Are there sex differences in cardiovascular outcomes in non-dialysis CKD patients?

Background: Sex differences for cardiovascular (CV) risk and outcomes in chronic kidney disease (CKD) patients not on dialysis have been scarcely or never investigated. We therefore studied this important aspect in a cohort of CKD stage 2-5 in the south of Italy. Methods: We tested the relationship between sex and fatal and non-fatal major CV events in a cohort of 759 stage 2-5 CKD patients followed up for a median time of 36 months. Results: Out of 759 patients, 455 were males (60%) and the remaining 304 patients were females (40%). During the follow-up, 42 patients died, and 118 had fatal and non-fatal CV events. On univariate Cox regression analyses, the male sex failed to be associated with all-cause mortality but was strongly related to the incidence rate of fatal and non-fatal major CV events [hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.18-2.60, P = .006]. Data adjustment for a series of major potential confounders did not materially affect the strength of this relationship (HR 1.78, 95% CI 1.03-3.09). Further analysis testing the effect of age on major CV outcomes by sex showed an effect modification by this risk factor on the same outcome (P = .037) because the HR of male versus female CV events increased progressively with aging. Conclusion: Male patients in stage G2-5 CKD had a higher risk for CV events compared with female patients. Age was shown to be a risk modifier for the association between sex and CV events and this risk increased linearly across a wide age spectrum in CKD patients.

Home Pulse Pressure Predicts Death and Cardiovascular Events in Peritoneal Dialysis Patients.

Increased arterial hypertension represents a prevalent condition in peritoneal dialysis patients that is often related to volume expansion. Pulse pressure is a robust predictor of mortality in dialysis patients, but its association with mortality is unknown in peritoneal patients. We investigated the relationship between home pulse pressure and survival in 140 PD patients. During a mean follow-up of 35 months, 62 patients died, and 66 experienced the combined event death/CV events. In a crude COX regression analysis, a five-unit increase in HPP was associated with a 17% increase in the hazard ratio of mortality (HR: 1.17, 95% CI 1.08-1.26 p < 0.001). This result was confirmed in a multiple Cox model adjusted for age, gender, diabetes, systolic arterial pressure, and dialysis adequacy (HR: 1.31, 95% CI 1.12-1.52, p = 0.001). Similar results were obtained considering the combined event death-CV events as an outcome. Home pulse pressure represents, in part, arterial stiffness, and it is strongly related to all-cause mortality in peritoneal patients. In these high cardiovascular risk populations, it is important to maintain optimal blood pressure control, but it is fundamental to consider all the other cardiovascular risk indicators, such as pulse pressure. Home pulse pressure measurement is easy and feasible and can add important information for the identification and management of high-risk patients.

Reducing salt intake by urine chloride self-measurement in non-compliant patients with chronic kidney disease followed in nephrology clinics: a randomized trial.

BACKGROUND: Adherence to low salt diets and control of hypertension remain unmet clinical needs in chronic kidney disease (CKD) patients. METHODS: We performed a 6-month multicentre randomized trial in non-compliant patients with CKD followed in nephrology clinics testing the effect of self-measurement of urinary chloride (69 patients) as compared with standard care (69 patients) on two primary outcome measures, adherence to a low sodium (Na) diet (<100 mmol/day) as measured by 24-h urine Na (UNa) excretion and 24-h ambulatory blood pressure (ABPM) monitoring. RESULTS: In the whole sample (N = 138), baseline UNa and 24-h ABPM were143 ± 64 mmol/24 h and 131 ± 18/72 ± 10 mmHg, respectively, and did not differ between the two study arms. Patients in the active arm of the trial used >80% of the chloride strips provided to them at the baseline visit and at follow-up visits. At the third month, UNa was 35 mmol/24 h (95% CI 10.8-58.8 mmol/24 h; P = 0.005) lower in the active arm than the control arm, whereas at 6 months the between-arms difference in UNa decreased and was no longer significant [23 mmol/24 h (95% CI -5.6-50.7); P = 0.11]. The 24-h ABPM changes as well as daytime and night-time BP changes at 3 and 6 months were similar in the two study arms (Month 3, P = 0.69-0.99; Month 6, P = 0.73-0.91). Office BP, the use of antihypertensive drugs, estimated Glomerular Filtration Rate (eGFR) and proteinuria remained unchanged across the trial. CONCLUSIONS: The application of self-measurement of urinary chloride to guide adherence to a low salt diet had a modest effect on 24-h UNa and no significant effect on 24-h ABPM.

Sleep-Disordered Breathing and 24-Hour Ambulatory Blood Pressure Monitoring in Renal Transplant Patients: Longitudinal Study.

Background Sleep-disordered breathing (SDB) is considered a strong risk factor for hypertension in the general population. This disturbance is common in end-stage kidney disease patients on long-term hemodialysis and improves early on after renal transplantation. Whether SDB may be a risk factor for hypertension in renal transplant patients is unclear. Methods and Results We investigated the long-term evolution of simultaneous polysomnographic and 24-hour ambulatory blood pressure (BP) monitoring recordings in a cohort of 221 renal transplant patients. Overall, 404 paired recordings were made over a median follow-up of 35 months. A longitudinal data analysis was performed by the mixed linear model. The apnea-hypopnea index increased from a median baseline value of 1.8 (interquartile range, 0.6-5.0) to a median final value of 3.6 (interquartile range, 1.7-10.4; P=0.009). Repeated categorical measurements of the apnea-hypopnea index were directly associated with simultaneous 24-hour, daytime, and nighttime systolic ambulatory BP monitoring (adjusted analyses; P ranging from 0.002-0.01). In a sensitivity analysis restricted to 139 patients with at least 2 visits, 24-hour, daytime, and nighttime systolic BP significantly increased across visits (P<0.05) in patients with worsening SDB (n=40), whereas the same BP metrics did not change in patients (n=99) with stable apnea-hypopnea index. Conclusions In renal transplant patients, worsening SDB associates with a parallel increase in average 24-hour, daytime, and nighttime systolic BP. These data are compatible with the hypothesis that the link between SDB and hypertension is causal in nature. Clinical trials are, however, needed to definitively test this hypothesis.

Lung ultrasound to detect and monitor pulmonary congestion in patients with acute kidney injury in nephrology wards: a pilot study.

INTRODUCTION: Lung congestion and frank pulmonary edema are established complications of acute kidney injury (AKI) and early detection and monitoring of lung congestion may be useful for the clinical management of AKI patients. METHODS: We compared standardized clinical criteria (including lung crackles and peripheral edema grading) and simultaneous chest ultrasound (US) to detect lung congestion in a series of 39 inpatients with AKI. RESULTS: At baseline, twelve patients (31%) were clinically euvolemic and twelve presented clear-cur cardiovascular congestion (31%) by clinical criteria. Fifteen patients (38%) were hypovolemic. The median number of US-B lines in patients with cardiovascular congestion was much higher (50, inter-quartile range 27-99) than in euvolemic (14, IQR 11-37) and hypovolemic patients (7, IQR 3-16, P < 0.001). Remarkably, a substantial proportion of asymptomatic euvolemic (66%) and hypovolemic (46%) patients had lung congestion of moderate to severe degree (> 15 US-B lines) by lung US. Crackles severity and the number of US-B lines over time were inter-related (Spearman's ρ = 0.38, P < 0.01) but the agreement (Cohen k statistics) between the two metrics was unsatisfactory. Forty-eight percent of patients had lung congestion of moderate to severe degree by lung US and this estimate by far exceeded that by clinical criteria (32%). CONCLUSIONS: This pilot study shows that chest US has potential for the detection of lung congestion at a pre-clinical stage in AKI. The results of this pilot study form the basis for a clinical trial testing the usefulness of this technique for guiding lung congestion treatment in patients with AKI.

Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease.

Background Excessive sodium intake is a risk factor for hypertension, cardiovascular disease and the risk for kidney failure in chronic kidney disease (CKD) patients. Methods We tested the diagnostic performance and the feasibility of an inexpensive method based on urine chloride strips for self-monitoring sodium intake in a series of 72 CKD patients. Results Twenty-four hour urinary chloride as measured by the reactive strips and 24 h urinary sodium were interrelated (r=0.59, p<0.001). Forty-nine out of 72 patients (78%) had a 24 h urinary sodium >100 mmol/24 h, i.e. the upper limit recommended by current CKD guidelines. The strip method had 75.5% sensitivity and 82.6% specificity to correctly classify patients with urine sodium >100 mmol/24 h. The positive and the negative predictive values were 90.2% and 61.3%, respectively. The overall accuracy (ROC curve analysis) of urine chloride self-measurement for the >100 mmol/24 h sodium threshold was 87% (95% CI: 77%-97%). The large majority of patients (97%) perceived the test as useful to help compliance with the prescribed dietary sodium and considered the test as simple and of immediate application (58%) or feasible but requiring attention (39%). Conclusions A simple and inexpensive test for urine chloride measurement has a fairly good performance for the diagnosis of excessive sodium intake. The test is feasible and it is perceived by CKD patients as helpful for enhancing compliance to the dietary sodium recommendations. The usefulness of this test for improving hypertension control in CKD patients will be tested in a clinical trial (Clinicaltrials.gov RF-2010-2314890).

Pruritus and quality of life in renal transplant patients.

BACKGROUND: Pruritus has a negative impact on quality of life (QoL) in dialysis patients. The reversibility of this symptom after renal transplantation and its impact upon QoL has scarcely been studied in these patients. METHODS: Pruritus was evaluated by the Visual Analogue Scale (VAS), the Visual Rating Scale (VRS), and the Numerical Rating Scale (NRS) in 133 unselected renal transplant patients, 62 healthy subjects, and 29 hemodialysis patients. QoL was assessed by KDQOL-SF™ 1.3. The reversibility of pruritus was studied by applying retrospectively the VRS. RESULTS: The prevalence of pruritus by the VRS was 62% in hemodialysis patients, 32% in renal transplant patients, and 11% in healthy subjects (P<.001). The prevalence of pruritus among transplant patients was 32% by VRS and 38% by VAS and NRS. The prevalence of pretransplantation pruritus (68%) by the VRS recall questionnaire was higher than the prevalence of pruritus in the same patients after renal transplantation (32%, P<.01). Pruritus in transplant patients was associated with important dimensions of QoL, including social, emotional, and working limitations (P<.05 for the three comparisons). CONCLUSIONS: The prevalence of pruritus markedly reduces after renal transplantation but remains substantially higher than in the general population and impacts upon quality of life in these patients.

[Obesity and chronic kidney disease]. / L'obesità come causa di insufficienza renale.

In the last century, life expectancy in the economically developed countries has significantly increased. In parallel there has been an increase in the prevalence of obesity and of chronic kidney disease. Abdominal obesity is a relevant risk factor for death and cardiovascular complications in chronic kidney disease and in dialysis patients as well.

The enzymatic machinery for ADMA synthesis and degradation is fully expressed in human adipocytes.

BACKGROUND: The endogenous inhibitor of nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), is implicated in endothelial dysfunction and is a marker of renal disease progression and cardiovascular (CV) complications. Various cell species exhibit the enzymatic system that generates and degrades this methylarginine, but it is unknown whether this machinery is expressed in adipocytes. The question is relevant because adipocyte-derived mediators are implicated both in renal and cardiovascular diseases. METHODS: We measured ADMA concentration in pure adipocytes in culture and measured mRNA levels of the enzymes involved in ADMA metabolism (real-time polymerase chain reaction) both in pure adipocytes in culture and in adipose tissue harvested in 9 healthy subjects. These enzymes included protein arginine N-methyltransferases type I (PRMTs) involved in ADMA synthesis, dimethylarginine dimethylaminohydrolases (DDAHs) responsible for ADMA degradation and constitutive and inducible forms of NOS (i.e., NOS1, NOS2A and NOS3 genes), the main functional target of ADMA. RESULTS: Human adipocytes express the whole gene set that codes for the enzymatic system responsible for the biosynthesis and the degradation of ADMA, and this methylarginine is actually released by adipocytes in culture. NOS gene isoforms have a low level of expression in human adipose tissue, indicating that putative functions of ADMA in fat cells may be in part mediated by mechanisms other than NOS inhibition. CONCLUSIONS: Human adipocytes produce ADMA and express the full enzymatic machinery responsible for ADMA metabolism. Studying the functional implication of these findings may be of relevance for clarifying the role of fat mass expansion in human disease.

Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/day ratio in nondiabetic, cardiovascular events-free hemodialysis patients.

BACKGROUND: The use of 24-hour ambulatory blood pressure monitoring is increasing in end-stage renal disease (ESRD) patients but the prediction power for cardiovascular complications of time-averaged ambulatory blood pressure components has been little investigated in these patients. METHODS: We analyzed the prognostic power of 24-hour ambulatory blood pressure monitoring for all-cause and cardiovascular mortality in 168 nondiabetic, events-free hemodialysis patients selected from a total dialysis population of about 450 patients. RESULTS: During the follow-up period (38 +/- 22 months), 48 patients died, 29 of them of cardiovascular causes. On univariate Cox regression analyses, the night/day systolic ratio resulted to be the sole blood pressure indicator to be associated with all-cause and cardiovascular mortality while left ventricular hypertrophy (LVH) was a strong predictor of these outcomes. In multivariable Cox models not including LVH, the night/day systolic ratio maintained an independent prognostic value for incident outcomes. However, when both risk factors, LVH and night/day systolic ratio, were introduced into Cox models, LVH was no longer a significant predictor while the night/day systolic ratio became a predictor of marginal statistical significance. CONCLUSION: The night/day ratio emerges as the sole ambulatory blood pressure monitoring-derived indicator providing significant prognostic information in patients with ESRD. However, this indicator as well as LVH loses substantial prediction power in statistical models including both risk factors. The results suggest that the night/day systolic ratio and LVH provide overlapping prognostic information, a phenomenon in keeping with the hypothesis that they represent a common pathway leading to adverse outcomes in ESRD.