[Gout, beyond the joint: How should we treat it?] / La gota, más allá de la articulación: ¿cómo debemos tratarla?

Gout is a disease caused by the chronic deposition of monosodium urate crystals. Its clinical presentation as an acute, self-limiting arthritis and the belief that it is a banal, self-inflicted disease have led to its poor management. Despite advances in the knowledge of the disease and the simplicity of its management, no more than 30% of patients are well treated. In Spain, the prevalence of gout is 2.5% and its incidence is increasing. In the following article we will review the pathogenesis of gout and hyperuricaemia, highlighting the greater weight of genetics and renal function over diet. We will look at the consequences of crystal deposition. Gout, in addition to its joint presentation and renal involvement, has been shown to be an independent cardiovascular risk factor. Hypouricemic therapy is the most important treatment, as it is the one that dissolves the crystals and cures the disease. This requires the sustained achievement of uricemia levels below 6mg/dl. We will also review preventive and flares treatment, as well as the role of patient education in terms of both lifestyle and dietary habits and adherence to pharmacological treatment.

Síndrome de DRESS asociado al consumo de alopurinol: reporte de caso

El síndrome de DRESS (por sus siglas en inglés Drug Reaction with Eosinophilia and Systemic Symptoms) representa una farmacodermia grave con diferentes manifestaciones clínicas y paraclínicas secundarias a una reacción de hipersensibilidad farmacológica. Su incidencia exacta es desconocida pero se estima entre 1 a 1000 y 1 a 10000 casos de exposición a fármacos asociados. Se caracteriza por dermatosis generalizada extensa en conjunto con afección orgánica, linfadenopatia, eosinofilia y linfocitosis atípica. Entre los fármacos comúnmente asociados se encuentran anticomiciales aromáticos, carbamazepina, sulfonamidas y el alopurinol. Mediante el uso de la puntuación RegiSCAR es posible confirmar o descartar una sospecha de diagnóstico. El tratamiento depende de la severidad de presentación incluyendo esteroides tópicos hasta esteroide sistémico de duración variable dependiendo respuesta clínica y bioquímica. Se reporta tasas de mortalidad del 10 al 20% siendo la insuficiencia hepática la principal causa de muerte en estos pacientes. Se presenta el caso de un paciente femenino de 71 años de edad que, posterior a tratamiento con alopurinol, debuta con eritrodermia secundaria a Síndrome de DRESS.

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) represents severe pharmacodermia with different clinical and paraclinical manifestations secondary to a drug hypersensitivity reaction. The exact incidence is unknown, but it is estimated to be between 1 in 1,000 and 1 in 10,000 cases of exposure to associated drugs. It is characterized by extensive generalized dermatosis, in conjunction with organic involvement, lymphadenopathy, eosinophilia, and atypical lymphocytosis. Commonly associated drugs include aromatic anticonvulsants, carbamazepine, sulfonamides, and allopurinol. By using the RegiSCAR score, it is possible to confirm or rule out a suspected diagnosis. Treatment depends on the severity of presentation, including topical steroids to systemic steroids of variable duration, depending on clinical and biochemical responses. Mortality rates of 10 - 20% have been reported, with liver failure being the main cause of death in these patients. We present the case of a 71-year-old female patient who, after treatment with allopurinol, developed erythroderma secondary to DRESS Syndrome.

¿Debemos manejar la hiperuricemia asintomática para proteger al riñón?

Contexto: el ácido úrico es el producto final de la degradación de las purinas en los primates, en condiciones normales es un agente antioxidante endógeno y participa en varias vías fisiológicas, sin embargo, cuando los niveles séricos de urato se incrementan, estos participan en el desarrollo de diversas enfermedades. Desde el siglo XIX se conoce de la asociación entre hiperuricemia y daño renal, aunque ninguna guía de manejo recomienda el uso de fármacos hipouricemiantes en pacientes asintomáticos, en algunos casos especiales, el manejo farmacológico beneficiará a pacientes con hiperuricemia, brindando protección al riñón y disminuyendo el riesgo de desarrollar enfermedad renal terminal. Objetivo: describir la relación entre hiperuricemia y daño renal, y analizar los casos en los que el manejo de esta condición con medicamentos resultará en un beneficio para el riñón de los pacientes. Metodología: revisión de la literatura sobre la participación de la hiperuricemia en el daño renal y análisis de los artículos revisados. Resultados: el manejo de la hiperuricemia asintomática puede proteger el riñón en algunas situaciones específicas. Conclusiones: hay situaciones específicas para la disminución de los niveles séricos de ácido úrico.

Background: Uric acid is the end product of purine degradation in primates, under normal conditions it is an endogenous antioxidant agent and participates in several physiological pathways. However, when serum urate levels are increased, they participate in the development of various diseases. Since the nineteenth century, the association between hyperuricemia and kidney damage has been known. Although no management guideline recommends the use of hypouricemic drugs in asymptomatic patients, in some special cases pharmacological management will benefit patients with hyperuricemia, providing protection to the kidney and decreasing the risk of developing end-stage renal disease. Purpose: To describe the relationship between hyperuricemia and kidney damage, and to analyze the cases in which the management of this condition with medications will result in a benefit for the kidney of patients. Methodology: Review of the literature on the involvement of hyperuricemia in kidney damage, analysis of the reviewed articles. Results: Management of asymptomatic hyperuricemia may protect the kidney in some specific situations. Conclusions: There are specific situations for the decrease of serum uric acid levels.

Características del síndrome de lisis tumoral en pacientes pediátricos oncológicos. Un estudio observacional de centro único / Characteristics of tumor lysis syndrome in pediatric oncology patients. A single-center observational study

Introducción:El síndrome de lisis tumoral (SLT) es una emergencia oncológica, que produce alteraciones en el metabolismo, causando manifestaciones clínicas y trastornos bioquímicos que ponen en peligro la vida del paciente.El objetivo del presente estudio fue identificar las características clínicas, de laboratorio y tratamiento del SLT, en pacientes pediátricos onco-lógicos, del Instituto del Cáncer SOLCA-Cuenca, en el periodo 2010 ­2020.Materiales y métodos:En este estudio se identificó las características del SLT, en pacientes pediátricos oncológicos, del Instituto del Cáncer SOLCA-Cuenca, en el periodo 2010 ­2020, a través de un estudio de tipo descriptivo-observacional.Resultados:Seincluyó 463 historias clínicas, en el cual se obtuvo que el SLT tuvo una frecuen-cia del 5.61 %, con predominio del sexo masculino (57.7%) y con una edad media de 7 ± 1.29 años. La presentación clínica más observada fue la deshidratación con náusea, vómito y dia-rrea (57.7%). Las alteraciones de laboratorio más frecuentes fueron la hiperuricemia y la hi-pocalcemia, con un 76.9 %y un 73.1 %respectivamente. La Leucemia linfoblástica aguda (LLA) fue el diagnósticooncológico con más casos (61.5 %). Los pilares del tratamiento fue-ron la hiperhidratación y el uso de alopurinol, utilizados en el 100% y un 80.8 %respectiva-mente.Conclusión:El SLT afectó más frecuentemente a varones, con diagnóstico de leucemia, ma-nifestaciones clínicas digestivas y alteraciones de laboratorio (hiperuricemia e hipocalcemia). El tratamiento empleado resultó eficaz y se basó en lo recomendado por la literatura médica

Introduction:Tumor lysis syndrome (TLS) is an oncological emergency that results in meta-bolic alterations, causing clinical manifestations and biochemical disorders that endanger pa-tients' lives. The objective of the present study was to identify the clinical, laboratory, and treat-ment characteristics of TLSsin pediatric oncology patients at the SOLCA-Cuenca Cancer Ins-titute from 2010­2020.Materials and methods: In this study, the characteristics of TLS were identified in pediatric oncology patients at the SOLCA-Cuenca Cancer Institute from 2010 to 2020 through a des-criptive observational study.Results: A total of463 medical records were included. TLSs were associated witha frequency of 5.61%, with a predominance of males(57.7%) and a mean age of 7 ± 1.29 years. The most commonclinical presentation was dehydration with nausea, vomiting, and diarrhea (57.7%). The most frequent laboratory alterations were hyperuricemia and hypocalcemia, with 76.9% and 73.1%,respectively. The oncological diagnosis was acutelymphoblastic leukemia (ALL) in most patients(61.5%). The pillars of treatment were hyperhydration and allopurinol, used in 100% and 80.8%, respectively.Conclusion: TLSsmore frequently affectmen with a diagnosis of leukemia, digestive clinical manifestations, orlaboratory alterations (hyperuricemia and hypocalcemia). The treatment used was effective and based on what the medical literature recommended

Síndrome de DRESS asociado a alopurinol con fracaso renal agudo: a propósito de un caso / DRESS syndrome associated with alopurinol with acute kidney injury: a case report

Introducción: El síndrome de DRESS es una reacción mucocutánea y visceral grave provocada por fármacos que puede llegar a provocar la muerte por la afectación de hígado y riñón.Caso Clínico: Varón de 46 años que presentó un exantema generalizado no pruriginoso, junto con fiebre, síntomas digestivos, adenopatías cervicales y sudoración nocturna coincidiendo con la toma previa de alopurinol. Tras el ingreso en el hospital se le diagnostica hepatitis aguda y deterioro de la función renal con oliguria, necesitando realización de hemodiálisis urgente. Tras un tratamiento multidisciplinar entre los servicios de nefrología, digestivo y hematología, el paciente es dado de alta con mejora de su función renal, pero continúa en seguimiento ambulatorio.Conclusiones: El alopurinol, fármaco muy utilizado en la práctica clínica, puede tener reacciones adversas muy graves, poniendo en riesgo la vida del paciente.El síndrome de DRESS, al ser muy poco frecuente, no tiene un tratamiento estandarizado. En el caso concreto de nuestro paciente, una detección temprana, junto a un tratamiento efectivo, con recambios plasmáticos con albúmina, hemodiálisis y corticoides, propiciaron una evolución favorable del paciente, con recuperación de la función renal. (AU)

Introduction: DRESS syndrome is a severe drug-induced mucocutaneous and visceral reaction that can be fatal due to liver and kidney damage. Case report: A 46-year-old man developed a generalised, non-pruritic rash, together with fever, digestive symptoms, cervical lymphadenopathy and night sweats coinciding with the previous intake of allopurinol. On hospital admission, he was diagnosed with acute hepatitis and deterioration of renal function including oliguria, requiring urgent hemodialysis. After a multidisciplinary treatment by the nephrology, digestive and haematology departments, the patient was discharged with an improvement in renal function, although he continued to be monitored on an ambulatory service. Conclusions: Allopurinol, a widely used drug in clinical prac-tice, can cause severe and life-threatening adverse reactions.DRESS syndrome, being very rare, has no standardised treat-ment. Specifically in the case of the patient, early detection, combined with effective treatment, including plasma replace-ment with albumin, hemodialysis and corticosteroids, favou-rably influenced the patient’s evolution, with recovery of renal function. (AU)

Hyperuricemia and chronic kidney disease: to treat or not to treat / Hiperuricemia e doença renal crônica: tratar ou não tratar

Abstract Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.

Resumo A hiperuricemia é comum na doença renal crônica (DRC) e pode estar presente em até 50% dos pacientes que se apresentam para diálise. A hiperuricemia pode ser secundária ao comprometimento da taxa de filtração glomerular (TFG) que ocorre na DRC. No entanto, ela também pode preceder o desenvolvimento da doença renal e mesmo prever uma DRC incidente. Estudos experimentais de modelos hiperuricêmicos descobriram que tanto o ácido úrico solúvel quanto o cristalino podem causar danos renais significativos, caracterizados por isquemia, fibrose tubulointersticial e inflamação. Entretanto, a maioria dos estudos de randomização Mendeliana falhou em demonstrar uma relação causal entre o ácido úrico e a DRC, e os ensaios clínicos têm apresentado resultados variáveis. Aqui sugerimos explicações potenciais para os achados clínicos e genéticos negativos, incluindo o papel do ácido úrico cristalino, do ácido úrico intracelular e da atividade da xantina oxidase na lesão renal mediada por ácido úrico. Propomos ensaios clínicos futuros, bem como um algoritmo para o tratamento de hiperuricemia em pacientes com DRC.

Estudio de utilización de fármacos antigotosos en población colombiana, 2016 / Patterns of anti-gout drug use in a Colombian population: 2016

RESUMEN Objetivo: Identificar las características clínicas de los pacientes con gota y la forma de utilización de los medicamentos antigotosos en Colombia. Métodos: Estudio de corte transversal en el que se analizaron 310 historias clínicas de pacientes atendidos en el último trimestre del 2016 y que recibieron un medicamento antigotoso. Se identificaron variables sociodemográficas, clínicas, farmacológicas, comorbilidades y paraclínicas. Para cada medicamento antigotoso se determinó si el uso fue según las recomendaciones aprobadas por la Federal Drug Administration (FDA). Se realizaron análisis descriptivos, bivariados y multivariados. Resultados: Se evaluaron pacientes de 14 diferentes ciudades de Colombia, con un predominio masculino del 70,3% (n = 218) y una mediana de edad de 64 arios (RIC: 26-94 arios). El antigotoso más frecuentemente utilizado fue alopurinol (n = 255; 82,3%), seguido de colchicina (n = 54; 17,4%). Los diagnósticos hallados como indicación fueron: hiperuricemia (n = 181; 58,4%), gota (n = 34; 11%), artritis gotosa (n = 28; 9%). El 74,5% (n = 231) de las prescripciones tenía un uso aprobado según la FDA, especialmente alopurinol en el manejo de gota e hiperuricemias, mientras que colchicina se encontró siendo utilizada en indicaciones no aprobadas (n = 44; 81,4%). Las comorbilidades más frecuentes fueron hipertensión (68,4%) y dislipidemia (55,8%). Conclusiones: Los pacientes con gota en tratamiento farmacológico tienen una elevada frecuencia de comorbilidades cardiovasculares, y están siendo tratados con alopurinol para la prevención a largo plazo, mientras que una menor proporción recibe colchicina que comúnmente es utilizada para indicaciones no aprobadas por las agencias reguladoras.

ABSTRACT Objective: To identify the clinical characteristics of patients with gout, and the prescription patterns of anti-gout medications in Colombia. Methods: Cross-sectional study, that analysed the data from 310 medical records of patients treated in the last quarter of 2016, and who received an anti-gout medication. Sociodemographic, clinical, pharmacological, comorbidities, and paraclinical variables were identified. For each anti-gout drug used, it was determined whether the use was in accordance with Federal Drug Administration (FDA) approved recommendations. Descriptive, bivariate and multivariate analyses were performed. Results: Patients from 14 different cities in Colombia were evaluated, with a male predominance of 70.3% (n = 218) and a median age of 64 years (RIC: 26-94 years). The most frequently used anti-gout medication was allopurinol (n = 255; 82.3%), followed by colchicine (n = 54; 17.4%). The main diagnoses found as an indication were: hyperuricaemia (n=181, 58.4%), gout (n = 34; 11.0%), and gouty arthritis (n = 28; 9.0%). Almost three-quarters (74.5%; n = 231) of the prescriptions had an approved use according to the FDA, especially allopurinol in the management of gout and hyperuricaemia, while colchicine was found to be used in unapproved indications (n = 44, 81.4%). The most frequent comorbidities were hypertension (68.4%) and dyslipidaemia (55.8%). Conclusions: Patients with gout who are under pharmacological treatment have a high frequency of cardiovascular comorbidities. They were being treated with allopurinol for long-term prevention, while a smaller proportion received colchicine, which is often used for indications not approved by regulatory agencies.

Síndrome Dress relacionada ao uso de Alopurinol: relato de caso / Dress Syndrome related to the use of allopurinol: case report

A síndrome DRESS é uma reação adversa a medicamentos pouco conhecida dentro da prática clínica, porém com grande potencial de letalidade devido a combinação de manifestações cutâneas e envolvimento de múltiplos órgãos. Objetivo: identificar possíveis reações adversas graves e incomuns secundárias ao uso de medicações usadas frequentemente na prática clínica. Métodos: Trata-se de um relato de caso construído com base em levantamento de dados do prontuário do paciente e análise a partir de um referencial teórico para comprovação de sua relevância na prática clínica. Resultado: Enfatizou-se a importância de um reconhecimento precoce dessa condição, a fim de evitar desfechos graves

The DRESS syndrome is an adverse drug reaction that is unsual in clinical practice, but with a high potential for lethality, due to the combination of cutaneous manifestations and involvement of multiple organs. Objective: identify possible serious and unusual adverse reactions secondary to the use of medications frequently used in clinical practice. Methods: This is a case report built on the basis of data collection from the patient's medical record and analysis from a theoretical framework to prove its source in clinical practice. Outcome: The importance of early recognition of this condition was emphasized, in order to avoid serious outcomes

Síndrome de DRESS secundario a alopurinol / DRESS syndrome secondary to allopurinol

RESUMEN El síndrome de hipersensibilidad por fármacos, también conocido como síndrome de DRESS, es una farmacodermia grave que se caracteriza por una erupción polimorfa diseminada, fiebre y compromiso multiorgánico. Este padecimiento tiene una incidencia que oscila entre el 0,1 % y el 0,01 % de las exposiciones farmacológicas, con una probabilidad de fallecimiento de un 20 % al 30 %. Fue descrito por primera vez en el año 1936, como una reacción adversa a la fenitoína. En la actualidad se reconoce que puede estar asociado a otros fármacos como: abacavir, metronidazol, doxiciclina, isoniazida, carbamacepina, fenobarbital, beta-bloqueadores, dapsona, ranitidina, antiinflamatorios no esteroideos y el alopurinol. Se presenta un paciente de 69 años de edad que desarrolló un síndrome de DRESS secundario a alopurinol. El paciente mostró signos poco frecuentes de esta rara enfermedad: linfocitos atípicos, hepatomegalia y afección renal; falleció poco después debido a un choque séptico por estafilococo áureo.

ABSTRACT Drug hypersensitivity syndrome, also known as DRESS syndrome, is a severe pharmacodermia characterized by a polymorphous disseminated rash, fever, and multi-organ involvement. Its incidence ranges between 0.1 to 0.01% from the pharmacological exposures, with a probability of death ranging from 20 to 30%. It was first described in 1936 as an adverse reaction to phenytoin. Nowadays, it is known that it can also be associated with other drugs such as abacavir, metronidazole, doxycycline, isoniazid, carbamazepine, phenobarbital, beta-blockers, dapsone, ranitidine, nonsteroidal anti-inflammatory drugs and allopurinol. We present a 69-year-old male patient who developed a DRESS syndrome secondary to alupurinol. The patient showed unusual signs of this rare disease such as atypical lymphocytes, hepatomegaly and kidney disease; he dies shortly after from a septic shock due to Staphylococcus aureus.

Síndrome DRESS / DRESS syndrome

Resumen: El síndrome DRESS es un reacción de hipersensibilidad a fármacos severa e idiosincrásica, caracterizada por exantema, fiebre, adenopatías, alteraciones hematológicas y afectación de varios órganos. La heterogeneidad de la manifestación clínica representa un desafío diagnóstico para el médico clínico, se requiere alto índice de sospecha y descartar un amplio espectro de diagnósticos diferenciales. Las reacciones cutáneas asociadas con fármacos pueden ser cuadros potencialmente mortales, el diagnóstico oportuno puede modificar el pronóstico del paciente. Describimos el cuadro clínico y tratamiento de un paciente de 15 años con insuficiencia renal crónica que fue hospitalizado por lesiones morbiliformes generalizadas concomitantes con fiebre, linfadenopatías, esplenomegalia y eosinofilia. Descartar procesos infecciosos, autoinmunitarios y neoplásicos fue posible con estudios complementarios; el antecedente de ingestión reciente de alopurinol y los datos clínicos y de laboratorio permitieron establecer el diagnóstico definitivo de síndrome DRESS. El paciente recibió corticoesteroides tópicos y sistémicos, las manifestaciones clínicas revirtieron a partir de la segunda semana de hospitalización. Se insiste en la importancia de la identificación de factores de riesgo asociados con la aparición de este síndrome.

Abstract: Dress syndrome is a severe and idiosyncratic reaction of hypersensitivity to drugs, characterized by rash, fever, lymphadenopathy, hematological alterations and systemic compromise, the heterogeneity of the clinical presentation represents a diagnostic challenge for the clinician, a high clinical suspicion is required and the need to rule out a wide spectrum of differential diagnoses. Cutaneous reactions associated with drugs can be potentially fatal, early diagnosis can modify the patient's prognosis. We describe the clinical case and treatment of a 15-year-old male patient with chronic renal failure who was hospitalized for generalized morbilliform lesions associated with fever, lymphadenopathy, splenomegaly and eosinophilia. Complementary studies ruled out infectious, autoimmune and neoplastic processes; the antecedent of recent intake of allopurinol together with clinical and laboratory data allowed to establish a definitive diagnosis of DRESS syndrome. Patient received topical and systemic corticosteroids, clinical manifestations reverted from the second week of hospitalization. We emphasize the importance of identifying risk factors associated with the development of this syndrome.

Hiperuricemia e hipertensión arterial sistémica: ¿cuál es la relación? / Hyperuricemia and systemic arterial hypertension: what is the relationship?

Resumen El ácido úrico es producto final del metabolismo de las purinas, transformadas finalmente a ácido úrico. No existe definición universal de hiperuricemia, en la práctica, el punto de corte es a partir de 6.8 mg/dL en plasma. Estudios experimentales han demostrado una correlación positiva lineal entre la presión arterial y las concentraciones de ácido úrico, así como disminución de las cifras tensionales al administrar tratamiento hipouricemiante con alopurinol. Se han identificado numerosos mecanismos a través de los cuales la hiperuricemia puede causar hipertensión: reducción de las concentraciones de óxido nítrico endotelial, estimulación de estrés oxidativo, expresión en las células de músculo liso del endotelio vascular de receptor URAT-1, activación del eje renina angiotensina, estimulación de la proliferación de músculo liso vascular, además, favorece la enfermedad microvascular renal. La evidencia reciente ha aportado nuevo conocimiento acerca de los múltiples mecanismos a través de los cuales el ácido úrico tendría un papel preponderante en la hipertensión arterial sistémica y en múltiples alteraciones metabólicas; sin embargo, hace falta desarrollar estudios clínicos a gran escala, bien diseñados, que comprueben de manera más contundente estas teorías, antes de considerar tratamientos enfocados en el manejo de la hiperuricemia asintomática en la práctica clínica diaria.

Abstract Uric acid is the end product of purine metabolism, ultimately converted to uric acid. There is no universal definition of hyperuricemia, in practice, the cutoff point is from 6.8mg/dL in plasma. The relationship between hyperuricemia and hypertension has been demonstrated in many experimental studies. Experimental studies have shown a linear positive correlation between blood pressure and uric acid levels, as well as a decrease in blood pressure figures with therapy with allopurinol. Numerous mechanisms have been identified through which hyperuricemia can cause hypertension: reduction of endothelial nitric oxide levels, stimulation of oxidative stress, expression in smooth muscle cells of the vascular endothelium of URAT-1 receptor, activation of the renin-angiotensin axis, stimulation of vascular smooth muscle proliferation also favors the development of renal microvascular disease. Recent evidence has provided new insight into the multiple mechanisms through which UA would play a major role both in systemic arterial hypertension and in multiple metabolic alterations; however, large-scale, well-designed clinical studies are needed, which prove more conclusively these theories, before considering therapies focused on the management of asymptomatic hyperuricemia in daily clinical practice

The effect of some medications given to CKD patients on vitamin D levels.

BACKGROUND: Vitamin D deficiency and polypharmacy is a common problem over chronic kidney disease (CKD) population. OBJECTIVES: To assess the clinical and analytical characteristics of CKD patients with 25-OH-D3 deficiency (<15 ng/mL), including the possible role of associated drugs. METHODS: A single center observational review of 137 incident patients referred to our outpatient clinic with different stages of CKD and 25-OH-D3<15ng/mL (male gender 53.3%, mean age 70.8 [±16.1] years, mean GFR (MDRD-4) 43.6 [±25.5] ml/min/1.73 m²). 25-OH-D3 levels were collected in spring. Clinical and biochemical data and associated medications were recorded. RESULTS: Mean 25-OH-D3 levels were 8.23 [±4.03] ng/ml. Eighty-eight patients (64.7%) had 3 or more concomitant drugs. Only 7 patients (5.1%) were not receiving any medication. Patients were divided in three groups according the therapies into none (n=26), RAS inhibitors or allopurinol (n=81), and RAS inhibitors plus allopurinol (n=30); with the aim to study the influence of statin therapy. Patients under renin angiotensin (RAS) inhibitors or Allopurinol treatment presented significantly higher 25-OH-D3 levels (p=0.001 and p=0.01 respectively), however patients with Statins treatment had lower 25-OH-D3 level (p=0.039). Personal history of diabetes, cardiovascular events or other therapies did not modify 25-OH-D3 levels, adjusted by age and eGFR. CONCLUSIONS: CKD patients with vitamin D deficiency who received RAS inhibitors or Allopurinol treatment had higher 25-OH-D3 levels, however those with statins treatment had lower vitamin D levels. Randomized controlled trials are required to confirm these findings.

What is the effect on cardiovascular events of reducing hyperuricemia with allopurinol? An evidence-based review.

INTRODUCTION: High levels of uric acid (UA) have been associated with cardiovascular (CV) disease, but its role as an independent risk factor is the subject of debate. Treating hyperuricemia may be useful in reducing CV risk. OBJECTIVE: To review the evidence on the effect of treatment with allopurinol in patients with hyperuricemia on reducing CV events. METHODS: We searched medical databases for randomized controlled trials (RCT), cohort studies (CS) and case-control studies (CCS), meta-analyses, systematic reviews and guidelines, published between January 2002 and December 2013 in Portuguese and English. Level of evidence (LE) and strength of recommendation were graded according to the definitions used by the European Society of Cardiology. RESULTS: Out of 46 articles, one RCT, three CS and one CCS were included. In the RCT, treatment with allopurinol decreased CV events in patients with moderate chronic renal failure by 71% compared to controls (LE B). In one CS, patients treated with high doses had a greater reduction in CV events compared to low doses (LE B). The other two CS, in patients with heart failure (HF), found similar benefits in patients treated with high doses of allopurinol (LE B). In the CCS, in patients with HF and a history of gout, treatment with allopurinol reduced HF admission and all-cause mortality (LE B). DISCUSSION AND CONCLUSIONS: Prolonged treatment with high doses of allopurinol may be associated with a reduction in morbidity and mortality in high CV risk populations (class of recommendation IIa). More studies evaluating the effect of therapy with allopurinol in reducing CV events in patients with and without risk are needed.

Papel del alopurinol en las adherencias peritoneales al colocar una malla de polipropileno: Estudio experimental en ratas / Role of alopurinol in peritoneal adherences when placing a polypropylene mesh: Experimental study in rats

Objetivo: Determinar el efecto del alopurinol en las adherencias peritoneales al colocar una malla de polipropileno. Sede: Cirugía Experimental de la Universidad de Guanajuato. Diseño: Estudio experimental, prospectivo, comparativo, controlado, doble ciego, con asignación al azar. Análisis estadístico: χ². Material y métodos: Se compararon dos grupos de 30 ratas Wistar cada uno, a quienes se les colocó una malla de polipropileno: el grupo A, sin tratamiento versus el grupo B, alopurinol a 25 mg/kg/día por sonda orogástrica. Resultados: Este estudio determinó que la prevalencia de adherencias protésicas-peritoneales viscerales en ratas Wistar, al colocar una malla de polipropileno, es del 100% sin tratamiento y con alopurinol. Conclusiones: No obtuvimos diferencia estadística del efecto beneficioso del alopurinol en la prevención de adherencias, esto puede hablarnos de que la acción del alopurinol sólo se ejerce en la prevención de adherencias cuando su etiología es la isquemia y no debido a la presencia de reacción a cuerpo extraño de tipo granulomatoso.

Objective: To determine the effect of allopurinol on peritoneal adhesions when placing a polypropylene mesh. Setting: Experimental Surgery Unit of the University of Guanajuato, México. Design: Experimental, prospective, comparative, controlled, double-blinded, randomized assignment study. Statistical analysis: χ². Material and Methods: We compared two groups of 30 Wistar rats each, in which we placed a polypropylene mesh: Group A, without treatment, versus group B with allopurinol at mg/kg per day administered through an orogastric catheter. Results: This study determined that the prevalence of visceral peritoneal-prosthetic adhesions in Wistar rats when placing a polypropylene mesh is of 100% with and without allopurinol treatment. Conclusions: We did not obtain statistical differences of the beneficial effect of allopurinol in preventing adhesions, this can indicate that allopurinol's effect is only exerted in preventing adhesions when they are due to ischemia but not when they are caused by a granulomatous-type foreign body reaction.

Propriedades micromeríticas e análise físico-química de matérias-primas de alopurinol / Micromeritic properties and physicochemical analysisof allopurinol raw materials

O controle de qualidade de matérias-primas é imprescindível, pois visa assegurar a qualidade do produto acabado. O objetivo do trabalho foi avaliar a qualidade físico-química e farmacotécnica de matérias-primas de alopurinol, fármaco utilizado para a prevenção e o tratamento de crises de gota, amplamente prescrito e produzido por indústrias e farmácias magistrais. As amostras (A, B, C e D) de alopurinol oriundas de diferentes fornecedores foram submetidas a ensaios farmacopeicos (características organolépticas; solubilidade; ensaios de identificação: teste de precipitação e varredura no UV; ensaios de pureza: limpidez de solução, perda por dessecação, cinzas sulfatadas; doseamento), análise térmica (DSC, TG), análise granulométrica e determinação das propriedades de fluxo (ângulo de repouso, densidade bruta e de compactação, fator de Hausner, índice de compressibilidade e compactabilidade). As amostras foram aprovadas em todos os ensaios farmacopeicos. Nas curvas de DSC, o ponto de fusão foi de cerca de 380 °C para todas as amostras e, após a fusão houve a degradação, confirmada pelas curvas TG, com uma perda de massa de aproximadamente 100 %. A partir da distribuição granulométrica as amostras A e B foram classificadas como pós finos e as C e D como finíssimos. Os valores de ângulo de repouso caracterizaram as amostras A, B, C e D como de fluxo fraco e, o fator de Hausner e índice de compressibilidade caracterizaram as amostras como amostras de fluxo bastante deficiente. Os ensaios demonstraram-se úteis para avaliar a qualidade das amostras. A adição de adjuvantes apropriados durante o preparo das formulações de alopurinol é essencial para melhoramento do fluxo.

The quality control of raw materials is intended to ensure the quality of the finished product. The objective of this study was to carry out physicochemical and pharmacotechnical assessments of allopurinol raw materials. This drug is widely prescribed for the prevention and treatment of gout and is produced both by drug manufacturers and compounding pharmacies. Samples (A, B, C and D) from 4 different suppliers were subjected to pharmacopoeial testing (organoleptic characteristics; solubility; identification tests: precipitation and scanning UV; purity tests: clarity of solution, loss on drying, sulphated ash; assay), thermal analysis (DSC, TG), particle size analysis and flow property tests (angle of repose, bulk density and tapped density, Hausner ratio, compressibility and compactibility). The samples were approved in all the pharmacopoeial tests. In the DSC curves, the melting point was about 380 °C for all samples and after fusion there was degradation, confirmed by TG, with a weight loss of approximately 100%. From the particle size distributions, samples A and B were classified as fine powders and C and D as very fine powders. The angles of repose characterized the samples A, B, C and D as having weak flow, while the Hausner ratio and compressibility index indicated that they had very, very poor flow. The tests proved useful for assessing the quality of the samples and showed that appropriate adjuvants need to be added to the allopurinol formulations to improve the flow.

El pretratamiento con alopurinol disminuye la translocación bacteriana y atenúa los cambios morfológicos de la mucosa intestinal en un modelo de isquemia-reperfusión intestinal en ratas / Pretreatment with allopurinol reduces bacterial translocation and ameliorates the morphological changes of the intestinal mucosa in an intestinal ischemia-reperfusion rat model

Objetivo. Evaluar el efecto protector contra la lesión por isquemia-reperfusión intestinal del pretratamiento con alopurinol en ratas. Materiales y métodos. Se llevó a cabo un experimento controlado en animales. Un grupo de 10 ratas Wistar de características morfométricas comparables se mantuvo en bioterio bajo condiciones controladas por tres días. A cinco animales se les administró 50 mg/kg diarios de alopurinol por vía oral durante los tres días y, una dosis adicional, antes de inducir isquemia intestinal por ligadura quirúrgica durante 60 minutos seguida de 60 minutos de reperfusión. El otro grupo de cinco ratas no recibió el medicamento. Se hizo el análisis histológico de la mucosa intestinal al final del experimento por medio de la clasificación de Chou y se tomaron hemocultivos de la cavidad cardiaca. Resultados. Se encontraron hemocultivos positivos en 20 % de los animales pretratados con alopurinol, en comparación con el 100 % de las ratas control (p<0,0001). Se evidenció lesión profunda en la mucosa intestinal en todos los casos. La administración previa a la injuria de alopurinol redujo significativamente la lesión por isquemia-reperfusión (p<0,001). Conclusiones. La administración de alopurinol antes de la isquemia intestinal, reduce los cambios morfológicos ocasionados por isquemia-reperfusión. El efecto benéfico se demostró con el pretratamiento por tres días.

Objective: To evaluate the protective effect of pretreatment with allopurinol in an intestinal ischemia-reperfusion injury rat model. Materials and methods: A controlled animal trial was conducted; 10 Wistar rats were kept under controlled conditions for three days. One group (n=5) received allopurinol 50 mg/kg per day for the 3-day period and an additional dose immediately prior to surgical mesenteric artery clamping (60 minutes) and reperfusion (60 minutes). The other group (n=5) did not receive the medication. Hystologic analysis of intestinal mucosa by means of Chou grading system was performed, and blood cultures from the heart were withdrawn. Results: Positive blood cultures were found in 20% of the allopurinol group as compared with 100% in the control group (p<0.0001). Deep mucosal lesion was evidence in all cases. Allopurinol pretreatment reduced significantly the ischemia-reperfusion injury (p<0.001). Conclusions: Allopurinol administration prior to intestinal ischemia ameliorated morphologic changes related to the ischemia-reperfusion process. The beneficial effect of allopurinol was demonstrated with pretreatment for three days.

Necrólise epidérmica tóxica desencadeada por alopurinol: relatode caso / Toxic epidermal necrolysis initiated by allopurinol: case report

JUSTIFICATIVA E OBJETIVOS: A necrólise epidérmica tóxica (NET) é uma farmacodermia rara, com possibilidade de morte pelas suas complicações. O objetivo deste relato foi apresentar um caso desta farmacodermia devido ao uso de alopurinol, um medicamento de uso comum. RELATO DO CASO: Paciente do sexo masculino, 65 anos, apresentou o quadro após utilização de alopurinol concomitante a uso pregresso de grande quantidade de álcool diariamente,anti-hipertensivos e diclofenaco irregularmente. Admitido no serviço com lesões descamativas de aspecto de grande queimado em mais de 50% do corpo, dispneia, taquicardia, hematúria macroscópica e conjuntivite bolhosa. O paciente foi tratado na unidade de terapia intensiva, com suspensão da medicação e teve boa evolução, com resolução total do quadro após 32 dias do seu início. CONCLUSÃO: O tratamento para NET ainda não é consensual, assim como a suspensão do medicamento que a originou. Entretanto, cuidados preferencialmente em unidades de queimado e prevenção e profilaxia com antibióticos para infecções são essenciais para uma boa evolução. O conhecimento médico sobre esta rara síndrome e sobre o seu tratamento adequado pode fazer a diferença no diagnóstico diferencial e na sua conduta.

BACKGROUND AND OBJECTIVES: Epidermal toxic necrolysis (TEN) is a rare dermatological reaction to drugs, feasible to death due to medical complications. This article reports a caseof such reaction due to the use of allopurinol, a rather common drug.CASE REPORT: Male patient, 65 year old, presenting the reaction after the use of allopurinol along with previous daily ingestion of great amounts of alcohol, antihypertensive medications, and irregular diclofenac. He was admitted with desquamating lesions similar to skin burns in over 50% of body surface, dyspnea, tachycardia, macroscopic hematuria and bullosa conjunctivitis.The patient was taken care of in the Intensive Care Unit, his medication was suspended and he improved importantly, resolving the reaction after 32 days since its initial development. CONCLUSION: There is no consensus for the treatment of TEN, a neither as for the medication suspension. However, intensive care in burns unit and prevention and prophylaxis with antibiotics for infections are essential for good resolution. Knowing such rare syndrome and its adequate treatment might makethe difference during the differential diagnosis and conducts.

Physicochemical characterization and solubility enhancement studies of allopurinol solid dispersions / Caracterização físico-química e estudos de solubilidade de melhoria de dispersões sólidas de alopurinol

Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with treatment of diuretic conditions. One of the major problems with the drug is that it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation, kneading method, co-precipitation method, co-grinding method and closed melting methods to increase its water solubility. Hydrophilic carriers such as polyvinylpyrrolidone, polyethylene glycol 6000 were used in the ratio of 1:1, 1:2 and 1:4 (drug to carrier ratio). The aqueous solubility of allopurinol was favored by the presence of both polymers. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, powder X-ray diffraction, UV and Fourier Transform Infrared spectroscopy. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure allopurinol, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. Solid dispersion prepared with polyvinylpyrrolidone showed highest improvement in wettability and dissolution rate of allopurinol. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the present study showed that polyvinylpyrrolidone and polyethylene glycol 6000 have a significant solubilizing effect on allopurinol.

Alopurinol é fármaco comumente utilizado no tratamento de gota crônica ou hiperuricemia associada com o tratamento em condições diuréticas. Um dos maiores problemas com o fármaco é que este é praticamente insolúvel em água, o que resulta em baixa biodisponibilidade na administração oral. No presente estudo, dispersões sólidas de alopurinol foram preparadas pela evaporação do solvente, pelos métodos de amassamento, de coprecipitação, de comoagem e fusão fechada para aumentar sua solubilidade em água. Transportadores hidrofílicos, como polivinilpirrolidona, polietilenoglicol 6000 foram utilizados nas proporções de 1:1. 1:2 e 1:4 (fármaco: transportador). A solubilidade aquosa do alopurinol foi favorecida pela presença de ambos os polímeros. Estas novas formulações forma caracterizadas no estado líquido pelos estudos de solubilidade de fase e no estado sólido pela calorimetria diferencial de varredura, difração de Raio-X, espectroscopia de UV e de IV com transformada de Fourier. As caracterizações do estado sólido indicaram que o alopurinol estava presente como material amorfo e embebido em matriz polimérica. Ao contrário da velocidade de dissolução lenta do alopurinol puro, a dispersão do fármaco nos polímeros aumentou consideravelmente a taxa de dissolução. A dispersão sólida preparada com polivinilpirrolidona mostrou as maiores melhorias na molhabilidade e taxa de dissolução do alopurinol. A modelagem matemática dos dados da dissolução in vitro indicou o melhor ajuste ao modelo de Korsemeyer-Peppas e a cinética de liberação do fármaco primariamente como difusão não-Fickiana. Assim, o presente estudo mostrou que a polivinilpirrolidona e o polietilenoglicol 6000 têm efeito significativo na solubilização do alopurinol.