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Resumen Antecedentes y objetivo Describir las caracteristicas clinicas de los pacientes tratados con evolocumab, las razones del inicio de la terapia y los efectos del tratamiento en la fase inicial de disponibilidad de evolocumab en las unidades de nefrologia de Espana. Material y metodos Estudio retrospectivo, observacional y multicentrico que incluye los pacientes que iniciaron tratamiento con evolocumab (desde febrero de 2016 a agosto de 2018) en 15 unidades de nefrologia en Espana. Se revisaron las caracteristicas demograficas y clinicas de los pacientes, el tratamiento hipolipemiante y la evolucion de los perfiles lipidicos entre 24 semanas antes y 12 ± 4 semanas despues del inicio de evolocumab. Resultados Se incluyeron 60 pacientes: 53,3% mujeres, edad media (DE) de 56,9 (12,8) anos, el 45,0% con hipercolesterolemia familiar (HF) (5,0% homocigota y 40,0% heterocigota) y el 65,0% con enfermedad cardiovascular aterosclerotica (ECVA) previa. El filtrado glomerular estimado (FGe) medio fue de 62,6 (30,0) ml/min/1,73 m2 (51,7% pacientes con FGe 2]), el 50,0% con proteinuria (> 300 mg/g) y el 10,0% con sindrome nefrotico. Otros factores de riesgo CV fueron: hipertension (75,0%), diabetes mellitus (25,0%) y habito tabaquico (21,7%). El 40,0% eran intolerantes a estatinas. Al inicio de evolocumab, el 41,7% tomaban estatinas de alta intensidad, el 18,3% estatinas de moderada intensidad y el 50,0% ezetimiba. Los niveles medios (DE) de c-LDL al inicio de evolocumab fueron de 179,7 (62,9) mg/dl (53,4% pacientes con c-LDL ≥ 160 mg/dl y 29,3% ≥ 190 mg/dl). Despues de 12 semanas del tratamiento con evolocumab se observo una reduccion de los niveles de c-LDL del 60,1%. A la semana 12, el 90,0% de los pacientes alcanzo niveles c-LDL Conclusiones En las unidades de nefrologia de Espana, evolocumab se ha prescrito principalmente en pacientes con HF, enfermedad renal cronica (ERC > 2) y prevencion secundaria, con niveles de c-LDL muy por encima de los recomendados por las guias. Evolocumab utilizado en practica clinica, redujo significativamente los niveles de c-LDL en todos los pacientes incluidos en el estudio.

Este artículo de investigación se encuentra disponible en la siguiente URL: https://www.revistanefrologia.com/es-pdf-S0211699521001570 En este artículo de investigación también participan: Ramón A. García-Trabanino, Miguel Hueso, Pedro Trinidad, Aquiles Jara, Mónica Furlano, Rosana Gelpi, Ana Vila-Santandreu, César A. Restrepo, Maya Sánchez-Baya, Carolt Arana, Marián Goicoechea, Verónica Coll, Julián Segura, Orlando Gutiérrez, Kamyar Kalantar-Zadeh, Emilio Sánchez y Alejandro Ferreiro.

Background: Acute changes in glomerular filtration rate (GFR) can occur following initiation of interventions for chronic kidney disease (CKD) progression. These complicate the interpretation of treatment effects on long term progression of (CKD). We sought to assess the magnitude and consistency of acute effects in randomized clinical trials (RCT) and explore factors that might impact them. Methods: We performed a meta-analysis of 53 RCTs for CKD progression enrolling 56,413 participants that had at least one estimated GFR measurement by six months following randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable meta-regression to assess the impact of intervention type, disease state, baseline GFR and albuminuria on the magnitude of acute effects. Results: The mean acute effect across all studies was -0.21 mL/min/1.73m2 (95% CI -0.63 to 0.22) over three months, with substantial heterogeneity across interventions (95% coverage interval across studies, -2.50 to +2.08 mL/min/1.73m2). Negative average acute effects were observed in renin angiotensin system blockade, blood pressure lowering and sodium-glucose cotransporter 2 inhibitor trials while positive acute effects were observed in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with higher mean baseline GFR. Conclusion: The magnitude and consistency of acute GFR effects varies across different interventions, and is larger at higher baseline GFR. Understanding the nature and magnitude of the acute effects can help inform the optimal design of RCTs in CKD evaluating kidney disease progression.

Introduction Obesity is a major health problem worldwide. It carries a markedly increased risk for multiple diseases such as type 2 diabetes mellitus, hypertension, cardiovascular disease (CVD) and chronic kidney disease (CKD). To complicate an already difficult topic a new subtype of obesity has been defined lately, the metabolically healthy obese. Our study aimed to clarify the association between obesity, metabolic syndrome and kidney disease progression. Methods Observational retrospective single centre study including 212 patients with stage 3–4 CKD with no previous history of rapid kidney disease progression. Patients were divided according to BMI status and presence of metabolic syndrome. Anthropometric, clinical and laboratory data were collected to follow-up. Propensity score matching was performed for age, albuminuria and baseline renal function. During follow-up renal and cardiovascular events were recorded. Results After a mean follow-up of 88.44 ± 36.07 months a total of 18 patients reached the renal outcome in the non-obese group and 21 in the obese group. Differences were not statistically significant (log rank = 0.21: p = 0.64). Multiple Cox regression analysis showed that obesity was not predictor for worse renal outcomes [HR 1.01, 95% CI 0.45–2.24; p = 0.97]. When stratifying the sample according to baseline metabolic syndrome and obesity presence there was no difference in renal survival (log rank = 0.852; p = 0.35) A total of 48 cardiovascular events were registered: seventeen in the non-obese group and thirty-one in the obese group. Differences in event-free time between both groups were statistically significant (log rank = 4.44; p = 0.035), especially after four years of follow-up. After stratifying for MS and obesity presence at baseline the event-free time differences where again statistically significant (log rank = 16.86; p = 0.001), specially for the obese patients with metabolic syndrome. Conclusions Obesity has little impact on chronic kidney disease progression despite the presence or absence of metabolic syndrome in a cohort matched for age, baseline renal function and albuminuria. Obesity conferred greater cardiovascular risk when combined with metabolic syndrome.

Autologous arteriovenous fistula (AVF) is the best vascular access for hemodialysis. Distal forearm radiocephalic fistula is the best option, although the primary failure rate ranges from 20% to 50%. The main objective of the PHYSICALFAV trial was to evaluate the effect of preoperative isometric exercise on vascular caliber, percentage of distal arteriovenous fistula, and primary failure rate. The PHYSICALFAV trial (NCT03213756) is an open-label, multicenter, prospective, randomized, controlled trial (RCT). A total of 138 patients were randomized 1:1 to the exercise group (exercises combining a handgrip device and an elastic band for 8 weeks) or the control group (no exercise) and followed up with periodic Doppler ultrasound (DU) examinations. After 8 weeks of preoperative isometric exercise, in the exercise group, significant increases were detected in venous caliber (2.80 ± 0.95 mm vs 3.52 ± 0.93 mm [p

SARS-CoV-2-pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), even less in patients on maintenance hemodialysis (MHD) therapy than in the general population. In this retrospective observational single-center study we analyzed the clinical course and outcomes of all MHD patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and non-survivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died and 7 could be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 Liters/minute and radiological worsening. Significantly 11 out of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. However, a longer time on hemodialysis (hazard ratio 1.008(95% confidence interval 1.001-1.015) per year), increased LDH levels (1.006(1.001-1.011), and lower lymphocyte count (0.996 (0.992-1.000) one week after clinical onset were all significantly associated with higher mortality risk. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Lymphopenia and increased LDH levels were associated with poor prognosis., Graphical abstract

Background Low-molecular-weight heparins (LMWHs) are easily dialysable with high-flow membranes; however, it is not clear whether the LMWH dose should be adjusted according to the membrane type and dialysis technique. This study aimed to evaluate the influence of the dialyser on anticoagulation of the extracorporeal dialysis circuit. Methods Thirteen patients received the same dose of LMWH through the arterial port via three dialysis techniques: high-flux haemodialysis (HF-HD), online haemodiafiltration (HDF) and expanded haemodialysis (HDx). All dialysis was performed under similar conditions: duration, 4 h; blood flow, 400 mL/min; and dialysate flow, 500 mL/min. Antifactor Xa (aXa) activity and activated partial thromboplastin time (APTT) were measured before and after the dialysis. Clotting time of the vascular access site after haemodialysis, visual clotting score of the dialyser and any complications with the extracorporeal circuit or bleeding were registered. Results Post-dialysis aXa activity in HF-HD (0.26 ± 0.02 U/mL) was significantly different from that in HDF (0.21 ± 0.02 U/mL, P = 0.024), and there was a trend in HDx (0.22 ± 0.01 U/mL, P = 0.05). APTT post-dialysis in HF-HD (30.5 ± 0.7 s) was significantly different from that in HDx (28.2 ± 0.64 s, P = 0.009) and HDF (28.8 ± 0.73 s, P = 0.009). Conclusions AXa activity in HDF was significantly lower than that in HF-HD, possibly because of more losses of LMWH through the dialyser. Given the higher anticoagulant loss in HDF and probably in HDx than in HF-HD, the enoxaparin dose administered may be adjusted according to the dialysis technique.

BackgroundDiabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes.MethodsRetrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014.ResultsIn total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02–1.05, P ConclusionsThe most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Red de Investigación Renal (RedInRen); European Renal Association-European Dialysis and Transplant Association (ERA-EDTA); Fundación Renal Iñigo Álvarez de Toledo (FRIAT); Fundación para la Investigación Biomédica Hospital 12 de Octubre (i+12); Centre National de la Recherche Scientifique; Fondation Maladies Rares (LAM-RD_20170304); National Research Agency (ANR, grants MNaims ANR-17-CE17-0012-01); "Investments for the Future" Laboratory of Excellence SIGNALIFE, a network for innovation on signal transduction pathways in life sciences (ANR-11-LABX-0028-01); Initiative of Excellence (IDEX; UCAJedi ANR-15-IDEX-01); Fondation pour la Recherche Médicale (FRM, ING20140129210, DEQ20180339193, FDT201805005509). A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.

Background: Native autologous arteriovenous fistula (AVFn) is the preferred vascular access for hemodialysis due to its long term patency and low complication rate. A challenging limitation is the anatomical inability to perform AVFn and failure of maturation. Preoperative isometric exercise (PIE) can increase vascular calibers and improve the rate of distal AVF. However, it is unknown whether PIE might enhance the performance of AVFn in patients who are not initially candidates. Methods: A retrospective observational study was conducted over a population of 45 patients evaluated in vascular access clinic, 23 were not initially candidates for radiocephalic (NRC-AVF) and 22 were not candidates for autologous fistula at all (NA-AVF). They were assigned to perform PIE with handgrip device and revaluated. Results: After 4–8 weeks of PIE, a AVFn was performed in 16 patients from NA-AVF group and a radiocephalic AVFn was performed in 21 patients from NRC-AVF group. Both groups experienced a significant and similar increase in venous caliber 0.91 ± 0.43 mm in NA-AVF versus 0.76 ± 0.47 mm in NRC-AVF ( p = 0.336) and arterial caliber 0.18 ± 0.24 mm versus 0.18 ± 0.21 mm ( p = 0.928), respectively. Nevertheless, primary failure rate was significantly higher in NA-AVF ( n = 8, 50%) than in NRC-AVF group ( n = 3, 14.3%) ( p = 0.030). After 6 months, the fistula usability for dialysis was only 50% in NA-AVF, while 86.7% were dialyzed by fistula in NRC-AVF group ( p = 0.038). Conclusions: PIE allowed the allocation of an AVFn in patients not initially candidates, but entailed a high rate of maturation failure. Patients not candidates to radiocephalic AVF benefited from PIE and preserved a long term usability of AVF for dialysis.

Low-density lipoprotein (LDL) apheresis has been considered the last option to treat refractory hyperlipidemia in patients with familiar hypercholesterolemia (FH). Evolocumab is a monoclonal antibody which has shown significant reduction of low-density lipoprotein cholesterol (LDL-C) serum levels and cardiovascular events. The aim of the study was to examine the comparative impact of LDL-apheresis vs Evolocumab vs the combination of both LDL-apheresis and Evolocumab on lipid and lipoprotein parameters, and other metabolic/inflammatory measures. DESIGN OF THE STUDY Non-randomized open case series study of 10 adult patients diagnosed with FH already on long-term LDL-apheresis therapy. The study was developed in three consecutive phases to compare LDL-apheresis, Evolocumab treatment and the combination of both. Laboratory parameters were collected pre and post LDL-apheresis and before Evolocumab administration. The primary endpoint was the reduction of LDL-C during the three phases. RESULTS Reduction of LDL-C levels with Evolocumab were 31.4% vs LDL-apheresis from 153 ± 35 mg/dL to 105 ± 56 mg/dL (P

Pentoxifylline could reduce proteinuria and slow renal disease progression. We previously conducted a single-blind, randomized, controlled trial that showed that pentoxifylline decreases inflammatory markers and stabilizes renal function. 91 participants (46 in the pentoxifylline group and 45 in the control group) followed up for 7 additional years. Post hoc analysis of a long-term follow-up after completion of the 12-months trial. Pentoxifylline treatment (400 mg/twice a day) or standard treatment. Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥ 50% decrease in estimated glomerular filtration rate) and cardiovascular mortality. During follow-up, a renal event was recorded in 24 patients from control group (13 initiated dialysis therapy and serum creatinine doubled in 11) and 11 patients from PTF group (7 initiated dialysis and serum creatinine doubled in 4) (log Rank: 5.822, p = 0.016). The possible protector effect of PTF was more significant in albuminuric patients and was independently of diabetes mellitus presence. Treatment with PTF reduced the renal events by 35% compared to the control group in a Cox model adjusted for diabetes mellitus, albuminuria and basal renal function (HR 0.65 (0.45–0.94), p = 0.022). Cardiovascular mortality was significantly reduced in PTF treatment (2 patients vs. 10 in control group) (log Rank 5.0977, p = 0.024). PTF treatment reduced cardiovascular mortality in 55% adjusted for diabetes mellitus and age (HR 0.45 (0.21–0.98), p = 0.044) (Table 3). Small sample size, single center, not double blind and post hoc follow-up analysis. Long-term treatment with pentoxifylline may slow the rate of progression of kidney disease and reduce cardiovascular risk.

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular-weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.

INTRODUCTION: Four vaccines against Covid-19 have been approved to date. Their acceptance and safety have not been addressed on healthcare workers. The aim of the present study is to evaluate vaccination rates and side effects among Spanish nephrologists. METHODS: All the Spanish nephrologists were invited to participate in this survey. Data on demographics, Covid-19 infection status, received vaccine doses and side effects were collected. Acceptance and side effects were analyzed for Covid-19 vaccination. Factors associated to vaccination were assessed and a multivariate adjusted model was constructed to determine independent predictors for Covid-19 vaccine side effects. RESULTS: A total of 708 nephrologists answered the survey (460 [65%] women, mean age 44±11 years). Six-hundred and eight (86%) had received the first dose and 513 (72%) were fully vaccinated. Most of the subjects (565, 93%) received BNT162b2 (Pfizer-BioNTech®) vaccine. Among vaccinated nephrologists, 453 (75%) presented any side effect; the most frequent was local reaction (68%), followed by myalgia (44%), tiredness (39%) and headache (34%). Age (OR 0.97, 95%CI [0.95-0.99], p

Kidney transplant recipients are at increased risk for infection, including coronavirus disease 2019 (COVID-19), given ongoing immunosuppression. In individuals with COVID-19, complications including thrombosis and endothelial dysfunction portend worse outcomes. In this report, we describe a kidney transplant recipient who developed severe thrombotic microangiopathy with a low platelet count (12 ×109/L), anemia (hemoglobin, 7.5 g/dL with 7% schistocytes on peripheral-blood smear), and severe acute kidney injury concurrent with COVID-19. The clinical course improved after plasma exchange. Given this presentation, we hypothesize that COVID-19 triggered thrombotic microangiopathy.

There is no evidence about the potential role of body composition on cardiovascular mortality in dialysis patients. The aim of this study was to assess the relationship between body composition and changes in ventricular function. We conducted an observational study over a population of 78 patients on chronic hemodialysis. A transthoracic echocardiogram and a bioimpedance were performed at the beginning and at the end of the study. The mean follow-up time was 30.6 months. Patients who had a higher fat tissue index (FTI > 9.20 kg/m2 ) experienced a worsening in right and left ventricular function. They developed a greater fall in tricuspid annular plane systolic excursion (TAPSE) (-1 ± 4.3 mm) and left ventricular ejection fraction (LVEF)(-4.2 ± 6.8%), compared to those with lower FTI (p = 0.032 and p = 0.045, respectively). No associations were found between any other echocardiography or body composition parameters and overall mortality. Patients with right ventricular dysfunction (determined as TAPSE) experienced a tendency to higher mortality rate along the study (HR for mortality of 13.5 (95% CI, 1.1-166.7; p = 0.041)]. A higher fat tissue index could be associated with a deleterious effect over right and left ventricular function in dialysis patients.

Background and Aims Although metformin-associated lactic acidosis (MALA) is a very rare event, is frequently seen in patients on metformin with risk factors for developing acute kidney injury (AKI). The long-term prognosis in patients with metformin-associated lactic acidosis (MALA) and renal failure remains unknown. To describe the characteristics and prognosis of AKI in patients with MALA and investigate whether prescription of RRT and previous renal function are associated with long-term outcomes. Method A retrospective single-centre case series. One hundred and nine patients affected with MALA and AKI admitted between Marx 2007 and February 2019 were included. We analysed comorbidities, laboratory tests, clinical parameters and prescription pattern of RRT at admission. After discharging, renal outcomes (doubling serum creatinine or starting dialysis) and mortality were assessed in the long-term. Results We included 109 patients (59 males and 50 females), mean age of 74.2±8.6 years and mean Charlson comorbidity index of 8.0±2.4. 54 out of 109 patients had previous chronic kidney disease (eGFR < 60 ml/min/1.72 m2). Precipitating causes of AKI associated MALA included; acute dehydration (84.4%), exposure to iodinated contrast (7.3%) and non-specified causes (8.3%). During the admission, renal replacement therapy (RRT) was performed in 72 patients (continuous renal replacement therapy in 47 and dialysis in 25). RRT requirements was significantly associated with lactate, acidosis and serum creatinine levels, but not was associated with higher mortality rate during admission. The patients were followed a median time of 33 (10-65) months after discharging. 33 patients had a renal event and 55 patients died. The patients with CKD before admission had higher number of renal events (log Rank 6.346, p=0.012) and higher mortality (log Rank 12.943, p Conclusion The renal function prior to the episode of AKI associated to MALA and the RRT at admission are the main factors related to renal outcomes and mortality in the long-term.

Background and Aims Since the introduction of direct-acting antivirals (DAAs), few data have been published about kidney outcome in hepatitis C virus related mixed cryoglobulinaemia (HCV-MC) patients treated with combined DAAs and rituximab. We aimed to asses if combined treatment with DAAs and rituximab in patients with HCV-MC improves kidney survival and immunological response. Method Observational, multicentre, cohort study of 100 patients with HCV-MC from 14 Spanish centres treated with DAAs. Patients were followed up for a median duration of 138 months (11.5 years). Long-term kidney survival and immunological response were evaluated based on immunosuppressive treatment received. Kidney event was defined as duplication of creatinine level or 50% decrease in glomerular filtration rate, dependence on renal replacement therapy or non-reduction of proteinuria by 50% compared to baseline. Immunological response was defined as the decrease in cryocrit ≤1%. Results Sustained virological response was attained in 98 (98%) patients. 49 patients were treated with immunosuppressive treatment associated with DAAs, 26 with rituximab and the rest (23) with steroids and/or cyclophosphamide. Patients receiving immunosuppressive treatment had higher basal cryocrit (6.3±4.5 vs 3.8±3.9%, p=0.011), lower glomerular filtration rate (55±27 vs 68±25 ml/min/1.73 m2) and more haematuria (p=0.001). The 26 patients treated with rituximab had more severe disease: higher viral load (p=0.001), cryocrit (p=0.011), proteinuria (p=0.004), microhaematuria (p=0.012) and hypertension (p=0.012) and lower glomerular filtration rate (p=0.001). 15 patients had a kidney event at the end of follow-up. Predictive variables of kidney events were lower age (HR 0.94, 95%CI 0.89-0.99; P= 0.038) and lower glomerular filtrate rate (HR 0.97, 95%CI 0.94-0.99; p=0.026), in a model adjusted to proteinuria and microhaematuria. Immunosuppressive treatment with or without rituximab did not change kidney survival. Regarding the immunological response, only 19 patients had a cryocrit >1% at the end of follow-up. There were no differences in age, viral load, proteinuria and basal glomerular filtration rate between these patients with no immunological response and those who had a sustained immunological response over time. The only differences between these two groups were a higher basal cryocrit and a minor C4 levels. Immunosuppressive treatment with or without rituximab did not changed the immunological response. Conclusion Patients with more severe HCV-MC are those receiving immunosuppressive treatment. However, immunosuppressive treatment does not change kidney survival nor immunological response of these patients in the long term.

Background and Aims Right ventricular dysfunction is common among hemodialysis (HD) patients and it has been recently described as a marker of cardiovascular morbidity and mortality. Nevertheless, mechanisms responsible for have not been clearly elucidated. Volume overload, retrograde left ventricular dysfunction, pulmonary hypertension, left-right shunt and mineral bone disease have been related. Similarly, body composition and chronic fluid overload are closely linked to survival in dialysis patients. However, there are no data about correlation between body composition and echocardiographic parameters in previous studies The aim of this study was to assess the relationship between body composition and changes in right and left ventricular function in patients on maintenance hemodyalisis. Method We conducted a retrospective and longitudinal observational cohort study over a population of 78 patients on maintenance hemodyalisis at a single hospital. They were on chronic hemodyalisis program of three weekly sessions of 240 minutes duration. A transthoracic echocardiogram (TTE) and a bioimpedance (BI) were performed in the same month, in the first inter-dialysis day of the week, being the patients asymptomatic and clinically stable, at the beginning and at the end of the study. The follow-up time since the completion of first and second ETT and BI was 19.5 months, with an average total follow-up of 29.7 months. Cardiovascular and general mortality events were recorded during that period. Echocardiography data about cardiac cavities measurement, ventricular and valvular function was collected. Left ventricular ejection fraction was evaluated by Simpson’s method (LVEF, %) and right ventricular function by tricuspid annular plane systolic excursion (TAPSE, mm).We gathered information about fluid status and corporal composition. Statistical analysis was performed using SPSS Statistics, version 21 (SPSS, Inc., Chicago, IL, USA). Results Patients with RV dysfunction (35.7%), determined as TAPSE < 20, experienced a higher mortality rate (20%) compared to those who maintained TAPSE ≥ 20 (63.2%), who had a mortality rate of 2.3%. These results were statistically significant in the Kaplan-Meier survival analysis (Log Rank 6.65; p = 0.010). There were not statistically significant differences regarding age, diabetes, years on dialysis and status of volume overload between patients with and without right ventricular dysfunction. No significant differences were found between any other of the echocardiography parameters and overall mortality. Equally, neither bioimpedance measure at the beginning of the study was associated with mortality. Patients who had an FTI above the average (9.20 kg / m2) suffered a greater fall in TAPSE (-1 ± 4.3 mm) (p = 0.032) and LVEF (-4.2 ± 6.8) (p = 0.045), regarding those with lower FTI: TAPSE +2.3 ± 4.3 and LVEF +3.7± 10.4. These results seems to be related to a disproportionate LTI/LTI index rather than a greater total mass of fat due to patients with FTI > 9.2 kg/m2 had a mean LTI/FTI index of 1.1, meanwhile those with FTI < 9.2 kg/m2 a mean LTI/FTI of 5.9. No statistically significant relationship was found with absolute or relative volume overload, nor with changes in them over time. Conclusion The results presented suggest that high fat tissue index, and an underlying lower LTI/FTI index, could be associated with a higher risk of right and left ventricular dysfunction, which has been associated with higher mortality in hemodialysis patients.

Background and Aims Online haemodiafiltration (OL- HDF) is the gold standard therapy in hemodialysis, as it has shown to reduce all-cause mortality in hemodialysis patients. Frequent hemodialysis has also shown to improve survival and quality of life. Home hemodialysis facilitates frequent therapy, and it is possible to perform OL-HDF at home, althought there is lack of evidence on its use. We report the evolution of a cohort of patients undergoing home OL-HDF during a 3 year follow up period. Method We designed a prospective, descriptive study to determine the evolution of prevalent and incident patients in home OL-HDF since 2016. Demographic and clinical variables were collected, including those related to hemodialysis technic and its potential complications. Results Three patients with a mean age of 47 years underwent home OL-HDF during follow up. All patients were males and caregiver was the couple in all cases. Two patients had an arteriovenous fistula (AVF) and one had a catheter. After a mean training period of 2.5 months at hospital, they started home OL- HDF with the assitance of a nephrologist, a nurse and a technician in the first session at home. We used the “5008-home”®FMC monitor and the AquaC®FMC for water treatment. Water cultures allways fulfilled the criteria for ultrapurity. Dialysis scheme was 2 hour sessions daily, 6 days a week. During a mean follow up of 15 months, one patient received a kidney transplant. None needed hospitalization. One patient attended the emergency room once for fluid overload and needed ultrafiltration. The patient with catheter needed a catheter replacement due to hole infection. No vascular access problems were recorded in patients with AVF. Regarding dialysis efficacy, mean week KtV was over 2.1 in all cases and mean convective volumen achieved was 94 l/week. Conclusion In our experience, home OL-HDF is a safe and effective technic.

Background and Aims Cardiovascular disease is the primary cause of morbidity and mortality in patients with chronic kidney disease (CKD). Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers serum low density lipoprotein cholesterol (LDL-C) levels. Evolocumab is indicated for adult patients with hypercholesterolaemia or mixed dyslipidaemia who are unable to reach LDL-C goals with the maximum tolerated dose of statin or are statin intolerant. This study was conducted to describe clinical characteristics, reasons for therapy initiation and treatment effects in patients treated with evolocumab in Spanish Nephrology units. Method Retrospective, observational, chart review of consecutive patients initiating evolocumab (Feb-2016 to Aug-2018) in 15 Spanish Nephrology Units. Patient characteristics, lipid modifying therapies and lipid profiles over time were retrospectively collected at 24 weeks pre- and 12±4 weeks post-evolocumab initiation. Results 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years; mean (SD) body mass index, 28.0 (4.7) kg/m2; 45.0% had familial hypercholesterolemia (FH) (5.0% homozygous, 23.3% heterozygous, 16.7% undetermined FH); from the total population, 35% were in primary prevention and 65.0% started evolocumab after previous Atherosclerotic Cardiovascular Disease [ASCVD]. Regarding renal function, mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2; 51.7% of patients had eGFR 2), 50.0% had proteinuria (>300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%); 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-C at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-C≥160; 29.3% ≥190). Mean (SD) baseline HDL-C and total cholesterol were 48.5 (15.0) mg/dL and 273.1 (82.7) mg/dL, respectively. After 12 weeks, evolocumab resulted in LDL-C reductions of 60.1%, to a mean (SD) of 72.7 (80.3) mg/dL, with similar results observed in patients in primary/secondary prevention, with CKD stage >2/≤2 or with/without proteinuria. Conversely, patients with/without FH showed significant differences between their reductions (46.6% vs 76.6%, respectively, p=0.0276). At week 12, 90.0% of patients reached LDL-C levels Conclusion In Spanish Nephrology Units, evolocumab was predominantly prescribed in patients with FH, ASCVD and/or CKD stage >2. Initial evolocumab use was aligned with ESC/EAS dyslipidaemia guidelines, but with higher baseline LDL-C levels than the recommended thresholds. After 12 weeks of evolocumab treatment, LDL–C levels were more than halved and the majority of patients achieved both the 2016 and 2019 EAS/ESC targets of LDL-C control.

Background and Aims Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in Fabry disease patients on ERT. Method Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). Results In 69 patients (42 males, 27 females, mean age 44.6 ±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242 to 128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤60 ml/min/1.73 m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043), being these differences more relevant in females (log Rank 18.514, p Conclusion GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. For the first time, we show that initiation of ERT in women before renal function deteriorates has a similar or even larger impact as in Fabry males to prevent clinical events.

Background and Aims Retention of ß2microglobulin (ß2M), an uremic toxin in the middle molecular range, has been associated with cardiovascular morbidity and mortality in dialysis patients. Although ß2M levels are usually measured in hemodialysis patients, this practice is not common among peritoneal dialysis (PD) patients. The aim of this study is to evaluate the evolution of serum ß2M levels in incident PD patients. Method Prospective, observational study including incident PD patients in our hospital from January 2015 to October 2019. Patients with cardiorrenal syndrome or patients coming from hemodialysis were excluded. Serum ß2M levels were collected before starting PD and during follow up. Weekly KtV, residual renal function and cardiovascular events were also collected during follow up. Results We included 30 patients with a mean age of 57 +/- 17 years. 56.3% were male and 15.6% were diabetic. Mean follow up was 19.8 +/- 16.9 months. 18 patients were on continous ambulatory PD and 12 in automated PD. Mean serum ß2M levels before starting PD were 12.8 +/- 6.6 mg/l and they remained stable during follow up (12.9 +/- 5.2 mg/l, 15 +/- 4.2 mg/l, 14.3 +/- 6.9 mg/l, 10.2+/- 4.5 mg/l at month 6, 12, 24 and 36, respectively; p NS). No differences in serum ß2M levels were observed between continous ambulatory PD and automated PD. Serum ß2M levels were inversely and significantly correlated with weekly KtV (r= -0.943; p 0.009) and residual renal function (r= -0.829; p 0.042). One cardiovascular event was recorded during follow up. Conclusion Serum ß2M levels remain stable during follow up in our cohort of incident PD patients and is significantly and inversely correlated with weekly KtV and residual renal function. Serum ß2M levels monitoring could be helpful in these patients and would yield important information in this population.

In the general population, hypomagnesemia has been associated with cardiovascular events and hypermagnesemia with overall mortality. In chronic kidney disease (CKD) the evidence is not so strong. The objective of our study was to investigate the relationship between serum magnesium (SMg) concentration and cardiovascular morbidity and mortality, all-cause mortality, and the progression to kidney failure in a population with CKD.Observational study of a cohort of 746 patients with CKD. Baseline characteristics and analytical profile were collected at the first visit, and patients were followed for a mean of 42.6 months.A cohort of 746 patients were analyzed, age 70 ± 13 years, 62.9% were male, 45.2% had CKD grade 3, and 35.9% grade 4. The mean SMg concentration was 2.09 ± 0.33 mg/dL, with a close correlation between SMg concentration and serum creatinine, phosphorus, and intact parathyroid hormone (iPTH) values. Use of calcitriol was associated with higher SMg (SMgH) concentration, while calcium supplements and proton pump inhibitors (PPIs) were associated with lower SMg concentration. For risk of cardiovascular events, patients with hypermagnesemia had an overall higher risk on a crude analysis (Log Rank 4.83, P = .28) and adjusted analysis (HR = 1.34, CI 1.02-1.77, P = .037). For risk of all-cause mortality, patients with hypermagnesemia had an overall higher risk on crude analysis (Log Rank 13.11, P .001) and adjusted analysis (HR = 1.5424, IC = 1.002-2.319, P = .049). After performing a propensity score matching for SMg concentration, we achieved two comparable groups of 287 patients, finding again higher all-cause mortality in the hypermagnesemia group (LogRank 15.147, P .001), that persisted in the Cox model adjusted for calcium, phosphorus, and iPTH. No association was found between SMg concentration and initiation of kidney replacement therapy (KRT).Magnesium concentration increases with decreasing kidney function. Hypermagnesemia predicts cardiovascular events and all-cause mortality in this same population. Thus, magnesium supplementation should be used with caution in these patients.

Introduction Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin–angiotensin–aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. Materials and methods The PROERCAN trial (trial registration, NCT03195023 ) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3–4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. Results and conclusions The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified.

Background Direct-acting antiviral agents (DAAs) have shown high rates of sustained virological response in chronic hepatitis C virus (HCV) infection. However, the influence of DAAs on the course of kidney involvement in HCV-associated mixed cryoglobulinaemia (HCV-MC) has been little studied. The aim of this study was to analyse the effects of antiviral treatment on kidney prognosis and evolution in patients diagnosed with HCV-MC. Methods The RENALCRYOGLOBULINEMIC study is an observational multicentre cohort study of 139 patients with HCV-MC from 14 Spanish centres. Clinical and laboratory parameters were measured before and after antiviral treatment. Primary endpoints were kidney survival and mortality after HCV-MC diagnosis. Secondary endpoints were clinical, immunological and virological responses after antiviral treatment. Results Patients were divided into three groups based on the treatment received: treatment with DAAs (n = 100) treatment with interferon (IFN) and ribavirin (RBV) (n = 24) and no treatment (n = 15). Patients were followed up for a median duration of 138 months (interquartile range 70–251. DAA treatment reduced overall mortality {hazard ratio [HR] 0.12 [95% confidence interval (CI) 0.04–0.40]; P Conclusions Results from the RENALCRYOGLOBULINEMIC study indicated that DAA treatment in patients with HCV-MC improves kidney survival and reduces mortality.

Resumen Introduccion y objetivo Existe controversia sobre el riesgo/beneficio de anticoagular/antiagregar a pacientes con enfermedad renal cronica (ERC). Analizamos el impacto de la anticoagulacion/antiagregacion en pacientes con ERC sobre el riesgo hemorragico, cardiovascular y la mortalidad. Pacientes y metodos Se estudio a 232 pacientes (81 controles, 91 anticoagulados y 60 antiagregados) con ERC en estadios 3 y 4, que fueron seguidos durante un tiempo medio de 33,7 ± 14,8 meses. Se recogieron eventos hemorragicos, cardiovasculares y mortalidad. Resultados La hemoglobina serica y los niveles de ferritina fueron significativamente mayores en pacientes controles (hemoglobina 13,7 ± 1,6; 13,3 ± 1,8 y 12,7 ± 1,9 g/dl; p = 0,004; ferritina 170 ± 145; 140 ± 138; 105 ± 99 μg/l; p = 0,023). Durante el seguimiento hubo 36 eventos hemorragicos: 4 en pacientes control, 23 en anticoagulados y 9 en antiagregados (log rank 12,5; p = 0,002). En un modelo de Cox ajustado para edad, funcion renal y niveles de hemoglobina, la anticoagulacion aumento el riesgo de sangrado 4 veces (HR 4,180; 1,955-8,937; p = 0,001) y la antiagregacion en casi 3 veces (HR 2,780; 1,257-6,149; p = 0,012). Se registraron 64 eventos cardiovasculares, 21 de los cuales fueron clasificados como eventos ateroscleroticos: 10 en el grupo de antiagregacion, 8 en el grupo control y 3 en el grupo de anticoagulacion (log rank: 8,351; p = 0,015). El tratamiento anticoagulante demostro un efecto protector frente al riesgo de padecer eventos ateroscleroticos (HR 0,136; 0,033-0,551; p = 0,005), mientras que el tratamiento antiagregante no lo modifico (HR 1,566; 0,569-4,308; ns). Conclusiones La anticoagulacion y la antiagregacion aumentan el riesgo hemorragico en pacientes con ERC y empeoran la anemia. La anticoagulacion disminuye el riesgo de eventos cardiovasculares ateroescleroticos en mas de un 85% y la antiagregacion no lo modifica.

Background and objective There is controversy concerning the risk/benefit of anticoagulation/antiaggregation in chronic kidney disease (CKD) patients. We analyzed the impact of anticoagulation/antiaggregation on anaemia and haemorrhagic events in CKD patients. Patients and methods A total of 232 CKD patients stages 3 and 4 were followed during a mean follow-up time of 36.7 ± 11.6 months: 81 patients did not receive any anticoagulation or antiaggregation treatment, 91 received anticoagulation treatment and 60 patients received platelet antiaggregation. Haemorrhagic and cardiovascular events were recorded. Results Haemoglobin and ferritine levels were significantly higher in patients who did not receive anticoagulation or antiaggregation (Hb 13.7 ± 1.6, 13.3 ± 1.8 and 12.7 ± 1.9 g/dl, p = 0.004; ferritine 170 ± 145, 140 ± 138, 105 ± 99 μg/l, p = 0.023). During follow up, 36 haemorrhagic events were registered: 4 in the control group, 23 in the anticoagulation group and 9 in the antiaggregation group (log rank 12.5; p = 0.002). In a Cox model adjusted by age, renal function and haemoglobin levels, the anticoagulation increased the risk of bleeding by 4 times (HR 4.180, 1.955–8.937); p = 0.001) and antiaggregation by almost 3 times (HR 2.780, 1.257–6.149, p = 0.012). A total of 64 cardiovascular events were registered, 21 of which were classified as atherosclerotic events: 10 in the antiaggregation group, 8 in the control group and 3 in the anticoagulation group (log rank: 8.351; p = 0.015). Anticoagulation treatment showed a reduction in the risk of atherosclerotic events (HR 0.136, 0.033–0.551, p = 0.005) while platelet antiaggregation did not modified this risk (HR 1.566, 0.569–4.308). Conclusions Anticoagulation and antiaggregation increase haemorrhagic risk in patients with CKD and worsen anaemia. Anticoagulation reduces atherosclerotic events by more than 85% while platelet antiaggregation does not modify this risk.

Background Obesity is a risk factor for incident chronic kidney disease (CKD) in the general population. C1q/tumour necrosis factor-related protein 1 (CTRP1) is a new adipokine with multiple vascular and metabolic effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP1 levels and CKD progression. Methods Patients with Stages 3 and 4 CKD without previous cardiovascular events were enrolled and divided into two groups according to body mass index (BMI). Demographic, clinical and analytical data and CTRP1 levels were collected at baseline. During follow-up, renal events [defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate (Modification of Diet in Renal Disease)] were registered. Results A total of 71 patients with CKD were divided into two groups: 25 obese (BMI >30 kg/m2) and 46 non-obese. CTRP1 in plasma at baseline was higher in obese patients [median (interquartile range) 360 (148) versus 288 (188) ng/mL, P = 0.041]. No significant association was found between CTRP1 levels and CKD stage, presence of diabetes, aldosterone and renin levels, or blood pressure. Obese patients had higher systolic blood pressure (P = 0.018) and higher high-sensitivity C-reactive protein (P = 0.019) and uric acid (P = 0.003) levels, without significant differences in the percentage of diabetic patients or albuminuria. During a mean follow-up of 65 months, 14 patients had a renal event. Patients with CTRP1 in the lowest tertile had more renal events, both in the overall sample (log rank: 5.810, P = 0.016) and among obese patients (log rank: 5.405, P = 0.020). Higher CTRP1 levels were associated with slower renal progression (hazard ratio 0.992, 95% confidence interval 0.986–0.998; P = 0.001) in a model adjusted for obesity, aspirin, albuminuria and renal function. Conclusions CTRP1 levels are higher in obese than in non-obese patients with CKD. High CTRP1 levels may have a renal protective role since they were associated with slower kidney disease progression. Interventional studies are needed to explore this hypothesis.

Resumen: Objetivo: Estudio observacional retrospectivo con pacientes consecutivos con ERC para valorar el grado de cumplimiento de los objetivos terapéuticos en hipertensión arterial y dislipidemia recomendados por las guías JNC 8 y KDIGO-2013 ERC, y el impacto de su aplicación con respecto a las guías previas. Resultados: Se recogieron 618 pacientes, edad media 67 ± 15 años, el 61,33% varones. El FGe medio era 45,99 ± 18,94 ml/min, la mediana de albúmina/creatinina 26 (0-151) mg/g. Un 87,6% recibían tratamiento antihipertensivo y un 50,2% estatinas. Según las guías KDIGO, 520 pacientes (84,14%) deberían recibir estatinas, pero solo 304 (58,46%) las recibían. Los pacientes en tratamiento con estatinas tenían más DM e hipertensión arterial, más antecedentes cardiovasculares y menor nivel de colesterol total y colesterol-LDL.El 97,7% de los pacientes eran menores de 60 años o tenían FGe

Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular events. However, limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression. Prospective, multicenter, open-label randomized controlled trial. One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15–60 ml/min/1.73 m2 without previous cardiovascular events. Aspirin treatment (100 mg/day) (n = 50) or usual therapy (n = 61). Mean follow-up time was 64.8 ± 16.4 months. The primary endpoint was composed of cardiovascular death, acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral arterial disease. Secondary endpoints were fatal and nonfatal coronary events, renal events (defined as doubling of serum creatinine, ≥ 50% decrease in eGFR, or renal replacement therapy), and bleeding episodes. During follow-up, 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups, respectively. Aspirin did not significantly reduce primary composite endpoint (HR, 0.396 (0.146–1.076), p = 0.069. Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group. Aspirin significantly reduced the risk of coronary events (log-rank, 5.997; p = 0.014). Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group. Aspirin treatment decreased renal disease progression in a model adjusted for age, baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077–0.955; p = 0.043) but did not when adjusted for albuminuria. No differences were found in minor bleeding episodes between groups and no major bleeding was registered. Small sample size and open-label trial. Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint; however, there were reductions in secondary endpoints with fewer coronary events and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.

Background and objectives: Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. Design, setting, participants, & measurements: Retrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36-98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. Results: One hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall −1.6 ml/min/1.73 m2/year (−3.0, −0.7)). Male gender, albuminuria >100 mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p = 0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06-2.63), p = 0.023; 1.02 (1.01-1.03), p = 0.001 and HR: 2.14 (1.26-3.64), p = 0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p = 0.006). Conclusions: Hyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass. Resumen Introducción: Grandes estudios observacionales han asociado el aumento del ácido úrico sérico con el desarrollo y progresión de ERC. Esta hipótesis no ha sido contrastada en pacientes con disminución de la masa renal. Métodos: Estudio retrospectivo en 324 pacientes de una consulta externa que se siguieron durante 60 (36-98) meses. Se recogieron anualmente variables demográficas, factores cardiovasculares, fármacos concomitantes, albuminuria y niveles de ácido úrico. El endpoint primario era la caída anual de FGe por MDRD-4. Dividimos la muestra en tres grupos (A1: pacientes con caída del FGe menor que la media, A2: mayor que la media, B: sin caída del FGe). Analizamos los predictores del empeoramiento de la función renal. Resultados: 170 de los 324 pacientes tuvieron caída de FGe (grupo A) (media de caída -1.6 ml/min/1.73 m2/año (-3.0, -0.7). Se asociaron con la progresión de ER género masculino, albuminuria > 100 mg/d e hipertensión arterial. La hiperuricemia fue más frecuente entre los pacientes con mayor progresión de ER (grupo A2) (33% vs 49%, p = 0.04) comparado con los de menor progresión (grupo A1). El modelo de regresión de Cox ajustado mostró que la hiperuricemia, la presión arterial y la albuminuria eran predictores independientes de la progresión de enfermedad renal: HR 1.67 (1.06-2.63), p = 0.023; 1.02 (1.01-1.03), p = 0.001 y HR: 2.14 (1.26-3.64), p = 0.005). La progresión de ER fue mayor en la atrofia o agenesia renal que en la nefrectomía (log rank: 7.433, p = 0.006). Conclusión: La hiperuricemia se asocia de forma independiente con la progresión de enfermedad renal en pacientes con masa renal disminuida.

Lesinurad is an oral inhibitor of the monocarboxylic/urate transporter URAT1 encoded by the SLC22A12 gene. Market authorization was granted in February 2016 in Europe and December 2015 in the USA. As a potentially nephrotoxic uricosuric drug acting on the kidney, nephrologists should become familiar with its indications and safety profile. The approved indication is treatment of gout in combination with a xanthine oxidase (XO) inhibitor in adult patients who have not achieved target serum uric acid levels with an XO inhibitor alone. It is not indicated for asymptomatic hyperuricaemia or for patients with estimated creatinine clearance

Resumen Introducción: Las escalas de predicción del riesgo cardiovascular (RCV) suelen infraestimar el riesgo, al no estar validadas en población con enfermedad renal crónica (ERC). Dos de las más empleadas son la clásica escala de Framingham (FRS-CVD) y la contemporánea ASCVD (AHA/ACC 2013). El objetivo del estudio es evaluar la capacidad predictiva de sufrir un evento cardiovascular (ECV) mediante estas 2 escalas en población con ERC. Material y métodos: Estudio observacional prospectivo de 400 pacientes prevalentes con ERC (estadios 4 y 5 según KDOQI, no en diálisis). Se calculó el RCV según las 2escalas y se analizó su poder predictivo de ECV ateroscleróticos (infarto agudo de miocardio, evento cerebro vascular isquémico y hemorrágico, enfermedad vascular periférica) y no ateroscleróticos (insuficiencia cardíaca). Resultados: Con una media de seguimiento de 40,3 ± 6,6 meses se registraron 49 ECV ateroscleróticos. Ambas escalas clasificaron a la mayoría de los pacientes en el grupo de alto RCV (59% según FRS-CVD y 75% según ASCVD). Todos los ECV sucedieron en el grupo de alto RCV, y ambas escalas (FRS-CVD log rank: 12,2; p < 0,001; HR 3,1 [IC 95%: 1,3-7,1]; p: 0,006 y ASCVD log rank: 8,5 p < 0,001; HR 3,2 [IC 95% 1,1-9,4] p: 0,03) fueron predictores independientes ajustados a función renal, albuminuria y antecedente de ECV. Conclusiones: Las escalas de predicción de RCV (FRS-CVD y ASCVD [AHA/ACC 2013]) pueden estimar la probabilidad de sufrir ECV ateroscleróticos en pacientes con ERC independientemente de la función renal, albuminuria y antecedente de ECV. Abstract Introduction: Scores underestimate the prediction of cardiovascular risk (CVR) as they are not validated in patients with chronic kidney disease (CKD). Two of the most commonly used scores are the Framingham Risk Score (FRS-CVD) and the ASCVD (AHA/ACC 2013). The aim of this study is to evaluate the predictive ability of experiencing a cardiovascular event (CVE) via these 2 scores in the CKD population. Material and methods: Prospective, observational study of 400 prevalent patients with CKD (stages 4 and 5 according the KDOQI; not on dialysis). Cardiovascular risk was calculated according to the 2 scores and the predictive capacity of cardiovascular events (atherosclerotic events: myocardial infarction, ischaemic and haemorrhagic stroke, peripheral vascular disease; and non-atherosclerotic events: heart failure) was analysed. Results: Forty-nine atherosclerotic cardiovascular events occurred in 40.3 ± 6.6 months of follow-up. Most of the patients were classified as high CVR by both scores (59% by the FRS-CVD and 75% by the ASCVD). All cardiovascular events occurred in the high CVR patients and both scores (FRS-CVD log-rank 12.2, P < .001, HR 3.1 [95% CI: 1.3-7.1] P: 0.006 and ASCVD log-rank 8.5 P < .001, HR 3.2 [95% CI: 1.1-9.4] P: 0.03) were independent predictors adjusted to renal function, albuminuria and previous cardiovascular events. Conclusion: The cardiovascular risk scores (FRS-CVD and ASCVD [AHA/ACC 2013]) can estimate the probability of atherosclerotic cardiovascular events in patients with CKD regardless of renal function, albuminuria and previous cardiovascular events.

Background Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world, but there is little epidemiological data about possible changes in its presentation over the years. Available information about the influence of age on the form of clinical presentation is also scarce. Methods The aim of the study was to analyse all renal biopsies performed between 1994 and 2013 and recorded in the Spanish Registry of Glomerulonephritis with a histological diagnosis of IgAN. The study was divided into five 4-year periods (1994-97, 1998-2001, 2002-05, 2006-09 and 2010-13) and patients were divided into four age groups: ≤16, 17-44, 45-64 and ≥65 years. Results From 20.974 renal biopsies recorded, 2961 (14.1%) corresponded to IgAN. The prevalence of IgAN remained stable, but a significant increase in age [from 37.6 (SD 17.7) in 1994-97 to 44.9 (SD 16.8) years in 2010-13; P = 0.001] and worse renal function at presentation [from serum creatinine (SCr) 1.9 (SD 1.9) in 1994-97 to 2.3 (SD 2.1) mg/dL in 2010-13; P = 0.001] were observed over the years. Nephrotic-range proteinuria and acute kidney injury (AKI) as forms of presentation were significantly more common among patients ≥65 years (17.7% and 43.2%, respectively) as compared with the other age groups [≤16 (11.4% and 13.1%, respectively), 17-44 (13.1% and 13%, respectively) and 45-64 (12.1% and 21.3%, respectively)]. Blood pressure, SCr and proteinuria were also significantly higher at presentation among elderly patients. Conclusions Although the prevalence of IgAN in Spain has remained stable over the years, patients are significantly older and present with significantly worse renal function in the last years. The incidence of nephrotic-range proteinuria (17.7%) and AKI (43.2%) as forms of presentation is remarkable among patients ≥65 years of age.

High-volume online hemodiafiltration (OL-HDF) has been associated with improved patient survival compared to conventional hemodialysis in recent trials, where the importance of convective volume (CV) in this benefit is noted. The purpose of this study was to determine the corporal composition parameters influencing the efficacy of CV in the removal of different molecular weight (MW) molecules. Demographic data, corporal composition parameters with bioimpedance spectroscopy, dialysis features and the reduction rates of different MW molecules in a four-hour OL-HDF session were collected in 61 patients. We observed a significant negative correlation of β2-microglobulin, cystatin-C, myoglobin and prolactin reduction rates with body surface area, weight, total body extracellular (ECW) and intracellular water (ICW), lean tissue mass and body cellular mass. The multivariable regression analysis identified ECW and ICW as the only corporal composition factors independently associated to the relative elimination of β2-microglobulin (Beta: -0.801, P = 0.002 for ECW and Beta: -1.710, P = 0.001 for ICW), cystatin-C (Beta: -0.656, P = 0.010 for ECW and Beta: -1.511, P = 0.004 for ICW) and myoglobin (Beta: -0.745, P = 0.014 for ECW and Beta: -2.103, P = 0.001 for ICW), in addition to CV. Prolactin reduction was only associated with ICW (Beta: -1.540, P = 0.028). When adjusting CV with ECW and ICW, only the ratio CV/ECW was an independent predictor for higher elimination of β2-microglobulin, cystatin-C and myoglobin. The corporal composition parameters independently associated to the reduction of medium-sized molecules are the extracellular and intracellular water. The ratio "convective volume/extracellular water" predicts higher efficacy of convective transport. Adjusting the convective volume to patient features could be useful to monitor the efficacy of OL-HDF and to prescribe individualized therapies.

Mixed cryoglobulinaemia (MCG) is one of the most severe extrahepatic hepatitis C virus (HCV)-associated complications, and could involve several organs, including the kidney. MCG prognosis relies on HCV response to antiviral treatment and has changed over the last years, especially after the introduction of new direct acting antivirals (DAA). MCG persistence despite sustained virological response (SVR) is uncommon and has a poorly known meaning and prognosis. We report a case of a patient with chronic HCV infection treated with DAA who developed MCG vasculitis despite the SVR.

Background Change in albuminuria has strong biological plausibility as a surrogate endpoint for progression of chronic kidney disease, but empirical evidence to support its validity is lacking. We aimed to determine the association between treatment effects on early changes in albuminuria and treatment effects on clinical endpoints and surrograte endpoints, to inform the use of albuminuria as a surrogate endpoint in future randomised controlled trials.Methods In this meta-analysis, we searched PubMed for publications in English from Jan 1, 1946, to Dec 15, 2016, using search terms including "chronic kidney disease", "chronic renal insufficiency", "albuminuria", "proteinuria", and "randomized controlled trial"; key inclusion criteria were quantifiable measurements of albuminuria or proteinuria at baseline and within 12 months of follow-up and information on the incidence of end-stage kidney disease. We requested use of individual patient data from the authors of eligible studies. For all studies that the authors agreed to participate and that had sufficient data, we estimated treatment effects on 6-month change in albuminuria and the composite clinical endpoint of treated end-stage kidney disease, estimated glomerular filtration rate of less than 15 mL/min per 1.73 m(2), or doubling of serum creatinine. We used a Bayesian mixed-effects meta-regression analysis to relate the treatment effects on albuminuria to those on the clinical endpoint across studies and developed a prediction model for the treatment effect on the clinical endpoint on the basis of the treatment effect on albuminuria.Findings We identified 41 eligible treatment comparisons from randomised trials (referred to as studies) that provided sufficient patient-level data on 29 979 participants (21 206 [71%] with diabetes). Over a median follow-up of 3.4 years (IQR 2.3-4.2), 3935 (13%) participants reached the composite clinical endpoint. Across all studies, with a meta-regression slope of 0.89 (95% Bayesian credible interval [BCI] 0.13-1.70), each 30% decrease in geometric mean albuminuria by the treatment relative to the control was associated with an average 27% lower hazard for the clinical endpoint (95% BCI 5-45%; median R-2 0.47, 95% BCI 0.02-0.96). The association strengthened after restricting analyses to patients with baseline albuminuria of more than 30 mg/g (ie, 3.4 mg/mmol; R-2 0.72, 0.05-0.99]). For future trials, the model predicts that treatments that decrease the geometric mean albuminuria to 0.7 (ie, 30% decrease in albuminuria) relative to the control will provide an average hazard ratio (HR) for the clinical endpoint of 0.68, and 95% of sufficiently large studies would have HRs between 0.47 and 0.95.Interpretation Our results support a role for change in albuminuria as a surrogate endpoint for the progression of chronic kidney disease, particularly in patients with high baseline albuminuria; for patients with low baseline levels of albuminuria this association is less certain. Copyright (c) 2019 Elsevier Ltd. All rights reserved.

Resumen La hipertensión arterial (HTA) resistente en un problema frecuente en pacientes con enfermedad renal crónica (ERC). El descenso del filtrado glomerular (FGe) y el incremento en la albuminuria se asocian a HTA resistente, sin embargo, hay pocos estudios publicados sobre la prevalencia de esta entidad en los pacientes con ERC. Objetivo: Estimar la prevalencia de la HTA resistente en pacientes con diferentes grados de enfermedad renal y analizar sus características. Métodos: Se incluyó a 618 pacientes con HTA y ERC estadios I-IV, de los cuales 82 (13,3%) cumplían criterios de HTA resistente. Resultados: La prevalencia de HTA resistente se incrementó de forma significativa con la edad, el grado de ERC y la albuminuria. La prevalencia de HTA resistente fue del 3,2% en pacientes menores de 50 años, del 13,8% entre 50 y 79 años, y alcanzó el 17,8% en mayores de 80 años. En relación con la función renal, la prevalencia fue del 4, del 15,8 y del 18,1%, en pacientes con filtrado glomerular estimado (FGe) de >60, de 30-59 y de 300 mg/g, respectivamente. En un modelo de regresión logística las características que se asociaron con la HTA resistente fueron la edad, el antecedente de enfermedad cardiovascular, el FGe, la albuminuria y la diabetes mellitus. El 47,5% de los pacientes con HTA resistente tenían la PA controlada ( 60, 30-59 and < 30 ml/min/1.73 m2, respectively, and 8.9, 15.9 and 22.5% for a urine albumin to creatinine ratio (UACR) < 30, 30-299 and > 300 mg/g respectively. In a logistic regression model, the characteristics associated with resistant hypertension were age, history of cardiovascular disease, GFR, albuminuria and diabetes mellitus. A total of 47.5% of patients with resistant hypertension had controlled BP (

Abstrat Objective No consensus has been established as to which is the best fourth-line agent in patients with resistant hypertension (RHT). The aim of the present study was to assess the effect of intensifying diuretic treatment with loop diuretic (furosemide) or aldosterone antagonist (spironolactone) on blood pressure (BP) control in RHT. Methods The study population comprised 30 patients with RHT who were divided into two treatment arms. Fifteen patients received furosemide 40 mg/day and 15 patients received spironolactone 25 mg/day. Ambulatory BP monitoring was performed baseline, 3 and 6 months. Results Baseline BP was 162 ± 8/90 ± 6 mmHg, 70% men, mean age 63.3 ± 9.1 years 56.1% diabetic and estimated glomerular filtration rate (eGFR) 55.8 ± 16.5 mL/min per 1.73 m2. There were no significant differences between groups at baseline in age, gender, percentage diabetics, eGFR, BP, number of antihypertensive drugs, or aldosterone levels. At 6 months, systolic BP decreased by 24 ± 9.2 mmHg (from 163.6 ± 8.6 to 139.6 ± 8.1 mmHg) in the spironolactone group, compared with 13.8 ± 2.8 mmHg (from 162 ± 7.9 to 148 ± 6.4 mmHg) in the furosemide group (P

Background Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk. Study Design Post hoc analysis of a long-term follow-up after completion of the 2-year trial. Setting & Participants 113 participants (57 in the allopurinol group and 56 in the control group) initially followed up for 2 years and 107 participants followed up to 5 additional years. Intervention Continuation of allopurinol treatment, 100mg/d, or standard treatment. Outcome Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥50% decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction, coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and peripheral vascular disease). Results During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up, an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus, during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P=0.004; adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the control group (HR, 0.43; 95% CI, 0.21-0.88; P=0.02; adjusted for age, sex, and baseline kidney function). Limitations Small sample size, single center, not double blind, post hoc follow-up and analysis. Conclusions Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk.

Background. Increased interarm systolic blood pressure difference (IASBPD) is associated with mortality and cardiovascular (CV) events both in the general population and in patients at high CV risk. The aim of the present study was to assess the value of IASBPD ≥10 mmHg for predicting CV events in patients with chronic kidney disease (CKD). Methods. The study sample comprised 652 patients with CKD (age 67 ± 15 years, 58.1% men). Follow-up was 19 ± 5 months. We recorded increased IASBPD and related factors and assessed the predictive value of this variable for CV events. Results. We recorded diabetes mellitus in 136 patients (20.8%), history of CV disease in 213 (32.6%) and dyslipidaemia in 327 (50.1%). The mean glomerular filtration rate was 45.9 ± 18.9 mL/min/1.73 m 2 , and the median albumin/creatinine ratio was 26(0–151) mg/g. IASBPD was ≥10 mmHg in 184 patients (28.1%). The factors associated with IASBPD ≥10 mmHg were age, systolic blood pressure levels, history of congestive heart failure, lower levels of high-density lipid cholesterol and higher use of hypertensive drugs. Fifty-eight patients (8.5%) developed a CV event during the follow-up. IASBPD ≥10 mmHg [HR, 1.802, 95%CI (1.054–3.079); P = 0.031] was an independent predictor of CV events. Conclusions. Increased IASBPD is an independent predictor of CV events in CKD patients.

Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15-epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients.Open label randomized clinical trial.50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months.Aspirin (100mg/day) or standard treatment.To analyze the effect of aspirin on plasma 15-epi-LXA4 levels and inflammatory markers in CKD patients.Baseline plasma15-epi-LXA4 levels were lower in diabetic (1.22 ± 0.99ng/ml) than in non-diabetic CKD patients (2.05 ± 1.06ng/ml, p0.001) and inversely correlated with glycosylated hemoglobin levels (r = -0.303, p = 0.006). In multivariate analysis, diabetes was associated with lower 15-epi-LXA4 levels, adjusted for age, inflammatory markers and renal function (p = 0.005). In the whole study population, 15-epi-LXA4 levels tended to increase, but not significantly (p = 0.45), after twelve months on aspirin (from mean ± SD 1.84 ± 1.06 to 2.04 ± 0.75ng/ml) and decreased in the standard care group (1.60 ± 1.15 to 1.52 ± 0.68ng/ml, p = 0.04). The aspirin effect on 15-epi-LXA4 levels was more striking in diabetic patients, increasing from 0.94 ± 0.70 to 1.93 ± 0.74ng/ml, p = 0.017.Diabetic patients with CKD have lower circulating 15-epi-LXA4 levels than non-diabetic CKD patients. Low dose aspirin for 12 months increased 15-epi-LXA4 levels in diabetic patients. Given its anti-inflammatory properties, this increase in 15-epi-LXA4 levels may contribute to the beneficial effects of low dose aspirin.