Alfonso Miguel

Continuous ambulatory peritoneal dialysis as a therapeutic alternative in patients with advanced congestive heart failure

Continuous ambulatory peritoneal dialysis (CAPD) has been proposed as an additional therapeutic resource for patients with advanced congestive heart failure (CHF). The objective of this study was to determine the therapeutic role of CAPD, in terms of surrogate endpoints, in the management of patients with advanced CHF and renal dysfunction.

Importance of Residual Renal Function in Continuous Ambulatory Peritoneal Dialysis: Its Influence on Different Parameters of Renal Replacement Treatment

Objective: To study the influence of residual renal function (RRF) on different parameters of the renal substitutive treatment offered by peritoneal dialysis. Methods: We analyzed the impact of RRF on dialysis dose, nutrition parameters, anemia and phosphocalcic metabolism in 37 patients with end-stage renal disease (ESRD) treated by continuous ambulatory peritoneal dialysis (CAPD). Analytical controls were done every 6 months after an initial assessment at the end of the first month of treatment. Multiple lineal regression models were used as the statistical method to analyze the influence of RRF on different theoretically dependent factors. RRF was calculated as a mean of creatinine and urea clearances. Three observations per patient were used: one at the end of the first month of treatment; a final one at the end of follow-up (mean time 24.2 ± 11.4 months), and at a mean time between them (13.4 ± 6.7 months), with a final number of 111 observations. Results: Dialysis dose: RRF was the most important factor in terms of creatinine clearance (r2 = 0.94; β = 0.999), KT/V (r2 = 0.68; β = 0.819) and β2-microglobulin levels (r2 = 0.46; β = –0.489). Nutrition parameters: RRF was a determinant factor for normalized protein catabolic rate (r2 = 0.53; β = 0.471), percent lean body mass (r2 = 0.45; β = 0.446) and albumin levels (r2 = 0.25; β = 0.229). Anemia: RRF was the most important factor when studying hemoglobin levels (r2 = 0.28; β = 0.407). Phosphocalcic metabolism: Between the analyzed factors, RRF was the only one which reached significance on serum phosphate levels (r2 = 0.19; β = –0.594). RRF did not show any relationship with either calcium or PTH levels. Conclusions: Independent of other factors, RRF in CAPD is positively and directly related to dialysis dose, β2-microglobulin levels, nutrition parameters (albumin, normalized protein catabolic rate and percent lean body mass, hemoglobin and serum phosphate levels.

N-acetilcisteína: beneficio clínico a corto plazo tras coronariografía en pacientes renales de alto riesgo

Introduccion y objetivos. El papel de la N-acetilcisteina en la prevencion de la nefropatia por contraste tras coronariografia y sus efectos a largo plazo se presentan con resultados contradictorios en la literatura previa. Este estudio pretende clarificar su beneficio clinico. Metodos. Estudio prospectivo, aleatorizado y a doble ciego de pacientes sometidos a angiografia coronaria con insuficiencia renal cronica (creatinina plasmatica = 1,4 mg/dl). Representa asi el segundo brazo del diseno del estudio principal, previamente publicado, respecto al brazo de pacientes con funcion renal normal. Igualmente, se los aleatorizo a recibir N-acetilcisteina intravenosa (600 mg/12 h) o placebo. El objetivo principal es el desarrollo de nefropatia inducida por contraste. Resultados. Se incluyo a 81 pacientes (N-acetilcisteina, 39 pacientes; placebo, 42 pacientes), equiparables respecto a las caracteristicas clinicas basales. La incidencia total de nefropatia por contraste fue del 14,8% (12 pacientes), el 5,1% (2 pacientes) en el grupo con N-acetilcisteina y el 23,8% (10 pacientes) en el grupo a placebo (odds ratio [OR] = 0,17; intervalo de confianza [IC] del 95%, 0,03-0,84); p = 0,027). Un paciente de este ultimo grupo requirio dialisis mientras se encontraba ingresado en la unidad coronaria (1,2%). En el analisis multivariable, la N-acetilcisteina resulto factor protector independiente de la variable compuesta por nefropatia inducida por contraste, necesidad de dialisis y mortalidad durante la estancia en la unidad coronaria (OR = 0,20; IC del 95%, 0,04-0,97; p = 0,04). Sin embargo, no se observaron diferencias significativas en cuanto a mortalidad hospitalaria y al ano de seguimiento (el 10,3 frente al 16,7% y el 15,4 frente al 21,4% en los grupos con N-acetilcisteina y placebo respectivamente). Conclusiones. La administracion profilactica de N-acetilcisteina conlleva importantes beneficios clinicos a corto plazo en los pacientes renales con alto riesgo sometidos a angiografia coronaria.

Comorbidity and mortality in peritoneal dialysis: a comparative study of type 1 and 2 diabetes versus nondiabetic patients. Peritoneal dialysis and diabetes.

We conducted a retrospective study with 750 peritoneal dialysis (PD) patients in a Spanish multicenter registry between 1993 and 1999 to analyze comorbidity and mortality in type 1 diabetes (T1D), type 2 diabetes (T2D) and nondiabetic (ND) patients. 163 patients (21.7%) were diabetic – 96 T1D (58.8%) and 67 T2D (42.2%) – while 587 were not (78.3%). Different comorbidity factors such as the presence of cardiovascular disease, age over 70 and dyslipidemia at the start of PD were analyzed as well as the incidence of peritonitis, the peritonitis-free interval, need for hospitalization, mortality rate, early mortality rate, survival curves (log rank) and the impact factor (Cox) on mortality for the different variables. The comorbidity index (number of comorbidity factors when starting the treatment) and the peritonitis incidence were higher for T2D. Hospitalization rates were similar, but mortality rates were higher for T2D and early mortality rates (death during the 1st year of treatment) were higher for T1D. The actuarial survival curves showed a higher mortality for T2D with no differences between ND and T1D after adjustment for age. The mortality odds ratio was 1.78 for T2D and 1.13 for T1D, differences which were not significant after adding age over 70 and cardiovascular disease to the variables analyzed. Our results show that associated comorbidity is the most important difference between ND, T1D and T2D. While cardiovascular comorbidity is responsible for the higher percentage of early mortality found in T1D when compared to ND, both age and cardiovascular disease are responsible for the higher comorbidity and mortality found in T2D.

N-acetylcysteine: Short-Term Clinical Benefits After Coronary Angiography in High-Risk Renal Patients

INTRODUCTION AND OBJECTIVES Previous studies on the role of N-acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography and on the drugs long-term effects have produced contradictory findings. The aim of this study was to clarify the benefits of N-acetylcysteine. METHODS A prospective, randomized, double-blind study was carried out in patients with chronic renal failure (plasma creatinine= >or=1.4 mg/dL) who underwent coronary angiography. This study concerns the second arm of the main study. Findings on the arm involving patients with normal renal function have been published previously. As before, patients were randomly assigned to receive either N-acetylcysteine, 600 mg every 12 h intravenously, or placebo. The primary end-point was the development of contrast-induced nephropathy. RESULTS The study included 81 patients (39 on N-acetylcysteine, 42 on placebo) with comparable baseline clinical characteristics. The overall incidence of contrast-induced nephropathy was 14.8% (12 patients): 5.1% (2 patients) in the N-acetylcysteine group and 23.8% (10 patients) in the placebo group (odds ratio [OR]=0.17; 95% confidence interval [CI], 0.03-0.84; P=.027). One patient (1.2%) in the latter group required dialysis while in the coronary unit. Multivariate analysis showed that N-acetylcysteine was an independent protective factor against the composite end-point of contrast-induced nephropathy, need for dialysis and mortality during the coronary unit stay (OR=0.20; 95% CI, 0.04-0.97; P=.04). Nevertheless, no significant difference was observed between the N-acetylcysteine and placebo groups in the rates of in-hospital (10.3% vs. 16.7%, respectively) or 1-year mortality (15.4% vs. 21.4%, respectively). CONCLUSIONS Prophylactic administration of N-acetylcysteine provided significant short-term clinical benefits in high-risk renal patients who underwent coronary angiography.

Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient’s survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat’s death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood–brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

Diálisis peritoneal ambulatoria continua y evolución clínica de pacientes con insuficiencia cardiaca congestiva refractaria

INTRODUCTION AND OBJECTIVES Peritoneal dialysis has been proposed as a therapeutic alternative for patients with refractory congestive heart failure. The objective of this study was to assess its effect on long-term clinical outcomes in patients with advanced heart failure and renal dysfunction. METHODS A total of 62 patients with advanced heart failure (class III/IV), renal dysfunction (glomerular filtration<60 mL/min/1.73 m(2)), persistent fluid congestion despite loop diuretic treatment and at least 2 previous hospitalizations for heart failure were invited to participate in a continuous ambulatory peritoneal dialysis program. Of these, 34 patients were excluded and adjudicated as controls. The most important reasons for exclusion were refusal to participate, inability to perform the technique and abdominal wall defects. The primary endpoint was all-cause mortality and the composite of death/readmission for heart failure. To account for baseline imbalance, a propensity score was estimated and used as a weight in all analyses. RESULTS The peritoneal dialysis (n=28) and control groups (n=34) were alike in all baseline covariates. During a median follow-up of 16 months, 39 (62.9%) died, 21 (33.9%) patients were rehospitalization for heart failure, and 42 (67.8%) experienced the composite endpoint. In the propensity score-adjusted models, peritoneal dialysis (vs control group) was associated with a substantial reduction in the risk of mortality using complete follow-up (hazard ratio=0.40; 95% confidence interval, 0.21-0.75; P=.005), mortality using days alive and out of hospital (hazard ratio=0.39; 95% confidence interval, 0.21-0.74; P=.004) and the composite endpoint (hazard ratio=0.32; 95% confidence interval, 0.17-0.61; P=.001). CONCLUSIONS In refractory congestive heart failure with concomitant renal dysfunction, peritoneal dialysis was associated with long-term improvement in clinical outcomes. Full English text available from:www.revespcardiol.org.

Antigen carbohydrate 125 in heart failure: Not just a surrogate for serosal effusions?

Wehave readwith interest the letter CA-125andheart failure:Deja vu or “still to be seen” by Topatan B and Basaran A [1] where the authors concisely reviewed the current pathophysiological knowledgeof CA125 in heart failure (HF). As discussed by these authors, the pathogenesis of this biomarkers elevation inHF is complex andmultifactorial,with apparently different driven forces. For instances, a proinflammatory stimulus (IL-1, tumour necrosis factor-α, lipopolysaccharide) and mesothelial-induced stress appear thekeymechanisms related to the increaseof this biomarker in HF [1–5]. However, no clear evidence exists in regard to how these two mechanisms differentially participate in CA-125 elevation in individual patients with HF. Therefore, despite the fact that the presence of serosal effusion has shown to be importantly correlated to higher CA125 values [1], considering this biomarker just a simple surrogate for serosal effusion seems quite unfair. Along this line, we have new evidence pointing-out against the fact that CA125elevation represents justmerely a surrogate for mesothelial irritation. Since July 2008 to the end of July 2010we included in an ambulatory continuous peritoneal dialysis program17 patientswith advanced congestive HF that meet the following criteria: a) NYHA III/IV despite standard pharmacological treatment; b) estimated glomerular filtration rate b60 ml/min/1.73 m; c) clinical evidence of systemic congestion and; d) at least two admissions for acute HF. Clinical characteristics of the sample are shown in the supplementary file. The peritoneal dialysis program consisted of 2 to 3-day time exchange with dialysate solution (1.36%–2.27% of glucose) with the aim to decrease the grade of systemic congestion. In these patients, and despite the peritoneal irritation induced by the presence of an osmotic solution into the peritoneum, we observed a sustained and sizable CA125 reduction at 45 [70.86 (46.14–206.7)U/ml vs 28.77 (22.09–38.6)U/ml, p=0.002] and 120 days after dialysis onset [70.86 UI/ml (46.14–206.7) vs 27.47 (16.7– 30.05)UI/ml, pb0.001] as shown in Fig. 1a. In fact, whereas only 11.8% (n=2) of patients showed CA125 serum values within normal ranges (CA125b35 U/ml) at the moment of peritoneal dialysis onset, 70.6% (n=12) and 82.3% (n=14) of the patients displayed CA125b35 U/ml at 45 and 120 days, respectively (pb0.05 for both comparisons). Paralleling to this decrease in CA125 values, an improvement in the NYHA functional class and an increase of the relative lymphocyte count (as a marker of improvement of the inflammatory state) were observed (Fig. 1b and c). With this data, we aim to stress the concept that CA125 is more than a simple surrogate for the presence of serosal effusions and mesothelial irritation, under the assumption that peritoneal dialysate is a well known irritator of the peritoneum [6,7]. Nevertheless, why most of the studies assessing the role of CA125 in HF have shown a close relationship with the presence of serosal effusions? Obviously, this question is still unsolved, although we hypothesize that CA125 is synthesized by mesothelial cells in response to certain mechanisms activated in the congestive states, and supported by recent evidence showing a pathogenic role of venous congestion in triggering a proinflammatory state [8,9], which at the end, would activate themesothelial cells to synthesize CA125. In this framework, CA125 increase and serosal effusion are parallel processes caused by the similar pathophysiological mechanisms although not necessarily a cause–effect phenomenon. No matter which pathophysiological mechanism is behind the kinetic of this biomarker, there are certain properties that make CA125 serum determination a promising tool for HF risk stratification: a) wide availability, b) additional prognostic utility beyond clinical and biochemical markers (including natriuretic peptides) [5] and; c) in contrast of cytokines and other inflammatory markers that exhibit high variability [10], CA125 changes over time are sustained (half-life higher than 1 week) and correlated with clinical status and prognosis [11,12]. Finally, we believe there is still much to be seen regarding this biomarker, and encourage researchers in HF field to focus into the pathophysiology, biological role and the clinical utility of this glycoprotein for monitoring and guiding therapy in HF setting. The following is the supplementary material related to this article. Table 1. Baseline characteristics of the study sample. Supplementary materials related to this article can be found online at doi:10.1016/j.ijcard.2010.12.027. This study was supported by unrestricted grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, RED HERACLES RD06/0009/1001 (Madrid, Spain), Ayuda para proyectos de grupos emergentes ano 2010 de la Conselleria de Sanitat de Valencia (DOCV 6.175, 30/12/2009-Annex III), Sociedad Espanola de Cardiologia (Beca Esteve 2009) and Fresenius Medical Care. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [13].

Repercusión ecocardiográfica del estado de hidratación en los pacientes en diálisis

INTRODUCTION Cardiovascular disease is the main cause of death in Chronic Kidney Disease patients. Left ventricular hypertrophy is the most common manifestation and it is linked to arterial hypertension and overhydration. The goal of this paper is to stratify dialyzed patients according to hydration status and to make an evaluation about the possible echocardiography alterations of the different groups. METHODS A transversal study was carried out with 117 patients: 65 were on hemodialysis and 52 on peritoneal dialysis. We performed the following tests: multifrequency bioimpedance with the BCM-Body Composition Freesenius’ Monitor system, transthoracic echocardiography, and blood tests. If ECW/TBW (extracellular water vs total body water) normalization ratio for age and gender was > 2.5% SD, the patient was considered overhydrated. RESULTS HD patients are significantly overhydrated before HD (67.1%) compared to DP patients (46.1%), and almost half of the overhydrated population presents arterial hypertension. However, after an HD session, a better control of the hydration status is reached (26.1%). DP patients frequently present high arterial pressure and/or are under antihypertensive treatment (DP 76.9% vs HD 49.2%). Left ventricular hypertrophy is much more common in HD overhydrated patients, eccentric LVH being more prevalent. Overhydrated patients present significantly high values of LAVI, ILVM, OH/ECW. CONCLUSIONS Bioimpedance technique allows for the detection of a large number of overhydrated patients. Echocardiographic alterations in dialyzed patients show a high correlation between the hydration stage by ECW/TBW normalized ratio for age and gender and the LAVI and ILVM.