Marcela Ávila-Díaz

NT-proBNP, fluid volume overload and dialysis modality are independent predictors of mortality in ESRD patients

BACKGROUND N-terminal fragment of B-type natriuretic peptide (NT-proBNP) is a marker of both fluid volume overload and myocardial damage, and it has been useful as a predictor of mortality in patients with end-stage renal disease (ESRD). It has been suggested that continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD) and haemodialysis (HD) may have different effects on fluid volume and blood pressure control; however, whether the independent predictive value of NT-proBNP for mortality is preserved when analysed in conjunction with fluid overload and dialysis modality is not clear. METHODS A prospective multicentre cohort of 753 prevalent adult patients on CAPD, APD and HD was followed up for 16 months. Plasmatic levels of NT-proBNP, extracellular fluid volume/total body water ratio (ECFv/TBW) and traditional clinical and biochemical markers for cardiovascular damage risk were measured, and their role as predictors of all-cause and cardiovascular mortality was analysed. RESULTS NT-proBNP level, ECFv/TBW and other cardiovascular damage risk factors were not evenly distributed among the different dialysis modalities. NT-proBNP levels and ECFv/TBW were correlated with several inflammation, malnutrition and myocardial damage markers. Multivariate analysis showed that NT-proBNP levels and ECFv/TBW were predictors of both all-cause and cardiovascular mortality, independently of dialysis modality and the presence of other known clinical and biochemical risk factors. CONCLUSIONS NT-proBNP is a reliable predictor of death risk independently of the effect of dialysis modality on fluid volume control, and the presence of other clinical and biochemical markers recognized as risk factors for all-cause and cardiovascular mortality. NT-pro-BNP is a good predictor of mortality independently of fluid volume overload and dialysis modality.

Increments in whole body bone mineral content associated with weight and length in pre-term and full-term infants during the first 6 months of life.

BACKGROUND The objective of the present study was to assess bone mineral content (BMC) of the whole skeleton in pre-term and full-term healthy infants and the factors influencing BMC, such as bone area, birth weight, birth length, current weight, current length, gender, and gestational age. METHODS Forty-eight healthy full-term infants and 34 healthy premature infants fed predominantly with intact human milk were studied. BMC was measured monthly with dual energy X-ray absorptiometry (DEXA). At the same time, length and weight were measured and registered. Pre-term infants were studied at 60-day intervals. RESULTS For both full-term and pre-term infants, BMC increased during the first months of life. However, the values of pre-term infants never reached the values of full-term infants, even after correcting for age and weight. For both full-term and pre-term infants, BMC was significantly correlated at the second month with birth weight (r = 0.901), birth length (r = 0.860), gestational age (r = 0.803), bone area (r = 0.960), current weight (r = 0.920), and current length (r = 0.840, p <0.001 for all correlation coefficients). Multivariate analysis revealed that bone area was the most important factor in predicting BMC. CONCLUSIONS Pre-term children have lower BMC than full-term children. The main factor explaining this apparent osteopenia is bone area. Pre-term children have a higher daily mineralization rate than full-term children, but this catch-up mineralization is not enough to reach BMC levels seen in full-term children.

Cola Beverage Consumption Induces Bone Mineralization Reduction in Ovariectomized Rats

BACKGROUND A significant association of cola beverage consumption and increased risk of bone fractures has been recently reported. The present study was carried out to examine the relationship of cola soft drink intake and bone mineral density in ovariectomized rats. METHODS Study 1. Four groups of 10 female Sprague-Dawley rats were studied. Animals from groups II, III, and IV were bilaterally ovariectomized. Animals from groups I and II received tap water for drinking, while animals from groups III and IV each drank a different commercial brand of cola soft drink. After 2 months on these diets, the following were measured: solid diet and liquid consumption; bone mineral density; calcium in bone ashes; femoral cortex width; calcium; phosphate; albumin; creatinine; alkaline phosphatase; 25-OH hydroxyvitamin D, and PTH. RESULTS Study 2. Two groups of seven ovariectomized rats were compared. Group A animals received the same management as the group III animals from study 1 (cola soft drink and rat chow ad libitum), while rats from group B received tap water for drinking and pair-feeding. After 2 months plasmatic ionized calcium, phosphate, creatinine, albumin, calcium in femoral ashes, and femoral cortex width were measured. Study 1. Rats consuming cola beverages (groups III and IV) had a threefold higher liquid intake than rats consuming water (groups I and II). Daily solid food intake of rats consuming cola soft drinks was one-half that of rats consuming water. Rats consuming soft drinks developed hypocalcemia and their femoral mineral density measured by DEXA was significantly lower than control animals as follows: group I, 0.20 +/- 0.02; group II, 0.18 +/- 0.01; group III, 0.16 +/- 0.01, and group IV, 0.16 +/- 0.01 g/cm(2). Study 2. To rule out the possibility that these calcium and bone mineral disorders were caused by decreased solid food intake, a pair-fed group was studied. Despite a lower body weight, pair-fed animals consuming tap water did not develop bone mineral reduction or hypocalcemia. CONCLUSIONS These data suggest that heavy intake of cola soft drinks has the potential of reducing femoral mineral density.

Echocardiographic, electrocardiographic and blood pressure changes induced by icodextrin solution in diabetic patients on peritoneal dialysis

The use of icodextrin as an osmotic agent in solutions for peritoneal dialysis (PD) has important cardiovascular effects related with better control of extracellular volume. Among them, reduction of arterial pressure and an improvement in echocardiographic parameters stand out. In diabetic patients, icodextrin has additional potential advantages related with better metabolic control. In a multicenter, open-label randomized controlled trial, the effects of icodextrin solutions were compared to glucose solutions on echocardiographic, electrocardiographic, and blood pressure changes in diabetic patients on PD. Two phases were noted in the follow-up. In the early phase (6 months), reduction in ambulatory blood pressure (ABP) and left ventricular end diastolic diameter were found in the icodextrin group. These changes correlated with changes in body fluids. In the late phase (12 months), a trend towards baseline values in ABP was seen. Changes in inferior vena cava diameter and in low frequency R-R variability spectral analysis in the icodextrin group suggest that icodextrin increases circulating blood volume and sympathetic tone, probably by accumulation of icodextrin metabolites in the bloodstream and improvement in diabetic neuropathy as a result of lower peritoneal glucose absorption. The effects of icodextrin in diabetic patients were related to better fluid management and metabolic control.

Effect of Parathyroidectomy on Cardiac Fibrosis and Apoptosis: Possible Role of Aldosterone

Background/Aim: It has been demonstrated that parathyroidectomy prevents left ventricular hypertrophy in uremic animals. Although this effect may be mediated by direct actions of parathormone (PTH), it may also be exerted through regulation of profibrotic factors such as aldosterone. In adrenal cortex cell cultures, PTH increases aldosterone release. The objective of this work is to assess the effect of parathyroidectomy on aldosterone levels and on cardiac fibrosis and apoptosis in uremic rats. Methods: Four groups of rats were studied: C, control; 5/6Nx, 5/6 nephrectomy; PTx, parathyroidectomy, and 5/6NxPTx, 5/6 nephrectomy plus parathyroidectomy. Thirty days after the last surgical procedure the animals were sacrificed. Serum creatinine, ionized calcium, aldosterone, PTH, cardiac weight, fibrosis and apoptosis were measured. Results: Serum creatinine levels were significantly higher in 5/6Nx and 5/6NxPTx groups (1.62 ± 0.21 and 1.38 ± 0.15 mg/dl) than in C and PTx groups (0.66 ± 0.02 and 0.47 ± 0.01 mg/dl, p < 0.001). Potassium levels were significantly higher in the 5/6Nx and 5/6NxPTx groups (5.2 ± 0.3 and 5.4 ± 0.3 mg/dl) than in the C group (4.3 ± 0.06 mg/dl, p < 0.05). Values in 5/6Nx and 5/6NxPTx groups were not significantly different from each other. PTH levels were significantly higher in the 5/6Nx group (470.5 ± 156.3 µg/ml) than in the controls (102.3 ± 14.3 µg/ml). PTH levels in the PTx group (1.78 ± 0.52 µg/ml) and in the 5/6NxPTx group (81.64 ± 32.15 µg/ml) were similar to control values. Ionized calcium was lower in PTx and 5/6NxPTx groups (0.80 ± 0.07 and 0.89 ± 0.07 mmol/l) as compared with C and 5/6Nx groups (1.14 ± 0.01 and 0.96 ± 0.01 mmol/ l, p < 0.01). The heart weight as percentage of the body weight increased significantly in 5/6Nx animals (4.20 ± 0.15%) compared to the C group (3.41 ± 0.27%, p < 0.05); parathyroidectomy reversed the heart weight increment in the 5/6NxPTx animals (3.58 ± 0.16%). Myocardial fibrosis was significantly higher in the 5/6Nx group (12.5 ± 1.1%) than in the C group (7.3 ± 1.5%, p < 0.001); in the 5/6NxPTx animals fibrosis returned towards control values (8.9 ± 0.2%). Myocardial apoptosis rose significantly in 5/6Nx animals (24.3 ± 1.2%) compared to the C group (6.7 ± 0.83%, p < 0.001); parathyroidectomy reversed the apoptosis in the 5/6NxPTx animals (10.4 ± 0.49%). Aldosterone levels increased significantly in the 5/6Nx group (2,461 ± 257 pg/ml) compared to the C group (703 ± 81 pg/ml, p < 0.001); in the 5/6NxPTx animals aldosterone levels were below control values (509 ± 99 pg/ml). Conclusions: Uremia was associated to myocardial hypertrophy, fibrosis and apoptosis. Surgically induced hypoparathyroidism prevented the development of these disorders. Our results suggest that in the remnant kidney rat model myocardial hypertrophy, fibrosis, and apoptosis are mediated by high circulating aldosterone levels. Aldosterone, in turn, may be regulated by PTH.

Inflammation and Myocardial Damage Markers Influence Loss of Residual Renal Function in Peritoneal Dialysis Patients

BACKGROUND Residual renal function (RRF) has been identified as the most important component in dialysis adequacy and has a strong effect on clinical outcomes. This justifies any effort in understanding the mechanism behind the preservation or decline in RRF. The aim of this study was to analyze the possible association of components of cardio-renal syndrome with the rate of decline in RRF. METHODS A retrospective cohort study was performed in a group of prevalent adult patients on continuous ambulatory peritoneal dialysis (CAPD). Patients were analyzed at baseline and after a 30-month follow-up. Evaluations included measurements of residual renal function, dialysis adequacy parameters, cardiovascular comorbidity, and measurements of biochemical markers of cardiovascular disease (CVD) and inflammation, as well as resting electrocardiography. RESULTS We included 129 patients in the study who were divided into groups according to loss of RRF, considering the cut-off point as 100 mL/day of 24 h urine volume. At baseline, there were no differences between groups: patients who lost RRF showed low values of 24 h urine volume, higher levels of systolic blood pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), IL-6, and low values of serum albumin. In the multivariate analysis, age, albumin, CRP, and NT-proBNP were significant risk factors for the loss of RRF. CONCLUSIONS Data indicate a close relationship between heart and kidney function where chronic kidney disease (CKD) affects and is an effect of, heart function, indicative of a bi-directional influence that leads to a vicious cycle, promoting deleterious effects on both systems.

Threefold Peritoneal Test of Osmotic Conductance, Ultrafiltration Efficiency, and Fluid Absorption

♦ Background: Fluid removal during peritoneal dialysis depends on modifiable factors such as tonicity of dialysis fluids and intrinsic characteristics of the peritoneal transport barrier and the osmotic agent—for example, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption. The latter parameters cannot be derived from tests of the small-solute transport rate. We here propose a simple test that may provide information about those parameters. ♦ Methods: Volumes and glucose concentrations of drained dialysate obtained with 3 different combinations of glucose-based dialysis fluid (3 exchanges of 1.36% glucose during the day and 1 overnight exchange of either 1.36%, 2.27%, or 3.86% glucose) were measured in 83 continuous ambulatory peritoneal dialysis (CAPD) patients. Linear regression analyses of daily net ultrafiltration in relation to the average dialysate-to-plasma concentration gradient of glucose allowed for an estimation of the osmotic conductance of glucose and the peritoneal fluid absorption rate, and net ultrafiltration in relation to glucose absorption allowed for an estimation of the ultrafiltration effectiveness of glucose. ♦ Results: The osmotic conductance of glucose was 0.067 ± 0.042 (milliliters per minute divided by millimoles per milliliter), the ultrafiltration effectiveness of glucose was 16.77 ± 7.97 mL/g of absorbed glucose, and the peritoneal fluid absorption rate was 0.94 ± 0.97 mL/min (if estimated concomitantly with osmotic conductance) or 0.93 ± 0.75 mL/min (if estimated concomitantly with ultrafiltration effectiveness). These fluid transport parameters were independent of small-solute transport characteristics, but proportional to total body water estimated by bioimpedance. ♦ Conclusions: By varying the glucose concentration in 1 of 4 daily exchanges, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption could be estimated in CAPD patients, yielding transport parameter values that were similar to those obtained by other, more sophisticated, methods.

De novo Development of Heart Valve Calcification in Incident Peritoneal Dialysis Patients

BACKGROUND AND AIMS Cardiac valve calcification (VC) is a frequent complication in chronic kidney disease and is considered a risk factor for all-cause and cardiovascular mortality. However, little is known about the pathophysiology mechanisms that originate it and the factors associated with its development. We undertook this study to analyze the frequency and factors related to de novo development of mitral valve calcification (MVC) and aortic valve calcifications (AVC) in incident peritoneal dialysis (PD) patients. METHODS A prospective cohort of 124 incident PD patients was studied. Demographic and clinical data were recorded and blood assayed at baseline and after 1 year of follow-up for calcium, phosphorus, glucose, urea, creatinine, cholesterol, triglycerides by spectrophotometry assay; high-sensitivity C-reactive protein (CRP) by immunoturbidimetric ultrasensitive assay, intact parathormone (iPTH) and osteocalcin by electrochemiluminescence, fetuin-A and osteoprotegerin by EDI-ELISA. Valve calcification was evaluated by M-mode bidimensional echocardiogram. RESULTS Sixty eight percent of patients were male, ages 43 ± 13 years; 51% were diabetic with 1.4 ± 1 months on PD. After 12.3 ± 1 months, 57 patients (46%) developed VC: AVC in 33 (57.8%), MVC in 15 (26.3%) and 9 (15.8%) patients in both valves. There was no correlation between AVC and MCV. In univariate logistic regression analysis, age, diabetes and elevated concentrations of OPG, iPTH and CRP were risk factors for development MVC. In multivariate analysis, only iPTH remained an independent risk factor as was also the case in AVC. CONCLUSIONS Age, diabetes, osteoprotegerin, parathormone and C-reactive protein are risk factors related to de novo development of MVC and iPTH for AVC in incident dialysis patients.

Cardiovascular and Renal Effects of Bromocriptine in Diabetic Patients with Stage 4 Chronic Kidney Disease

Objective. The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D). Research Design and Methods. A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. Results. Both BEC and PBO groups decreased blood pressure—but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54 ± 0.15 to 0.32 ± 0.17 pg/mL) and increased in PBO (0.37 ± 0.15 to 0.64 ± 0.17 pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group. Conclusions. BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged.

Reaching Targets for Mineral Metabolism Clinical Practice Guidelines and Its Impact on Outcomes Among Mexican Chronic Dialysis Patients

BACKGROUND AND AIMS An increasing number of studies have been published concerning meeting targets of clinical guidelines for different aspects of the diagnosis and treatment of patients with end-stage renal disease. Most of these studies have shown that guideline recommendations are not always satisfied, and results outside target limits have been associated with high rates of mortality and morbidity. The objective of this study was to analyze the frequency of reaching mineral and bone metabolism-related guideline targets and its impact on clinical outcomes in Mexican chronic dialysis patients. METHODS A cohort of prevalent peritoneal dialysis (PD) and hemodialysis (HD) patients were analyzed at baseline and followed for at least 16 months. Patients were on continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD), and HD and contracted HD modalities where patients received HD sessions outside institution facilities. RESULTS We studied 753 patients. The percentage of patients within target limits for phosphorus was 35%, for calcium 32%, and for PTH 12%. The most frequent pattern was hyperphosphatamia, hypercalcemia, and low PTH. This was even more frequent in CAPD patients, probably due to the high percentage of diabetic patients. Hypercalcemia was found as an independent risk factor for mortality. CONCLUSIONS The most important results suggest that guideline recommendations are not usually satisfied and that hypercalcemia, in addition to other traditional risk factors, is associated with high mortality rates. The study also detected some opportunities to improve the quality of treatment by reducing the calcium content of dialysis solutions and reducing the use of calcium carbonate as a phosphate binder.