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RATIONALE & OBJECTIVE: Chronic kidney disease of unknown etiology (CKDUE) is one of the main global causes of kidney failure. Genetic studies may identify an etiology in these patients, but few studies have implemented genetic testing of CKDUE in a population-based series of patients, which was the focus of the GENSEN Study. STUDY DESIGN: Case series. SETTINGS & PARTICIPANTS: 818 patients aged≤45 years at 51 Spanish centers with CKDUE, and either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation. OBSERVATIONS: Genetic testing for 529 genes associated with inherited nephropathies using high-throughput sequencing (HTS). Pathogenic and/or likely pathogenic (P/LP) gene variants concordant with the inheritance pattern were detected in 203 patients (24.8%). Variants in type IV collagen genes were the most frequent (COL4A5, COL4A4, COL4A3; 35% of total gene variants), followed by NPHP1, PAX2, UMOD, MUC1, and INF2 (7.3%, 5.9%, 2.5%, 2.5%, and 2.5%, respectively). Overall, 87 novel variants classified as P/LP were identified. The top 5 most common previously undiagnosed diseases were Alport syndrome spectrum (35% of total positive reports), genetic podocytopathies (19%), nephronophthisis (11%), autosomal dominant tubulointerstitial kidney disease (7%), and congenital anomalies of the kidney and urinary tract (CAKUT, 5%). A family history of kidney disease was reported by 191 participants (23.3%) and by 65 of 203 patients (32.0%) with P/LP variants. LIMITATIONS: Missing data, and selection bias resulting from voluntary enrollment. CONCLUSIONS: Genomic testing with HTS identified a genetic cause of kidney disease in approximately one quarter of young patients with CKDUE and advanced kidney disease. These findings suggest that genetic studies are a potentially useful tool for the evaluation of people with CKDUE. PLAIN-LANGUAGE SUMMARY: The cause of kidney disease is unknown for 1 in 5 patients requiring kidney replacement therapy, reflecting possible prior missed treatment opportunities. We assessed the diagnostic utility of genetic testing in children and adults aged≤45 years with either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation. Genetic testing identified the cause of kidney disease in approximately 1 in 4 patients without a previously known cause of kidney disease, suggesting that genetic studies are a potentially useful tool for the evaluation of these patients.
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BACKGROUND: There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity. RESULTS: Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titres in HD (P = .001) and ND-CKD (P = .014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titres at 12 months were independently associated with repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titres and not being a KT recipient. Breakthrough COVID-19 was registered in 137 (6%) patients, 5% of whom required admission. Admitted patients had prior titres <620 UI/ml and median values were lower (P = .020) than in non-admitted patients. CONCLUSIONS: A fourth vaccine dose increased anti-Spike antibody titres or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titres or KT recipients) derived the least benefit in terms of antibody titres. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titres.
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COVID-19 , Insuficiência Renal Crônica , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Estudos Prospectivos , SARS-CoV-2 , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Anticorpos AntiviraisRESUMO
BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe coronavirus disease 2019 (COVID-19). The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in CKD patients. Safety and immediate humoral response results are reported here. METHODS: Four cohorts of patients were included: kidney transplant (KT) recipients, and haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on Day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analysed. RESULTS: A total of 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (P < 0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated with KT (odds ratio 20.56, P = 0.001) and with BNT162b2 vaccine (odds ratio 6.03, P = 0.023). CONCLUSION: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Potential differences between COVID-19 vaccines should be explored in prospective controlled studies.
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Vacinas contra COVID-19 , COVID-19 , Insuficiência Renal Crônica , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , SARS-CoV-2RESUMO
High glutamate levels after head trauma or cerebral ischemia have neurotoxic effects. The objective of the present study was to evaluate the efficacy of hemodialysis to remove glutamate from the blood and to assess the behavior of this small molecule. Ten patients with end-renal disease on hemodialysis were included in the study. Glutamate clearance was evaluated within the first hour of hemodialysis on a midweek dialysis day on five patients who underwent low flux hemodialysis, whereas the other five patients underwent highly efficient hemodialysis (high flux hemodialysis on one day and online hemodiafiltration on another day). Glutamate clearance with hemodialysis was very effective and did not show any differences between the techniques (low flux: 214 [55], high flux: 204 [37], online hemodiafiltration: 202 [16], median (interquartile range), P = .7). Glutamate clearance was almost equivalent to vascular access plasma flow and it was not affected by dialyzer permeability or ultrafiltration rate. After a hemodialysis session, a significant decrease in glutamate blood level was observed (prehemodialysis: 59.7 [36.1], posthemodialysis 37.0 [49.2], P = .005). Dialysis performed under fasting condition showed higher glutamate reduction rate (60%) than that under feeding condition (20%). Hemodialysis may be an effective method to reduce glutamate blood levels, and the molecule clearance does not differ between the different techniques used. Considering previous results in experimental models, hemodialysis without hemodynamic stress, could be considered for reducing glutamate neurotoxic effects in acute ischemic strokes of patients in chronic hemodialysis programs.
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Ácido Glutâmico/metabolismo , Hemodiafiltração/métodos , Diálise Renal/métodos , Idoso , Isquemia Encefálica/terapia , Jejum/sangue , Feminino , Ácido Glutâmico/sangue , Humanos , AVC Isquêmico/terapia , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: 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. STUDY DESIGN: Prospective, multicenter, open-label randomized controlled trial. SETTING AND PARTICIPANTS: One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73 m2 without previous cardiovascular events. INTERVENTION: Aspirin treatment (100 mg/day) (n = 50) or usual therapy (n = 61). Mean follow-up time was 64.8 ± 16.4 months. OUTCOMES: 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. RESULTS: 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. LIMITATIONS: Small sample size and open-label trial. CONCLUSIONS: 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.
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Aspirina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Rim/efeitos dos fármacos , Prevenção Primária/métodos , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Aspirina/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemorragia/induzido quimicamente , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Espanha , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: High-circulating level of parathyroid hormone (PTH) is associated with elevated mortality in dialysis patients. The Japanese Society for Dialysis Therapy guideline suggests a lower PTH target than other international guidelines; thus, PTH control may differ in Japan compared with other regions, and be associated with mortality. METHODS: We analyzed data from hemodialysis patients with ≥3 measurements of PTH during the first 9 months after enrollment in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4-5 (2009-2015). PTH control was assessed by the mean, slope, and mean squared error (MSE) of all PTH measurements over the 9-month run-in period. Distribution of each PTH control was assessed by regions (Europe/Australia/New Zealand [Eur/ANZ], Japan and North America) and dialysis vintage. Mortality rates were compared across PTH control categories using Cox regression models. RESULTS: Mean PTH was lower in Japan than in other regions across dialysis vintage categories. In patients with dialysis vintage < 90 days, PTH level was more likely to decline > 5% per month in Japan (48% of patients) versus Eur/ANZ (35%) and North America (35%). In patients with dialysis vintage > 1 year, Japanese patients maintained steady PTH, while patients in Eur/ANZ and North America were more likely to experience a PTH increase. Mean PTH was associated with mortality in the overall samples (highest mortality rate for PTH > 600 pg/mL, hazard ratio, 1.35; 95% confidence interval, 1.20 to 1.52 vs PTH 200-399 pg/mL), and the association was obvious in the prevalent patients (hazard ratio, 1.44; 95% confidence interval, 1.26 to 1.65). PTH slope and MSE did not show significant association with mortality in the overall sample as well as in subjects stratified both by region and dialysis vintage. CONCLUSION: PTH control in hemodialysis patients, as measured by keeping a stable PTH level over 9 months, was observed in Japan contrasted with other regions. High PTH mean, but not increased PTH slope and MSE, was associated with mortality especially in prevalent patients.
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Densidade Óssea , Doenças Ósseas/prevenção & controle , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Hormônio Paratireóideo/sangue , Diálise Renal/métodos , Adulto , Europa (Continente)/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Padrões de Prática Médica , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal/mortalidadeRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent among patients on hemodialysis (HD) and is associated with poor prognosis. Treatment with interferon and ribavirin is poorly tolerated, and few data are available on the impact of new direct-acting antivirals (DAAs). This study was intended to analyze the efficacy and safety of treatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin in HCV-infected patients on HD from 3 hospitals. METHODS: This is a multicentric study. We analyze the clinical course of all patients on HD with HCV infection who had been treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir in 3 hospitals in Madrid, Spain. All patients under treatment had undergone Transient elastography (FibroScan®) and HCV RNA (PCR) and HCV genotype were determined simultaneously. RESULTS: Thirty-five patients aged 53.3 ± 8.9 years (68.6% males) and with genotypes 1 and 4 were treated with the DAA regimen, and 17 were also given ribavirin. The most common etiology was glomerular disease. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions. CONCLUSION: A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin for the treatment of HCV in patients on HD is highly effective and causes minimal side effects. This regimen represents a major advance in disease management. A considerable improvement in prognosis seems likely.
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Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Resposta Viral Sustentada , 2-Naftilamina , Idoso , Anilidas/administração & dosagem , Antivirais/administração & dosagem , Carbamatos/administração & dosagem , Ciclopropanos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/virologia , Humanos , Lactamas Macrocíclicas , Compostos Macrocíclicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Diálise Renal , Ribavirina/administração & dosagem , Ritonavir/administração & dosagem , Espanha , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/análogos & derivados , ValinaRESUMO
BACKGROUND: Patients receiving long-term dialysis have among the highest mortality and hospitalization rates. In the nonrenal literature, functional dependence is recognized as a contributor to subsequent disability, recurrent hospitalization, and increased mortality. A higher burden of functional dependence with progressive worsening of kidney function has been observed in several studies, suggesting that functional dependence may contribute to both morbidity and mortality in dialysis patients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 7,226 hemodialysis patients from 12 countries in the DOPPS (Dialysis Outcomes and Practice Patterns Study) phase 4 (2009-2011) with self-reported data for functional status. PREDICTOR: Patients' ability to perform 13 basic and instrumental activities of daily living was summarized to create an overall functional status score (range, 1.25 [most dependent] to 13 [functionally independent]). OUTCOME: Cox regression was used to estimate the association between functional status and all-cause mortality, adjusting for several demographic and clinical risk factors for mortality. Median follow-up was 17.2 months. RESULTS: The proportion of patients who could perform each activity of daily living task without assistance ranged from 97% (eating) to 47% (doing housework). 36% of patients could perform all 13 tasks without assistance (functional status = 13), and 14% of patients had high functional dependence (functional status < 8). Functionally independent patients were younger and had many indicators of better health status, including higher quality of life. Compared with functionally independent patients, the adjusted HR for mortality was 2.37 (95% CI, 1.92-2.94) for patients with functional status < 8. LIMITATIONS: Possible nonresponse bias and residual confounding. CONCLUSIONS: We found a high burden of functional dependence across all age groups and across all DOPPS countries. When adjusting for several known mortality risk factors, including age, access type, cachexia, and multimorbidity, functional dependence was a strong consistent predictor of mortality.
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Atividades Cotidianas , Internacionalidade , Diálise Renal/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Prospectivos , Diálise Renal/tendências , Resultado do TratamentoRESUMO
BACKGROUND: Increasing dialysate flow rates (Qd) from 500 to 800 ml/min has been recommended to increase dialysis efficiency. A few publications show that increasing Qd no longer led to an increase in mass transfer area coefficient (KoA) or Kt/V measurement. Our objectives were: 1) Studying the effect in Kt of using a Qd of 400, 500, 700 ml/min and autoflow (AF) with different modern dialysers. 2) Comparing the effect on Kt of water consumption vs. dialysis time to obtain an individual objective of Kt (Ktobj) adjusted to body surface. METHODS: This is a prospective single-centre study with crossover design. Thirty-one patients were studied and six sessions with each Qd were performed. HD parameters were acquired directly from the monitor display: effective blood flow rate (Qbe), Qd, effective dialysis time (Te) and measured by conductivity monitoring, final Kt. RESULTS: We studied a total of 637 sessions: 178 with 500 ml/min, 173 with 700 ml/min, 160 with AF and 126 with 400 ml/min. Kt rose a 4% comparing 400 with 500 ml/min, and 3% comparing 500 with 700 ml/min. Ktobj was reached in 82.4, 88.2, 88.2 and 94.1% of patients with 400, AF, 500 and 700 ml/min, respectively. We did not find statistical differences between dialysers. The difference between programmed time and Te was 8' when Qd was 400 and 500 ml/min and 8.8' with Qd = 700 ml/min. Calculating an average time loss of eight minutes/session, we can say that a patient loses 24' weekly, 312' monthly and 62.4 hours yearly. Identical Kt could be obtained with Qd of 400 and 500 ml/min, increasing dialysis time 9.1' and saving 20% of dialysate. CONCLUSIONS: Our data suggest that increasing Qd over 400 ml/min for these dialysers offers a limited benefit. Increasing time is a better alternative with demonstrated benefits to the patient and also less water consumption.
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Soluções para Diálise/administração & dosagem , Soluções para Diálise/farmacocinética , Falência Renal Crônica/terapia , Diálise Renal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Velocidade do Fluxo Sanguíneo , Distribuição de Qui-Quadrado , Estudos Cross-Over , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/efeitos adversos , Espanha , Adulto JovemRESUMO
INTRODUCTION: Chronic kidney disease (CKD) of non-inherited etiology is one of the main causes of renal replacement therapy in our setting. Previous studies in other territories suggest that hereditary diseases could be one of the potential causes of this pathology, especially in younger patients. The GENSEN study will evaluate the presence of pathogenic genetic variants in subjects who have developed CKD category G5 before the age of 46 years, of non-inherited etiology. METHODS: Observational, prospective, multicenter study, which evaluates the diagnostic utility of massive high-throughput sequencing (HTS) directed to a set of genes, in the identification of the cause of CKD. Patients from all over Spain will be included, from whom a blood or saliva sample will be taken and a panel of 529 genes associated with hereditary kidney disease will be analyzed. This publication communicates the study protocol. CONCLUSION: The GENSEN study will make it possible to evaluate the diagnostic performance of the gene panel study in young subjects in our setting with the development of CKD category G5 without a clear cause. An etiological diagnosis would offer potential benefits for patients and relatives (targeted therapies, clinical trials, detection of extrarenal manifestations, evaluation of relatives for live donation, estimation of the risk of recurrence in the renal graft, genetic counseling, among others) and would allow to apply this genetic study to the nephrology of our country.
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BACKGROUND: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. SUMMARY: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. KEY MESSAGES: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.
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Síndrome Cardiorrenal , Humanos , Síndrome Cardiorrenal/terapia , Síndrome Cardiorrenal/fisiopatologia , Gerenciamento ClínicoRESUMO
Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).
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Consenso , Insuficiência Cardíaca , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Humanos , Doença Aguda , Sociedades Médicas , Espanha , CardiologiaRESUMO
Benefits and risks of antithrombotic agents remain unclear in the hemodialysis population. To help clarify this we determined variation in antithrombotic agent use, rates of major bleeding events, and factors predictive of stroke and bleeding in 48,144 patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases I-IV. Antithrombotic agents including oral anticoagulants (OACs), aspirin (ASA), and anti-platelet agents (APAs) were recorded along with comorbidities at study entry, and clinical events including hospitalization due to bleeding were then collected every 4 months. There was wide variation in OAC (0.3-18%), APA (3-25%), and ASA use (8-36%), and major bleeding rates (0.05-0.22 events/year) among countries. All-cause mortality, cardiovascular mortality, and bleeding events requiring hospitalization were elevated in patients prescribed OACs across adjusted models. The CHADS2 score predicted the risk of stroke in atrial fibrillation patients. Gastrointestinal bleeding in the past 12 months was highly predictive of major bleeding events; for patients with previous gastrointestinal bleeding, the rate of bleeding exceeded the rate of stroke by at least twofold across all categories of CHADS2 score, including patients at high stroke risk. Appropriate risk stratification and a cautious approach should be considered before OAC use in the dialysis population.
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Fibrinolíticos/efeitos adversos , Hemorragia Gastrointestinal/epidemiologia , Falência Renal Crônica/terapia , Padrões de Prática Médica/estatística & dados numéricos , Diálise Renal , Acidente Vascular Cerebral/epidemiologia , Idoso , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.
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COVID-19 , Insuficiência Renal Crônica , Humanos , Estudos Prospectivos , Vacinas contra COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinação , Anticorpos Monoclonais , Insuficiência Renal Crônica/terapiaRESUMO
Cardiorenal syndromes (CRS) are broadly defined as disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. CRS are currently classified into five categories, mostly based on disease-initiating events and their acuity or chronicity. CRS types 3 and 4 (also called renocardiac syndromes) refer to acute and chronic kidney dysfunction resulting in acute and chronic heart dysfunction, respectively. The notion of renocardiac syndromes has broadened interest in kidney-heart interactions but uncertainty remains in the nephrological community's understanding of the clinical diversity, pathophysiological mechanisms and optimal management approaches of these syndromes. This triple challenge that renocardiac syndromes (and likely other cardiorenal syndromes) pose to the nephrologist can only be faced through a specific and demanding training plan to enhance his/her cardiological scientific knowledge and through an appropriate clinical environment to develop his/her cardiological clinical skills. The first must be the objective of the subspecialty of cardionephrology (or nephrocardiology) and the second must be the result of collaboration with cardiologists (and other specialists) in cardiorenal care units. This review will first consider various aspects of the challenges that renocardiac syndromes pose to nephrologists and, then, will discuss those aspects of cardionephrology and cardiorenal units that can facilitate an effective response to the challenges.
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Anemia is a common complication of chronic kidney disease (CKD) and is associated with a decrease in quality of life and an increased risk of transfusions, morbidity and mortality, and progression of CKD. The Anemia Working Group of the Sociedad Española de Nefrología conducted a Delphi study among experts in anemia in CKD to agree on relevant unanswered questions by existing evidence. The RAND/UCLA consensus methodology was used. We defined 15 questions with a PICO structure, followed by a review in scientific literature databases. Statements to each question were developed based on that literature review. Nineteen experts evaluated them using an iterative Two-Round Delphi-like process. Sixteen statements were agreed in response to 8 questions related to iron deficiency and supplementation with Fe (impact and management of iron deficiency with or without anemia, iron deficiency markers, safety of i.v. iron) and 7 related to erythropoiesis stimulating agents (ESAs) and/or hypoxia-inducible factor stabilizers (HIF), reaching consensus on all of them (individualization of the Hb objective, impact and management of resistance to ESA, ESA in the immediate post-transplant period and HIF stabilizers: impact on ferrokinetics, interaction with inflammation and cardiovascular safety). There is a need for clinical studies addressing the effects of correction of iron deficiency independently of anemia and the impact of anemia treatment with various ESA on quality of life, progression of CKD and cardiovascular events.
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Anemia , Deficiências de Ferro , Insuficiência Renal Crônica , Humanos , Técnica Delphi , Consenso , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Anemia/tratamento farmacológico , Anemia/etiologia , Doença CrônicaRESUMO
Chronic kidney disease (CKD) is a pathology with a high worldwide incidence and an upward trend affecting the elderly. When CKD is very advanced, the use of renal replacement therapies is required to prolong its life (dialysis or kidney transplantation). Although dialysis improves many complications of CKD, the disease does not reverse completely. These patients present an increase in oxidative stress, chronic inflammation and the release of extracellular vesicles (EVs), which cause endothelial damage and the development of different cardiovascular diseases (CVD). CKD patients develop premature diseases associated with advanced age, such as CVD. EVs play an essential role in developing CVD in patients with CKD since their number increases in plasma and their content is modified. The EVs of patients with CKD cause endothelial dysfunction, senescence and vascular calcification. In addition, miRNAs free or transported in EVs together with other components carried in these EVs promote endothelial dysfunction, thrombotic and vascular calcification in CKD, among other effects. This review describes the classic factors and focuses on the role of new mechanisms involved in the development of CVD associated with CKD, emphasizing the role of EVs in the development of cardiovascular pathologies in the context of CKD. Moreover, the review summarized the EVs' role as diagnostic and therapeutic tools, acting on EV release or content to avoid the development of CVD in CKD patients.
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Doenças Cardiovasculares , MicroRNAs , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , Calcificação Vascular/etiologia , Calcificação Vascular/patologia , InflamaçãoRESUMO
INTRODUCTION: Chronic hyperkalemia has negative consequences in the medium and long term, and determines the suspension of nephro and cardioprotective drugs, such as renin-angiotensin-aldosterone system inhibitors (RAASi). There is an alternative to the suspension or dose reduction of these treatments: the administration of potassium chelators. The aim of this study is to estimate the economic impact of the use of patiromer in patients with chronic kidney disease (CKD) or heart failure (HF) and hyperkalemia in Spain. MATERIALS AND METHOD: The annual economic impact of the use of patiromer has been estimated from the perspective of the Spanish society. Two scenarios were compared: patients with CKD or HF and hyperkalemia treated with and without patiromer. The costs have been updated to 2020 euros, using the Health Consumer Price Index. Direct healthcare costs related to the use of resources (treatment with RAASi, CKD progression, cardiovascular events and hospitalization due to hyperkalemia), direct non-healthcare costs (informal care: costs derived from time dedicated by patient's relatives), the indirect costs (productivity loss), as well as an intangible cost (due to premature mortality) were considered. A deterministic sensitivity analysis was performed to validate the robustness of the study results. RESULTS: The mean annual cost per patient in the scenario without patiromer is 9,834.09 and 10,739.37 in CKD and HF, respectively. The use of patiromer would lead to cost savings of over 30% in both diseases. The greatest savings in CKD come from the delay in the progression of CKD. While in the case of HF, 80.1% of these savings come from premature mortality reduction. The sensitivity analyses carried out show the robustness of the results, obtaining savings in all cases. CONCLUSIONS: The incorporation of patiromer allows better control of hyperkalemia and, as a consequence, maintain treatment with RAASi in patients with CKD or HF. This would generate a 32% of annual savings in Spain (3,127 in CKD; 3,466 in HF). The results support the positive contribution of patiromer to health cost in patients with only CKD or in patients with only HF.
Assuntos
Insuficiência Cardíaca , Hiperpotassemia , Polímeros , Insuficiência Renal Crônica , Humanos , Hiperpotassemia/tratamento farmacológico , Hiperpotassemia/etiologia , Espanha , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
Introduction: This study aimed to assess the feasibility of applying natural language processing (NLP) to analyze real-world data (RWD) and resolve clinical problems in patients with secondary hyperparathyroidism and chronic kidney disease undergoing hemodialysis (SHPT/CKD-HD). The primary objective was to evaluate how well the guideline-recommended analytical goals are achieved in a Spanish cohort of SHPT/CKD-HD patients based on RWD. Methods: Unstructured data in the electronic health records (EHRs) from 8 hospitals were retrospectively analyzed using the EHRead® technology, based on NLP and machine learning. Variables extracted from EHRs included demographics, CKD-related clinical characteristics, comorbidities and complications, mineral and bone disorder parameter levels, and treatments at baseline, 6-month, and 12-month follow-up. Results: A total of 623 prevalent SHPT/CKD-HD patients were identified; of those, 282 fulfilled the inclusion criteria. They were predominantly elderly males with cardiovascular comorbidities, and the first cause of CKD was diabetic nephropathy. Diagnosis of SHPT was associated with an improvement in median values for PTH, calcium, and phosphate. However, the percentage of patients with normal PTH ranges remained stable during the study period (52.8-60.4%), while the percentage of patients with within-target range serum calcium or phosphate values showed an increasing trend (43.2-60% and 38.8-50%). At baseline, 74.1% of patients were using SHPT-related medication, including at least one vitamin D or analog (63.1%), phosphate binders (46.8%), and/or calcimimetics (9.6%). Conclusions: This study represents the first attempt to use clinical NLP to analyze SHPT/CKD-HD patients based on unstructured clinical data. This methodology is useful to address clinical problems based on RWD and identified a high rate of out-of-range mineral-bone analytical values in patients with HPT/CKD-HD and an increasing trend of out-of-range values for serum calcium and phosphate.