Ramón Paniagua

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.

Predictive Value of Brain Natriuretic Peptides in Patients on Peritoneal Dialysis: Results from the ADEMEX Trial

BACKGROUND AND OBJECTIVES Natriuretic peptides have been suggested to be of value in risk stratification in dialysis patients. Data in patients on peritoneal dialysis remain limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients of the ADEMEX trial (ADEquacy of peritoneal dialysis in MEXico) were randomized to a control group [standard 4 x 2L continuous ambulatory peritoneal dialysis (CAPD); n = 484] and an intervention group (CAPD with a target creatinine clearance > or =60 L/wk/1.73 m(2); n = 481). Natriuretic peptides were measured at baseline and correlated with other parameters as well as evaluated for effects on patient outcomes. RESULTS Control group and intervention group were comparable at baseline with respect to all measured parameters. Baseline values of natriuretic peptides were elevated and correlated significantly with levels of residual renal function but not with body size or diabetes. Baseline values of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) but not proANP(1-30), proANP(31-67), or proANP(1-98) were independently highly predictive of overall survival and cardiovascular mortality. Volume removal was also significantly correlated with patient survival. CONCLUSIONS NT-proBNP have a significant predictive value for survival of CAPD patients and may be of value in guiding risk stratification and potentially targeted therapeutic interventions.

Consumption of soft drinks with phosphoric acid as a risk factor for the development of hypocalcemia in children: A case-control study

A comparison of 57 cases (in children with serum calcium concentration < 2.2 mmol/L) and 171 controls (in children with serum calcium level > or = 2.2 mmol/L) was carried out to assess whether the intake of at least 1.5 L/wk of soft drinks containing phosphoric acid is a risk factor for the development of hypocalcemia. A significant association was found: odds ratio = 5.27; 95% confidence interval, 3.17 to 8.75; p < 0.001. The hypothesis of a causal relationship between intake of phosphoric acid-containing soft drinks and hypocalcemia warrants further investigation.

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.

Clinical outcomes and peritoneal histology in patients starting peritoneal dialysis are related to diabetic status and serum albumin levels

Peritoneal morphological changes seem to be related to dialysis solutions bioincompatibility and to infections, but the uremic milieu per se may also contribute to peritoneal changes. The influence of diabetes and diabetes-associated comorbidities on peritoneal histological changes in the pre-dialysis stage have been insufficiently studied. The aim of this study is to analyze the effect of diabetes and serum albumin levels on peritoneal histology and certain clinical variables such as peritoneal permeability, technique failure, and general mortality in patients starting peritoneal dialysis (PD) treatment. Eighteen PD patients without diabetes (uremic non-diabetic group, U-ND) and 65 with diabetes (uremic diabetic group, U-D) were studied prospectively. Clinical and biochemical variables were registered, and a parietal peritoneum biopsy was obtained at the time of the peritoneal catheter placement. Peritoneal histology was evaluated by light microscopy and immunohistochemistry. A control group of 15 non-uremic, non-diabetic (NU-ND) patients who underwent non-complicated elective abdominal surgery was also studied and used as control. The proportion of patients with peritoneal morphological changes as evaluated by light microscopy was higher in the two groups of uremic patients than in the control. The U-D group had higher mesothelial loss (40.9 vs 29.4%), higher mesothelial basement membrane thickening (45.5 vs 23.5%), higher proportion of vascular wall thickening/sclerosis (39.7 vs 11.1%), and higher proportion of inflammatory infiltrate (45.4 vs 23.6%) than the U-ND group. Uremic patients had lower density of mesothelial cells and higher density of inflammatory cells than the control, as evaluated by immunohistochemistry. These changes were even more striking in the U-D group than in the U-ND group. On the other hand, inflammatory infiltration to the peritoneum, mesothelial cell loss, and mesothelial basement membrane thickening were associated with higher technique failure and mortality. However, when the serum albumin level was introduced into the model, the aforementioned associations became nonsignificant. In conclusion, uremia and diabetes were associated with important peritoneal histological changes before starting PD treatment. Diabetes associated with uremia was more strongly related to the peritoneal changes than uremia per se. Hypoalbuminemia and peritoneal inflammatory infiltrate were markedly associated with technique failure and mortality in patients starting PD treatment.

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.

Renal function in protein-energy malnutrition.

Summary: So far, most studies on renal function in children with advanced protein-energy malnutrition have shown an impairment of glomerular filtration rate and renal plasma flow, as well as diminished ability to excrete an acid load and a concentrated urine. Investigation of these functions in eight marasmic infants and eight children with kwashiorkor once they were free of obvious infections and acute electrolyte disturbances has shown a practically normal renal performance.Speculation: Advanced protein-energy malnutrition does not per se cause renal dysfunction, which rather appears to be due to the usual complications of malnutrition. Various abnormalities in kidney function have been described in chronic, severe, protein-energy malnutrition. Those most frequently found are a diminished glomerular filtration rate and renal plasma flow, an impairment of renal concentrating ability, and a decreased capacity to excrete a maximally acid urine after an ammonium chloride load (2, 8, 10). However, normal values for various functions (4, 7, 9, 17) have been found in malnutrition not complicated by gastrointestinal or respiratory infections. Present results support the latter notion.

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.