Background Nondipping status is associated with greater cardiovascular morbidity and mortality and faster progression of chronic kidney disease (CKD). We examined whether shifting 1 antihypertensive ...drug from morning to evening restores the circadian rhythm of blood pressure in nondipper patients with CKD. Study Design 8-week clinical trial without a control group. Setting & Participants We selected from our outpatient renal clinic 32 patients with CKD with estimated glomerular filtration rate less than 90 mL/min/1.73 m2 and night-day ratio of mean ambulatory blood pressure (ABP) greater than 0.9, but with normal daytime ABP (<135/85 mm Hg) to avoid the required therapy intensification. Intervention Shifting 1 antihypertensive drug from morning to evening. Outcomes Percentage of patients changing the night-day ratio of mean ABP from greater than 0.9 to 0.9 or less 8 weeks after the shift. Measurements Office blood pressure/ABP and proteinuria at baseline and after the shift. Results There were 55% men with a mean age of 67.4 ± 11.3 years and estimated glomerular filtration rate of 46 ± 12 mL/min/1.73 m2 . They were treated with 2.4 ± 1.4 antihypertensive drugs. After the drug shift, the night-day ratio of mean ABP decreased in 93.7% of patients, with normal circadian rhythm restored in 87.5%. The nocturnal systolic and diastolic ABP decrease was not associated with an increase in diurnal ABP and was independent from number and class of shifted drug. Office blood pressure in the morning also decreased (from 136 ± 16/77 ± 10 to 131 ± 13/75 ± 8 mm Hg; P = 0.02). Urinary protein excretion decreased from 235 ± 259 to 167 ± 206 mg/d ( P < 0.001). Limitations Absence of a control group and patients with severe proteinuria or uncontrolled daytime ABP. Conclusions In nondipper patients with CKD, changing the timing of antihypertensive therapy decreases nocturnal blood pressure and proteinuria.
Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients ...and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1−/−) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1−/− resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1−/− resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Results show that a primary function of HCDs in cardiac muscle is the regulation of Ca2+ handling and excitation-contraction coupling.
Background. The role of white coat hypertension (WCH) in the poor control of blood pressure (BP) in chronic kidney disease (CKD) is ill defined. Methods. We measured systolic clinical (CBP) and ...ambulatory blood pressure (ABP) in 290 consecutive patients with non-dialysis CKD glomerular filtration rate (GFR) <60 ml/min/1.73 m2. We defined normotension (NOR) if CBP and daytime ABP <130 mmHg, sustained hypertension (SH) when both BP ≥130 mmHg, WCH if only daytime ABP <130 mmHg, and masked hypertension (MH) when only CBP <130 mmHg. Results. NOR patients were 15.5%, WCH 31.7%, SH 46.9% and MH 5.9%. Due to the high prevalence of WCH, achievement of BP target (<130 mmHg) was more than doubled by daytime ABP than CBP (47.2 vs 21.4%). WCH was characterized by prevalence of diabetes (31.5%), left ventricular hypertrophy (LVH; 50.0%) and CBP values (146 ± 12 mmHg) lower than in SH (41.9%, 71.3% and 158 ± 18 mmHg) but greater than in NOR (17.8%, 37.8% and 118 ± 7 mmHg). Among patients with CBP ≥130 mmHg, the independent risk of having SH rather than WCH increased in the presence of higher CBP Odds ration (OR) 1.61, 95% confidence intervals (CI) 1.29–2.02, LVH (OR 1.94, 95% CI 1.03–3.63) and proteinuria (OR 3.12, 95% CI 1.31–7.43). In the WCH group, 24 h, daytime and nighttime ABP were 118 ± 7/68 ± 8, 120 ± 7/71 ± 8 and 112 ± 12/63 ± 9 mmHg, respectively. Conclusions. In CKD, WCH is highly prevalent and can be predicted in the absence of higher CBP, LVH and proteinuria. In these patients, pursuing a low BP target may not be safe because of the risk of cardio–renal hypoperfusion especially at nighttime.
To evaluate effect of age on hypertensive status in chronic kidney disease (CKD).
We studied 459 prevalent CKD patients (stages 2-5, no dialysis), grouped by age (< 55, 55-64, 65-74, >or= 75 years), ...undergoing clinical blood pressure (CBP) and ambulatory blood pressure (ABP) measurement.
Prevalence of diabetes, left ventricular hypertrophy and previous cardiovascular disease progressively increased with aging; glomerular filtration rate (GFR) and hemoglobin decreased. Achievement of CBP target decreased from 16% in patients < 55 years to 6% in those >or= 75 years (P = 0.023). ABP 24-h systolic rose while diastolic decreased, with a consequent pulse pressure increase from 45 +/- 8 to 65 +/- 14 mmHg (P < 0.0001). Age, proteinuria, diabetes, cardiovascular disease and anemia but not GFR predicted higher 24-h pulse pressure. CBP overestimated systolic/diastolic daytime ABP by 14 +/- 18/7 +/- 11 mmHg on average, a greater difference in older than younger groups (P < 0.005). Conversely, CBP night-time ABP difference did not vary among groups (24 +/- 20/16 +/- 11 mmHg). These age-dependent differences determined a rising prevalence of white-coat hypertension (from 19 to 40%, P = 0.001) and night/day ratio of at least 0.9 (from 43 to 66%, P = 0.0004). Age, diabetes, left ventricular hypertrophy and anemia but not GFR predicted nondipping status. Among the oldest patients, 13% had diastolic CBP below 70 mmHg, with 48% below the corresponding values of daytime (< 69 mmHg) or night-time ABP (< 60 mmHg).
In CKD, prevalence of white-coat hypertension, nondipping status and potentially dangerous low diastolic ABP increases with aging. This suggests wider use of ABP monitoring in older patients and need for trials addressing identification of an age-specific blood pressure target.
we evaluated prevalence and prognosis of mild anemia, defined as Hb (g/dl) 11-13.5 in males and 11-12 in females, in a prospective cohort of stage 3-5 chronic kidney disease (CKD) patients.
we ...enrolled 668 consecutive patients in 25 renal clinics during 2003. Patients with frank anemia (Hb <11 or erythropoiesis-stimulating agents) at enrolment were excluded. Mild anemia was evaluated at two visits planned with an interval of 18 ± 6 months to identify four categories: no anemia at both visits, mild anemia at visit 1 resolving at visit 2 (RES), mild anemia persisting at both visits (PER), and progression from no anemia or mild anemia at visit 1 to mild or frank anemia at visit 2 (PRO).
mild anemia was present in 41.3% at visit 1 and 34.1% at visit 2. We identified PER in 22% patients, RES in 10%, and PRO in 26%. In the subsequent 40 months, 125 patients developed end-stage renal disease (ESRD) and 94 died. At competing risk model, PER predicted ESRD (hazard ratio, HR, 1.82, 95% confidence interval, CI, 1.01-3.29) while PRO predicted both ESRD (HR 1.81, 95% CI 1.02-3.23) and death (HR 1.87, 95% CI 1.04-3.37).
in non-dialysis chronic kidney disease, mild anemia is prevalent and it is a marker of risk excess when persistent or progressive over time.
Background:
Postdialytic rebound (PDR) of plasma solutes is a relevant drawback of intermittent hemodialysis, but its pathophysiological process remains undefined. We assessed the independent effects ...of efficiency and length of dialytic session on PDR of urea, phosphate, and potassium.
Methods:
Uremic patients were evaluated at the beginning and end of dialysis and after 180 minutes in 2 randomized crossover studies. In study 1, we compared the effect of standard versus higher efficiency acetate-free biofiltration (AFB) while maintaining the same duration of 4 hours. In study 2, we compared the effect of 3- versus 5-hour AFB sessions while maintaining similar efficiency.
Results:
In study 1, greater Kt/V (1.49 ± 0.20 versus 1.22 ± 0.15;
P < 0.0001) was coupled with significant increases in both absolute removal and PDR of urea and phosphate (PDR of urea, +45% versus +29%; PDR of phosphate, +79% versus +52%), but not of potassium. Similarly, in study 2, shortening the AFB session while maintaining similar absolute removal and Kt/V (1.28 ± 0.09 versus 1.31 ± 0.09) significantly increased PDR of urea and phosphate (PDR of urea, +32% versus +19%; PDR of phosphate, +63% versus +36%), but not of potassium. In both studies, greater PDRs of urea and phosphate were associated with estimated greater removal of these solutes per hour.
Conclusion:
The rate of removal of phosphate and urea is a critical determinant of their PDR; conversely, potassium is not influenced by removal rate, likely because of its marked cell compartmentalization.
Guidelines have indicated the achievement of blood pressure target (BP <130/80 mmHg) as a priority in the conservative treatment of chronic kidney disease (CKD), but the current implementation of ...these recommendations in clinical practice is unknown.
We assessed control rates, treatment and clinical correlates of hypertension in 1201 adult non-dialyzed CKD patients followed up by a nephrologist for at least 6 months.
Estimated glomerular filtration rate (GFR) was 32 (SD 15) mL/min/1.73 m2. BP target was not achieved in 88% of patients (95% confidence interval (95% CI): 86-90%). In 84% of patients, BP levels were also above the target at the first visit to the nephrology unit 4.5 yrs previously. The risk of not achieving BP target during the nephro-logy follow-up was associated with older age (odds ratio (OR): 1.24, 95% CI 1.06-1.45, p=0.008), diabetes (OR: 2.25, 95% CI 1.20-4.20, p=0.011), and the duration of hypertension (OR: 1.13, 95% CI 1.02-1.24, p=0.016). Among patients with uncontrolled BP, about 70% received multidrug antihypertensive therapy including renin-angiotensin system (RAS) inhibitors; conversely, diuretic treatment was prescribed in a minority of patients (37%), and at insufficient doses in half the cases, despite the insufficient implementation of a low salt diet (18%).
BP target was not reached in most CKD patients routinely seen in the renal clinics. The main barrier to guideline implementation is possibly the inadequate treatment of extracellular volume expansion despite the large prevalence of factors, such as older age and diabetes, which further enhance the intrinsic BP salt sensitivity of CKD.
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