IgA nephropathy with early kidney disease is associated with increased arterial stiffness and renin-angiotensin system activity.

BACKGROUND: IgA nephropathy is associated with increased cardiovascular risk, though whether this is due to loss of kidney function or proteinuria is unclear. METHODS: For this study 10 normotensive IgA nephropathy subjects with early kidney disease (41±5 yrs, glomerular filtration rate (GFR) 87±9 ml/min, proteinuria 720±300 mg/d) and 10 gender- and blood pressure-matched healthy controls (36±1 yrs, estimated GFR 102±5 ml/min, proteinuria 70±6 mg/d) were studied in high-salt balance. Blood pressure and arterial stiffness, expressed as pulse wave velocity and aortic augmentation index, were measured at baseline and in response to 60 min of angiotensin II (AngII) infusion. RESULTS: At baseline, IgA nephropathy subjects demonstrated similar pulse wave velocity (8.6±0.7 vs. 8.0±0.4 m/s, p=0.5) but increased aortic augmentation index (12.6±3.1 vs. 1.8±4%, p=0.04) and a trend towards increased circulating renin-angiotensin system (RAS) components (plasma renin activity, 0.55±0.18 vs. 0.21±0.05 ng/l/s, p=0.08; angiotensin II, 25±5 vs. 16±1 ng/l, p=0.08) compared with controls. However, despite similar baseline blood pressure values (p=0.8), IgA nephropathy was associated with reduced arterial sensitivity to AngII challenge (Δmean arterial pressure: 19±4 vs. 29±1 mm Hg, p=0.05; Δpulse wave velocity: -0.06±0.6 vs. 1.5±0.3 m/s, p=0.07) compared with controls, even after multivariate analysis. CONCLUSION: Even in the setting of early kidney disease, IgA nephropathy is associated with increased arterial stiffness and decreased angiotensin II responsiveness, a marker of increased RAS activity.

Sex influences the effect of body mass index on the vascular response to angiotensin II in humans.

OBJECTIVE: Sex influences the cardiorenal risk associated with body mass index (BMI). The role of the renin-angiotensin-aldosterone system in adiposity-mediated cardiorenal risk profiles in healthy, non-obese men and women was investigated. METHODS: Systemic and renal hemodynamic responses to angiotensin-II (AngII) as a function of BMI, waist and hip circumference, waist-hip ratio, as well as fat and lean mass were measured in 18 men and 25 women in high-salt balance, stratified by BMI (<25 kg/m2 (ideal body weight (IBW)) vs. ≥25 kg/m2 overweight)). RESULTS: In men (n = 7, BMI 23 ± 1 kg/m2) and women (n = 14, BMI 22 ± 2 kg/m2) of IBW, BMI was not associated with the systolic blood pressure (SBP) response to AngII. In contrast, overweight men (n = 11, 29 ± 2 kg/m2) demonstrated a progressively more blunted vasoconstrictor SBP response to AngII challenge as BMI increased (P = 0.007), even after adjustment for covariates. Women maintained the same relationship between BMI and the SBP response to AngII irrespective of weight status (P = 0.2, IBW vs. overweight women). Compared to BMI, other adiposity measures showed similar associations to systemic AngII responsiveness in men but not in women. Increasing BMI was associated with a blunted renovasoconstrictor response to AngII in all subjects, but was more pronounced in men. CONCLUSION: Sex influences the effect of adiposity on vascular angiotensin-responsiveness.

A dedicated vascular access program can improve arteriovenous fistula rates without increasing catheters.

PURPOSE: We describe the development and implementation of a comprehensive multidisciplinary vascular access (VA) program and describe its impact on VA distribution rates. METHODS: A retrospective review of all incident and prevalent patients in our hemodialysis (HD) unit was conducted in September 2001 to determine baseline data including: type of VA along with patient characteristics and comorbidities. Similar data was extracted from the database in 2005 for incident and prevalent patients. RESULTS: The VA program had a significant impact on arteriovenous fistulae (AVF) rates in both incident and prevalent HD patients: incident AVF rates increased from 14 to 39% (p=0.04) and prevalent AVF rates from 60 to 64% (p=0.015). Multivariate analysis revealed that male gender (OR 1.79 [CI 0.85-0.98, p=0.006]) and year of dialysis initiation 2005 vs. 2001 (OR 1.65 [CI 1.09-2.5, p=0.017]) were associated with AVF use among prevalent HD patients. Furthermore, age (per 5 years over 70) is associated with a decreased likelihood of having an AVF (OR 0.91 [CI 0.85-0.98, p=0.009]) whereas comorbidities of cardiovascular disease and diabetes had no impact. CONCLUSION: We demonstrate that a structured VA program can increase the number of functioning fistulas without a corresponding increase in catheters in incident and prevalent HD patients.

Wave-intensity analysis: a new approach to left ventricular filling dynamics.

In order to explore a new approach to the analysis of diastolic dysfunction, we adapted wave-intensity analysis (WIA), a time-domain analysis that provides information regarding both upstream and downstream events, to left ventricular (LV) filling. WIA considers the pressure and flow waves as summations of successive wavelets, characterised by the direction they travel and by the sign of the pressure gradient associated with them. Wave intensity is the product, dPdU, calculated from the incremental differences in LV pressure (dP) and mitral velocity (dU) and, during the diastolic filling interval, yields up to five dPdU peaks. Peak 1 is caused by backward-travelling expansion waves that accelerate the blood while LV pressure falls, and may be related to "diastolic suction". Peak 2 is caused by forward-travelling compression waves which occur if acceleration continues after LV pressure begins to increase. Peak 3 is caused by backward compression waves and is associated with rising LV pressure and deceleration. Peak 4 is caused by forward compression waves and is associated with the increasing LV pressure and acceleration caused by atrial contraction. Peak 5 is caused by backward compression waves and is associated with increasing pressure and deceleration. These preliminary observations suggest that WIA can be useful in describing the mechanics of LV filling and, after much further work has been accomplished, it might prove useful in the detection and characterization of diastolic dysfunction.