Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

Medicina de precisión: «Point of Care Ultrasound» (PoCUS) en el abordaje diagnóstico del paciente con hiponatremia / Precision medicine: “Point of Care Ultrasound” (PoCUS) in the diagnostic approach to the patient with hyponatremia

La hiponatremia es un trastorno multifactorial definido como una disminución en la concentración plasmática de sodio. Su diagnóstico diferencial requiere una evaluación adecuada del volumen extracelular. Sin embargo, la determinación del volumen extracelular, simplemente basada en la historia clínica, las constantes vitales, el examen físico y los hallazgos de laboratorio, conducen en ocasiones a un diagnóstico erróneo por lo que el enfoque terapéutico puede ser equivocado. El empleo de ecografía a pie de cama (Point-of-Care Ultrasound [PoCUS]), mediante la combinación de ecografía pulmonar (Lung Ultrasound [LUS]), Venous Excess UltraSound (VExUS) y la ecocardioscopia (Focused Cardiac Ultrasound [FoCUS]) permiten, en combinación con el resto de los parámetros, una valoración holística mucho más precisa del estado del volumen extracelular del paciente.(AU)

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume. However, extracellular volume determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (PoCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's extracellular volume status in combination with the other parameters.(AU)

Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Chronic Kidney Disease-Associated Pruritus and Quality of Life: Learning from Our Patients.

Chronic kidney disease-associated pruritus is itching directly related to kidney disease that cannot be explained by any other condition. Despite technological advances in the different aspects of dialysis sessions and the best treatment for chronic kidney disease patients, it is still a common problem in our patients. The many complex physiological mechanisms involved, the different hypotheses made over the years on the aetiology of the condition, and the great clinical variability may partially explain the limited knowledge about this problem and the difficulties in treating it. The presence of all these factors leads to the persistence of unpleasant symptoms, which must affect the disease burden and quality of life of kidney patients. Through the presentation of an illustrative clinical case, the aim of this review article is to highlight the need for adequate diagnosis and an improved approach to all aspects of chronic kidney disease-associated pruritus, in view of the heavy burden of the disease and the huge impact on the patient's quality of life.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP).

INTRODUCTION: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. OBJECTIVES: The objective of this study was to analyse the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. RESULTS: 135 nephrologists, most of them engaged in haemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their centre is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anaesthetics (93%) and modification of the dialysis regimen (70%). CONCLUSIONS: Pruritus associated with chronic kidney disease is still a current problem, it is underdiagnosed, not codified and with a lack of indicated, effective and safe treatments. Nephrologists do not know its real prevalence and the different pathophysiological mechanisms involved in its development. Many therapeutic options are used with very variable results, ignoring their efficacy and applicability at the present time. The new emerging kappa-opioid-receptor agonist agents offer us an opportunity to reevaluate this age-old problem and improve the quality of life for our patients with chronic kidney disease.

Percepción de los nefrólogos españoles sobre un problema antiguo no resuelto: Prurito asociado a la enfermedad renal crónica (Pa-ERC) / Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP)

Introducción: El prurito asociado a enfermedad renal crónica se define como la sensación desagradable que provoca la necesidad de rascarse en una parte del cuerpo o en todo en personas con enfermedad renal crónica, tras haberse descartado otras causas dermatológicas o sistémicas. Es un problema antiguo y conocido cuya prevalencia ha podido disminuir con la mejoría de la eficacia dialítica pero que todavía persiste y está infradiagnosticado. Objetivos: El objetivo de este estudio fue analizar la percepción y práctica actual de los nefrólogos sobre este problema que impacta en la calidad de vida de las personas con enfermedad renal crónica a través de una encuesta anónima. Resultados: Participaron 135 nefrólogos, la mayoría dedicados a hemodiálisis. Un 86% consideró que el prurito asociado a enfermedad renal crónica sigue siendo un problema en la actualidad que afecta a la calidad de vida. La mayoría de los nefrólogos opinan que la principal causa fisiopatológica son las toxinas urémicas (60%) y solo un 16% cree que se debe a la desregulación del sistema opioide/endorfinas-dinorfinas. Únicamente un 16% comenta que la prevalencia de prurito en su centro es mayor del 20%. Un 40% cree que el diagnóstico se realiza porque lo manifiesta el paciente y solo un 27% porque lo pregunta el facultativo. Además, no es habitual usar escalas ni codificarlo en la historia clínica. El tratamiento más común son los antihistamínicos (96%), seguido de las cremas hidratantes/anestésicas (93%) y la modificación de la pauta de diálisis (70%). (AU)

Introduction: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. Objectives: The objective of this study was to analyze the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. Results: 135 nephrologists, most of them engaged in hemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their center is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anesthetics (93%) and modification of the dialysis regimen (70%). (AU)

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.

Background: 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.

Recomendaciones para el manejo de la hiperpotasemia en urgencias / Recommendations for the management of hyperkalemia in the emergency department

La hiperpotasemia es un trastorno electrolítico frecuente en los servicios de urgencias y un manejo adecuado impacta en el pronóstico de los pacientes. Este requiere de la integración de datos clínicos y analíticos sobre el estado de la función renal, la hidratación, el equilibrio ácido-base y la afectación cardiaca. Además, es necesaria una precisa toma de decisiones sobre la corrección de la concentración de potasio en el tiempo indicado para cada caso. Por estos mo- tivos la SEMES (Sociedad Española de Medicina de Urgencias y Emergencias), la SEC (Sociedad Española de Cardiología) y la SEN (Sociedad Española de Nefrología) unen esfuerzos en consensuar definiciones y tratamientos que podrían mejorar el abordaje de estos pacientes en los servicios de urgencias hospitalarios. El calcio intravenoso, la insulina con glucosa y el salbutamol siguen siendo los tratamientos que se emplean en la hiperpotasemia aguda. Los diuréticos de asa y tiazídicos también pueden ayudar en pacientes no depleccionados, y la hemodiálisis puede ser necesaria en hiperpotasemias graves en el contexto de insuficiencia renal. Los efectos secundarios y la baja tolerabilidad de las resinas de intercambio iónico están haciendo que caigan en desuso mientras que los nuevos intercambiadores catiónicos gastrointestinales van ganando su espacio e incluso podrían tener algún valor en el tratamiento agudo. Es fundamental el ajuste del tratamiento evitando retirar fármacos que, a pesar de favorecer la hiperpotasemia, mejoren el pronóstico a largo plazo, por lo que es imperativo buscar alternativas válidas para cada grupo de pacientes, asegurando después un estrecho seguimiento. (AU)

Hyperkalemia, a common electrolyte disorder, is seen often in emergency departments. Patient outcomes are impacted by proper management, which requires consideration of both clinical and laboratory findings in relation to kidney function, hydration, the acid–base balance, and heart involvement. Delicate decisions about the timing of potassium level correction must be tailored in each case. For these reasons the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Cardiology (SEC), and the Spanish Society of Nephrology (SEN) joined forces to come to a consensus on defining the problem and recommending treatments that improve hospital emergency department management of hyperkalemia. Intravenous calcium, insulin and glucose, and salbutamol continue to be used to treat acute hyperkalemia. Either loop or thiazide diuretics can help patients if volume is not depleted, and dialysis may be necessary if there is kidney failure. Ion-exchange resins are falling into disuse because of adverse effects and poor tolerance, whereas novel gastrointestinal cation-exchange resins are gaining ground and may even be of some use in managing acute cases. It is essential to adjust treatment rather than discontinue medications that, even if they favor the development of hyperkalemia, will improve a patient’s long-term prognosis. Valid alternative treatment approaches must therefore be sought for each patient group, and close follow-up is imperative. (AU)

Recommendations for the management of hyperkalemia in the emergency department. / Recomendaciones para el manejo de la hiperpotasemia en urgencias.

TEXT: Hyperkalemia, a common electrolyte disorder, is seen often in emergency departments. Patient outcomes are impacted by proper management, which requires consideration of both clinical and laboratory findings in relation to kidney function, hydration, the acid-base balance, and heart involvement. Delicate decisions about the timing of potassium level correction must be tailored in each case. For these reasons the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Cardiology (SEC), and the Spanish Society of Nephrology (SEN) joined forces to come to a consensus on defining the problem and recommending treatments that improve hospital emergency department management of hyperkalemia. Intravenous calcium, insulin and glucose, and salbutamol continue to be used to treat acute hyperkalemia. Either loop or thiazide diuretics can help patients if volume is not depleted, and dialysis may be necessary if there is kidney failure. Ion-exchange resins are falling into disuse because of adverse effects and poor tolerance, whereas novel gastrointestinal cation-exchange resins are gaining ground and may even be of some use in managing acute cases. It is essential to adjust treatment rather than discontinue medications that, even if they favor the development of hyperkalemia, will improve a patient's long-term prognosis. Valid alternative treatment approaches must therefore be sought for each patient group, and close follow-up is imperative.

TEXTO: La hiperpotasemia es un trastorno electrolítico frecuente en los servicios de urgencias y un manejo adecuado impacta en el pronóstico de los pacientes. Este requiere de la integración de datos clínicos y analíticos sobre el estado de la función renal, la hidratación, el equilibrio ácido-base y la afectación cardiaca. Además, es necesaria una precisa toma de decisiones sobre la corrección de la concentración de potasio en el tiempo indicado para cada caso. Por estos motivos la SEMES (Sociedad Española de Medicina de Urgencias y Emergencias), la SEC (Sociedad Española de Cardiología) y la SEN (Sociedad Española de Nefrología) unen esfuerzos en consensuar definiciones y tratamientos que podrían mejorar el abordaje de estos pacientes en los servicios de urgencias hospitalarios. El calcio intravenoso, la insulina con glucosa y el salbutamol siguen siendo los tratamientos que se emplean en la hiperpotasemia aguda. Los diuréticos de asa y tiazídicos también pueden ayudar en pacientes no depleccionados, y la hemodiálisis puede ser necesaria en hiperpotasemias graves en el contexto de insuficiencia renal. Los efectos secundarios y la baja tolerabilidad de las resinas de intercambio iónico están haciendo que caigan en desuso mientras que los nuevos intercambiadores catiónicos gastrointestinales van ganando su espacio e incluso podrían tener algún valor en el tratamiento agudo. Es fundamental el ajuste del tratamiento evitando retirar fármacos que, a pesar de favorecer la hiperpotasemia, mejoren el pronóstico a largo plazo, por lo que es imperativo buscar alternativas válidas para cada grupo de pacientes, asegurando después un estrecho seguimiento.

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

BACKGROUND: The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. METHODS: From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). RESULTS: Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). CONCLUSIONS: COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.