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Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.

Introduction Since infammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifer of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients. Objective and methods We investigated the efect modifcation by systemic infammation (serum CRP) on the relationship between a surrogate of the flling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantifed by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model. Results At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r=0.23, P

AimTo examine international time trends in the incidence of renal replacement therapy (RRT) for end‐stage renal disease (ESRD) by primary renal disease (PRD).MethodsRenal registries reporting on patients starting RRT per million population for ESRD by PRD from 2005 to 2014, were identified by internet search and literature review. The average annual percentage change (AAPC) with a 95% confidence interval (CI) of the time trends was computed using Joinpoint regression.ResultsThere was a significant decrease in the incidence of RRT for ESRD due to diabetes mellitus (DM) in Europe (AAPC=‐0.9; 95%CI‐1.3;‐0.5) and to hypertension/renal vascular disease (HT/RVD) in Australia (AAPC=‐1.8; 95%CI‐3.3;‐0.3), Canada (AAPC=‐2.9; 95%CI‐4.4;‐1.5) and Europe (AAPC=‐1.1; 95%CI‐2.1;‐0.0). A decrease or stabilization was observed for glomerulonephritis in all regions and for autosomal dominant polycystic kidney disease (ADPKD) in all regions except for Malaysia and the Republic of Korea. An increase of 5.2% to 16.3% was observed for DM, HT/RVD and ADPKD in Malaysia and the Republic of Korea.ConclusionLarge international differences exist in the trends in incidence of RRT by primary renal disease. Mapping of these international trends is the first step in defining the causes and successful preventative measures of CKD.

Background Kidney fibrosis has been reported to be a prognostic factor in chronic kidney disease (CKD) progression. Previous studies have shown that the assessment of urinary Dickkopf-3 (uDKK3), a stress-induced tubular epithelial-derived profibrotic glycoprotein, might be a potential tubulointerstitial fibrosis biomarker and might identify patients at short-term risk of glomerular filtration rate loss. We aim to evaluate uDKK3 as a potential biomarker for progression of CKD in a cohort with various aetiologies of CKD and subsequently in an overt diabetic nephropathy cohort. Methods We prospectively studied two independent cohorts comprising a total of 351 patients with Stages 2 and 3 CKD. Combined primary outcome consisted of a 50% increase in serum creatinine, end-stage kidney disease or death. The Progreser cohort included patients with heterogeneous aetiologies and the Pronedi cohort (101 patients) with overt diabetic nephropathy. The median follow-up time was 36 months [interquartile range (IQR) 30–39] and 36 (16–48), respectively. Results At baseline, median uDKK3 was 2200 pg/mg (IQR 671–7617) in the Progreser cohort and 3042 pg/mg (IQR 661–9747) in the Pronedi cohort. There were no statistically significant differences in the uDKK3 ratio between both cohorts nor between CKD aetiologies. Baseline uDKK3 was significantly higher in patients who reached the primary outcome. In the Cox proportional hazards model, the highest levels of uDKK3 were found to be an independent factor for renal progression in the Progreser cohort {hazard ratio [HR] 1.91 [95% confidence interval (CI) 1.04–3.52]} and in the Pronedi cohort [HR 3.03 (95% CI 1.03–8.92)]. uDKK3 gradually increased in the following months, especially in patients with higher proteinuria. Treatment with renin–angiotensin–aldosterone system blockers did not modify uDKK3 after 4 or 12 months of treatment. Conclusions uDKK3 identifies patients at high risk of CKD progression regardless of the cause of kidney injury. uDKK3 might serve as a useful biomarker for kidney disease progression and therefore could be used by clinicians to optimize staging for renal progression and monitor the response to potential treatments.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

According to data from the EPIRCE1 (epidemiology of chronic renal disease in Spain) research study, chronic kidney disease (CKD) affects up to 9.2% of the Spanish population, 6.8% of which have advanced-stage disease, including prior definition of chronic renal failure (CRF) or estimated glomerular filtration rate (GFR) of

Epidemiological studies have highlighted the role of arterial stiffness as a risk factor for development of cardiovascular (CV) diseases. Moreover, aortic stiffness has been shown to be a significant predictive factor of all-cause and CV mortality in different populations including patients with end-stage renal disease. Pulse-wave velocity (PWV) is the most widely used technique to assess arterial stiffness. Although PWV can be measured on any artery or between any arterial sites, only carotid-to-femoral PWV, representing stiffness of the aorta and iliofemoral axes, has been shown to have predictive value for morbidity and mortality. The several available commercial devices differ according to the type of signal (pressure, distension, flow) or by recording both sites simultaneously or using ECG synchronization. It is also possible to directly measure arterial diameter changes during the cardiac cycle and link them to local pulse-pressure changes, which provides the pressure-diameter relationship and stress-strain relationship if arterial wall thickness is also measured. These techniques are based on high-precision vascular echo tracking or magnetic resonance imaging and applanation tonometry. This paper summarizes the basic principles of arterial haemodynamics and various methodologies to assess stiffness and the latest consensus recommendations for clinical applications.

Patients with chronic kidney disease (CKD) are at a particularly high risk for cardiovascular disease. Vascular calcification (VC) is considered a cardiovascular risk marker, so in CKD patients screening for the presence of VC is suggested in current guidelines. VC is the result of both passive and active processes that involve a variety of proteins and factors. In the CKD population, numerous studies have identified circulating biomarkers potentially responsible for VC and have evaluated their link with this process. This narrative review, and an accompanying analysis performed on the Amiens CKD database, focuses on selected VC biomarkers-namely phosphate, fibroblast growth factor 23 (FGF23), osteopontin (OPN), osteoprotegerin (OPG), matrix Gla protein and fetuin A-all of which have been implicated as major players in VC in experimental studies in vitro or in animal models. None of the VC biomarkers considered in this review have qualified as a reliable predictor of meaningful clinical events or as a valid indicator of the risk of having VC. In the analysis based on the Amiens-CKD database, no biomarker outperformed age and the classical risk factors as a predictor of VC either in the aorta or in the coronaries. Well-designed clinical trials are now urgently needed to test the potential value of these biomarkers as a guide for interventions targeting VC.

Pulmonary arterial hypertension is a rare disease often associated with positive antinuclear antibody and high mortality. Pulmonary hypertension, which rarely is severe, occurs frequently in patients with chronic kidney disease (CKD). The prevalence of pulmonary hypertension ranges from 9%-39% in individuals with stage 5 CKD, 18.8%-68.8% in hemodialysis patients, and 0%-42% in patients on peritoneal dialysis therapy. No epidemiologic data are available yet for earlier stages of CKD. Pulmonary hypertension in patients with CKD may be induced and/or aggravated by left ventricular disorders and risk factors typical of CKD, including volume overload, an arteriovenous fistula, sleep-disordered breathing, exposure to dialysis membranes, endothelial dysfunction, vascular calcification and stiffening, and severe anemia. No specific intervention trial aimed at reducing pulmonary hypertension in patients with CKD has been performed to date. Correcting volume overload and treating left ventricular disorders are factors of paramount importance for relieving pulmonary hypertension in patients with CKD. Preventing pulmonary hypertension in this population is crucial because even kidney transplantation may not reverse the high mortality associated with established pulmonary hypertension.

Background and objectives Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. Design, setting, participants, & measurements In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound–guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre– and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. Results Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ -statistics ( κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. Conclusions Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

El hiperparatiroidismo secundario (HPTS) es una complicación habitual en pacientes con enfermedad renal crónica que se caracteriza por unos niveles elevados de hormona paratiroidea (PTH) y una serie de anomalías en el metabolismo mineral-óseo. En pacientes con HPTS, el tratamiento con paricalcitol, un activador selectivo de los receptores de la vitamina D, ha demostrado reducir los niveles de PTH con mínimas variaciones del calcio y del fósforo séricos. El efecto clásico de paricalcitol es el de mediador en la homeostasis mineral y ósea. Sin embargo, estudios recientes han indicado que los beneficios del tratamiento con paricalcitol van más allá de la reducción de PTH, por ejemplo, ocasionando efectos positivos en la enfermedad cardiovascular y en la supervivencia. El objetivo del presente trabajo es revisar los estudios más significativos sobre los llamados efectos pleiotrópicos del tratamiento con paricalcitol en pacientes con ERC. Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival. The objective of this study is to review the most significant studies on the so-called pleiotropic effects of paricalcitol treatment in patients with CKD.

Background. No previous randomized controlled studies have been reported examining de novo, once every 4 weeks (Q4W) administration of erythropoiesis-stimulating agents in chronic kidney disease (CKD) patients. We report results from a randomized multinational study that compared continuous erythropoietin receptor activator (C.E.R.A.) Q4W with darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) for the correction of anaemia in non-dialysis CKD patients. Methods. Patients were randomized (1:1) to receive either 1.2 μg/kg C.E.R.A. Q4W or darbepoetin alfa QW/Q2W during a 20-week correction period and an 8-week evaluation period. Two primary end points were assessed: the haemoglobin (Hb) response rate and the change in average Hb concentration between baseline and evaluation. Results. The Hb response rate for C.E.R.A. was 94.1%, significantly higher than the protocol-specified 60% response rate [95% confidence interval (CI): 89.1, 97.3; P < 0.0001] and comparable with darbepoetin alfa (93.5%; 95% CI: 88.4, 96.8; P < 0.0001). C.E.R.A. Q4W was non-inferior to darbepoetin alfa QW/Q2W, with similar mean Hb changes from baseline of 1.62 g/dL and 1.66 g/dL, respectively. Patients receiving C.E.R.A. showed a steady rise in Hb, with fewer patients above the target range during the first 8 weeks compared with darbepoetin alfa [39 patients (25.8%) versus 72 patients (47.7%); P < 0.0001]. Adverse event rates were comparable between the treatment groups. Conclusion. C.E.R.A. Q4W successfully corrects anaemia and maintains stable Hb levels within the recommended target range in non-dialysis CKD patients.

Maintenance of target hemoglobin (Hb) values in hemodialysis patients treated with erythropoiesis-stimulating agents (ESAs) remains difficult. We examined Hb variability in the clinical setting in hemodialysis patients. Hemodialysis patients treated with ESAs who maintained the recommended Hb range of 11-13 g per 100 ml over 3 months and were not admitted to hospital, did not require transfusion, and did not experience any major clinical event during this period were followed prospectively for 1 year. Anemia events, Hb variation events (any value out of +/-1.5 g per 100 ml of the median Hb level in the total follow-up period for the individual patient), risk factors for anemia, and Hb variation events were assessed. We studied 420 patients (63% males, mean age 61 years), 222 received short-acting erythropoietin (EPO) and 198 long-acting darbepoetin. A total of 4654 blood samples (mean 11.1 per patient-year) were analyzed. Only 3.8% of patients were maintained within the target Hb levels (11-13 g per 100 ml) during 1 year. Hb variation events occurred in 20.8% of laboratory values and anemia events in 14.7%, with a median time to the first event of 3 months. Treatment with short-acting EPO (vs long-acting darbepoetin), change of ESA dose in the previous visit, resistance index, and hospitalization were significant risk factors for both anemia events and Hb variation events. Our results show that Hb values are rarely maintained within the recommended guidelines even in more stable hemodialysis patients. Hb variability is frequently associated with clinical events or ESA dose changes. Long-acting darbepoetin achieved better Hb stability than short-acting EPO.

[Abstract] Background. Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3–5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Methods. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. Results. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Conclusions. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event.

Losartan reduces the burden and cost of ESRD: Public health implications from the RENAAL study for the European Union. Type 2 diabetes is the leading cause of end-stage renal disease (ESRD) in most industrialized countries in Europe. The RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) Study evaluated the renal protective effects of losartan versus placebo on a background of non-ACE-I/non-AIIA conventional antihypertensive therapy in 1513 patients with type 2 diabetes and nephropathy. Losartan reduced the incidence of doubling of serum creatinine, end-stage renal disease (ESRD), or death by 16% (P = 0.022) and reduced the risk of progression to ESRD, defined as the initiation of dialysis or transplantation, by 29% (P = 0.002). We set out to estimate the potential effect of losartan on the burden and costs associated with ESRD over 3.5 years in the European Union (EU). The risk reduction in new cases of ESRD was calculated by combining type 2 diabetes population estimates for the EU with the percent absolute risk reduction of ESRD in patients treated with losartan as observed in RENAAL. The number of days each patient experienced ESRD was defined as the length of time from onset of ESRD until the minimum of death or 3.5 years. ESRD-free person-years avoided with losartan treatment were calculated by combining the population estimate with the ESRD days avoided divided by number of days in a year. ESRD costs from Germany were used to approximate the potential cost savings from reduced time with ESRD and fewer ESRD cases on a EU wide basis. There are approximately 700,000 diagnosed type 2 diabetes patients with proteinuria (urine albumin/creatinine ≥300 mg/g) in the EU. The addition of losartan to the treatment regimen of these patients is expected to lead to a reduction of 44,100 cases of ESRD, 64,400 fewer person-years with ESRD, and reduce ESRD-related costs by € 2.6 billion over 3.5 years based on RENAAL data. Treatment with losartan not only reduced the incidence of ESRD, but also can result in substantial cost savings in the European Union.

C.E.R.A. (continuous erythropoietin receptor activator, pegilated-rHuEPO ß) corrects and maintains stable hemoglobin levels in once-monthly administration in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the management of anemia with C.E.R.A. in CKD patients not on dialysis in the clinical setting.Two hundred seventy two anemic CKD patients not on dialysis treated with C.E.R.A. were included in this retrospective, observational, multicentric study during 2010. Demographical characteristics, analytical parameters concerning anemia, treatment data and iron status were recorded.C.E.R.A. achieved a good control of anemia in both naïve patients (mean Hemoglobin 11.6g/dL) and patients converted from a previous ESA (mean Hemoglobin 11.7g/dL). Most naïve patients received C.E.R.A. once monthly during the correction phase and required a low monthly dose (median dose 75 µg/month). The same median dose was required in patients converted from a previous ESA, and it was lower than recommended in the Summary of Product Characteristics (SPC). Iron status was adequate in 75% of anemic CKD patients, but only 50% of anemic patients with iron deficiency received iron supplementation.C.E.R.A. corrects and maintains stable hemoglobin levels in anemic CKD patients not on dialysis, requiring conversion doses lower than those recommended by the SPC, and achieving target hemoglobin levels with once-monthly dosing frequency both in naïve and converted patients.

Invasive pneumococcal disease (IPD) is a serious problem in some risk groups: patients with stage 4 and 5 chronic kidney disease, stage 3 CKD undergoing immunosuppressive treatment, nephrotic syndrome or diabetes. These individuals are more susceptible to infections and more prone to suffering more severe and worsening symptoms. Vaccination is one of the strategies for preventing IPD, although vaccination coverage in this group at present is lower than desired. Currently, there are two vaccinations for adults. The polysaccharide vaccine (PPSV23), used for decades in patients over the age of 2, includes most serotypes (23), but it does not generate immune memory, causing the immune tolerance phenomenon and it does not act on nasopharyngeal colonisation. The conjugate vaccine (VNC13) can be used from infancy until adulthood (advice in patients over 18 years old received approval from the European Medicines Agency in July 2013) and generates a more powerful immune response than PPSV23 against the majority of the 13 serotypes that it includes. The 16 scientific societies most directly associated with the groups at risk of IPD have discussed and drafted a series of vaccination recommendations based on scientific evidence related to pneumococcal vaccination in adults with underlying conditions and pathologies, which are the subject of the documentldquo;Pneumococcal vaccination in adults with underlying pathologyrdquo;. This text sets out the vaccination recommendations for the chronic kidney disease population.

The Anemia Working Group of ERBP in 2010 recommended a target hemoglobin (Hb) level in the range of 11-12 g/dL, without intentionally exceeding 13 g/dL during the treatment with erythropoiesis stimulating agents (ESAs). This study evaluated if there was a clinical impact of this statement in the anemia management of chronic kidney disease (CKD) patients treated with ESAs not on dialysis in routine clinical practice in Spain.This was an observational and cross-sectional study carried out in CKD patients not on dialysis in Spain who initiated ESA treatment (naïve), or were shifted from a previous ESA to another ESAs (converted) since January 2011.Of 441 patients evaluated, 67.6% were naïve and 32.4% were converted. At the study visit, 42.5% of naïve patients achieved the Hb target of 11-12 g/dL, with a mean Hb of 11.3±1.3 g/dL (vs 10.1±0.9 g/dL at the start of ESA therapy). Only 35.3% of converted patients maintained Hb levels within the recommended target at the study visit. Yet, 8.2% of naïve patients and 7.9% of those converted had Hb levels13 g/dL. Hb levels were similar across subgroups of patients, regardless of the presence of significant comorbidities.Anemia management in CKD patients treated with ESAs by Spanish nephrologists seems to be aimed at preventing Hb levels11 g/dL, while50% of patients were within the narrow recommended Hb target range. This, together with the lack of individualization in Hb targets according to patients' comorbidities show that there is still room for improvement in renal anemia management in the clinical setting.

Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic diseases that represent a significant public health problem and require multidisciplinary management. T2DM is the main cause of CKD in our setting and it is also a major comorbidity of non-diabetic nephropathy. Patients with diabetes and renal failure represent a special risk group as they have higher morbidity and mortality and are at a higher risk of hypoglycaemia than diabetic individuals with normal renal function. Treatment of T2DM in patients with CKD is controversial because of the scarcity of evidence available. This consensus document aims to facilitate the appropriate selection and dosage of anti-diabetic drugs as well as establishing glycaemic control safety targets in patients with CKD.

To assess whether the correction dose recommended by the summary of product characteristics was adequate and to confirm the adequacy of the recommended conversion dosing strategies from shorter-acting erythropoiesis-stimulating agents (ESAs) to continuous erythropoietin receptor activator (C.E.R.A) in anaemic chronic kidney disease (CKD) patients in the clinical setting.This was a 12-month, multicenter, prospective, observational study in anaemic CKD patients on haemodialysis and not on dialysis receiving C.E.R.A (at least one dose).A total of 227 patients were included (not on dialysis; n = 142; haemodialysis: n = 85). The present analysis was conducted on ESA-naïve patients (not on dialysis: n = 31) and patients switched from other ESA (not on dialysis: n = 63; haemodialysis: n = 57). Both on and not on dialysis patients switched from other ESA received lower starting C.E.R.A doses than those recommended, and remained stable during the 12-month period. The higher the previous ESA dose was, the more beneficial the C.E.R.A dose conversion factor was. The proportion of patients with stable haemoglobin within the target range (11-13 g/dL) did not vary during the 12-month period both in nondialysis CKD patients and in those undergoing dialysis [baseline: 42 (66.7 %) and 34 (59.6 %); month 6: 21 (55.3 %) and 26 (50.0 %); month 12: 20 (64.5 %) and 25 (69.4 %), respectively]. In naïve patients, the mean weight-adjusted C.E.R.A dose during the study (1.19 ± 0.49 µg/kg/month) was similar to the recommended one. C.E.R.A was well tolerated.Conversion from shorter-acting ESAs to C.E.R.A doses lower than those recommended can efficiently maintain target haemoglobin levels both in nondialysis and haemodialysis CKD patients, particularly when switching from higher ESA doses. A monthly C.E.R.A dose of 1.2 µg/Kg seems adequate for anaemia correction.

Chronic kidney disease (CKD) is a major public health problem that, in its different stages, may affect up to 10% of the Spanish population and results in high morbidity and mortality, as well as high consumption of National Health System resources. Ten scientific societies involved in the management of kidney patients agreed to update the 2007 CKD consensus document. The current version is an abridged edition of the detailed general document, which can be consulted on the webpages of each signatory society. It includes the following aspects: CKD definition, epidemiology and risk factors and criteria on diagnosis, assessment and staging of CKD, albuminuria and glomerular filtration estimation. Progression factors and concept. Criteria for referral to Nephrology. Patient follow-up, attitudes and objectives by specialty. Prevention of nephrotoxicity. Detection of cardiovascular damage. Attitudes, lifestyle and treatment: management of high blood pressure, dyslipidaemia, hyperglycaemia, smoking, obesity, hyperuricaemia, anaemia and mineral and bone metabolism disorders. Coordinated follow-up by Primary Carendash; other specialtiesndash; Nephrology. Management of renal replacement therapy, haemodialysis, peritoneal dialysis and renal transplantation patients. Palliative treatment of terminal uraemia. We hope that this document will be very useful in the multidisciplinary management of CKD patients, in view of the updated recommendations.

Objective: To update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. Methods: This document was approved by a panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Nephrology (S.E.N.), and the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC). The quality of evidence and the level of recommendation were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, Urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glucosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document advises on the optimal time for referral of a patient to the nephrologist and provides indications for renal biopsy. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Conclusions: Renal function should be monitored in all HIV-infected patients. The information provided in this document should enable clinicians to optimize the evaluation and management of HIV-infected patients with renal disease.

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. (C) 2014 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

Anaemia is a common complication of chronic kidney disease (CKD). The aim of this study was to determine the prevalence and clinical management of anaemia in patients with stages 3-5 CKD not on dialysis treated in outpatient Nephrology clinics (OC) in Catalonia.Epidemiological, cross-sectional cohort, multicentre study under routine clinical practice conditions. Data collection by electronic data collection log-book (e-DCL) including personal information and data related to anaemia (haemoglobin, iron status, treatment with erythropoiesis-stimulating agents [ESA] and other anaemia treatments). Anaemia was defined as haemoglobin levels13.5 g/dL in males or12 g/dL in females or patients who receive treatment with ESA.We included 504 patients (56.4% male, mean age of 67.8 ± 15.5 years): 61.5% had stage 3 CKD, 30.2% stage 4 and 8.3% stage 5. The main causes of CKD were vascular and diabetic nephropathy. The prevalence of anaemia was 58.5% (n=295), however, only 14.9% of patients had haemoglobin levels11 g/dL. Mean haemoglobin levels decreased and ESA treatment was more common as CKD progressed, but no significant differences were observed regarding the prescription of iron, according to CKD stages. ESA and intervals most frequently prescribed were darbepoetin alfa with a median dose of 40 μg/biweekly, followed by C.E.R.A. with a median dose of 75 μg/month and epoetin beta with a median dose of 5,000 IU/week. Among the patients with anaemia (n=295), 36.3% (n=107) had iron deficiency and only 53.3% of these patients were treated with iron supplements.This study demonstrates the high prevalence of anaemia, which increases as the disease progresses and its good control in a CKD patient population treated in Nephrology outpatient clinics in Catalonia. This control is achieved with moderate doses of ESA and iron supplements prescribed in more than 50% of anaemic CKD patients.

Fluvastatin and low-density lipoprotein oxidation in hypercholesterolemic renal transplant patients. Background Hyperlipidemia contributes to the development and progression of vascular disease in organ transplant patients. Oxidative modification of low-density lipoproteins (LDLs) has been suggested as a key event in early atherogenesis. Methods We conducted a pilot study in renal transplanted patients with persistent hypercholesterolemia above 6.5 mmol/liter. We studied the LDL oxidation before and after one year of fluvastatin treatment. Twenty patients (12 males and 8 females, 46 ± 10 years old) who received a kidney transplant 24 ± 18 months before the study were treated with fluvastatin (20 mg/day for 12 weeks). Patients with a total cholesterol under 6.3 mmol/liter continued to receive 20 mg/day for another 40 weeks (group I, N = 10). Nine patients with a total cholesterol above 6.3 mmol/liter received 40 mg/day for a further 40 weeks (group II). Results Cyclosporine levels did not experience a significant variation. Total and LDL cholesterol decreased significantly in both groups (21.7 and 27.9% in group I, 18.3 and 27.2% in group II, respectively). The lag-phase time, which was significantly enlarged before fluvastatin treatment in the patients with respect to the controls ( N = 18, 82 ± 45 vs. 50 ± 8 min) was shortened after one year of fluvastatin treatment (64 ± 24 vs. 50 ± 8 min, P = 0.04). Fluvastatin was stopped in only one patient because of nausea and vomiting. Transaminases and creatin-phospho-kinase were not altered. All of the patients maintained a functioning graft during the study period. Conclusions Fluvastatin significantly reduced total and LDL cholesterol, without interferences with cyclosporine A through levels. Fluvastatin has not demonstrated an antioxidant effect in our renal hypercholesterolemic transplant patients.

Introduction. Calcineurin inhibitors may be associated with decreased arterial elasticity and increased vascular risk. We measured pulse wave velocity (PWV) in large or small arteries as an index of elasticity. The aim of our study was to determine aortic and radial arterial elasticity in 30 stable kidney transplant patients treated with calcineurin inhibitor immunosuppression. Patients and methods. In stable kidney transplant patients we determined the usual biochemical parameters as well as lipid profiles, 24-hour blood pressure (BP) monitoring (CBPM) using a chronobiological program (Garapa), and PWV with a HDI-PWV CR-2000 monitor. Results. Sixteen patients received cyclosporine (CsA, G-1) and 14 tacrolimus (G-2) immunosuppression. There were no baseline differences regarding age (G-1: 56 ± 12 years, G-2: 56 ± 14 years), renal transplant follow-up (G-1: 7 ± 3 years, G-2: 7.5 ± 3 years), Systolic BP, pulse pressure or plasma creatinine (G-1: 163 ± 35 umol/L, G-2: 173 ± 26 umol/L). Patients in the G-1 showed higher diastolic BP (79 ± 11 vs 74 ± 8 mm Hg), greater proteinuria (1.26 ± 0.4 vs 0.6 ± 0.2 g/d, P

Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic diseases, which represent an important public health problem and require a multidisciplinary management. T2DM is the main cause of CKD and it also causes a significant comorbidity with regard to non-diabetic nephropathy. Patients with diabetes and kidney disease represent a special risk group as they have higher morbi-mortality as well as higher risk of hypoglycemia than diabetic individuals with a normal kidney function. Treatment of T2DM in patients with CKD is controversial because of the scarcity of available evidence. The current consensus report aims to ease the appropriate selection and dosage of antidiabetic treatments as well as the establishment of safety objectives of glycemic control in patients with CKD.

Current characterization of the immune risk in renal transplant patients is only focused on the assessment of preformed circulating alloantibodies; however, alloreactive memory T cells are key players in mediating allograft rejection. Immune monitoring of antidonor alloreactive memory/effector T cells using an IFN-γ Elispot has been shown to distinguish patients at risk for immune-mediated graft dysfunction, suggesting a potential tool for immunosuppression individualization. In this nonrandomized study, we prospectively assessed donor and nondonor T-cell alloreactivity in 60 highly alloreactive patients receiving calcineurin inhibitor-based immunosuppression and in non-T-cell alloreactive transplant recipients treated with a calcineurin inhibitor-free regimen. The impact was evaluated using 1-year allograft outcome. We found a strong association between ongoing antidonor T-cell alloreactivity and histological lesions of acute T cell–mediated rejection in 6-month protocol biopsies, distinguishing those patients with better 1-year graft function, regardless of immunosuppression regimen. Interestingly, evidence for enhanced immune regulation, driven by circulating Foxp3-demethylated regulatory T cells, was only observed among patients achieving antidonor T-cell hyporesponsiveness. Thus, prospective evaluation of donor-specific T-cell sensitization may add crucial information on the alloimmune state of transplanted patients to be used in daily clinical practice.

Background: Patients undergoing conventiona l hemodialysis (C-HD) present a greater immuno-inflam- matory state probably related to uremia, sympathetic nervous system (SNS) activation and /or membrane bioincompat ibility, which could improve with a technique-switch ing to online hemodiafiltration (OL-HD). The antigen-indep endent pathway activation of this modified immunologic state turns dendritic cells (DC) into an accurate cell model to study these patients. The aim of this study is to further evaluate the immune-inflammat ory state of patients in C-HD assessed by DC maturation. Methods: 31 patients were submitted to C-HD and after 4 months switched to the OL-HD technique. Monocytes-derive d DCs from HD patients were cultured in the presence of IL-4/GM-CSF. DC-maturation was evaluated by assessing the maturation phenotype by flow cytometry (FACs). DCs-functiona l capacity to elicit T-cell alloresponse was studied by mixed leuco- cyte reaction. Cytokine release was assessed by FACs and SNS was evaluated measuring renalase levels by ELISA. Results: An up-regulation of maturation markers was observed in C-HD DCs which induced two fold more T cells proliferation than OL-HD DCs. Also, C-HD-mDCs presented with over-produc- tion of pro-inflammatory cytokines (IL-6, IL-1 β , IL-8, IL-10 and TNF- α ) compared with OL- HD-mDC (P < 0·05). Results were correlated with clinical data. When SNS was evaluated, hypotension events and blood pressure were significantly lower and renalase levels were significantly higher after conversion to OL-HD. Diabetes mellitus type 2 patients also found beneficial reduction of mDC when converted to OL-HD compared to non-diabetics. Conclusions: OL-HD could interfere with immuno-inflammatory state in HD patients with an improvement of renalase levels as potential key mediators in the mechanistic pathway of down-regulation of DC maturation

Methoxy polyethylene glycol-epoetin beta (PEG-EPO) is indicated for the treatment of anaemia due to chronic kidney disease. Its long half-life allows it to be administered once per month in maintenance therapy.To evaluate the use, effectiveness and cost of PEG-EPO in a group of pre-dialysis chronic renal failure patients.Retrospective observational study in pre-dialysis patients who began treatment with PEG-EPO between May 2008 and February 2009. The following data were gathered: age, sex, haemoglobin levels (Hb) and erythropoiesis-stimulating agent (ESA) dose and frequency. The follow-up period was 12 months.We included 198 patients. Mean Hb upon starting PEG-EPO in patients who had received no prior treatment was 10.8g/l, and 11.6g/l at 90 days (P.0001). In patients previously treated with ESA, mean Hb before starting PEG-EPO treatment was 11.2g/l, and 11.4g/l at 12 months (P=.846). Hb values were higher than 12g/l (P.0001) after 12 months of treatment in 25% of patients; of these, 45% had values above 13g/l. We observed doses 39% lower than those indicated on the drug leaflet, resulting in a reduction in the originally expected theoretical costs.The doses of PEG-EPO administered to patients with a prior history of ESA treatment were lower than those indicated by the drug leaflet, and Hb remained stable after 12 months of treatment. A large portion of the patients had levels above the 13g/l threshold.

Prognosis, risk stratification and monitoring the effects of treatment are fundamental elements in the decision-making process when implementing prevention strategies for chronic kidney disease. The use of biomarkers is increasingly proposed as a method to refine risk stratification and guide therapy. In this Review, we present basic concepts regarding the validation of biomarkers and highlight difficulties inherent to the identification of useful new biomarkers in patients on hemodialysis. We focus on prognostic biomarkers that have been consistently linked to survival in this group of patients. To date, no biomarker has had sufficient full-scale testing to qualify as a useful addition to standard prognostic factors or to guide the prescription of specific treatments in this population. Furthermore, little information exists on the relative strength of various biomarkers for their prediction of mortality. A multimarker approach might refine prognosis in patients on hemodialysis, but this concept needs to be properly evaluated in large longitudinal studies and clinical trials. The potential of proteomics for the identification and study of new biomarkers in the pathophysiology of cardiovascular disease in patients with end-stage renal disease is also discussed.

The presence of albuminuria or proteinuria constitutes a sign of kidney damage and, together with the estimation of glomerular filtration rate, is based on the evaluation of chronic kidney disease. Proteinuria is a strong marker for progression of chronic kidney disease, and it is also a marker of increased cardiovascular morbimortality. Filtration of albumin by the glomerulus is followed by tubular reabsorption, and thus, the resulting albuminuria reflects the combined contribution of these 2 processes. Dysfunction of both processes may result in increased excretion of albumin, and both glomerular injury and tubular impairment have been involved in the initial events leading to proteinuria. Independently of the underlying causes, chronic proteinuric glomerulopathies have in common the sustained or permanent loss of selectivity of the glomerular barrier to protein filtration. The integrity of the glomerular filtration barrier depends on its 3-layer structure (the endothelium, the glomerular basement membrane, and the podocytes). Increased intraglomerular hydraulic pressure or damage to glomerular filtration barrier may elicit glomerular or overload proteinuria. The mechanisms underlying glomerular disease are very variable and include infiltration of inflammatory cells, proliferation of glomerular cells, and malfunction of podocyte-associated molecules such as nephrin or podocin. Albumin is filtered by the glomeruli and reabsorbed by the proximal tubular cells by receptor-mediated endocytosis. Internalization by endocytosis is followed by transport into lysosomes for degradation. The multiligand receptors megalin and cubilin are responsible for the constitutive uptake in this mechanism. Albumin and its ligands induce expression of inflammatory and fibrogenic mediators resulting in inflammation and fibrosis resulting in the loss of renal function as a result of tubular proteinuria. TGF-β, which may be induced by albumin exposure, may also act in a feedback mechanism increasing albumin filtration and at the same time inhibiting megalin- and cubilin-mediated albumin endocytosis, leading to increased albuminuria. Urinary proteins themselves may elicit proinflammatory and profibrotic effects that directly contribute to chronic tubulointerstitial damage. Multiple pathways are involved, including induction of tubular chemokine expression, cytokines, monocyte chemotactic proteins, different growth factors, and complement activation, which lead to inflammatory cell infiltration in the interstitium and sustained fibrogenesis. This tubulointerstitial injury is one of the key factors that induce the renal damage progression. Therefore, high-grade proteinuria is an independent mediator of progressive kidney damage. Glomerular lesions and their effects on the renal tubules appear to provide a critical link between proteinuria and tubulointerstitial injury, although several other mechanisms have also been involved. Injury is transmitted to the interstitium favoring the self-destruction of nephrons and finally of the kidney structure.

BACKGROUND Prognosis of HIV-infected patients on dialysis has improved. Few studies have compared survival between HIV-infected and HIV-negative patients on dialysis in the combined antiretroviral therapy (cART) era. We compared the outcome of HIV-infected patients on dialysis with a matched HIV-negative cohort. METHODS National, multicenter, retrospective cohort study of HIV-infected patients starting dialysis in Spain (1999-2006). Matching criteria for HIV-negative patients were dialysis center, year of starting dialysis, age, sex, and race. RESULTS The study population comprised 122 patients, 66 HIV-infected, and 66 HIV-negative patients. Median age was 41 years, and all but 4 HIV-infected patients were white. HIV-associated nephropathy was only present in 4 cases. HIV-infected patients were less frequently included on the kidney transplantation waiting list (17% vs 62%, P < 0.001). They also had more hepatitis C virus coinfection (76% vs 11%, P < 0.001), fewer cardiovascular events (62% vs 88%, P = 0.001), fewer kidney transplants (4.5% vs 38%, P < 0.001), and higher mortality (32% vs 1.5%, P < 0.001). Survival rates [95% confidence interval (CI)] at 1, 3, and 5 years for HIV-infected patients were 95.2% (89.9%-100%), 71.7% (59.7%-83.7%), and 62.7% (46.6%-78.8%). Five-year survival for HIV-negative patients was 94.4% (83.8%-100%) (P < 0.001). Multivariate analysis revealed the following variables to be associated with death in HIV-infected patients: peritoneal dialysis vs hemodialysis [hazard ratio; (95% CI): 2.88 (1.16-7.17)] and being on effective cART [hazard ratio (95% CI): 0.39 (0.16-0.97)]. CONCLUSIONS Medium-term survival of HIV-infected patients on dialysis was lower than that of matched HIV-negative patients. Fewer HIV-infected patients had access to kidney transplantation. Being on effective cART improves survival. Further studies are needed to determine whether peritoneal dialysis increases mortality.

A large number of patients with cardiovascular risk exhibit metabolic syndrome and are attended by several specialists. There is no information about possible differences in the clinical characteristics and management of these patients by these specialists. The aim of the present study was to evaluate possible differences in clinical features, blood pressure control, therapeutic effort, and therapeutic inertia among medical specialities attending hypertensive patients with metabolic syndrome (MS).Cross-sectional study carried out in 17 autonomous communities in Spain, in hypertensive patients with MS consecutively recruited in ambulatory units from departments of cardiology, internal medicine, endocrinology and nephrology. Demographic and clinical data, as well as blood pressure control were assessed. Therapeutic effort was defined as the proportion of patients using 3 or more antihypertensive drugs. Therapeutic inertia was defined as the proportion of patients without any change in antihypertensive treatment despite a lack of blood pressure control (values ≥ 140 and/or 90 mmHg).2,453 patients (40% women) with a mean age of 64 (11) years were included in the study. We observed some differences in the specific MS components among specialities. Atherogenic dyslipidemia, defined as elevated triglycerides (97%) and/or HDL-cholesterol (61%) was more common in patients attended by cardiologists. Blood pressure control was better achieved by nephrologists (16-33%, depending on the criteria used), and it was accompanied by a greater therapeutical effort (59%). Therapeutical inertia in relation to antihypertensive treatment was more common among endocrinologists (56%).Hypertensive patients with MS attended by different specialists have similar clinical features, although some differences are present, especially driven by more frequent lipid alterations among those attending cardiology departments. Nephrologists make a greater therapeutic effort and achieve a better blood pressure control. On the contrary, therapeutical inertia is higher among endocrinologists.

C.E.R.A., a continuous erythropoietin receptor activator is approved for the treatment of anemia in patients with chronic kidney disease (CKD). The ARCTOS (administration of C.E.R.A. in CKD patients to treat anemia with a twice-monthly schedule) phase 3 study demonstrated the efficacy and safety of C.E.R.A. in correcting anemia when administered once every 2 weeks (Q2W) subcutaneously in patients with CKD not on dialysis. We assessed the feasibility and long-term safety of converting patients who responded to treatment with C.E.R.A. Q2W to C.E.R.A. once every 4 weeks (Q4W) during a 24-week extension period. After the core ARCTOS study period (28 weeks), 296 patients entered the 24-week extension period. At week 29, patients who responded to C.E.R.A. Q2W during the core period were rerandomized to receive subcutaneous C.E.R.A. Q2W or Q4W. Patients in the comparator arm could receive darbepoetin alfa once weekly or Q2W. Dosage was adjusted to maintain hemoglobin (Hb) between 11 and 13 g/dL. Mean Hb levels remained stable in all groups, and were comparable at the end of the extension period (mean [standard deviation], C.E.R.A. Q2W, 11.92 [0.90] g/dL; C.E.R.A. Q4W, 11.70 [0.86] g/dL; darbepoetin alfa, 11.89 [0.98] g/dL). Mean within-patient standard deviation values for Hb were also comparable in all groups (0.66, 0.62, and 0.65 g/dL for C.E.R.A. Q2W, C.E.R.A. Q4W and darbepoetin alfa, respectively). All treatments were well tolerated. Subcutaneous C.E.R.A. Q4W is safe and effective in maintaining stable Hb levels in patients with CKD not on dialysis following correction with subcutaneous C.E.R.A. Q2W. Hemodial Int

It has been suggested that hemodialysis patients may be under increased oxidative stress and may therefore benefit from the long-term use of antioxidants (particularly for the reduction of the risk of heart disease). The aim of this study was, first, to evaluate the effect of hemodialysis by itself on lipid and lipoprotein oxidation profiles and, second, to analyze the effect of vitamin C supplementation in patients with end-stage renal disease starting hemodialysis. Forty-one patients with end-stage renal disease were enrolled and randomized to receive 1000 mg/d vitamin C or matching placebo before starting hemodialysis. We measured lipid profile and the susceptibility of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) to oxidation using copper ions at the moment of inclusion and after 1 year. All lipoperoxidation parameters were included. Hemodialysis by itself improved the lipid profile, lowering total cholesterol (176.4 +/- 48.4 to 154.2 +/- 28.8 mg/dL, P < .01), LDL cholesterol (94.1 +/- 39.6 to 76.1 +/- 26.6 mg/dL LDL, P < .03), and phospholipids levels (196.5 +/- 36.7 to 182.9 +/- 36.1 mg/dL, P < .05) in all patients on maintenance hemodialysis. The HDL cholesterol was also decreased (49.4 +/- 19.8 to 43.4 +/- 24.1 mg/dL HDL, P < .03). No significant differences were detected between patients receiving vitamin C and those receiving placebo. Thiobarbituric acid reactive substances (TBARS) and lipoperoxides increased in patients after a year of hemodialysis, but the difference was lower in those administered vitamin C for a year-TBARS LDL (in nanograms per gram LDL): 0.25 +/- 0.20 to 0.38 +/- 0.2 in vitamin C-treated subjects and 0.28 +/- 0.17 to 0.46 +/- 0.21 in those treated with placebo (P < .007); TBARS HDL (in nanograms per gram HDL): 0.22 +/- 0.12 to 0.34 +/- 0.30 in patients receiving vitamin C and 0.20 +/- 0.18 to 0.28 +/- 0.19 in those receiving placebo (P = .071). Hemodialysis by itself seems to improve the lipid profile in patients with a previous prooxidative state such as uremia. Although our results failed to demonstrate significant differences between vitamin C-treated and untreated patients, and despite the small number of patients, the trend toward a decrease in oxidation products due to vitamin C supplementation may be beneficial for oxidation parameters. This area remains controversial and under active investigation. Further research is necessary before a firm conclusion can be reached.

Epidemiology of diabetic nephropathy in Spain. Background The incidence of diabetes mellitus (DM) has increased persistently in recent years and is becoming an epidemic. Some have estimated that 4.4% of the world's population will be diabetic by the year 2030. The increase incidence of DM has been accompanied by an increased incidence in diabetic nephropathy (DN), the main cause of end-stage renal disease. Methods and Results In 1996, a pharmaco-economic study estimated that 162,000 people in Spain had type 1 DM and 1,354,900 had type 2 DM. More recent studies have estimated that 6% to 10% of the Spanish population might be diabetic. This percentage is higher in some autonomous communities, such as Canarias, in which 12% of the population is thought to have DM. Based on these studies, we estimate that more than 33,000 residents of Canarias have DN associated with type 1 DM, and more than 405,000 have DN associated with type 2 DM. The percentage of diabetic patients starting renal replacement therapy each year is currently around 21% in Spain but much higher (35%) in Canarias, which equates to 78 patients per million population (pmp) per year. In Catalonia, the number of DM patients entering renal replacement therapy has increased from 8.6 pmp per year in 1984 to 32.4 pmp per year in 2003. We estimate that the systematic application of converting enzyme inhibitors or angiotensin receptor blockers could save more than €2.690 million over 15 years in Spain. Conclusion This epidemic could be prevented, or its impact reduced, through multifactorial and multidisciplinary early intervention, under the observance of guides, Spanish consensus documents, and clinical practice recommendations, together with an integrated educational program aimed at people with diabetes and the improvement of the standard of medical care.

Diabetes mellitus (DM) is a widespread prevalent illness, currently the main cause of end-stage renal disease (ESRD).In a longitudinal, prospective study we compared two cohorts of patients starting dialysis therapy, diabetic and non-diabetic ESRD patients. Perceived health was measured by the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire, functional status by the Karnofsky scale and comorbidity by the Charlson age-comorbidity index. A broad spectrum of variables in relation to diabetes, ESRD, comorbidity and renal replacement therapy (RRT) were studied, as well as the distribution of comorbidity frequencies at dialysis start.Thirty-four Spanish centers included 232 diabetic patients, 43 type 1 and 189 type 2, mean diabetes duration 18 +/- 9 yrs, and five centers included 121 non-diabetic patients. Out of the 232 diabetic patients, 187 patients (81%) started hemodialysis (HD) and 45 patients (19%) started peritoneal dialysis (PD) (vs. 82% and 18%, respectively in non-diabetic patients). Transient vascular access (VA) for starting RRT was required in 54% of the diabetic patients vs. 53% in the nondiabetic patients. When both study groups were compared, diabetic patients required antihypertensive drugs more frequently than non-diabetic patients and showed higher systolic blood pressure (BP), as well as higher cardiovascular (CV) complication incidences, poorer SF-36 physical component summary scores and mental component summary scores and worse Karnofsky scale scores, with the Charlson age-comorbidity score being higher.Diabetic patients starting dialysis in Spain are more often type 2 diabetics, have worse perceived health-related quality of life (HRQoL) in relation to non-diabetic patients, worse functional status and higher incidences of prognostic mortality markers.

Treatment of hypertension after renal transplantation: Long-term efficacy of verapamil, enalapril, and doxazosin. Normal blood pressure is a good marker of graft survival after renal transplantation, and effective antihypertensive treatment reduces the progression of graft damage. We conducted a long-term follow-up study of 88 hypertensive renal transplant recipients, all of whom were taking sustained cyclosporine A (CsA) immunosuppression. The patients were treated for at least three years, and initially received 240mg/day of verapamil (N = 24, group I), 5mg/day of enalapril (N = 24, group II) or 1mg/day of doxazosin (N = 40, group III). Baseline creatinine did not differ in the three groups, but proteinuria was higher in the enalapril group (7 patients had proteinuria >1.5g/day). Treatment was withdrawn in 5 patients in the verapamil group, 5 in the enalapril group and 2 in the doxazosin group due to drug-related side effects. Blood pressure (BP) control at three years was equivalent in the three groups (systolic BP, group I 157 ± 12; group II 149 ± 19; group III 154 ± 21; diastolic BP, group I 90 ± 8.7, group II 84 ± 9.8, group III 90.5 ± 16; mean BP, group I 113 ± 7, group II 106 ± 10, group III 106 ± 29). Two patients in group I, 3 in group II and 15 in group III required additional antihypertensive drugs. CsA levels increased in the verapamil-treated patients, allowing for an early decrease in CsA doses (1year doses, 3.3 ± 1mg/kg body wt/day in group I, 4.3 ± 1.6 in group II, 3.7 ± 1.6 in group III). Six cardiovascular events occurred, 3 in group I, 1 in group II, and 2 in group III patients. One patient died in the enalapril group and another in the doxazosin group. Eight verapamil-treated patients, 8 enalapril-treated patients and 4 doxazosin-treated patients lost their grafts due to biopsy-proven chronic transplant nephropathy. In conclusion, the three antihypertensive agents are effective in reducing blood pressure, with no clear advantage of one above any other. Verapamil allows the CsA dose to be reduced, thus decreasing the cost of immunosupression. Enalapril can be a more effective antiproteinuric agent, but hyperkalemia or impaired allograft function may occur in patients with non-optimal allograft function. Doxazosin offers an excellent safety and efficacy profile, and when not efficient by itself in controlling blood pressure, is an ideal concomitant agent in hypertensive renal transplant patients.

To 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). Methods: Multicenter 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. Results: In 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 erythropoiesisstimulating 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. Conclusion: This 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

Background: Anemia 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). Methods: This 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. Results: During 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. Conclusions: Renal 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, This study was partially supported by a grant from Amgen S.A., Barcelona, Spain, through the Spanish Society of Nephrology.

Background and objectives: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. Method: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. Results: Vitamin D deficiency (250HD(3) = 2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100 pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. Conclusions: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients. Antecedentes y objetivos: La relación entre las alteraciones del metabolismo mineral, las fracturas óseas y las calcificaciones vasculares en receptores de un trasplante renal no han sido establecidas. Método: Realizamos un estudio transversal en 727 receptores estables procedentes de 28 centros de trasplante españoles. Se determinaron de manera centralizada los parámetros del metabolismo mineral; también se centralizó la semicuantificación de las fracturas vertebrales y de las calcificaciones de la aorta abdominal. Resultados: La deficiencia de vitamina D (25OHD3 < 15 ng/ml) fue más frecuente en mujeres y en los estadios CKD-T I-III (29, 6 vs. 44, 4%; p = 0, 003). La relación inversa y significativa observada entre los niveles de 25OHD3 y PTH fue modificada por el género de tal manera que la pendiente fue mayor en las mujeres que en los hombres (p = 0, 01). Un 15% de los receptores mostró alguna fractura vertebral (VFx) con un grado de deformidad =2. Los factores relacionados con la VFx diferían en función del género: en los hombres, la edad (OR: 1, 04; IC 95%: 1, 01-1, 06) y el tratamiento con CsA (OR: 3, 2; IC 95: 1, 6-6, 3); en las mujeres la edad (OR: 1, 07; IC 95%: 1, 03-1, 12) y los niveles de PTH (OR per 100 pg/ml increase: 1, 27; IC 95%: 1, 043-1, 542). Las calcificaciones de la aorta abdominal fueron comunes (67, 2%) y se relacionaron con los factores de riesgo clásicos, pero no con los parámetros del metabolismo mineral. Conclusiones: La deficiencia de vitamina D es más frecuente en las mujeres receptoras de un trasplante renal y en los estadios más tempranos de la CKD-T, y es un factor que contribuye al desarrollo de hiperparatiroidismo secundario. Las VFx prevalentes están relacionadas con unos niveles más elevados de PTH solamente en las mujeres.