Characterization of hypersensitivity reactions to polysulfone hemodialysis membranes.

BACKGROUND: In recent years, cases have been reported in which unexpected systemic hypersensitivity reactions occurred in patients dialyzed with polysulfone- or polyethersulfone-biocompatible membranes in the absence of other risk factors. The pathomechanisms involved in these reactions are largely unknown. OBJECTIVE: To characterize hypersensitivity reactions to polysulfone hemodialysis using clinical and laboratory data and to identify biomarkers suitable for endotype identification and diagnosis. METHODS: We prospectively collected data from 29 patients with suspected hypersensitivity reactions to polysulfone hemodialysis membranes. Clinical laboratory parameters such as tryptase, blood cell counts, and complement levels were recorded. Acute samples were obtained from 18 cases for the ex vivo assessment of basophil activation by flow cytometry analysis of CD63, CD203, and FcεRI cell membrane expression. Serum cytokines and anaphylatoxin concentrations were evaluated in 16 cases by Luminex and cytometric bead array analysis. RESULTS: Tryptase was elevated during the acute reaction in 4 cases. Evidence of basophil activation was obtained in 10 patients. Complement activation was found in only 2 cases. However, C5a serum levels tended to increase during the acute reaction in those patients with hypoxemia. Significantly higher serum levels of interleukin-6 were observed during the acute reactions to polysulfone hemodialysis (P = .0103). CONCLUSION: Based on biomarker analysis, various endotypes were identified, including type I-like (with the involvement of mast cells or basophils), complement, and cytokine (interleukin-6) release-related reactions, with some patients showing mixed reactions. Further research is needed to unravel the exact mechanisms involved in the activation of these cellular and molecular pathways.

AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.

BACKGROUND: Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability. METHODS: We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether AQP1 variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an AQP1 variant and investigate mitigation strategies. RESULTS: The common AQP1 promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (±SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506±237 ml vs. 626±283 ml, P = 0.007) and in the validation phase (368±603 ml vs. 563±641 ml, P = 0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P = 0.001), as well as a higher risk of death from any cause (24% vs. 15%, P = 0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in AQP1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant. CONCLUSIONS: A common variant in AQP1 was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.).

Incidencia y resultados de la COVID-19 en una unidad de diálisis domiciliaria en Madrid (España) durante el pico de la pandemia / COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic

INTRODUCCIÓN: La enfermedad por coronavirus 2019 (COVID-19) es una infección viral causada por un nuevo coronavirus que está afectando a todo el mundo. Hay estudios previos de pacientes en hemodiálisis en centro, pero hay pocos datos sobre población en diálisis domiciliaria. Nuestro objetivo es estudiar la incidencia y evolución de la COVID-19 en una unidad de diálisis domiciliaria (UDD) durante el pico de la pandemia. MÉTODOS: Estudio observacional y retrospectivo que incluye todos los pacientes diagnosticados de COVID-19 de la UDD del Hospital Universitario La Paz (Madrid, España) entre el 10 de marzo y el 15 de mayo de 2020. Se recogieron los datos clínicos de la UDD (57 pacientes en diálisis peritoneal y 22 pacientes en hemodiálisis domiciliaria) y comparamos las características clínicas y la evolución de los pacientes con o sin infección por COVID-19. RESULTADOS: Doce pacientes fueron diagnosticados de COVID-19 (9 diálisis peritoneal, 3 hemodiálisis domiciliaria). No hubo diferencias estadísticamente significativas entre las características clínicas de los pacientes con COVID-19 y el resto de la unidad. La edad media fue 62 ± 18,5 años; la mayoría eran varones (75%). Todos los pacientes menos uno necesitaron hospitalización. Diez pacientes (83%) fueron dados de alta tras una media de 16,4 ± 9,7 días de hospitalización. Dos pacientes fueron diagnosticados durante su hospitalización por otro motivo y fueron los únicos que fallecieron. Los fallecidos eran de mayor edad que los supervivientes. CONCLUSIÓN: La incidencia de COVID-19 en nuestra UDD en Madrid durante el pico de la pandemia fue alto, especialmente en los pacientes en diálisis peritoneal, sin observarse un potencial beneficio para prevenir la infección en los pacientes en diálisis domiciliaria. La edad avanzada y la transmisión nosocomial fueron los principales factores relacionados con peor pronóstico

INTRODUCTION: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis, but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. METHODS: An observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz (La Paz University Hospital) (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis and 22 patients on home hemodialysis) and compared the clinical characteristics and course of patients with and without COVID-19 infection. RESULTS: Twelve patients were diagnosed with COVID-19 (9 peritoneal dialysis; 3 home hemodialysis). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62 ± 18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4 ± 9.7 days of hospitalization. Two patients were diagnosed while hospitalized for other conditions, and these were the only patients who died. Those who died were older than those who survived. CONCLUSION: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on peritoneal dialysis. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis

[Interleukin-17A: Possible mediator and therapeutic target in hypertension]. / Interleuquina-17A: posible mediador y diana terapéutica en la hipertensión.

Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 lymphocytes and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and target organ damage. Studies in mice have shown that IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Preclinical studies on arterial hypertension have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17 lymphocytes and γδ lymphocytes that express IL-17A. In addition, in experimental models of hypertension, blocking IL-17A by genetic strategies, or using neutralising antibodies, lowers blood pressure by acting on the vascular wall and tubule sodium transport and reduces damage to target organs. As a whole, the data presented in this review suggest that IL-17A participates in the regulation of blood pressure and in the genesis and maintenance of arterial hypertension, and may constitute a therapeutic target in the future.

The Effect of Nutritional Interventions on Long-Term Patient Survival in Advanced Chronic Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at high risk of malnutrition and subsequent related mortality when starting dialysis. However, there have been few clinical studies on the effect of nutritional interventions on long-term patient survival. A 2-year longitudinal study was conducted from January 2012 to December 2016. A total of 186 patients with non-dialysis ESKD started the nutritional education program (NEP), and 169 completed it. A total of 128 patients participated in a NEP over 6 months (personalized diet, education and oral supplementation, if needed). The control group (n = 45) underwent no specific nutritional intervention. The hospitalization rate was significantly lower for the patients with NEP (13.7%) compared with the control patients (26.7%) (p = 0.004). The mortality odds ratio for the patients who did not receive NEP was 2.883 (95% CI 0.993-8.3365, p = 0.051). The multivariate analysis showed an independent association between mortality and age (OR, 1.103; 95% CI 1.041-1.169; p = 0.001) and between mortality and the female sex (OR, 3.332; 95% CI 1.054-10.535; p = 0.040) but not between mortality and those with NEP (p = 0.051). Individualized nutrition education has long-term positive effects on nutritional status, reduces hospital admissions and increases survival among patients with advanced CKD who are starting dialysis programs.

Interleukin-17A: Potential mediator and therapeutic target in hypertension.

Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and in target organ damage. Preclinical studies in mice have shown that systemic adminstration of IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Many studies in hypertensive mice models have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17 lymphocytes and γδ lymphocytes that express IL-17A. In addition, in experimental models of hypertension, the blockade of IL-17A by genetic strategies or using neutralizing antibodies, disminished blood pressure, probablyby acting on the small mesenteric arteries as well as in the regulation of tubule sodium transport. Moreover, IL-17A inhibition reduces end-organs damage. As a whole, the data presented in this review suggest that IL-17A participates in the regulation of blood pressure and in the genesis and maintenance of arterial hypertension, and may constitute a therapeutic target of hypertension-related pathologies in the future.

COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic.

INTRODUCTION: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis (HD), but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. METHODS: an observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz [La Paz University Hospital] (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis [PD] and 22 patients on home hemodialysis [HHD]) and compared the clinical characteristics and course of patients with and without COVID-19 infection. RESULTS: twelve patients were diagnosed with COVID-19 (9 PD; 3 HHD). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62 ± 18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4 ± 9.7 days of hospitalization. Two patients were diagnosed while hospitalised for other conditions, and these were the only patients who died. Those who died were older than those who survived. CONCLUSION: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on PD. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis.

[COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic]. / Incidencia y resultados de la COVID-19 en una unidad de diálisis domiciliaria en Madrid (España) durante el pico de la pandemia.

INTRODUCTION: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis, but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. METHODS: An observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz (La Paz University Hospital) (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis and 22 patients on home hemodialysis) and compared the clinical characteristics and course of patients with and without COVID-19 infection. RESULTS: Twelve patients were diagnosed with COVID-19 (9 peritoneal dialysis; 3 home hemodialysis). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62±18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4±9.7 days of hospitalization. Two patients were diagnosed while hospitalized for other conditions, and these were the only patients who died. Those who died were older than those who survived. CONCLUSION: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on peritoneal dialysis. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis.

Evaluation of a system for sorbent-assisted peritoneal dialysis in a uremic pig model.

A system for sorbent-assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single-lumen peritoneal catheter with the regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by the maintenance of a high plasma-to-dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8-hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance the clearance of phosphate and organic waste solutes during the day. Uremic pigs (n = 3) were treated with the day- (n = 3) and nighttime system (n = 15) for 4-8 hr per treatment. Plasma clearance (Cl), MTAC, and total mass transport (MT) of urea, creatinine, phosphate, and potassium were compared with a static dwell (n = 28). Cl, MTAC, and MT of urea, creatinine, phosphate, and potassium were low in the pig as compared to humans due to the pig's low peritoneal transport status and could be enhanced only to a limited extent by SAPD treatment compared with a static dwell (nighttime system: Cl urea: ×1.5 (p = .029), Cl creatinine: ×1.7 (p = .054), Cl phosphate: ×1.5 (p = .158), Cl potassium: ×1.6 (p = .011); daytime system: Cl creatinine: ×2.7 (p = .040), Cl phosphate: ×2.2 (p = .039)). Sorbent-assisted peritoneal dialysis treatment in a uremic pig model is safe and enhances small solute clearance as compared to a static dwell. Future studies in humans or animal species with higher peritoneal transport should elucidate whether our SAPD system enhances clearance to a clinically relevant extent as compared to conventional PD.

Influence of dialysate temperature on creatinine peritoneal clearance in peritoneal dialysis patients: a randomized trial.

BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (PD) are encouraged to warm dialysate to 37 °C before peritoneal infusion; main international PD guidelines do not provide specific recommendation, and patients generally warm dialysate batches partially or do not warm them at all. Warming of dialysate is a time-consuming procedure, not free from potential risks (i.e. degradation of glucose), and should be justified by a clear clinical benefit. METHODS: We designed a single blind randomized controlled trial where 18 stable PD patients were randomized to receive a peritoneal equilibration test either with dialysate at a controlled temperature of 37 °C (intervention group) or with dialysate warmed with conventional methods (control group). Primary end-point was a higher peritoneal creatinine clearance in patients in the intervention group. RESULTS: Patients in the intervention group did not show a significantly higher peritoneal creatinine clearance when compared to the control group (6.38 ± 0.52 ml/min vs 5.65 ± 0.37 ml/min, p = 0.2682). Similar results were obtained for urea peritoneal clearance, mass transfer area coefficient of creatinine and urea. There were no significant differences in total abdominal discomfort questionnaire score, blood pressure and body temperature between the two groups. CONCLUSIONS: Using peritoneal dialysate at different temperatures without causing significant side effects to patients appears feasible. We report a lack of benefit of warming peritoneal dialysate to 37 °C on peritoneal clearances; future PD guidelines should not reinforce this recommendation. TRIAL REGISTRATION: NCT04302649, ClinicalTrials.gov ; date of registration 10/3/2020 (retrospectively registered).

IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis.

Chronic kidney disease (CKD) is a health problem reaching epidemic proportions. There is no cure for CKD, and patients may progress to end-stage renal disease (ESRD). Peritoneal dialysis (PD) is a current replacement therapy option for ESRD patients until renal transplantation can be achieved. One important problem in long-term PD patients is peritoneal membrane failure. The mechanisms involved in peritoneal damage include activation of the inflammatory and immune responses, associated with submesothelial immune infiltrates, angiogenesis, loss of the mesothelial layer due to cell death and mesothelial to mesenchymal transition, and collagen accumulation in the submesothelial compact zone. These processes lead to fibrosis and loss of peritoneal membrane function. Peritoneal inflammation and membrane failure are strongly associated with additional problems in PD patients, mainly with a very high risk of cardiovascular disease. Among the inflammatory mediators involved in peritoneal damage, cytokine IL-17A has recently been proposed as a potential therapeutic target for chronic inflammatory diseases, including CKD. Although IL-17A is the hallmark cytokine of Th17 immune cells, many other cells can also produce or secrete IL-17A. In the peritoneum of PD patients, IL-17A-secreting cells comprise Th17 cells, γδ T cells, mast cells, and neutrophils. Experimental studies demonstrated that IL-17A blockade ameliorated peritoneal damage caused by exposure to PD fluids. This article provides a comprehensive review of recent advances on the role of IL-17A in peritoneal membrane injury during PD and other PD-associated complications.

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients.

Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-ß1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.

STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation.

Elucidating the contribution of somatic mutations to cancer is essential for personalized medicine. STK11 (LKB1) appears to be inactivated in human cancer. However, somatic missense mutations also occur, and the role/s of these alterations to this disease remain unknown. Here, we investigated the contribution of four missense LKB1 somatic mutations in tumor biology. Three out of the four mutants lost their tumor suppressor capabilities and showed deficient kinase activity. The remaining mutant retained the enzymatic activity of wild type LKB1, but induced increased cell motility. Mechanistically, LKB1 mutants resulted in differential gene expression of genes encoding vesicle trafficking regulating molecules, adhesion molecules and cytokines. The differentially regulated genes correlated with protein networks identified through comparative secretome analysis. Notably, three mutant isoforms promoted tumor growth, and one induced inflammation-like features together with dysregulated levels of cytokines. These findings uncover oncogenic roles of LKB1 somatic mutations, and will aid in further understanding their contributions to cancer development and progression.

Co-occurrence of neurofibromatosis type 1 and optic nerve gliomas with autosomal dominant polycystic kidney disease type 2.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and neurofibromatosis type 1 (NF1) are both autosomal dominant disorders with a high rate of novel mutations. However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and NF1 in a single individual have been reported, but the possible implications of this association are unknown. METHODS: We report an ADPKD male belonging to a family of several affected members in three generations associated with NF1 and optic pathway gliomas. The clinical diagnosis of ADPKD and NF1 was performed by several image techniques. RESULTS: Linkage analysis of ADPKD family was consistent to the PKD2 locus by a nonsense mutation, yielding a truncated polycystin-2 by means of next-generation sequencing. The diagnosis of NF1 was confirmed by mutational analysis of this gene showing a 4-bp deletion, resulting in a truncated neurofibromin, as well. The impact of this association was investigated by analyzing putative genetic interactions and by comparing the evolution of renal size and function in the proband with his older brother with ADPKD without NF1 and with ADPKD cohorts. CONCLUSION: Despite the presence of both conditions there was not additive effect of NF1 and PKD2 in terms of the severity of tumor development and/or ADPKD progression.

In vitro efficacy and safety of a system for sorbent-assisted peritoneal dialysis.

A system for sorbent-assisted peritoneal dialysis (SAPD) was designed to continuously recirculate dialysate via a tidal mode using a single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbent technology. We hypothesize that SAPD treatment will maintain a high plasma-to-dialysate concentration gradient and increase the mass transfer area coefficient of solutes. Thereby, the SAPD system may enhance clearance while reducing the number of exchanges. Application is envisaged at night as a bedside device (12 kg, nighttime system). A wearable system (2.0 kg, daytime system) may further enhance clearance during the day. Urea, creatinine, and phosphate removal were studied with the daytime and nighttime system (n = 3 per system) by recirculating 2 liters of spent peritoneal dialysate via a tidal mode (mean flow rate: 50 and 100 mL/min, respectively) for 8 h in vitro. Time-averaged plasma clearance over 24 h was modeled assuming one 2 liter exchange/day, an increase in mass transfer area coefficient, and 0.9 liters ultrafiltration/day. Urea, creatinine, and phosphate removal was 33.2 ± 4.1, 5.3 ± 0.5, and 6.2 ± 1.8 mmol, respectively, with the daytime system and 204 ± 28, 10.3 ± 2.4, and 11.4 ± 2.1 mmol, respectively, with the nighttime system. Time-averaged plasma clearances of urea, creatinine and phosphate were 9.6 ± 1.1, 9.6 ± 1.7, and 7.0 ± 0.9 mL/min, respectively, with the nighttime system and 10.8 ± 1.1, 13.4 ± 1.8, and 9.7 ± 1.6 mL/min, respectively, with the daytime and nighttime system. SAPD treatment may improve removal of uremic toxins compared with conventional peritoneal dialysis, provided that peritoneal mass transport will increase.

Validación de un Cuestionario Multidimensional de Adaptación a la Enfermedad para Pacientes Renales en Diálisis (CMAE-RD) diseñado a partir de un cuestionario para pacientes oncohematológicos / Validation of a Multidimensional Questionnaire to Assess Adaptation to Illness to Renal Patients under Dialysis Treatment designed from a questionnaire from oncohaematologic patients

OBJETIVOS: El objetivo de este trabajo es estudiar las propiedades psicométricas de un cuestionario multidimensional de adaptación a la enfermedad para pacientes con enfermedad renal en diálisis (CMAE-RD). MÉTODOS: Esta herramienta está diseñada para ser administrada por un profesional de la psicología en forma de entrevista semiestructurada y fue diseñado a partir de un cuestionario previo para pacientes oncohematológicos. Un total de 113 pacientes en hemodiálisis fueron entrevistados mediante el CMAE-RD y completaron dos cuestionarios adicionales con propósitos de validación: el HADS (para evaluar ansiedad y depresión) y el CDRISC-2 (para evaluar resiliencia). RESULTADOS: La consistencia interna para las áreas del CMAE-RD estuvo comprendida entre 0,53 y 0,70, y se obtuvieron evidencias de validez relacionada con un criterio externo y concurrente especialmente para las áreas que evaluaban el grado en que el paciente está informado y su estado de ánimo. CONCLUSIONES: CMAE-RD presenta niveles adecuados de fiabilidad y validez, siendo una herramienta útil desde el punto de vista clínico, pues permite evaluar las necesidades y recursos de los pacientes, guiando la intervención psicológica

OBJECTIVES: The present study aims to explore the psychometric properties of a multidimensional questionnaire to assess adaptation to illness in patients with end stage renal disease under hemodialysis (CMAE-RD for its Spanish acronym). METHODS: This instrument was developed to be administered by a psychologist as a semi structured interview and it was adapted from a previous questionnaire for patients with oncohaematologic diseases. A total of 113 patients receiving hemodialysis treatment were interviewed with the CMAE-RD and completed two additional questionnaires with validation purposes: the HADS (to assess anxiety and depression) and the CDRISC-2 (to assess resilience). RESULTS: Internal consistency scores for the areas of the CMAE-RD was comprised between.53 and.70. Evidences of validity related to an external criterion and concurrent validity were obtained for the areas which assess the level of information of the patient and their emotional state. CONCLUSIONS: We conclude that the CMAE-RD shows adequate levels of reliability and validity, being a useful measurement tool from the standpoint of health care, as it allows psychologist the needs and resources of renal patients, providing guidance for psychological intervention

Coexistence of autosomal dominant polycystic kidney disease type 1 and hereditary renal hypouricemia type 2: A model of early-onset and fast cyst progression.

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid-filled cyst development leading to end-stage renal disease. The rate of disease progression in ADPKD exhibits high inter- and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24-year-old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next-generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.

Interleukin-17A induces vascular remodeling of small arteries and blood pressure elevation.

An important link exists between hypertension and inflammation. Hypertensive patients present elevated circulating levels of proinflammatory cytokines, including interleukin-17A (IL-17A). This cytokine participates in host defense, autoimmune and chronic inflammatory pathologies, and cardiovascular diseases, mainly through the regulation of proinflammatory factors. Emerging evidence also suggests that IL-17A could play a role in regulating blood pressure and end-organ damage. Here, our preclinical studies in a murine model of systemic IL-17A administration showed that increased levels of circulating IL-17A raised blood pressure induced inward remodeling of small mesenteric arteries (SMAs) and arterial stiffness. In IL-17A-infused mice, treatment with hydralazine and hydrochlorothiazide diminished blood pressure elevation, without modifying mechanical and structural properties of SMA, suggesting a direct vascular effect of IL-17A. The mechanisms of IL-17A seem to involve an induction of vascular smooth muscle cell (VSMC) hypertrophy and phenotype changes, in the absence of extracellular matrix (ECM) proteins accumulation. Accordingly, treatment with an IL-17A neutralizing antibody diminished SMA remodeling in a model of angiotensin II (Ang II) infusion. Moreover, in vitro studies in VSMCs reported here, provide further evidence of the direct effects of IL-17A on cell growth responses. Our experimental data suggest that IL-17A is a key mediator of vascular remodeling of the small arteries, which might contribute, at least in part, to blood pressure elevation.