Valor predictivo de los nuevos biomarcadores cardiacos y de los parámetros ecocardiográficos en hemodiálisis

Introducción. La principal causa de mortalidad de los pacientes con enfermedad renal crónica, y sobre todo en programa renal sustitutivo es la cardiovascular (CV). Los biomarcadores cardiacos y los parámetros ecocardiográficos pueden resultar herramientas útiles en la estratificación del riesgo CV en diálisis. Objetivo principal. Evaluar los factores de riesgo de mortalidad y eventos CV en una cohorte de pacientes prevalentes en hemodiálisis (HD) y los factores asociados. Material y métodos. Pacientes prevalentes y estables en HD. Se recogieron y analizaron variables epidemiológicas, clínicas y analíticas incluyendo los biomarcadores cardíacos así como datos ecocardiográficos. Durante el seguimiento (mediana de 39 (1-84) meses) se recogieron y analizaron los eventos CV y la mortalidad. Resultados. De los 211 pacientes incluidos (58 por ciento hombres, edad de 73 (60-80) años y un tiempo en HD de 83 (43-128) meses), el 64 por ciento presentaba hipertrofia de ventrículo izquierdo (HVI), el 36 por ciento disfunción diastólica (DD) y el 16 por ciento disfunción sistólica (DS). Excepto CK-MB, los marcadores cardiacos se encontraban basalmente elevados. Durante el seguimiento 94 pacientes (44,5 por ciento). Los factores asociados a padecer eventos CV fueron la edad, la historia de cardiopatía, los antecedentes de enfermedad vascular periférica (EVP), los niveles de hsTnT, CKMB, Nt-proBNP, la DD y la DS. En el modelo multivariante ajustado final sólo la albúmina (RR 0,422, p igual a 0,008) y la DD (RR 2,639, p igual a 0,003) resultaron predictores independientes de eventos CV. Durante el seguimiento, 98 pacientes (46,4 por ciento) fallecieron. Los factores asociados con la mortalidad fueron la edad, la historia de cardiopatía, EVP, el tiempo en HD, el acceso vascular diferente a fístula autóloga, los niveles de hsTnT, CKMB, Nt-proBNP y la DD. En el modelo multivariante ajustado final sólo la albúmina (RR 0,444, p igual a 0,014), el acceso vascular diferente a fístula autóloga (RR 2,190, p igual a 0,022) y la DD (RR 2,25, p igual a 0,027) resultaron predictores independientes. Conclusiones. Los biomarcadores cardiacos son buenos marcadores de riesgo en HD. Los predictores independientes de eventos CV en nuestra población fueron la DD y la albúmina. Ambos resultaron también ser predictores independientes de mortalidad junto con el acceso vascular diferente a fistula autóloga

Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. In the absence of targeted therapies, it invariably progresses to advanced chronic kidney disease. To date, the only approved treatment is tolvaptan, a vasopressin V2 receptor antagonist that has been demonstrated to reduce cyst growth and attenuate the decline in kidney function. However, it has various side effects, the most frequent of which is aquaresis, leading to a significant discontinuation rate. The strategies proposed to combat aquaresis include the use of thiazides or metformin and a reduction in the dietary osmotic load. Beyond the prescription of tolvaptan, which is limited to those with a rapid and progressive decline in kidney function, dietary interventions have been suggested to protect against disease progression. Moderate sodium restriction, moderate protein intake (up to 0.8 g/kg/day), avoidance of being overweight, and increased water consumption are recommended in ADPKD guidelines, though all with low-grade evidence. The aim of the present review is to critically summarize the evidence on the effect of dietary modification on ADPKD and to offer some strategies to mitigate the adverse aquaretic effects of tolvaptan

Long-Term Dynamic Humoral Response to SARS-CoV-2 mRNA Vaccines in Patients on Peritoneal Dialysis

COVID-19; Booster; Chronic kidney diseaseCOVID-19; Refuerzo; Enfermedad renal crónicaCOVID-19; Reforç; Malaltia renal crònicaIntroduction. Patients on peritoneal dialysis (PD) present an impaired humoral response against SARS-CoV-2, at least after the initial vaccination and booster dose. Until now, the effect of a fourth dose has not been established. The aim of the present study is to evaluate the long-term dynamics of the humoral response of PD patients to multiple doses of SARS-CoV-2 vaccines, focusing on the effect of the fourth dose. Methods. This is an analysis of the prospective and multicentric SENCOVAC study. We included patients on PD without additional immunosuppression that had received at least 3 SARS-CoV-2 mRNA vaccine doses. We evaluated anti-spike antibody titers after the initial vaccination, third and fourth doses, using prespecified fixed assessments (i.e., baseline, 28 days, 3, 6, and 12 months after completing the initial vaccine schedule). Breakthrough infections were also collected. Results. We included 164 patients on PD (69% males, 62 ± 13 years old). In patients who had received only two doses, the rates of positive humoral response progressively decreased from 96% at 28 days to 80% at 6 months, as did with anti-spike antibody titers. At 6 months, 102 (62%) patients had received the third vaccine dose. Patients with the third dose had higher rates of positive humoral response (p = 0.01) and higher anti-spike antibody titers (p < 0.001) at 6 months than those with only 2 doses. At 12 months, the whole cohort had received 3 vaccine doses, and 44 (27%) patients had an additional fourth dose. The fourth dose was not associated to higher rates of positive humoral response (100 vs. 97%, p = 0.466) or to statistically significant differences in anti-spike antibody titers as compared to three doses (p = 0.371) at 12 months. Prior antibody titers were the only predictor for subsequent higher anti-spike antibody titer (B 0.53 [95%CI 0.27–0.78], p < 0.001). The 2 (1.2%) patients that developed COVID-19 during follow-up had mild disease. Conclusions. PD presents an acceptable humoral response with three doses of SARS-CoV-2 vaccines that improve the progressive loss of anti-spike antibody titers following two vaccine doses.The present project has been supported by Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo, and ISCIII FEDER funds RICORS2040 (RD21/0005)

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

SARS-CoV-2; Booster; HemodialysisSARS-CoV-2; Refuerzo; HemodiálisisSARS-CoV-2; Reforç; HemodiàlisiBackground Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results A total of 711 patients [67% male, median age (range) 67 (20–89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P = .001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P = .693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P = .001), lower time from booster (P = .043) and past breakthrough SARS-CoV-2 infection (P < .001). Conclusions In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection.The present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005)

Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry

COVID-19; Kidney transplant; DialysisCOVID-19; Trasplantament de ronyó; DiàlisiCOVID-19; Trasplante de riñón; DiálisisBackground Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated. Results Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16–22% thereafter). Conclusions The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.We want to thank all the implicated Spanish centres for their altruist collaboration. A.O. research is supported by FIS/Fondos FEDER [PI18/01366, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009)], Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001), FEDER funds

Forensic archeology, the example of Viznar (Granada) as a methodological study of a civil conflict

URL del artículo en la web de la Revista: https://www.upo.es/revistas/index.php/romula/article/view/3959Con los trabajos realizados en el barranco de Víznar se da luz verde a la confirmaciónde evidencias forenses que demuestran la existencia de crímenes de lesa humanidad acaecidos en la provincia de Granada en general, y en los casos historiográficos de Víznar en particular. Estos fueron cometidos en el período comprendido entre el golpe militar de 1936 y la posterior dictadura franquista. Este trabajo trata de aclarar este debate histórico con metodología interdisciplinar a través de la arqueología y la antropología forense, además de aportar evidencias empíricas periciales que fundamenten la apertura de causa jurídica.The works performed in the ravine of Viznar provide forensic evidence confirming that crimes against humanity were committed in the province of Granada in general, and in the historiographic cases of Viznar in particular. These crimes were committed during the period between the 1936 military coup and the subsequent Francoist dictatorship. This essay aims to shed new light in the historical debate through an interdisciplinary methodology that uses archaeology and forensic anthropology, as well as through the provision of expert and empirical evidence to substantiate the initiation of legal proceedings.Universidad Pablo de Olavid

Practical approaches to building up a cardiorenal clinic

The population with concomitant heart and kidney disease (often termed 'cardiorenal' disease) is expected to grow, significantly impacting public health and healthcare utilization. Moreover, the cardiorenal nexus encompasses a bidirectional relationship that worsens prognosis and may complicate pharmacological management in often elderly and frail patients. Therefore, a more cohesive multidisciplinary team approach aiming to provide holistic, coordinated and specialized care would be a positive shift towards improving patient outcomes and optimizing healthcare resources. This article aims to define the organizational aspects and key elements for setting up a multidisciplinary cardiorenal clinical program as a potential healthcare model adapted to the particular characteristics of patients with cardiorenal disease

Proteinuria-lowering effects of proprotein convertase subtilisin/kexin type 9 inhibitors in chronic kidney disease patients : a real-world multicentric study

Control of dyslipidemia in chronic kidney disease (CKD) is not always guaranteed with statins and/or ezetimibe. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have opened up a new era in lipid control, but their effect on renal function and proteinuria in real life have not yet been evaluated. The aim of the present study was to analyze the evolution of renal function and proteinuria in a cohort of CKD patients treated with PCSK9i. This retrospective multicentric cohort study included CKD patients treated with PCSK9i. Baseline epidemiological data, comorbidities and laboratory findings (including estimated glomerular filtration rate [eGFR], proteinuria and lipid profile) were collected. The evolution of renal function, proteinuria and lipid profile was analyzed during the 1-year follow-up. The cohort included 76 patients (68% male, mean age 66 ± 10 years). The mean baseline creatinine was 1.55 ± 0.77 mg/dL, and the mean eGFR was 52 ± 22 mL/min/1.73 m2. Reductions in LDL-cholesterol, total cholesterol and triglycerides during the first month were 51 ± 25%, 32 ± 25% and 11 ± 40%, respectively, levels that remained stable throughout the first year (p < 0.001 for LDL-cholesterol and total cholesterol trends and p = 0.002 for triglyceride trend). During follow-up, proteinuria improved from 57 (9-481) to 30 (7-520) mg/g (p = 0.021). In addition, eGFR remained stable, and no adverse events were reported. In our cohort, dyslipidemia treatment with PCSK9i was associated with decreased proteinuria in CKD patients, an effect that might be due to reduced lipid nephrotoxicity. Clinical trials are needed to further investigate whether this impact on proteinuria can significantly slow CKD progression in the long term

Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients:the SENCOVAC study

BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe Covid-19. The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of 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, 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 analyzed. RESULTS: 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 to KT (OR 20.56, p = 0.001) and to BNT162b2 vaccine (OR 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

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy

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 patients on ERT. Study design: 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 (242-128mg/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≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. Conclusions: 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