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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.

Diabetis mellitus; Malaltia renal diabètica; Atenció multidisciplinària Diabetes mellitus; Diabetic kidney disease; Multidisciplinary care Diabetes mellitus; Enfermedad renal diabética; Atención multidisciplinaria Age-standardized rates of diabetes mellitus (DM)-related complications, such as acute myocardial infarction, stroke or amputations, have decreased in recent years, but this was not associated with a clear reduction of the incidence of advanced chronic kidney disease (CKD) requiring renal replacement therapy. The early detection of diabetic kidney disease (DKD) is a key to reduce complications, morbidity and mortality. Consensus documents and clinical practice guidelines recommend referral of DM patients to nephrology when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2 or when albuminuria exceeds 300 mg/g urinary creatinine. Conceptually, it strikes as odd that patients with CKD are referred to the specialist caring for the prevention and treatment of CKD only when >70% of the functioning kidney mass has been lost. The increasing global health burden of CKD, driven in large part by DKD, the suboptimal impact of routine care on DKD outcomes as compared with other DM complications, the realization that successful therapy of CKD requires early diagnosis and intervention, the advances in earlier diagnosis of kidney injury and the recent availability of antidiabetic drugs with a renal mechanism of action and lack of hypoglycaemia risk, which additionally are cardio- and nephroprotective, all point towards a paradigm shift in the care for DM patients in which they should be referred earlier to nephrology as part of a coordinated and integrated care approach. Sources of support: FIS/Fondos FEDER PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM.

Background and Aims Kidney fibrosis has been reported to be a key progression hallmark of chronic kidney disease (CKD). It seems likely that a precise biomarker of renal fibrosis extension would contribute to predict accurately the risk of a decline in glomerular filtration rate (eGFR). 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 eGFR loss. We aim to evaluate uDKK3 as a potential biomarker for long-term CKD progression in a cohort with various etiologies of CKD, and subsequently in an overt diabetic nephropathy cohort. We also tested the role of treatment with RAAS blockers on the uDKK3 levels and if the treatment could modify them. Method We prospectively studied two independent cohorts consisted of 356 patients with stage 2-3 CKD. Progreser cohort comprised 255 patients with heterogeneous etiologies of CKD and Pronedi cohort 101 patients with overt diabetic nephropathy. The primary outcome was the time to the first event of the composite endpoint (>50% increase in serum creatinine concentration, end-stage kidney disease [ESKD], or death). We divided patients into tertiles according to their baseline uDKK3 levels: less than 1092 pg/mg (Tertile 1, T1), between 1092-5050 pg/mg (Tertile 2, T2) and higher than 5050 pg/mg (Tertile 3, T3). We used the cut point of T3 as an exploratory cut-off. Cox regression models were used to adjust for potential effects of confounders or modifiers: age, gender, mean arterial pressure, body mass index (BMI), urine albumin/creatinine ratio, urine protein/creatinine ratio and serum creatinine. Mixed-effects models were adjusted to study longitudinal data. Results Progreser cohort and Pronedi cohort did not differ in their clinical baseline characteristics except in proteinuria. At baseline, uDKK3 levels were not different between different etiologies or both cohorts, median uDKK3 was 2199 (IQR: 658-7618) pg/mg in the Progreser cohort and 3041 (IQR: 653-9777) pg/mg in the Pronedi cohort (p:0.56). Median time of follow-up was 36 months. Forty-nine patients (19 %) in Progreser cohort and 31 patients (31%) in Pronedi cohort reached the primary composite outcome. Baseline uDKK3 was significantly higher in patients who reached primary outcome. In Cox multivariate model, after adjustment for potential confounders, the highest levels of uDKK3 were found to be an independent factor for renal progression in Progreser cohort (HR 1.83, CI95% 1.11-3.31) and in Pronedi cohort (HR 2.74, CI95% 1.09-6.98). Both in the Progreser and the Pronedi cohorts, uDKK3 levels above 5050 pg/mg, were associated with a lower eGFR, higher proteinuria and were independently associated with a worse renal survival. uDKK3 gradually increased in the following months, especially in patients with higher proteinuria. Treatment with RAAS-blockers did not modify uDKK3 after 4 or 12 months of treatment. Conclusion In this study, uDKK3 ratio identified patients at high risk for long-term kidney disease progression regardless of the etiology of CKD. The hypothesis was generated in a cohort of patients with CKD of heterogeneous etiologies and was further confirmed in a cohort with overt diabetic nephropathy. The predictive role of uDKK3 persisted after adjusting by eGFR and proteinuria. uDKK3 is the first non-invasive biomarker of renal fibrosis and might serve as a useful biomarker for kidney disease progression. Therefore uDKK3 could be used by clinicians to optimize staging for renal progression and monitor therapeutic efficacy of different measures to halt CKD progression.

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.

Resumen Introduccion y objetivos Los individuos con tasa de filtrado glomerular estimada (TFGe) disminuida tienen mayor riesgo de muerte por todas las causas (MT) y cardiovascular; se debate si los sujetos mayores con TFGe entre 45 y 59 ml/min/1,73 m2 tambien tienen un riesgo aumentado. Se evaluo la asociacion entre la TFGe y la MT y los eventos cardiovasculares (ECV) en individuos de edad 60-74 y ≥ 75 anos en un area de baja incidencia de enfermedad coronaria. Metodos Se realizo un estudio retrospectivo de cohortes utilizando registros electronicos de atencion primaria y hospital. Se incluyo a 130.233 individuos de 60 o mas anos con una determinacion de creatinina entre el 1 de enero de 2010 y el 31 de diciembre de 2011 y una TFGe segun la formula de la Chronic Kidney Disease Epidemiology Collaboration. Las asociaciones independientes entre la TFGe y la MT y el ingreso por ECV se evaluaron mediante modelos de regresion de Cox y Fine-Gray respectivamente. Resultados Media de edad, 70 anos; el 56,1% eran mujeres. El 13,5% tenia una TFGe Conclusiones En un area de baja incidencia de enfermedad coronaria, el riesgo de muerte y ECV fue de mayor a menor TFGe. A edades ≥ 75 anos, la categoria de TFGe 45-59, en el limite significativo de ECV, incluyo a muchos individuos sin riesgo adicional significativo.

Introduction: Variations in the use of healthcare services can be defined as systematic variations of adjusted rates for certain aggregation levels of the population. The study analyses how renal replacement therapy (RRT) is used, identifying RRT variability in Catalonia from 2002 to 2012. Material and methods: Ecological study by health area using data from the Catalan renal registry. We present incident rates, standardised incidence ratios and prevalence, while variability was calculated through direct and indirect standardisation methods. Results: From 2002 until 31/12/2012, 10,784 patients initiated RRT in Catalonia: 9238 on haemodialysis (HD) (50 treatments per 100,000 people 2010/2012), 1076 on peritoneal dialysis (PD) (8.2 treatments per 100,000 people 2010/2012) and 470 received an early kidney transplant (KT) (4.4 treatments per 100,000 people 2010/2012). Over the 10 years, the HD cumulative incidence rate fell (7%), while the PD and KT incidence rates increased (63% and 177%, respectively); both are higher in young patients (

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.

Background and objectives Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed. Design, setting, participants, & measurements The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3–5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models. Results VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P 6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event–free period (HR, 1.14; 95% CI, 1.06 to 1.22; P Conclusions VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.

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

Arterial stiffness is a biologic process related to ageing and its relationship with cardiovascular risk is well established. Several methods are currently available for non-invasive measurement of arterial stiffness that provide valuable information to further assess patients’ vascular status in real time. In kidney transplantation recipients, several factors could accelerate the stiffness process, such as the use of calcineurin inhibitors (CNIs), the presence of chronic kidney disease and other classical cardiovascular factors, which would explain, at least in part, the high cardiovascular mortality and morbidity. Despite the importance of arterial stiffness as a biomarker of cardiovascular risk, and unlike other cardiovascular risk factors (e.g. left ventricular hypertrophy), only a few clinical trials or retrospective studies of kidney recipients have evaluated its impact. In this review we describe the clinical impact of arterial stiffness as a prognostic marker of cardiovascular disease and the effects of different immunosuppressive regimens on its progression, focusing on the potential benefits of CNI-sparing protocols and supporting the rationale for individualization of immunosuppression in patients with lower arterial elasticity. Among the immunosuppressive drugs, a belatacept-based regimen seems to offer better vascular protection compared with CNIs, although further studies are needed to confirm the preliminary positive results.

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20- to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Diabetes Mellitus (DM) is a growing worldwide epidemic. It was estimated that more than 366 million people would be affected. DM has spread its presence over the world due to lifestyle changes, increasing obesity and ethnicities, among others. Diabetic nephropathy (DN) is one of the most important DM complications. A changing concept has been introduced from the classical DN to diabetic chronic kidney disease (DCKD), taking into account that histological kidney lesions may vary from the nodular or diffuse glomerulosclerosis to tubulointerstitial and/or vascular lesions. Recent data showed how primary and secondary prevention were the key to reduce cardiovascular episodes and improve life expectancy in diabetic patients. A stabilization in the rate of end stage kidney disease has been observed in some countries, probably due to the increased awareness by primary care physicians about the prognostic importance of chronic kidney disease (CKD), better control of blood pressure and glycaemia and the implementation of protocols and clinical practice recommendations about the detection, prevention and treatment of CKD in a coordinated and multidisciplinary management of the DM patient. And also the new hypoglycemic agents, - DDP4 inhibitors, GLP1R agonists, SLGT2 inhibitors-, can facilitate the management of DM and its complications in the patients with renal function impairment. Early detection of DM and DCKD is crucial to reduce morbidity, mortality and the social and economic impact of DM burden in this population.

ResumenIntroducciónLas variaciones en la utilización de servicios de salud pueden definirse como variaciones sistemáticas de las tasas ajustadas para ciertos niveles de agregación de la población. Analizamos el tratamiento sustitutivo renal (TSR) e identificamos la posible variabilidad en Cataluña entre 2002 y 2012.Material y métodosEstudio ecológico por áreas de salud con datos del registro de enfermos renales de Cataluña. Presentamos tasas de incidencia, incidencia estandarizada y prevalencia. Variabilidad calculada mediante estadarización directa e indirecta.ResultadosDesde 2002 hasta el 31/12/2012, 10.784 pacientes iniciaron TSR en Cataluña: 9.238 mediante hemodiálisis (HD) (50 tratamientos/100.000 habitantes 2010/2012), 1.076 diálisis peritoneal (DP) (8,2 tratamientos/100.000 hab. 2010/2012) y 470 recibieron un trasplante renal (TR) anticipado (4,4 tratamientos/100.000 hab. 2010/2012). Durante 10 años, la tasa de incidencia acumulada de HD ha descendido (7%) y las tasas de incidencia de DP y TR han aumentado (63 y 177%); ambas son más elevadas en pacientes jóvenes (

Diabetic kidney disease (DKD) defines the functional, structural and clinical abnormalities of the kidneys that are caused by diabetes. This complication has become the single most frequent cause of end-stage renal disease. The pathophysiology of DKD comprises the interaction of both genetic and environmental determinants that trigger a complex network of pathophysiological events, which leads to the damage of the glomerular filtration barrier, a highly specialized structure formed by the fenestrated endothelium, the glomerular basement membrane and the epithelial podocytes, that permits a highly selective ultrafiltration of the blood plasma. DKD evolves gradually over years through five progressive stages. Briefly they are: reversible glomerular hyperfiltration, normal glomerular filtration and normoalbuminuria, normal glomerular filtration and microalbuminuria, macroalbuminuria, and renal failure. Approximately 20-40% of diabetic patients develop microalbuminuria within 10-15 years of the diagnosis of diabetes, and about 80-90% of those with microalbuminuria progress to more advanced stages. Thus, after 15-20 years, macroalbuminuria occurs approximately in 20-40% of patients, and around half of them will present renal insufficiency within 5 years. The screening and early diagnosis of DKD is based on the measurement of urinary albumin excretion and the detection of microalbuminuria, the first clinical sign of DKD. The management of DKD is based on the general recommendations in the treatment of patients with diabetes, including optimal glycaemic and blood pressure control, adequate lipid management and abolishing smoking, in addition to the lowering of albuminuria.

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.

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.

AIM: To evaluate thresholds for serum 25(OH)D concentrations in relation to death, kidney progression and hospitalization in non-dialysis chronic kidney disease (CKD) population. METHODS: Four hundred and seventy non-dialysis 3-5 stage CKD patients participating in OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into 3 groups according to 25(OH)D levels at enrollment (less than 20 ng/mL, between 20 and 29 ng/mL, and at or above 30 ng/mL), considering 25(OH)D between 20 and 29 ng/mL as reference group. Association between 25(OH)D levels and death (primary outcome), and time to first hospitalization and renal progression (secondary outcomes) over a 3-year follow-up, were assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. To identify 25(OH)D levels at highest risk for outcomes, receiver operating characteristic (ROC) curves were performed. RESULTS: Over 29 ± 12 mo of follow-up, 46 (10%) patients dead, 156 (33%) showed kidney progression, and 126 (27%) were hospitalized. After multivariate adjustment, 25(OH)D < 20 ng/mL was an independent predictor of all-cause mortality (HR = 2.33; 95%CI: 1.10-4.91; P = 0.027) and kidney progression (HR = 2.46; 95%CI: 1.63-3.71; P < 0.001), whereas the group with 25(OH)D at or above 30 ng/mL did not have a different hazard for outcomes from the reference group. Hospitalization outcomes were predicted by 25(OH) levels (HR = 0.98; 95%CI: 0.96-1.00; P = 0.027) in the unadjusted Cox proportional hazards model, but not after multivariate adjusting. ROC curves identified 25(OH)D levels at highest risk for death, kidney progression, and hospitalization, at 17.4 ng/mL [area under the curve (AUC) = 0.60; 95%CI: 0.52-0.69; P = 0.027], 18.6 ng/mL (AUC = 0.65; 95%CI: 0.60-0.71; P < 0.001), and 19.0 ng/mL (AUC = 0.56; 95%CI: 0.50-0.62; P = 0.048), respectively. CONCLUSION: 25(OH)D < 20 ng/mL was an independent predictor of death and progression in patients with stage 3-5 CKD, with no additional benefits when patients reached the levels at or above 30 ng/mL suggested as optimal by CKD guidelines. Abbott and the Spanish Society of Nephrology

Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is incomplete. There is a scarcity of studies analysing the nephroprotective effect of antihyperglycaemic drugs beyond their glucose lowering effect and improved glycaemic control on the prevention and progression of diabetic nephropathy. This article analyzes the exisiting data about older and newer drugs as well as the mechanisms associated with hypoglycemic drugs, apart from their well known blood glucose lowering effect, in the prevention and progression of diabetic nephropathy. Most of them have been tested in humans, but with varying degrees of success. Although experimental data about most of antihyperglycemic drugs has shown a beneficial effect in kidney parameters, there is a lack of clinical trials that clearly prove these beneficial effects. The key question, however, is whether antihyperglycemic drugs are able to improve renal end-points beyond their antihyperglycemic effect. Existing experimental data are post hoc studies from clinical trials, and supportive of the potential renal-protective role of some of them, especially in the cases of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Dedicated and adequately powered renal trials with renal outcomes are neccessary to assess the nephrotection of antihyperglycaemic drugs beyond the control of hyperglycaemia.

Bidirectional mechanisms exist that link diseases affecting the heart and kidney. This link is complex and remains poorly understood; therefore, charting the shared territory of cardiovascular (CV) and renal medicine poses major problems. Until now, no convincing rationale for delineating new syndromes existed. The multiple connections of the arterial system and the heart and kidney with other systems, from energy and protein balance to the musculoskeletal, clearly require special focus and rigorous framing. Nephrologists have yet to fully understand why the application of dialysis has had only limited success in halting the parallel burdens of CV and non-CV death in patients with end-stage renal disease. Cardiologists, intensivists, and nephrologists alike should settle whether and when extracorporeal ultrafiltration benefits patients with decompensated heart failure. These sparse but interconnected themes spanning from the basic science–clinical transition phase to clinical science, epidemiology, and medical technology already form the basis for the young discipline of ‘CV and renal medicine'.

Despite many advances in the management of hypertensive chronic kidney disease (CKD) patients, both on and off dialysis, there exist several gaps in our knowledge. Although the modern techniques to measure blood pressure (BP) indirectly have been available for a long time, among those with CKD, how to best assess hypertension and the level to which it should be lowered are mired in controversy. Other controversial areas relate to a lack of a consensus definition of hypertension among hemodialysis patients, uncertainty in the definition and assessment of volume excess, and the lack of adequately powered randomized trials to evaluate the level to which BP can be lowered in those on dialysis. This review discusses the limitations of the available evidence base and suggests areas for future research. Suggestions include evaluation of techniques to assess volume, randomized trials to target different levels of BP among hypertensive hemodialysis patients, evaluation of ambulatory BP monitoring, and non-pharmacological means to lower BP in CKD. It is hoped that among patients with CKD these data will improve the dismal cardiovascular outcomes.

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.

Endothelial dysfunction resulting in disintegration of vascular structure and function is a key element in the progression of chronic kidney disease (CKD). Many risk factors—traditional and non-traditional—are thought to have a role in the progression and development of cardiovascular disease (CVD) in patients with CKD. However, many risk factors await definitive confirmation of their clinical relevance obtained from intervention trials. Moreover, the investigation of the relative contribution of these factors to the twin-risk problem of CVD and progression in patients with CKD is one of the most important future challenges for nephrologists.

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.

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.

Over the past decade, the research agenda in dialysis has been dominated by studies on risk factors associated with cardiovascular mortality. It has now become increasingly clear that in dialysis patients, non-cardiovascular causes of death are increased to the same extent as cardiovascular mortality, and therefore research efforts in this area deserve an equally prominent place on the nephrology research agenda. As previous research has suggested an association between cardiovascular disease and infections, more research on potential links between the causal pathways of cardiovascular events and infections is also warranted.