Prevalence and renal prognosis of left ventricular diastolic dysfunction in non-dialysis chronic kidney disease patients with preserved systolic function.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is common in non-dialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown. METHOD: We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e' velocity, average mitral valve E-wave/e' ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent estimated glomerular filtration rate (eGFR) change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated. RESULTS: Among 140 patients (age 66.2 ±â€Š14.5 years; 61% males; eGFR 39.8 ±â€Š21.8 ml/min per 1.73m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.7%). Logistic regression (odds ratio, 95% confidence interval [CI]) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94-0.99), older age (1.04, 1.01-1.06) and night-time systolic blood pressure (1.04, 1.00-1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6 years, eGFR decline (ml/min per 1.73m2; per year) was faster in patients with diastolic dysfunction (-2.12, 95% CI from -2.68 to -1.56) and in the indeterminate (11.2/100 pts per year) as compared to normal (-1.14, 95% CI from -1.64 to -0.63). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100 pts/year) than in normal group (3.5/100 pts per year)'. CONCLUSION: In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression.

Randomised Clinical Trial: Calorie Restriction Regimen with Tomato Juice Supplementation Ameliorates Oxidative Stress and Preserves a Proper Immune Surveillance Modulating Mitochondrial Bioenergetics of T-Lymphocytes in Obese Children Affected by Non-Alcoholic Fatty Liver Disease (NAFLD).

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the effective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days; subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child.

Blood Pressure Variability, Mortality, and Cardiovascular Outcomes in CKD Patients.

BACKGROUND AND OBJECTIVES: Short-term BP variability (derived from 24-hour ambulatory BP monitoring) and long-term BP variability (from clinic visit to clinic visit) are directly related to risk for cardiovascular events, but these relationships have been scarcely investigated in patients with CKD, and their prognostic value in this population is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of 402 patients with CKD, we assessed associations of short- and long-term systolic BP variability with a composite end point of death or cardiovascular event. Variability was defined as the standard deviation of observed BP measurements. We further tested the prognostic value of these parameters for risk discrimination and reclassification. RESULTS: Mean ± SD short-term systolic BP variability was 12.6±3.3 mm Hg, and mean ± SD long-term systolic BP variability was 12.7±5.1 mm Hg. For short-term BP variability, 125 participants experienced the composite end point over a median follow-up of 4.8 years (interquartile range, 2.3-8.6 years). For long-term BP variability, 110 participants experienced the composite end point over a median follow-up of 3.2 years (interquartile range, 1.0-7.5 years). In adjusted analyses, long-term BP variability was significantly associated with the composite end point (hazard ratio, 1.24; 95% confidence interval, 1.01 to 1.51 per 5-mm Hg higher SD of office systolic BP), but short-term systolic BP variability was not (hazard ratio, 0.92; 95% confidence interval, 0.68 to 1.25 per 5-mm Hg higher SD of 24-hour ambulatory systolic BP). Neither estimate of BP variability improved risk discrimination or reclassification compared with a simple risk prediction model. CONCLUSIONS: In patients with CKD, long-term but not short-term systolic BP variability is related to the risk of death and cardiovascular events. However, BP variability has a limited role for prediction in CKD.

Short-term blood pressure variability in nondialysis chronic kidney disease patients: correlates and prognostic role on the progression of renal disease.

OBJECTIVE: In chronic kidney disease (CKD), few cross-sectional studies evidenced an association between short-term BP variability (BPV) derived from ambulatory blood pressure (ABP) monitoring and renal damage. However, no study has evaluated the association of short-term BPV with the risk of CKD progression. METHODS: We performed a cohort study to assess the correlates and the predictive value for incident renal outcomes of short-term BPV in hypertensive patients with CKD stage G1-5. As measures of short-term BPV, we considered the weighted SD (W-SD), and the coefficient of variation of SBP (CV-24-h SBP). Primary outcome was a composite endpoint of ESRD (chronic dialysis or transplantation) or GFR decline of at least 50%. RESULTS: We included 465 patients (63.5 ±â€Š14.2 years; 54.7% men; eGFR: 44 ±â€Š22 ml/min per 1.73 m; proteinuria: 0.2 [0.1-0.9] g/day); W-SD, CV-24-h SBP and 24 h SBP were 12.5 ±â€Š3.3 mmHg, 11.1 ±â€Š2.8% and 127 ±â€Š16 mmHg, respectively. W-SD was independently associated with older age, history of cardiovascular disease, diagnosis of diabetic, hypertensive and polycystic nephropathy, and higher 24 h SBP whereas no association with eGFR and proteinuria was found. During follow-up (median, 6.4 years), 130 patients reached the renal outcome (107 ESRD and 23 GFR decline of ≥50%). Higher 24 h, daytime and night-time SBP robustly predicted the composite renal endpoint [1.18 (1.10-1.25) for 5 mmHg], whereas BPV as measured by the W-SD did not either when expressed as a continuous variable [hazard ratio 0.97 (95% CI 0.91-1.04)] or when categorized into tertiles [1.16 (0.70-1.92) and 0.95 (0.54-1.68) in II and III tertiles, respectively]. Similar findings were found with CV-24-h SBP. CONCLUSION: In CKD patients, short-term BPV is strongly associated with 24 h, night-time and daytime BP but is independent from the eGFR and proteinuria and does not predict CKD progression.

Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney Disease: Long-Term Cohort Study.

In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m(2), and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04-1.21 and 1.18, 1.08-1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005-0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29-3.59 and 1.71, 1.07-2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline.

Assessment of achieved clinic and ambulatory blood pressure recordings and outcomes during treatment in hypertensive patients with CKD: a multicenter prospective cohort study.

BACKGROUND: We investigated the effect of having clinic and/or ambulatory blood pressures (BPs) not at goal on cardiorenal risk in patients with non-dialysis-dependent chronic kidney disease (CKD). STUDY DESIGN: Multicenter prospective study. SETTING & PARTICIPANTS: 489 consecutive hypertensive patients with CKD (stages 1-5) with concomitant assessment of ambulatory and clinic BPs followed up in tertiary nephrology clinics. PREDICTORS: Achievement of goal for ambulatory (day- and night-time BPs <135/85 and <120/70mmHg, respectively) and clinic (<140/90mmHg) BPs was used to create 4 BP groups: clinic and ambulatory BPs at goal (group 1), clinic BP above goal and ambulatory BP at goal (group 2), clinic BP at goal and ambulatory BP above goal (group 3), and clinic and ambulatory BPs above goal (group 4). OUTCOMES: Composite cardiovascular event outcome (fatal and nonfatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and nontraumatic amputation) and a composite renal outcome (maintenance dialysis therapy or death). MEASUREMENTS: Clinic and 24-hour ambulatory BPs. RESULTS: Mean age was 64.4±14.2 (SD) years; 41% were women, and diabetes and previous cardiovascular disease were present in 36% and 30%, respectively. Groups 1-4 contained 16.8%, 22.1%, 14.5%, and 46.6%, respectively, of the overall number of participants. Median follow-up was 5.2 years. Compared to group 1, the adjusted risk of the composite cardiovascular outcome was higher in groups 3 (HR, 3.17; 95%CI, 1.50-6.69) and 4 (HR, 2.83; 95%CI, 1.50-5.34), but not in group 2 (HR, 1.55; 95%CI, 0.75-3.19). Similarly, the risk of the composite renal outcome was higher in groups 3 (HR, 3.59; 95%CI, 2.05-6.27) and 4 (HR, 2.96; 95%CI, 1.83-4.78), but not group 2 (HR, 1.24; 95%CI, 0.67-2.27). Sensitivity analyses confirmed that these results were independent from the thresholds used for defining groups. LIMITATIONS: Only white patients were enrolled. Observational design does not allow for causality to be established. CONCLUSIONS: In patients with treated CKD, clinic BP above goal and ambulatory BP at goal identify a low-risk condition, whereas clinic BP at goal and ambulatory BP above goal are associated with higher cardiorenal risk, similar to that observed in patients with both clinic and ambulatory BPs above goal.

Resistant hypertension in nondialysis chronic kidney disease.

Resistant hypertension (RH) is defined as blood pressure (BP) that remains above the target of less than 140/90 mmHg in the general population and 130/80 mmHg in people with diabetes mellitus or chronic kidney disease (CKD) in spite of the use of at least three full-dose antihypertensive drugs including a diuretic or as BP that reaches the target by means of four or more drugs. In CKD, RH is a common condition due to a combination of factors including sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system. Before defining the hypertensive patient as resistant it is mandatory to exclude the so-called "pseudoresistance." This condition, which refers to the apparent failure to reach BP target in spite of an appropriate antihypertensive treatment, is mainly caused by white coat hypertension that is prevalent (30%) in CKD patients. Recently we have demonstrated that "true" RH represents an independent risk factor for renal and cardiovascular outcomes in CKD patients.

Conversion of darbepoetin to low doses of CERA maintains hemoglobin levels in non-dialysis chronic kidney disease patients.

BACKGROUND/AIMS: Finding the lowest effective dose of erythropoietin-stimulating agents is critical in the management of renal anemia. We evaluated the efficacy of converting darbepoetin to CERA at doses lower than those usually recommended. METHODS: We selected consecutive non-dialysis chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week in absence of iron deficiency, recent blood transfusion, bleeding, neoplasia, myocardial infarction/stroke in the last 3 months. Darbepoetin ≤20 µg/week was shifted to CERA 75 µg/month, while darbepoetin 21-40 µg/week to CERA 100 µg/month. Primary endpoint was the change in hemoglobin (Hb goal, 11-13 g/dl) at month 3, 6, 9 and 12. RESULTS: Studied patients (n = 37) were aged 70 ± 13 years and GFR was 30 ± 12 ml/min/1.73 m(2); prevalence of males, diabetes and prior cardiovascular disease was 43, 45 and 40%, respectively. Before switching, efficacy population received darbepoetin 18 ± 10 µg/week with 28 patients receiving ≤20 µg/week. Prevalence of Hb goal at baseline was 75.7% and did not change at months 3 (70.3%), 6 (70.3%), 9 (72.2%), and 12 (80.0%). CERA dose remained unchanged during the study (81 ± 11, 82 ± 16, 91 ± 30, 90 ± 54 and 88 ± 61 µg/month). Out of the 438 visits performed, CERA dose was increased in 52 (11.9%) and reduced in 36 (8.2%) visits. Blood pressure, Hb, GFR, transferrin saturation and ferritin did not change. CONCLUSIONS: In chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week, CERA can be efficaciously used at doses lower than those recommended.

Survey of hidden costs of dialysis in Italian for-profit and not-for-profit centers.

BACKGROUND: Chronic dialysis exposes patients to several procedures that may influence lifestyle and quality of life. These hidden costs, however, have never been evaluated. AIM AND METHODS: To compare the costs related to diagnostic and therapeutic procedures between not-for-profit (nFP) and for-profit (FP) dialysis care systems, we mailed to Italian nephrology units a questionnaire on modalities of medical prescriptions and reservations, waiting time for tests and modalities of drugs distribution. RESULTS: 247 centers (42%) replied to the questionnaire: 177 nFP (72%) and 70 FP (28%). The response rate was 54% of nFP and 26% of FP centers. All centers provided hemodialysis (in satellite units, 42% nFP and 14% FP, p<0.001; at home, 23% nFP and 1% FP, p<0.001). Peritoneal dialysis was offered by 60% nFP and 6% FP (p<0.001). Centers provided dialysis care for 15,294 patients, 85% in nFP and 15% in FP. At least 1 general practitioner prescription for dialysis, diagnostic tests, specialist consultations and drugs, was requested to patients in 50% of nFP and 95% of FP centers (p<0.001). Reservations for tests and specialist visits were made by patients in 6% of nFP and 20% of FP centers (p<0.001). In nFP and FP centers, waiting time for tests was 2 vs. 4 days for lung x-ray (p<0.01), 7 vs. 11 days for gastroscopy (p<0.05) and 14 vs. 13 days for echocardiography (NS). Erythropoietin, phosphate binders and nutritional supplements, were supplied by patients in 7%, 46% and 37% of nFP centers, and 86%, 86% and 90% of FP centers (p<0.001). CONCLUSIONS: The dialysis care system charges patients a high hidden cost, represented by procedures related to dialysis. Higher costs and reduced choice of treatment modalities may characterize the for-profit dialysis system.