RESUMEN
Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy that can progress, when untreated, to end-stage renal disease. Most frequently, aHUS is caused by complement dysregulation due to pathogenic variants in genes that encode complement components and regulators. Among these genes, the factor H (FH) gene, CFH, presents with the highest frequency (15% to 20%) of variants and is associated with the poorest prognosis. Correct classification of CFH variants as pathogenic or benign is essential to clinical care but remains challenging owing to the dearth of functional studies. As a result, significant numbers of variants are reported as variants of uncertain significance. To address this knowledge gap, we expressed and functionally characterized 105 aHUS-associated FH variants. All FH variants were categorized as pathogenic or benign and, for each, we fully documented the nature of the pathogenicity. Twenty-six previously characterized FH variants were used as controls to validate and confirm the robustness of the functional assays used. Of the remaining 79 uncharacterized variants, only 29 (36.7%) alter FH expression or function in vitro and, therefore, are proposed to be pathogenic. We show that rarity in control databases is not informative for variant classification, and we identify important limitations in applying prediction algorithms to FH variants. Based on structural and functional data, we suggest ways to circumvent these difficulties and, thereby, improve variant classification. Our work highlights the need for functional assays to interpret FH variants accurately if clinical care of patients with aHUS is to be individualized and optimized.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/genética , Factor H de Complemento/genética , Síndrome Hemolítico Urémico Atípico/metabolismo , Síndrome Hemolítico Urémico Atípico/patología , Factor H de Complemento/química , Factor H de Complemento/metabolismo , Expresión Génica , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Modelos Moleculares , Mutación Puntual , Polimorfismo de Nucleótido Simple , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
aHUS is a rare disease characterized by episodes of TMA that frequently progresses to CKD and often recurs after KT. The most frequent cause of aHUS is defective regulation of complement activation because of genetic anomalies. Eculizumab interrupts the process of TMA and improves renal function. We describe one female patient with aHUS who debuted in 2005 at 3-mo-old with extrarenal manifestations and progressed to end-stage kidney disease (ESKD) within a year. Her family history included several affected members with similar bad outcomes. Our patient carries a strong aHUS genetic predisposition consisting in a pathogenic gain-of-function mutation in complement factor B concurrent with the MCP aHUS risk haplotype MCPggaac. She received a kidney transplant in 2011 without eculizumab prophylaxis. The graft, which was negative for the MCPggaac risk haplotype, had an unexpected excellent evolution without aHUS recurrence. Different retrospective studies have shown that the risk of aHUS recurrence after KT correlates well with the genetic load of aHUS risk factors. Knowing important contribution of the MCPggaac risk haplotype to the risk of developing aHUS in Factor B mutations carriers, we speculate whether the absence of this polymorphism in the graft that our patient received may have decreased the risk of aHUS recurrence after KT.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/genética , Trasplante de Riñón , Proteína Cofactora de Membrana/genética , Polimorfismo Genético , Femenino , Humanos , Lactante , Linaje , Medición de RiesgoRESUMEN
Complement overactivation has been reported in most patients with Barraquer-Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p < 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient's adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment.
Asunto(s)
Factor D del Complemento/metabolismo , Lipodistrofia/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/complicaciones , Proteínas del Sistema Complemento/genética , Hipertensión Maligna/epidemiología , Índice de Severidad de la Enfermedad , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/terapia , Inactivadores del Complemento/uso terapéutico , Femenino , Humanos , Hipertensión Maligna/diagnóstico , Hipertensión Maligna/genética , Hipertensión Maligna/terapia , Incidencia , Masculino , Persona de Mediana Edad , Plasmaféresis , Estudios Retrospectivos , Adulto JovenRESUMEN
Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy caused by complement pathogenic variants, mainly affects the kidney microvasculature. A retrospective genetic analysis in our aHUS cohort (n=513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene (CFHR1) that originates by recurrent gene conversion events between the CFH and CFHR1 genes. The novel CFHR1 mutants encode an FHR-1 protein with two amino acid substitutions, L290S and A296V, converting the FHR-1 C terminus into that of factor H (FH). Next-generation massive-parallel DNA sequencing (NGS) analysis did not detect these genetic abnormalities. In addition to the CFHR1 mutant, six patients carried the previously uncharacterized CFH-411T variant. In functional analyses, the mutant FHR-1 protein strongly competed the binding of FH to cell surfaces, impairing complement regulation, whereas the CFH-411T polymorphism lacked functional consequences. Carriers of the CFHR1 mutation presented with severe aHUS during adulthood; 57% of affected women in this cohort presented during the postpartum period. Analyses in patients and unaffected carriers showed that FH plasma levels determined by the nonmutated chromosome modulate disease penetrance. Crucially, in the activated endothelial (HMEC-1) cell assay, reduced FH plasma levels produced by the nonmutated chromosome correlated inversely with impairment of complement regulation, measured as C5b-9 deposition. Our data advance understanding of the genetic complexities underlying aHUS, illustrate the importance of performing functional analysis, and support the use of complementary assays to disclose genetic abnormalities not revealed by current NGS analysis.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/genética , Proteínas Sanguíneas/genética , Proteínas Inactivadoras del Complemento C3b/genética , Factor H de Complemento/genética , Conversión Génica , Adulto , Unión Competitiva , Línea Celular , Factor H de Complemento/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Linaje , Penetrancia , Estudios Retrospectivos , Análisis de Secuencia de ADN/métodos , Adulto JovenRESUMEN
Genetic analyses in atypical hemolytic uremic syndrome (aHUS) and C3-glomerulopathy (C3G) patients have provided an excellent understanding of the genetic component of the disease and informed genotype-phenotype correlations supporting an individualized approach to patient management and treatment. In this context, a correct categorization of the disease-associated gene variants is critical to avoid detrimental consequences for patients and their relatives. Here we describe a comprehensive procedure to measure levels and functional activity of complement regulator factor H (FH) encoded by CFH, the commonest genetic factor associated with aHUS and C3G, and present the results of the analysis of 28 uncharacterized, disease-associated, FH variants. Sixteen variants were not expressed in plasma and eight had significantly reduced functional activities that impact on complement regulation. In total, 24 of 28 CFH variants were unambiguously categorized as pathogenic and the nature of the pathogenicity fully documented for each. The data also reinforce the genotype-phenotype correlations that associate specific FH functional alterations with either aHUS or C3G and illustrate important drawbacks of the prediction algorithms dealing with variants located in FH functional regions. We also report that the novel aHUS-associated M823T variant is functionally impaired. This was unexpected and uncovered the important contribution of regions outside the N-terminal and C-terminal functional domains to FH regulatory activities on surfaces. Thus, our work significantly advances knowledge towards a complete functional understanding of the CFH genetic variability and highlights the importance of functional analysis of the disease-associated CFH variants.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/genética , Activación de Complemento/genética , Variación Genética , Glomerulonefritis/genética , Adolescente , Adulto , Síndrome Hemolítico Urémico Atípico/sangre , Síndrome Hemolítico Urémico Atípico/diagnóstico , Síndrome Hemolítico Urémico Atípico/inmunología , Niño , Preescolar , Complemento C3/inmunología , Factor H de Complemento/genética , Factor H de Complemento/inmunología , Factor H de Complemento/metabolismo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Glomerulonefritis/sangre , Glomerulonefritis/diagnóstico , Glomerulonefritis/inmunología , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Dominios Proteicos , Sistema de Registros , Factores de Riesgo , España , Relación Estructura-Actividad , Adulto JovenRESUMEN
Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis. Identification of inherited complement abnormalities explained nine of the 22 cases, with CFH mutations and CFH to CFHR1 gene conversion events being the most prevalent genetic alterations associated with this disorder (66%). In thirteen of the cases, pregnancy complications were sufficient to trigger a thrombotic microangiopathy in the absence of genetic or acquired complement alterations. The postpartum period was the time with highest risk to develop the disease and the group shows an association of cesarean section with pregnancy-associated aHUS. Seventeen patients underwent plasma treatments with a positive renal response in only three cases. In contrast, ten patients received eculizumab with an excellent renal response in all, independent of carrying or not inherited complement abnormalities. Although the cohort is relatively small, the data suggest that pregnancy-associated aHUS is not different from other types of aHUS and suggest the efficacy of eculizumab treatment over plasma therapies. This study may be useful to improve prognosis in this group of aHUS patients.
Asunto(s)
Síndrome Hemolítico Urémico Atípico , Complicaciones del Embarazo , Microangiopatías Trombóticas , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/epidemiología , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/inmunología , Síndrome Hemolítico Urémico Atípico/terapia , Cesárea , Activación de Complemento , Proteínas Inactivadoras del Complemento C3b/genética , Factor H de Complemento/genética , Femenino , Conversión Génica , Humanos , Inmunosupresores/uso terapéutico , Mutación , Paridad , Intercambio Plasmático , Periodo Posparto , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/terapia , Sistema de Registros , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , España/epidemiología , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/genética , Microangiopatías Trombóticas/inmunología , Microangiopatías Trombóticas/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. METHODS: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. RESULTS: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. CONCLUSION: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.
Asunto(s)
Lesión Renal Aguda/terapia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Síndrome Hemolítico Urémico Atípico/complicaciones , Inactivadores del Complemento/administración & dosificación , Intercambio Plasmático , Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Adulto , Anciano , Síndrome Hemolítico Urémico Atípico/terapia , Femenino , Estudios de Seguimiento , Humanos , Riñón/efectos de los fármacos , Riñón/fisiología , Masculino , Persona de Mediana Edad , Diálisis Renal , Estudios Retrospectivos , Prevención Secundaria/métodos , Resultado del TratamientoAsunto(s)
Síndrome Hemolítico Urémico Atípico/diagnóstico , Síndrome Hemolítico Urémico Atípico/genética , Complemento C2/genética , Mutación con Ganancia de Función , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Autoanticuerpos/inmunología , Activación de Complemento/genética , Estudios de Asociación Genética/métodos , Factor 2 Liberador de Guanina Nucleótido/genética , Humanos , Mutación Missense , FenotipoRESUMEN
The complement system is one of the first defense lines protecting from invading pathogens. However, it may turn offensive to the body's own cells and tissues when deregulated by the presence of rare genetic variants that impair physiological regulation and/or provoke abnormal activity of key enzymatic components. Factor B and complement C2 are examples of paralogs engaged in the alternative and classical/lectin complement pathway, respectively. Pathogenic mutations in the von Willebrand factor A domain (vWA) of FB have been known for years. Despite substantial homology between two proteins and the demonstration that certain substitutions in FB translated to C2 result in analogous phenotype, there was a limited number of reports on pathogenic C2 variants in patients. Recently, we studied a cohort of patients suffering from rare kidney diseases and confirmed the existence of two gain-of-function and three loss-of-function mutations within the C2 gene sequences coding for the vWA domain (amino acids 254-452) or nearly located unstructured region (243-253) of C2 protein. Herein, we report the functional consequences of amino acid substitution of glutamine at position 263. The p.Q263G variant resulted in the gain-of-function phenotype, similarly to a homologous mutation p.D279G in FB. Conversely, the p.Q263P variant found in a patient with C3 glomerulopathy resulted in the loss of C2 function. Our results confirm that the N-terminal part of the vWA domain is a hot spot crucial for the complement C2 function.
Asunto(s)
Complemento C2 , Factor de von Willebrand , Factor de von Willebrand/genética , Factor de von Willebrand/metabolismo , Complemento C2/genética , Factor B del Complemento/genética , Mutación , Secuencia de BasesRESUMEN
Dysregulation of the alternative complement pathway is a major pathogenic mechanism in two rare renal diseases: atypical haemolytic uraemic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). We report on a 66-year-old male with chronic hepatitis C virus (HCV) infection and a combined liver-kidney transplant that was diagnosed with MPGN at the age of 63 years and a 5-year-old boy who presented with aHUS at the age of 21 months following a Streptococcus pneumoniae infection. Both patients carried similar frameshift variants in the complement CFHR5 gene that segregate with reduced levels of factor H-related 5 (FHR-5). We conclude that low FHR-5 levels may predispose to viral and bacterial infections that then trigger different renal phenotypes.
RESUMEN
BACKGROUND: Kidney transplantation (KTx) is a strong trigger for the development of either recurrent or de novo atypical haemolytic uraemic syndrome (aHUS). According to previous studies, eculizumab (ECU) is effective for prophylaxis and for treatment of recurrence. METHODS: We evaluated the experiences of Spanish patients with recurrent and de novo aHUS associated with KTx, treated or not treated with ECU. In the de novo group, we classified patients as having early de novo (during the first month) or late de novo aHUS (subsequent onset). RESULTS: We analysed 36 cases of aHUS associated with KTx. All of the 14 patients with pre-KTx diagnosis of aHUS were considered to have high or moderate risk of recurrence. Despite receiving grafts from suboptimal donors, prophylactic ECU was effective for avoiding recurrence. The drug was stopped only in two cases with low-moderate risk of recurrence and was maintained in high-risk patients with no single relapse. There were 22 de novo aHUS cases and 16 belonged to the early de novo group. The median time of onset in the late group was 3.4 years. The early group had a better response to ECU than the late group, probably due to earlier diagnosis and use of the drug. No genetic pathogenic variant was detected in de novo aHUS cases, suggesting a secondary profile of the disease. ECU was stopped in all de novo patients with no relapses. ECU was well tolerated in all cases. CONCLUSIONS: Both groups (pre-aHUS and de novo) presented different clinical profiles, management approaches and outcomes. One should consider aHUS regardless of time after KTx. Genetic studies are crucial to stratify risks of relapse and to determine necessary lengths of treatment. We suggest short ECU treatment for de novo cases without pathogenic mutation and that ECU treatment be considered pre-emptively for patients with moderate or high risk of recurrence.
RESUMEN
Haemolytic Uraemic Syndrome associated with Streptococcus pneumoniae infections (SP-HUS) is a clinically well-known entity that generally affects infants, and could have a worse prognosis than HUS associated to E. coli infections. It has been assumed that complement genetic variants associated with primary atypical HUS cases (aHUS) do not contribute to SP-HUS, which is solely attributed to the action of the pneumococcal neuraminidase on the host cellular surfaces. We previously identified complement pathogenic variants and risk polymorphisms in a few Hungarian SP-HUS patients, and have now extended these studies to a cohort of 13 Spanish SP-HUS patients. Five patients presented rare complement variants of unknown significance, but the frequency of the risk haplotypes in the CFH-CFHR3-CFHR1 region was similar to the observed in aHUS. Moreover, we observed desialylation of Factor H (FH) and the FH-Related proteins in plasma samples from 2 Spanish and 4 Hungarian SP-HUS patients. To analyze the functional relevance of this finding, we compared the ability of native and "in vitro" desialylated FH in: (a) binding to C3b-coated microtiter plates; (b) proteolysis of fluid-phase and surface-bound C3b by Factor I; (c) dissociation of surface bound-C3bBb convertase; (d) haemolytic assays on sheep erythrocytes. We found that desialylated FH had reduced capacity to control complement activation on sheep erythrocytes, suggesting a role for FH sialic acids on binding to cellular surfaces. We conclude that aHUS-risk variants in the CFH-CFHR3-CFHR1 region could also contribute to disease-predisposition to SP-HUS, and that transient desialylation of complement FH by the pneumococcal neuraminidase may have a role in disease pathogenesis.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/genética , Proteínas Sanguíneas/genética , Proteínas Inactivadoras del Complemento C3b/genética , Factor H de Complemento/genética , Infecciones Neumocócicas/complicaciones , Síndrome Hemolítico Urémico Atípico/microbiología , Preescolar , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Lactante , Masculino , Polimorfismo Genético , Streptococcus pneumoniaeRESUMEN
The impairment of the alternative complement pathway contributes to rare kidney diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). We recently described an aHUS patient carrying an exceptional gain-of-function (GoF) mutation (S250C) in the classical complement pathway component C2 leading to the formation of hyperactive classical convertases. We now report the identification of the same mutation and another C2 GoF mutation R249C in two other patients with a glomerulopathy of uncertain etiology. Both mutations stabilize the classical C3 convertases by a similar mechanism. The presence of R249C and S250C variants in serum increases complement-dependent cytotoxicity (CDC) in antibody-sensitized human cells and elevates deposition of C3 on ELISA plates coated with C-reactive protein (CRP), as well as on the surface of glomerular endothelial cells. Our data justify the inclusion of classical pathway genes in the genetic analysis of patients suspected of complement-driven renal disorders. Also, we point out CRP as a potential antibody-independent trigger capable of driving excessive complement activation in carriers of the GoF mutations in complement C2.
Asunto(s)
Proteína C-Reactiva/metabolismo , Complemento C2/genética , Complemento C3/metabolismo , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Mutación con Ganancia de Función , HumanosRESUMEN
Thrombotic microangiopathy (TMA) has different etiological causes, and not all of them are well understood. In atypical hemolytic uremic syndrome (aHUS), the TMA is caused by the complement dysregulation associated with pathogenic mutations in complement components and its regulators. Here, we describe a pediatric patient with aHUS in whom the relatively benign course of the disease confused the initial diagnosis. A previously healthy 8-year-old boy developed jaundice, hematuria, hemolytic anemia, thrombopenia, and mild acute kidney injury (AKI) in the context of a diarrhea without hypertension nor oliguria. Spontaneous and complete recovery was observed from the third day of admission. Persistent low C3 plasma levels after recovery raised the suspicion for aHUS, which prompted clinicians to discard the initial diagnosis of Shigatoxin-associated HUS (STEC-HUS). A thorough genetic and molecular study of the complement revealed the presence of an isolated novel pathogenic C3 mutation. The relatively benign clinical course of the disease as well as the finding of a de novo pathogenic C3 mutation are remarkable aspects of this case. The data are discussed to illustrate the benefits of identifying the TMA etiological factor and the relevant contribution of the MCP aHUS risk polymorphism to the disease severity.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/genética , Complemento C3/genética , Proteína Cofactora de Membrana/genética , Síndrome Hemolítico Urémico Atípico/diagnóstico , Niño , Humanos , Masculino , Mutación , Linaje , Polimorfismo de Nucleótido SimpleRESUMEN
Objetivo: Explorar los sentimientos, emociones y forma de celebrar de las personas participantes en la Navidad 2020-2021 condicionada por la pandemia de COVID-19. Método: La actividad se desarrolló en siete centros de Atención Primaria del Servicio Murciano de Salud, desde el 16 de diciembre de 2020 hasta el 7 de enero de 2021. Participaron voluntariamente las personas que acudieron a los centros en el período de estudio, anotando qué tenían de especial esas Navidades en cartulinas que decoraban un árbol de Navidad. Se hizo un análisis interpretativo del contenido de las frases escritas, y su posterior codificación y categorización. Resultados: Se recogieron 151 cartulinas escritas y se establecieron tres categorías: 1) desiderata navideña: tradición, normalidad y solidaridad; 2) las Navidades que nos han hecho valorar lo realmente importante; y 3) disposición para mejorar la resiliencia. Conclusiones: A pesar de las restricciones, las personas participantes encontraron otras maneras de seguir celebrando la Navidad con una actitud positiva y resiliente y con la creencia de que volverá la normalidad. (AU)
Objective: To explore participants´ feelings, emotions and way of celebrating Christmas 2020-2021 conditioned by the COVID-19 pandemic. Method. The activity was carried out in seven Murcia Health Service primary care centres from 16 December 2020 to 7 January 2021. People who attended the centres during the study period took part voluntarily. They wrote down what was special about Christmas on cardboards that were then used to decorate a Christmas tree. The content of the written sentences and subsequent coding and categorization was analyzed in an interpretative manner. Results. A total of 151 written cards were collected and three categories were established: Christmas Desiderata: tradition, normality and solidarity; Christmas Seasons that have made us value what is really important; and Disposition to improve resilience. Conclusions. Despite the restrictions, participants found other ways to continue celebrating Christmas with a positive and resilient attitude and a belief that normality will return. (AU)
Asunto(s)
Humanos , Resiliencia Psicológica , Participación de la Comunidad , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Infecciones por Coronavirus/epidemiología , Atención Primaria de SaludRESUMEN
OBJETIVO: Evaluar la efectividad de una intervención mixta, con componentes educativos, de autoevaluación y retroinformación, para optimizar el control de la diabetes mediante la consecución de concentración de HbA1c en sangre capilar. MATERIAL Y MÉTODOS: Se realizó un estudio piloto, descriptivo, prospectivo, de un año de duración, en el Centro de Salud Primaria «El Carmen» (Área VII Murcia Este). Se incluyeron 266 pacientes con diabetes tipo 2, mayores de 16 años. Cuando el paciente acudía a consulta se realizaba una determinación de HbA1c capilar instantánea utilizando un medidor de HbA1c DCA VANTAGE de SIEMENS. Los pacientes se separaron en 4 grupos dependiendo de los valores de HbA1c inicial y la necesidad o no de intensificar su tratamiento (A: buen control sin cambio de tratamiento [HbA1c < 7% y < 8% en mayores de 70 años]; B: buen control con intensificación; C: mal control sin cambios en tratamiento; y D: mal control con modificación del tratamiento). RESULTADOS: La edad media de los pacientes fue de 66,36 ± 12,56 años y un IMC medio de 29,72 ± 4,92 kg/m2. La media inicial de HbA1c se situaba en 7,78 ± 1,57% y descendió hasta un valor medio de HbA1c final de 6,91 ± 1,07% (p < 0,001). Se objetivó un cambio en la «inercia terapéutica» de los profesionales del centro que lograron, con modificación del tratamiento, que el 74,81% de los pacientes con DM2 cumplieran sus objetivos de control de la diabetes, junto con un descenso de -0,34 ± 1,04 kg/m2 del IMC (p < 0,001) CONCLUSIONES: El control de la HbA1c instantánea supone un método rápido, simple y eficaz para conseguir un mayor control de la diabetes. Es necesario concienciar al personal sanitario en atención primaria a adoptar este tipo de intervención, tanto educativa y/o farmacológica en el tratamiento de todos los pacientes con DM2
OBJECTIVE: The aim of this study was to evaluate the effectiveness of a joint intervention, with educational, self-evaluation and feedback components, in order to optimize diabetes control by measuring HbA1c in capillary blood. MATERIAL AND METHODS: A prospective, pilot study, of one year duration was carried out in the Primary Care Health Centre «El Carmen» (VII Area Murcia East). A total of 266 patients over 16 years old were included in the study. Instant capillary HbA1c (DCA VANTAGE de SIEMENS) was measured on patients who attended the clinics. The patients were divided into 4 different groups, depending on HbA1c values and the requirement of intensifying treatment (Group A: patients with good control of their diabetes (HbA1c < 7%, or 8% in patients over 70 years old) and no changes in the treatment; B: patients with good control of their diabetes and required changes in the treatment; C: patients with poor control and no changes in treatment (non-optimization criteria); and D: patients with poor control and treatment intensification). RESULTS: The mean age was 66.36 ± 12.56 years, and the body mass index (BMI) was 29.72 ± 4.92 kg/m2. The initial HbA1c mean value was 7.79 ± 1.57%, which decreased to a final HbA1c mean value of 6.91 ± 1.07% (P < .001). A change in the therapeutic inertia was searched by the healthcare personnel, who found that the 74.81% of the diabetic patients reached the control objectives. BMI decreased by -0.34 ± 1.04 kg/m2 (P < .001). CONCLUSIONS: Instant capillary HbA1c is a simple, rapid and efficient method to improve diabetes control. It is necessary to sensitize the healthcare personnel in Primary Care to assume this kind of intervention, both educational and pharmacological, to improve values in type 2 diabetes patient