Fernando De Alvaro

Functional Longevity of the Human Peritoneum: How Long Is Continuous Peritoneal Dialysis Possible? Results of a Prospective Medium Long-term Study

Long-term peritoneal dialysis requires the maintenance of the transport function of the peritoneal membrane, and appropriate studies of possible changes are necessary. The quantification of peritoneal mass transfer coefficients (MTCs) has been judged to be the ideal method for the evaluation of peritoneal diffusion. The aim of the present study was to show the results of the prospective evaluations in long-term continuous ambulatory peritoneal dialysis patients. We have studied the clinical incidents and peritoneal function of 56 patients who started continuous ambulatory peritoneal dialysis between 1980 and 1988, and have completed at least 3 years of follow-up. Ultrafiltration capacity was calculated with a standardized formula. All patients were studied for peritoneal diffusion of urea and creatinine at least once a year. The evaluation consisted of a kinetic study done by means of a peritoneal equilibration curve for urea and creatinine, applying a bicompartmental mathematical model to calculate the MTCs. The sequential mean values for urea-MTC did not show significant changes over the observation period (20.7 +/- 5.9 mL/min for the first year v 19.8 +/- 6 mL/min for the fifth year). Creatinine-MTC values showed a significant increase over this period in the paired data analysis. The decrease of the urea-MTC to creatinine-MTC ratio may be an early and appropriate index for measuring these changes when the individual values are in the normal range. On the other hand, peritoneal ultrafiltration capacity significantly decreased over this period (1,800 +/- 530 mL/d v 1,400 +/- 600 mL/d, P < 0.01). The high rate of accumulated days of peritoneal inflammation was related to these significant changes, and thus may be proposed to be a good prognostic index of long-term peritoneal survival. These long-term functional changes might be related to the effect of injuries on the preservation of the normal peritoneal structure. We conclude that after 5 to 11 years, the human peritoneum shows functional stability (diffusion and water transport) in patients with low rates of peritoneal inflammation. With a few exceptions, represented by patients with a high rate of peritoneal inflammation, long-term peritoneal dialysis accomplished its newly entrusted task.

Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in spain: the MERENA observational cohort study

BackgroundTo obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD).MethodsMulticenter study from Spanish government hospital-based Nephrology outpatient clinics involving 1129 patients with CKD stages 3 (n = 434) and 4 (n = 695) defined by GFR calculated by the MDRD formula. Additional analysis was performed with GFR calculated using the CKD-EPI and Cockcroft-Gault formula.ResultsIn the cohort as a whole, median age 70.9 years, morbidity from all cardiovascular disease (CVD) was very high (39.1%). In CKD stage 4, CVD prevalence was higher than in stage 3 (42.2 vs 35.6% p < 0.024). Subdividing stage 3 in 3a and 3b and after adjusting for age, CVD increased with declining GFR with the hierarchy (stage 3a < stage 3b < stage 4) when calculated by CKD-EPI (31.8, 35.4, 42.1%, p 0.039) and Cockcroft-Gault formula (30.9, 35.6, 43.4%, p 0.010) and MDRD formula (32.5, 36.2, 42.2%,) but with the latter, it did not reach statistical significance (p 0.882). Hypertension was almost universal among those with stages 3 and 4 CKD (91.2% and 94.1%, respectively) despite the use of more than 3 anti-hypertensive agents including widespread use of RAS blockers. Proteinuria (> 300 mg/day) was present in more than 60% of patients and there was no significant differences between stages 3 and 4 CKD (1.2 ± 1.8 and 1.3 ± 1.8 g/day, respectively). A majority of the patients had hemoglobin levels greater than 11 g/dL (91.1 and 85.5% in stages 3 and 4 CKD respectively p < 0.001) while the use of erythropoiesis-stimulating agents (ESA) was limited to 16 and 34.1% in stages 3 and 4 CKD respectively. Intact parathyroid hormone (i-PTH) was elevated in stage 3 and stage 4 CKD patients (121 ± 99 and 166 ± 125 pg/mL p 0.001) despite good control of calcium-phosphorus levels.ConclusionThis study provides an overview of key clinical parameters in patients with CKD Stages 3 and 4 where delivery or care was largely by nephrologists working in a network of hospital-based clinics of the Spanish National Healthcare System.

Hipertensión arterial y política de salud en España

José R. Banegas a,b, , Albert Jovell , Benjamı́n Abarca , Manuel Aguilar Diosdado , Luis Aguilera , Pedro Aranda , Vicente Bertoméu , Pedro Capilla , Pedro Conthe , Fernando De Álvaro , Antonio Fernández-Pro , Xavier Formiguera , Jesús Frı́as , Lucı́a Guerrero , José L. Llisterri , José M. Lobos , Juan F. Macı́as , Ángel L. Martı́n De Francisco , Jesús Millán , Juan C. Morales , Vicente Palomo , Alex Roca-Cusachs , Javier Román , Carlos Sanchis , Antonio Sarriá , Julián Segura , Álex De La Sierra , Luis Verde , Julio Zarco n y Luis M. Ruilope a,u a Asociación de la Sociedad Española de Hipertensión y Liga Española para la Lucha contra la Hipertensión Arterial b Universidad Autónoma de Madrid, CIBERESP (CIBER de Epidemiologı́a y Salud Pública), Madrid c Foro Español de Pacientes d Sociedad Española de Medicina General e Sociedad Española de Diabetes f Sociedad Española de Medicina de Familia y Comunitaria g Sociedad Española de Cardiologı́a h Consejo General de Colegios Oficiales de Farmacéuticos i Sociedad Española de Medicina Interna j Sociedad Española de Nefrologı́a en el Comité Español Interdisciplinario para la Prevención Cardiovascular k Sociedad Española para el Estudio de la Obesidad l Departamento de Farmacologı́a y Terapéutica, Universidad Autónoma de Madrid, Madrid m Asociación de Enfermerı́a de Hipertensión y Riesgo Cardiovascular (EHRICA) n Sociedad Española de Médicos de Atención Primaria o Comité Español Interdisciplinar de Prevención Cardiovascular (CEIP) p Sociedad Española de Geriatrı́a y Gerontologı́a q Sociedad Española de Nefrologı́a r Sociedad Española de Arteriosclerosis s Sociedad Española de Farmacéuticos de Atención Primaria t Ibermutuamur-Corporación Mutua-Proyectos Sanitarios u Agencia de Evaluación de Tecnologı́as Sanitarias. Instituto de Salud Carlos III, Madrid v Asociación para la Prevención del Riesgo Cardiovascular (PRECAR) x Sociedad Española de Directivos de Atención Primaria, España

The Concept and the Epidemiology of Diabetic Nephropathy Have Changed in Recent Years

Diabetes Mellitus (DM) is a growing worldwide epidemic. It was estimated that more than 366 million people would be affected. DM has spread its presence over the world due to lifestyle changes, increasing obesity and ethnicities, among others. Diabetic nephropathy (DN) is one of the most important DM complications. A changing concept has been introduced from the classical DN to diabetic chronic kidney disease (DCKD), taking into account that histological kidney lesions may vary from the nodular or diffuse glomerulosclerosis to tubulointerstitial and/or vascular lesions. Recent data showed how primary and secondary prevention were the key to reduce cardiovascular episodes and improve life expectancy in diabetic patients. A stabilization in the rate of end stage kidney disease has been observed in some countries, probably due to the increased awareness by primary care physicians about the prognostic importance of chronic kidney disease (CKD), better control of blood pressure and glycaemia and the implementation of protocols and clinical practice recommendations about the detection, prevention and treatment of CKD in a coordinated and multidisciplinary management of the DM patient. Early detection of DM and DCKD is crucial to reduce morbidity, mortality and the social and economic impact of DM burden in this population.

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

BackgroundAnemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3).MethodsThis epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia.ResultsDuring the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia.ConclusionsRenal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patients.

Long daily hemodialysis sessions correct systemic complications of oxalosis prior to combined liver-kidney transplantation: case report.

Abstract:  An 18‐year‐old woman diagnosed with piridoxine‐resistent primary hyperoxaluria type 1 (PH‐1) and progressive renal insufficiency complicated with acute renal failure of obstructive origin who developed systemic oxalosis affecting the heart (cardiomyopathy), the skin (cutaneous ulcers) and vascular system (lower limb ischemia, as well as pulmonary and cerebral microcirculatory blockage resulting in pulmonary hemorrhage and tonic‐clonic general seizures. As conventional hemodialysis (HD) or peritoneal dialysis (PD) are unable to eliminate enough oxalate to avoid a continuous positive balance, long daily sessions (6–7 h) of high‐flux hemodialysis (highly permeable polyamide membrane of 2.1 m2) for 67 consecutive days normalized blood oxalate levels and reversed the systemic complications secondary to the calcium oxalate crystals deposit. The patient underwent a combined liver–kidney transplantation and has progressed well to the present time. The most important factors in PH‐1 treatment are analyzed. Even though combined liver–kidney transplantation is the treatment of choice and should be performed before the glomerular filtrate rate (GFR) falls below 25 mL/min/1.73 m2, intensive HD becomes necessary to prevent oxalosis in the face of acute renal failure. Also, as our case shows, intensive HD can achieve a negative oxalate balance and reverse both the systemic lesions and the oxalate deposits.

Guía Europea de Prevención Cardiovascular en la Práctica Clínica. Adaptación española del CEIPC 2008

Resumen Presentamos la adaptacion espanola realizada por el Comite Espanol Interdisciplinario para la Prevencion Cardiovascular (CEIPC) de la Guia Europea de Prevencion de las Enfermedades Cardiovasculares 2008. Esta guia recomienda el modelo SCORE de riesgo bajo para valorar el riesgo cardiovascular. El objetivo es prevenir la mortalidad y la morbilidad debidas a las enfermedades cardiovasculares (ECV) mediante el tratamiento de sus factores de riesgo en la practica clinica. La guia hace enfasis en la prevencion primaria y en el papel del medico y el personal de enfermeria de atencion primaria en la promocion de un estilo de vida cardiosaludable, basado en el incremento de los grados de actividad fisica, la adopcion de una alimentacion saludable y, en los fumadores, el abandono del tabaco. La meta terapeutica para la presion arterial es en general

Effects of Erythropoietin on Gonadotropin Responses to Gonadotropin-Releasing Hormone in Uremic Patients

Long-term therapy with recombinant human erythropoietin (rhEPO) in uremic male patients undergoing hemodialysis has been followed by an increase in plasma levels of testosterone and a decrease in baseline levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The aim of the present study was to assess the effect of acutely administered rhEPO on FSH and LH responses to gonadotropin-releasing hormone (GnRH) in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Sixteen clinically stable male patients (age, mean+/-SEM, 45.3+/-3.9 years) with chronic renal insufficiency and 12 healthy volunteers with a normal renal function, matched for age and body mass index, were studied. All patients were on CAPD therapy for at least 3 months, and none of them received rhEPO therapy. Patients were moderately anemic (hemoglobin 11.0+/-0.3 g/dl) and showed testosterone levels significantly lower than those found in control subjects (3.47+/-0.37 vs. 6.91+/-0.49 ng/ml, p < 0.001). Each subject was tested with GnRH (100 microg i.v. as bolus) and with GnRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before GnRH injection) on different days. Blood samples for FSH and LH were obtained between -30 and 120 min. In uremic patients the baseline FSH levels were higher than those found in control subjects (18.88+/-5.41 vs. 6.41+/-1.10 mU/ml, p < 0.05). After GnRH administration FSH values reached a maximum of 25.50+/-6.19 mU/ml in patients and of 12.50+/-2.02 mU/ml in controls (p < 0.05). rhEPO infusion produced a significant (p < 0.01) decrease in the area above the baseline value of FSH in uremic patients, with no other change in FSH responses to GnRH both in patients and controls. Baseline LH concentrations were significantly higher in patients than in controls (15.56+/-3.41 vs. 2.58+/-0.36 mU/ml, p < 0.001). LH peak and area under the curve of LH secretion after GnRH were significantly higher in patients than in controls (45.25+/-6.28 vs. 26.83+/-4.62 mU/ml, p < 0.05, and 77.02+/-11.30 vs. 34.40+/-5.22 mU x h/ml, p < 0.005, respectively). When GnRH was injected during the rhEPO infusion, a significant (p < 0.02) reduction in LH concentrations at 60, 90, and 120 min was found in uremic patients. Accordingly, the LH area under the curve was significantly reduced in patients (65.99+/-11.44 mU x h/ml, p < 0.05). rhEPO had no effect on GnRH-induced LH release in control subjects. These results suggest that acute rhEPO administration might reduce the exaggerated LH response to GnRH stimulation found in uremic male patients on CAPD.

Anemia Development and Cardiovascular Risk Management in Nonanemic Stage 3 Chronic Kidney Disease

Background/Aim. There is little information on the development of anemia in the early stages of chronic kidney disease. The aim of this study was to analyze the onset of renal anemia in a cohort of initially nonanemic chronic kidney disease patients followed up in nephrology clinics. Methods. This epidemiological, prospective, three-year, multicenter study enrolled patients aged 18–78 years with stage 3 chronic kidney disease without anemia. Interim analysis was performed on the data collected during the first 12 months. Results. The study included 432 patients, average age 63.6 years (range 22–78 years, 70% male). The main etiologies of chronic kidney disease were glomerular (11.6%), interstitial (10.4%), vascular (29.4%), and diabetic (16.9%). The percentages of patients with comorbidities were 33.8% diabetes (2.5% type 1), 69% dyslipidemia, and 93% hypertension. During the first year, 12.4% of patients developed anemia. The chronic kidney disease progression rate was low: proteinuria was 0.46 ± 0.8 g/24 h at one year versus 0.67 ± 1.0 g/24 h at baseline. Diabetic patients showed a greater prevalence of previous cardiovascular events (50.0% vs. 24.5%) and worse control of some modifiable cardiovascular risk factors: smoking (13.4% vs. 8.6%), obesity (BMI > 30 kg/m2, 33.6% vs. 25.3%), target blood pressure (<130/80 mmHg, 21.0% vs. 27.9%), and proteinuria (0.8 ± 1.1 vs. 0.6 ± 0.9 g/day). Conclusions. After one year, 12.4% of patients developed anemia. Diabetic patients had a higher cardiovascular risk and limited blood pressure control. The overall control of cardiovascular risk was unsatisfactory.