New oral anticoagulants in patients with chronic kidney disease. / Nuevos anticoagulantes orales en pacientes con enfermedad renal crónica.

Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.

Compliance with mineral metabolism targets in haemodialysis patients: moving backwards?

BACKGROUND: To standardize therapy and improve the clinical outcome for chronic haemodialysis (HD) patients, guidelines have been developed for mineral metabolism management. We evaluated compliance with different mineral metabolism guidelines. METHODS: 2,951 chronic HD patients from 61 dialysis centres in Spain were studied. Mineral metabolism management data from a 1-year period were analysed according to KDOQI, KDIGO, and Spanish guidelines. RESULTS: Only 1% (KDOQI), 6% (KDIGO) and 11% (Spanish guidelines) of patients continuously achieved total calcium (Ca), phosphate (P) and parathyroid hormone (PTH) target-range values during the year with higher percentages if we considered the 1-year average. The yearly Ca, P and iPTH average accomplished Spanish guidelines with different percentage among centres: CA 62-100%, P 59-91%, PTH 61-89%, and 28-77% considering all three targets together. The KDIGO guidelines recommend similar percentages except for P (33-77%). No differences were found related to eKt/V, online haemodiafiltration/HD, weight, body mass index, or dialysis vintage. They were only related to age, blood flow, effective treatment time, and dialysate calcium but without relevant clinical differences. Patients outside the target ranges generated significantly higher treatment costs. CONCLUSIONS: Compliance with mineral metabolism targets in HD patients was poor and showed a wide variation between treatment centres.

Economic impact of vitamin D treatment on chronic kidney disease patients.

During recent years, increasing recognition has been given to the endocrine action that vitamin D has on the extraskeletal system, and its deep involvement in CKD. This has meant that many vitamin D compounds (both nutritional and active) have been made available, with an important cost reduction. This review looks at the evidence available regarding the usefulness of different types of vitamin D (nutritional and active) for patients with stage 3-5 CKD and those undergoing dialysis. Emphasis is given to its usefulness to control hyperparathyroidism and its impact on morbidity and mortality. We also analysed pharmacoeconomic studies that have been published which compare active vitamin D metabolites. From this review, we are able to conclude that there is still not enough scientific evidence to be able to prefer one active vitamin D over another. In the meantime, doctors should follow the recommendations given in clinical practice guidelines, always taking into account their personal experience with patients. Furthermore, they must consider the economic impact that their treatment decisions may have.

Under-recognized renal insufficiency in hospitalized patients: implications for care.

BACKGROUND: The consequences of undetected low glomerular filtration rate (GFR) are important in hospitalized patients who receive potentially nephrotoxic drugs or undergo major surgery. This study estimated the prevalence of estimated GFR (eGFR) <60mL/min/1.73m(2) in hospitalized patients. METHODS: This cross-sectional descriptive study included 14,658 adults hospitalized at 10 centers in Spain. Serum samples were analyzed for hemoglobin, creatinine, albumin and urea nitrogen. eGFR was estimated using Modification of Diet in Renal Disease (MDRD) 4 or MDRD IDMS, and MDRD 6 when serum albumin and BUN were included (n=8611). Individuals were classified as having GFR>or=60mL/min/1.73m(2), stages 3, 4 and 5 (GFR 30-59, 15-29 and <15mL/min/1.73m(2), respectively). Additionally, stages 3a and 3b (GFR 45-59 and 30-44mL/min/1.73m(2), respectively) were assessed. RESULTS: MDRD 4 eGFR showed that 28.3% of patients had renal insufficiency stages 3-5 and 14.2% had stages 3b, 4 or 5, which represents important-severe renal deterioration. Forty-three percent of patients with stages 3-5 had hemoglobin or=60mL/min/1.73m(2). A good correlation was observed between eGFR MDRD 4 and MDRD 6. CONCLUSIONS: A high percentage of hospitalized patients in Spain have deteriorated renal function stages 3-5. Using eGFR equations to assess eGFR could identify more hospitalized patients with renal insufficiency, potentially leading to improved care.

[The Bahía 2008 Study: hydration barometer in the Spanish population]. / Estudio Bahía 2008: barómetro de la hidratación de la población española.

BACKGROUND: Vital functions require a balance between the loss and ingestion of liquids. There are no studies about hydration on Spanish population. MATERIAL AND METHODS: 6,508 questionnaires were applied to a randomly selected Spanish population, together with a 24-hour recall in order to measure liquid consumption and variables related to it. RESULTS: The average consumption of liquids was 2,089.5 +/- 771.4 and 6.05 drinking times/day. 3,423 persons (52.6% of the studied people, CI 95% 51.3%-53.8%) were well-hydrated when considering their individual intake. The frequency and volume of drinking decreased with age. 61% (CI 95% 58.64%-64.01%) of the population older than 65 years were badly hydrated. The greatest bottled water consumption corresponded to the youngest population (18-29 years). The greater the physical activity, the greater the beverages consumption (1,987.6 +/- 705.5 ml vs 2,345.8 +/- 928.1 ml, low vs. intense physical activity, respectively). With regard to the intake frequency and volume, mineral and tap water were the most consumed. Those who drank mineral water exceeded the 2 l-recommendation in order to maintain a good hydration status. 59.8% (CI 95% 57.83%-61.76%) of those who preferred mineral water drank more than 2 l/day and drank more times/day and in greater amounts. There was a greater frequency and amount of beverage consumption when people lived in the same house, and particularly more in houses where children were living (2,197.4 +/- 767.8 ml vs 2,055.7 +/- 769.86 ml and 6.4 +/- 2.2 times vs 5.9 +/- 1,9 times, in homes with or without children, respectively). Bottled water was preferred at home (79.07%) and at work (15.61%). CONCLUSIONS: Only half of the Spanish population is well hydrated. Sixty-one percent of people over the age of 65 years were poorly hydrated, consequence it is imperative to promote its consumption.

The phenomenon of hemoglobin variability with erythropoiesis stimulating agents in renal transplant patients.

Treatment with erythropoiesis-stimulating agents (ESA) is often associated with fluctuation in hemoglobin (Hb) levels that has been considered a factor that influences morbidity/mortality in hemodialysis patients. Our aim was to describe the hemoglobin variability during ESA treatment and to study associated factors in kidney transplants. Hb variability (defined as fluctuations of Hb +/- 1.5 g/dl) was assessed in 85 renal transplant patients treated with ESA for at least 3 months and with a minimum of 6 Hb measurements along 1 year. 58% of patients experienced Hb variability during follow-up. Although 71.3% of patients maintained Hb levels greater than 11 g/dl along the whole follow-up, only 3% of patients maintained stable Hb levels within the target range all the time (11 - 13 g/dl). By multivariate analysis, clinical factors associated with variability were changes in ESA dose (RR 2.92, p = 0.04), infectious events with hospitalization (RR 1.95, p = 0.03) and the use of sirolimus (RR 1.1, p < 0.05). Excluding dose changes and hospitalization in the analysis variability was an independent predictor of graft function deterioration. In conclusion, Hb variability is common in renal transplants treated with ESA. Only few patients maintained Hb levels in the therapeutic range (11 - 13 g/dl). Dose changes, inflammatory status and graft function deterioration are the determining factors.

Chronic renal disease in renal transplant patients: management of cardiovascular risk factors.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Despite improvements in short-term patient and graft outcomes, there has been no major improvement in long-term outcomes. The aim of this study was to determine the prevalence of cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes, chronic kidney disease, and obesity, and the impact of their control among 526 stable renal transplant recipients according to the guidelines in the general population. Mean blood pressure was 133 +/- 16/81 +/- 9 mm Hg. The proportion of patients on antihypertensive therapy was 75%, and on ACE inhibitors or angiotensin II receptor blockers, 26%. The mean cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were 195 +/- 41, 115 +/- 32, 51 +/- 17, and 137 +/- 75 mg/dL, respectively. The proportion of patients on statin treatment was 49.7%, and those with body mass indices between 25 and 30, 30 and 35, and >35 kg/m(2) were 35%, 15%, and 4%. We observed a high prevalence of chronic kidney disease, hypertension, dyslipidemia, and obesity among renal transplant patients. Suboptimal control was frequent and control of some of these complications was far below targets established for nontransplant patients despite progressive intensification of therapy with functional graft decline. The findings of this study may have an impact on the management of renal transplant recipients.

Survival after dialysis initiation: a comparison of transplant patients after graft loss versus nontransplant patients.

BACKGROUND: A substantial number of patients return to dialysis therapy after a renal transplant fails. It is not clear whether mortality increases among patients with graft failure relative to those who initiate dialysis but who have not yet received a kidney transplant. PATIENTS AND METHODS: We compared the outcomes of an incident cohort of patients (n = 194) with a cohort of renal transplant patients who returned to dialysis after graft loss (n = 74). We analyzed the morbidity and mortality after dialysis initiation and the parameters during the year beforehand. RESULTS: Mortality among post-graft loss dialysis patients was higher than transplant-naive patients (relative risk [RR]: 2.05; 95% confidence interval [CI]: 1.26-3.35). Additionally, complications, such as the number of hospitalizations during the first year after dialysis initiation, were higher (29% vs 57%; P > .001). At dialysis initiation no differences were found in glomerular filtration rate, although hemoglobin and albumin levels were lower and C-reactive protein was higher in post-graft loss dialysis patients. CONCLUSIONS: Mortality among patients on dialysis therapy after graft loss increased significantly compared with mortality among patients who initiated dialysis for the first time, despite specialty physicians being aware of them. Additional studies are urgently needed to define the mechanisms of the increased risk and strategies to decrease mortality.

Hemoglobin level variability in renal transplant patients treated with erythropoiesis stimulating agents.

OBJECTIVE: Treatment with erythropoiesis stimulating agents (ESA) is associated with fluctuations in hemoglobin (Hb) levels. Recently, variability of Hb has been considered a factor that influences comorbidity and mortality among hemodialysis patients. The purpose of this analysis was to describe the phenomenon of Hb variability during ESA treatment, to study associated factors among kidney transplant patients, and to assess the impact on patient and graft survivals. PATIENTS AND METHODS: Hb variability (defined as fluctuations of Hb +/- 1.5 g/dL) was assessed in 85 renal transplant patients treated with ESA for at least 3 months and with a minimum of 6 Hb measurements during 1 year. RESULTS: Fifty-eight percent of the patients experienced Hb variability during follow-up. Only 3% of patients maintained stable Hb levels within the target range (11-13 g/dL), although 83% of patients maintained Hb levels >11 g/dL. Multivariate analysis showed that the clinical factors associated with variability were changes in ESA dose (relative risk [RR]: 2.92; 95% confidence interval [CI]: 1.0-8.5; P < .05), infectious events with hospitalization (RR: 1.95; 95% CI: 1.23-2.13; P < .05), and the use of sirolimus (RR: 1.1; 95% CI: 1.0-3.6; P < .05). When dose changes and hospitalization were excluded from the analysis, variability was an independent predictor of worsening graft function. CONCLUSIONS: Hb variability is common in renal transplant patients treated with ESA. Only a few patients maintained Hb levels within the therapeutic range, although most had levels >11g/dL. Dose changes, inflammatory status, and worsening graft function are the determining factors of variability. Variability had no influence on patient survival, although it was a marker of worsening graft function.

[Dialysis and transplant. Spain in 2005]. / Informe de Situación de Diálisis y Trasplante en España, 2005.

In 2005, renal replace treatment (dialysis and transplant) was necessary for about 40,000 people, without being known the number accurate and either their basic characteristics, such as: time in treatment, modality or treatment changes. The presented data cover the 76% of the Spanish population and are the result of the cooperation among technicians of registries, nephrologists and transplant coordinations. 4,125 people started RRT in 2005, the total estimated acceptance rate for renal replacement therapy in adults in Spain was 126 pmp and regarding other European countries it locates us in an intermediate area. The incidence rate seems to keep stable in the last years although there were some differences among communities (from 104 pmp in Castile and Leon to 186 pmp in Canary Islands). Diabetes Mellitus is the most diagnosed cause of renal failure in 2005, more than 20% of patients, followed by vascular diseases. The estimated prevalence of renal replacement therapy in Spain at the end of 2005 was 903 pmp, with important variations among communities (from 806 pmp in Cantabria to 1056 pmp in Valencia Region). The 47% of prevalent RRT patients had a functioning transplant. Mortality on haemodialysis and peritoneal dialysis was 13.7% and 10.8% respectively. Mortality on transplant was 1.3%, one of the lowest values registered so far. Mortality on renal replacement therapy was around 5% among patients from 45 to 64 years, 11% between 65 and 74 years and 19% among the patients older than 75 years.

[Epidemiological study on chronic renal failure elderly patients on hemodialysis]. / Estudio epidemiológico de pacientes ancianos con insuficiencia renal crónica en hemodiálisis.

Hemodialysis shows an increased prevalence in elderly patients, a population which often presents poor nutrition, high prevalence of cardiovascular, neurological and osteoarticular diseases and psycho-social problems. The objective of this epidemiological, cross-sectional and multicenter study, in patients older than 65 years (n 625) and >75 years (n 558) from 29 Spanish medical institutions was to perform an epidemiological analysis It included demographic information, as well as data regarding chronic renal failure, functional and psychological abilities (Katz Index, Lawton and Karnofsky Scales), dialysis logistics and clinical parameters. The study analyzed data from 1,183 patients (678 female), mean age 75.4+/-5.5 years; mean duration of dialysis 4.3+/-5.1 years (57.7% were referred by the GP: general practitioner). The most frequent etiologies were diabetic nephropathy (21.2%) and vascular renal disease (20.9%). The main comorbilites were high blood pressure (75.6%), Diabetes Mellitus (32.9%) and vascular (29.0%) and osteoarticular (27.3%) diseases. The great majority of patients lived at their family home (85.0%), travelled to their dialysis units alone (80.8%) and by ambulance (56.7%), and it took them less than an hour to arrive (87.5%). Over 75% of patients were fully functional (79.4% under 75 years and 71.6% over 75); meanwhile 10.5% were partially impaired and 13,8% severely impaired. Karnofsky performance scale scored less than 70 in 59.4% of the patients. Analytical parameters rated Hb >or= 11 g/dL for 81.7% of patients; ferritin >or= 100 ng/dL for 98.5%; PTH 150-300 pg/mL for 31.9%; albumin >3.5 g/dL for 75.6%; and serum phosphor <5.5 mg/dL for 70.6%. For the dialysis Kt/V the mean value was 1.4+/-0.3 with a mean duration of dialysis session of 11.7+/-4.0 hours/week. High permeability membranes were used in 52.3% of patients and internal arteriovenous fistula in 74.0%. Around 75% of elderly patients on hemodialysis fulfill age-suitable daily living activities and display adequate dialysis quality parameters.

Prevention of murine lupus disease in (NZBxNZW)F1 mice by sirolimus treatment.

Sirolimus is a new immunosuppressive drug used to avoid allograft rejection. The immunosuppressive effect of sirolimus is due to inhibition of the mammalian target of rapamycin, necessary for the proliferation and clonal expansion of activated T-cells. Because T-cells play a central role in the pathogenesis of autoimmune disease developed in (NZBxNZW)F1 mice, we evaluated the therapeutic use of sirolimus in such mice. (NZBxNZW)F1 female mice received 1mg/kg/day of sirolimus from 12 to 37 weeks of age. The development of autoimmune disease was evaluated by measuring the serum levels of auto-antibodies (autoAbs) and their immunoglobulin isotypes, prevalence of glomerulonephritis and mortality rates. Sirolimus directly inhibited production of autoAbs, glomerular deposits of immunoglobulins and development of proteinuria; also the survival of these mice was prolonged. Our results demonstrate the beneficial effects of sirolimus in preventing the development of lupus disease in (NZBxNZW)F1 female mice.

[Prevalence of kidney insufficiency in primary care population in Spain: EROCAP study]. / Prevalencia de insuficiencia renal en Centros de Atención Primaria en España: Estudio EROCAP.

This cross-sectional, multicenter study investigated the prevalence of chronic kidney disease and associated disorders, in an adult population sample (> 18 years old) attending Primary Care services in Spain. Estimated glomerular filtration rate (Modification Diet in Renal Disease equation) was used for analysis of kidney disease prevalence according to NFK-KDOQI (The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) stages. Data were collected on serum creatinine, other laboratory parameters blood pressure, and medical history of cardiovascular risk factors or disease (hypertension, dislypidemia, diabetes, congestive heart failure, coronary artery disease, stroke or peripheral arteriopathy) in 7,202 patients attending Primary Care Centers. 47.3% were males, mean age 60,6 +/- 14,3 years, BMI 28.2 +/- 5.3, with 27,6% overweight (27-30 kg/m2) and 32,1% obese (BMI>or=30 kg/m2), The prevalence of cardiovascular risks factors were: absence in 17.3%, one factor 26.9% two 31.2%, and 23.6% presented three or more The frequency of CV risk factors was: hypertension (66.7%), dyslipidemia (48%) and diabetes (31.5%). Congestive heart failure, coronary artery disease, stroke or peripheral vascular disease frequency was lower than 10% The prevalence of eGFR < 60 ml/min x 1.73 m2 was: stage 3 (30-59 ml/min/1.73 m2) 19.7%; stage 4 (15-29 ml/min/1.73 m2) 1.2%; stage 5 no dialysis (GFR < 15 ml/min) 0.4%. This prevalence increased with age in both sexes and 33,7% of patients attending Primary Care services over 70 years presented a eGFR < 60 ml/min. Of the total patients with eGFR < 60 ml/min 37.3% had normal serum creatinine levels. This study documents the substantial prevalence of significantly abnormal renal function among patients at Primary Care level. Early identification and appropriate nephrological management of these patients with renal disease is an important opportunity for an adequate prescription of drugs that interfere with renal function, to delay the progression of renal disease and modify CV risk factors.

Acute renal failure associated with use of inhaled tobramycin for treatment of chronic airway colonization with Pseudomonas aeruginosa.

Aminoglycoside nephrotoxicity is a well-known clinical entity that complicates the course of infectious diseases treated under this antibiotic regime. Recently, a new administration form of tobramycin, inhaled tobramycin (TOBI), has been approved to improve the antibacterial activity and reduce nephrotoxicity. We describe the clinical case of a 73-year-old woman with chronic-obstructive pulmonary disease (COPD) who developed acute renal failure (ARF) after using TOBI. Clinical presentation and biochemical parameters were compatible with aminoglycoside-induced renal failure. Based on the clinical findings presented here, a surveillance program should be established to monitor the presence of factors predisposing to renal failure, and to measure serum levels of tobramycin.

Continuous Erythropoietin Receptor Activator (C.E.R.A.) administered at extended administration intervals corrects anaemia in patients with chronic kidney disease on dialysis: a randomised, multicentre, multiple-dose, phase II study.

This dose-finding, open-label study examined the potential of subcutaneous Continuous Erythropoietin Receptor Activator (C.E.R.A.) to correct anaemia at extended administration intervals in 61 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease (CKD) on dialysis. After a 4-week run-in, patients were randomised to C.E.R.A. 0.15, 0.30 and 0.45 microg/kg/week. Within these dose groups, patients were further randomised to once weekly, once every 2 weeks or once every 3 weeks treatment. Mean changes in haemoglobin (Hb) increased with increasing C.E.R.A. dose during a period of 6 weeks where no dose adjustments were permitted. The effect was independent of administration schedule. Erythropoietic responses were sustained until the end of the study (12 weeks) in all groups. In total, 90% of patients in the 0.30 microg/kg/week group and 79% in the 0.45 microg/kg/week group responded to treatment (Hb increase > or =1.0 g/dl), compared with 72% in the 0.15 microg/kg/week group. Faster median response time was associated with increasing dose (51, 38 and 31 days, respectively) and response was unrelated to administration frequency. C.E.R.A. was generally well tolerated. Our results suggest that 0.60 microg/kg twice monthly would be a suitable starting dose of C.E.R.A. for the initiation of anaemia correction in patients with CKD on dialysis. Phase III studies will confirm the feasibility of using C.E.R.A. at extended administration intervals in patients with CKD and anaemia.

Antibody-mediated pure red-cell aplasia (PRCA): the Spanish experience.

BACKGROUND: The incidence of antibody (Ab)-mediated pure red-cell aplasia (PRCA) in patients with chronic kidney disease (CKD) has increased between 1998 and 2002. After initially responding to treatment with recombinant human erythropoietic agents for CKD-associated anemia, patients became treatment-refractory and severely anemic. Although most PRCA cases have occurred in Europe, the varying epidemiologies among individual countries have not been well characterized. METHODS: We investigated Ab-mediated PRCA in 12 Spanish patients treated with epoetin alfa alone or prior to treatment with epoetin beta (n=1) or darbepoetin alfa (n=1). Serum Abs against epoetin alfa were detected by radioimmunoprecipitation (RIP) assay or bioassay. Following diagnosis of PRCA, erythropoietic treatment was stopped and patients received immunosuppressive therapy alone (n=11) or in combination with renal transplant (n=1). RESULTS: Treatments were administered for 16 months (average) before diagnosis of PRCA in bone marrow aspirates (n=8) or biopsies (n=4). At diagnosis, patients had an average of 0.68% blood reticulocytes and blood hemoglobin (Hb) level of 7.13 g/dL. Eight patients had anti-epoetin Abs detected by RIP, and 5 had neutralizing Abs measured in the bioassay. As of December 2003, 4 patients had died, 3 had no recovery, and 5 had recovered from anemia (blood Hb level, 9.9 g/dL). All 5 recovering patients received corticosteroid therapy alone, and 1 received a renal transplant as well as corticosteroids. CONCLUSIONS: Sudden onset of treatment-refractory anemia in CKD patients suggests a course of treatment cessation followed by diagnostic procedures for Ab-mediated PRCA, and immunosuppressive therapy. This study may serve as a model for a centralized global PRCA registry.