetic PD patients. In addition, the response was reduced when patients used icodextrin; glucose absorbed from the peritoneum was responsible for the postprandial increase in blood glucose. Because our PD patients often change their PD fluid before meals, the present study aimed to determine the blood glucose and insulin responses to PD fluid. The 26 patients who agreed to participate in the study protocol [16 with diabetes (12 men, 4 women; 11 receiving insulin; 5 being controlled with oral antidiabetic drugs; average duration from diagnosis with diabetes: 16.4 ± 11 years); 10 without diabetes (4 men, 6 women)] had an average age of 60.5 ± 13.0 years. Average PD vintage was 578.7 ± 352.9 days. Blood samples were taken during a peritoneal equilibration test (PET) with 2.5% glucose solution at baseline and at 0.5, 2, and 4 hours. Levels of blood glucose and insulin were analyzed. A rapid increase in blood glucose (peak at 0.5 hours, 23.5 ± 22.2 mg/dL increase from baseline) was observed in nondiabetic patients. A delayed but higher peak response was observed in diabetic patients (peak at 1 hour, 54.9 ± 38.3 mg/dL increase from baseline). Peak response of insulin occurred at 0.5 hours in nondiabetic patients; in diabetic patients it occurred at 2 hours. No differences in the average insulin level during the PET were observed in the two groups (nondiabetic: 35.3 ± 15.6 µU/mL; diabetic: 38.9 ± 7.6 µU/mL). The study results suggest that a delayed insulin response after a PD fluid exchange could participate in the exaggerated postprandial increase in blood glucose in diabetic PD patients, particularly when the PD fluid exchange is performed before food intake.

Association Between Home Blood Pressure and Body Composition by Bioimpedance Monitoring in Patients Undergoing Peritoneal Dialysis.

Home blood pressure (HBP) is an independent predictor of cardiovascular and renal function. However, no particular guidelines have been established for optimal HBP in peritoneal dialysis (PD) patients. Bioelectrical impedance analysis (BIA) is a beneficial tool for determining body composition. In the present study, we used BIA to determine body composition parameters that might play a role in the regulation of HBP in PD patients, and we compared HBP with office blood pressure (BP). Our study enrolled 15 patients (11 men, 4 women) receiving PD at Tohoku University Hospital, who, for 1 year, agreed to monitor HBP and to undergo body composition analysis. Patients were requested to measure HBP twice daily (morning, night) using a home BP device. A bioimpedance monitor was used to monitor body composition each month. Blood and urine samples were also analyzed each month. The relationships of average morning systolic HBP (sMHBP) with parameters of body composition and of blood and urine analyses were evaluated. The enrolledpatients were 66.3 ± 7.7 years of age and had a PD vintage of 28.3 ± 6.4 months. Overall, their sMHBP was 128 ± 13 mmHg and their office systolic BP was 126 ± 15 mmHg. Although office systolic BP and sMHBP both correlated with body fluid parameters [total body water (TBW)/height2], renal function (renal Kt/V serum creatinine), and heart function (left ventricular mass index), the correlation coefficient for sMHBP and TBW/height2 was highest, with sMHBP being the only independent predictor. Sodium intake was associated only with sMHBP. Our results suggest that body fluid status determined by BIA, heart and renal function, and sodium intake show better associations with sMHBP than with office systolic BP. Monitoring HBP and body composition by BIA are beneficial for the maintenance of volume status in PD patients.

Diurnal variations of blood glucose by continuous blood glucose monitoring in peritoneal dialysis patients with diabetes.

Exaggerated postprandial increase in blood glucose has been postulated to be associated with cardiovascular injury. The concentration of blood glucose is altered by glucose absorption from peritoneal dialysis (PD) fluids. In PD patients, we used continuous blood glucose monitoring (CGM) to analyze diurnal variations in blood glucose. Diurnal blood glucose was determined in 10 diabetic PD patients who used CGM (iPro2: Medtronic, Northridge, CA, U.S.A.) for 3 days. Blood glucose concentrations before and after glycemic control were monitored in 5 patients. Correlations between CGM parameters [standard deviation of blood glucose (SDG)], peritoneal function [dialysate-to-plasma ratio of creatinine (D/P Cr) and end-to-initial dialysate (D/D0) glucose], 24-hour peritoneal glucose absorption, and glycemic index were determined. In 5 patients, CGM was performed again after adjustments to antidiabetic drugs. A large diurnal variation, especially at night, was observed in this patient cohort. No correlation of HbA1c with mean blood glucose concentration was observed. Although SDG had no association with 24-hour peritoneal glucose absorption, it did show an association with D/P Cr and D/D0 glucose. The SDG was significantly lower after treatment with a dipeptidyl peptidase IV inhibitor or an increase in insulin dose. Results of the present study indicate that diurnal variations in glucose depend on the speed of peritoneal glucose absorption rather than the net glucose absorption.

Icodextrin-based continuous ambulatory peritoneal dialysis therapy effectively reduces left ventricular mass index and protects cardiac function in patients with end-stage renal disease.

Increased left ventricular mass index (LVMI) is commonly observed in patients undergoing peritoneal dialysis (PD). The present study aimed to determine the effect of icodextrin (Ico) on LVMI in PD patients with maintained residual renal function (RRF). This retrospective study included 18 patients (12 men, 6 women; average age: 62 +/- 10 years) diagnosed with indications for PD therapy and divided into two groups: those treated with Ico (Ico group) and without Ico (non-Ico group). Echocardiography was performed at the beginning of continuous ambulatory PD and after 6 and 12 months. A significant reduction in LVMI (p < 0.01) and an increase in ultrafiltration (p < 0.01) were observed after 6 months of lco treatment and were maintained for 12 months. Ejection fraction was significantly lower in the non-Ico group after 12 months (p < 0.01), but was not altered in the Ico group. Blood pressure, cardiothoracic ratio, urine volume, and N-terminal prohormone of brain natriuretic peptide were unaffected by PD treatment up to 12 months. The year-averaged ultrafiltration and the reduction in LVMI were significantly correlated (p < 0.05). Ico effectively improved LVMI and maintained ejection fraction in end-stage renal disease patients within 1 year from PD initiation. Notably, treatment with Ico resulted in a reduction of LVMI (associated with increased ultrafiltration), with no significant reduction in RRF.

Beneficial role of tolvaptan in the control of body fluids without reductions in residual renal function in patients undergoing peritoneal dialysis.

The V2 receptor antagonist tolvaptan has been approved for volume control in heart-failure patients in Japan. Tolvaptan increases renal blood flow, and so the present study was designed to ascertain whether tolvaptan could be a useful diuretic for volume control without reducing residual renal function (RRF) in peritoneal dialysis (PD) patients. Tolvaptan was administered in 15 PD patients (15 mg daily). Urine volume, body weight, and blood pressure were monitored Urinary excretion of urea nitrogen Na+, the osmolality of plasma and urine, and peritoneal and renal Kt/V were analyzed before and after tolvaptan treatment. In 11 of 15 patients, urine volume increased to more than 400 mL daily. A significant increase in diluted urine was observed, as indicated by a reduction in the specific gravity or osmolality of urine (or both). Urinary excretion of urea nitrogen, and Na+ was significantly increased Increases in renal Kt/V were observed, but peritoneal Kt/V was unchanged. Singnificant increase in creatinine clearance was also observed These data suggest that tolvaptan not only stimulates water diuresis, but also natriuresis, without reducing RRF in PD patients. Hence, tolvaptan could be a beneficial tool for the control of body fluid and maintenance of RRF in PD patients.

Albuminuria indicates the pressure-associated injury of juxtamedullary nephrons and cerebral strain vessels in spontaneously hypertensive stroke-prone rats.

Albuminuria is an indicator of renal injury and is closely linked with cardiovascular disease (CVD). However, the mechanism by which albumin is excreted in the urine remains unclear. As the juxtamedullary region of the kidney is highly susceptible to pressure increase, juxtamedullary injury is observed from an early phase in hypertensive rat models. Anatomical similarities are observed between the pre-glomerular vessels of the juxtamedullary nephron and the cerebral vasculature. We previously named these 'strain vessels' for their high vascular tone and exposure to higher pressures. The current studies were designed to determine whether albuminuria is the result of juxtamedullary nephron injury, indicating the presence of pressure injury to the strain vessels in spontaneously hypertensive stroke-prone rats (SHR-SP) fed a high-salt diet. Albuminuria was associated with juxtamedullary nephron injury, and the enhanced expression of monocyte chemotactic protein-1 (MCP-1) and tumor growth factor-beta (TGF-ß) in 12-week-old SHR-SP rats fed a 4% high-salt diet from the age of 6 weeks. The wall thickness of the pre-glomerular vessels of the juxtamedullary nephron was also associated with that of the perforating artery of the middle cerebral artery. Reducing the blood pressure with nifedipine reduced the degree of albuminuria and juxtamedullary nephron injury as well as MCP-1 and TGF-ß expression in the SHR-SP rats fed an 8% high-salt diet from the age of 9 weeks. Nifedipine inhibited stroke events in these animals until they were 14 weeks old. These results indicate that albuminuria is a result of juxtamedullary nephron injury and a marker of pressure-induced injury of the strain vessels.

Role of specific T-type calcium channel blocker R(-) efonidipine in the regulation of renal medullary circulation.

OBJECTIVES: Blockade of the T-type calcium channel (TCC), which is expressed in the renal efferent arterioles of the juxtamedullary nephron and vasa recta, has been shown to protect against renal injury. Studies were designed to determine the effects of a specific TCC blocker, R(-) efonidipine [R(-)EFO], on the regulation of renal circulation. METHODS AND RESULTS: Renal medullary blood flux (MBF) and cortical blood flux (CBF) were simultaneously monitored using laser-Doppler flowmetry in Sprague-Dawley rats. Responses were also determined in rats with angiotensin II (AngII) induced renal ischemia. Intravenous (i.v.) or renal interstitial (r.i.) infusion of R(-)EFO (0.25 mg/h, i.v. or r.i.) significantly increased MBF by 24.0 ± 7.0 and 21.0 ± 4.4%, respectively, but without changing CBF or mean arterial pressure. The nitric oxide (NO) synthase inhibitor NG-nitro-L-argininemethylester (L-NAME, 1 µg/kg per min, i.v. or r.i.) significantly attenuated R(-)EFO-induced increase in MBF. R(-)EFO inhibited the AngII-mediated (50 ng/kg per min, i.v.) reduction of MBF (28.4 ± 1.7%), which was associated with increased urinary NO(2) + NO(3) excretion and decreased urinary hydrogen peroxide (H(2)O(2)) excretion. Intracellular H(2)O(2) fluorescence (real-time fluorescence imaging) in the epithelial cells of isolated medullary thick ascending limb (mTAL) significantly increased following AngII stimulation (1 µmol/L, 235 ± 52 units), which was significantly inhibited by pre and coincubation with R(-)EFO. R(-)EFO stimulation also increased the intracellular NO concentration in the epithelial cells of mTAL (220 ± 62 units). CONCLUSION: These results suggest that TCC blockade with R(-)EFO selectively increases MBF, an effect that appears to be mediated by changes in renal NO and oxidative stress balance, which may protect against ischemic renal injury in the renal medullary region.