Multicentre external validation of the prognostic model kidney failure risk equation in patients with CKD stages 3 and 4 in Peru: a retrospective cohort study.

OBJECTIVES: To externally validate the four-variable kidney failure risk equation (KFRE) in the Peruvian population for predicting kidney failure at 2 and 5 years. DESIGN: A retrospective cohort study. SETTING: 17 primary care centres from the Health's Social Security of Peru. PARTICIPANTS: Patients older than 18 years, diagnosed with chronic kidney disease stage 3a-3b-4 and 3b-4, between January 2013 and December 2017. Patients were followed until they developed kidney failure, died, were lost, or ended the study (31 December 2019), whichever came first. PRIMARY AND SECONDARY OUTCOME MEASURES: Performance of the KFRE model was assessed based on discrimination and calibration measures considering the competing risk of death. RESULTS: We included 7519 patients in stages 3a-4 and 2798 patients in stages 3b-4. The estimated cumulative incidence of kidney failure, accounting for competing event of death, at 2 years and 5 years, was 1.52% and 3.37% in stages 3a-4 and 3.15% and 6.86% in stages 3b-4. KFRE discrimination at 2 and 5 years was high, with time-dependent area under the curve and C-index >0.8 for all populations. Regarding calibration in-the-large, the observed to expected ratio and the calibration intercept indicated that KFRE underestimates the overall risk at 2 years and overestimates it at 5 years in all populations. CONCLUSIONS: The four-variable KFRE models have good discrimination but poor calibration in the Peruvian population. The model underestimates the risk of kidney failure in the short term and overestimates it in the long term. Further research should focus on updating or recalibrating the KFRE model to better predict kidney failure in the Peruvian context before recommending its use in clinical practice.

Hospitalization and mortality during the pandemic in chronic hemodialysis patients and the general population in Peru / Hospitalização e mortalidade durante a pandemia em pacientes em hemodiálise crônica e na população em geral no Peru

ABSTRACT Background: Patients with chronic kidney disease have a higher risk of severe disease and mortality from COVID-19 than the general population. Objective: To compare hospitalization and mortality rates during the pandemic among chronic hemodialysis (HD) patients and the general population in Lima (Peru). Methods: This retrospective cohort included an assessment of the database of chronic HD patients of the health service providers of the social health insurance benefit networks of Lima and Callao between 2019 and 2021. Hospitalization and mortality rates were obtained for every 1,000 individuals, and variations in the percentages of COVID-19 cases and deaths were calculated. These rates were compared with those of the general population data and standardized by age and sex. Results: An average of 3,937 chronic HD patients were evaluated each month. Of these, 4.8% had COVID-19 and 64.97% were mild cases. The hospitalization rates per 1,000 patients were 19.5, 29.28, and 36.7 in 2019, 2020, and 2021, respectively. The mortality rates per 1,000 patients were 5.9, 9.74, and 11.49 in 2019, 2020, and 2021, respectively. When compared to the standardized general population, the peaks of both rates coincided with the plateaus of the waves during the pandemic. The hospitalization rate for COVID-19 was 12 times higher in HD patients than in the general population, and the mortality rate for COVID-19 was twice as high. Conclusion: HD patients had higher hospitalization and standardized mortality rates than the general population. Peaks in hospitalizations and mortality coincided with the plateaus of the first and second waves of the pandemic.

Resumo Histórico: Pacientes com DRC apresentam maior risco de doença grave e mortalidade por COVID-19 do que a população geral. Objetivo: Comparar taxas de hospitalização e mortalidade durante a pandemia entre pacientes em hemodiálise crônica (HD) e a população geral em Lima (Peru). Métodos: Esta coorte retrospectiva incluiu avaliação do banco de dados de pacientes em HD crônica dos prestadores de serviços de saúde das redes de benefícios do seguro social de saúde de Lima e Callao, entre 2019-2021. Obteve-se taxas de hospitalização e mortalidade para cada 1.000 indivíduos, e foram calculadas variações nas porcentagens de casos de COVID-19 e óbitos. Estas taxas foram comparadas com os dados da população geral e padronizadas por idade e sexo. Resultados: Uma média de 3.937 pacientes em HD crônica foram avaliados mensalmente. Destes, 4,8% tinham COVID-19, 64,97% eram casos leves. As taxas de hospitalização por 1.000 pacientes foram 19,5; 29,28; e 36,7 em 2019, 2020, e 2021, respectivamente. As taxas de mortalidade por 1.000 pacientes foram 5,9; 9,74 e 11,49 em 2019, 2020, e 2021, respectivamente. Quando comparados à população geral padronizada, os picos das taxas coincidiram com os platôs das ondas da pandemia. A taxa de hospitalização para COVID-19 foi 12 vezes maior em pacientes em HD do que na população geral e a taxa de mortalidade por COVID-19 foi duas vezes maior. Conclusão: Pacientes em HD apresentaram taxas de hospitalização e mortalidade padronizada mais elevadas do que a população geral. Os picos das hospitalizações e mortalidade coincidiram com os platôs da primeira e segunda ondas da pandemia.

Hospitalization and mortality during the pandemic in chronic hemodialysis patients and the general population in Peru.

BACKGROUND: Patients with chronic kidney disease have a higher risk of severe disease and mortality from COVID-19 than the general population. OBJECTIVE: To compare hospitalization and mortality rates during the pandemic among chronic hemodialysis (HD) patients and the general population in Lima (Peru). METHODS: This retrospective cohort included an assessment of the database of chronic HD patients of the health service providers of the social health insurance benefit networks of Lima and Callao between 2019 and 2021. Hospitalization and mortality rates were obtained for every 1,000 individuals, and variations in the percentages of COVID-19 cases and deaths were calculated. These rates were compared with those of the general population data and standardized by age and sex. RESULTS: An average of 3,937 chronic HD patients were evaluated each month. Of these, 4.8% had COVID-19 and 64.97% were mild cases. The hospitalization rates per 1,000 patients were 19.5, 29.28, and 36.7 in 2019, 2020, and 2021, respectively. The mortality rates per 1,000 patients were 5.9, 9.74, and 11.49 in 2019, 2020, and 2021, respectively. When compared to the standardized general population, the peaks of both rates coincided with the plateaus of the waves during the pandemic. The hospitalization rate for COVID-19 was 12 times higher in HD patients than in the general population, and the mortality rate for COVID-19 was twice as high. CONCLUSION: HD patients had higher hospitalization and standardized mortality rates than the general population. Peaks in hospitalizations and mortality coincided with the plateaus of the first and second waves of the pandemic.

Enfoque multidisciplinario en la atención de pacientes con enfermedad renal crónica. Una revisión narrativa / A multidisciplinary approach in the evaluation of patients with chronic renal disease.A narrative review

La enfermedad renal crónica (ERC) es un importante problema de salud pública. En el Perú al momento no existe un programa nacional de salud renal. Existe evidencia que el modelo multidisciplinario de atención en ERC mejora la calidad de atención y ha mostrado que enlentece la progresión de ERC y disminuye la mortalidad por todas las causas. Aunque aún hay puntos controversiales, como, por ejemplo, desde que nivel de tasa de filtración glomerular se debería iniciar el manejo multidisciplinario, es una práctica que ha mejorado la atención y el seguimiento de los pacientes renales. Sin embargo, se requiere para su implementación recursos financieros y profesionales y una capacidad organizativa del sistema de salud, que quizás en nuestro país se convierte en un reto.

SUMMARY Chronic renal disease (CRD) is an important public health problem. There is no a national renal health program in Peru. There is evidence that the multidisciplinary model of care in patients with CRD delays progression and reduces all-cause mortality. Although there is no agreement on certain topics, such as at which glomerular filtration rate should the multidisciplinary team work, it is clear that outcomes are improved. Human and financial resources are needed to implement this approach.

Guía de práctica clínica para el manejo de la Enfermedad Renal Crónica estadíos 3b, 4 y 5 en el Seguro Social de Salud del Perú (EsSalud)

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el manejo de la enfermedad renal crónica estadíos 3b, 4 y 5 en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el manejo de pacientes con enfermedad renal crónica estadíos 3b, 4 y 5 en EsSalud. Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas y metodólogos. El GEG formuló 9 preguntas clínicas. Se realizó búsquedas sistemáticas de revisiones sistemáticas y estudios primarios en PubMed entre diciembre del 2020 y agosto del 2021. Se seleccionó la evidencia para responder a las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). El GEG usó la metodología GRADE para revisar la evidencia y formular recomendaciones, los puntos de buena práctica clínica (BPC) y los flujogramas de manejo. Finalmente, la GPC fue aprobada con Resolución N° 88-IETSI-ESSALUD-2021. Resultados: La presente GPC abordó 9 preguntas clínicas. En base a dichas preguntas se formularon 17 recomendaciones (7 fuertes y 10 condicionales), 28 BPC, y 4 flujogramas de manejo. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el manejo de la Enfermedad Renal Crónica estadíos 3b, 4 y 5 en EsSalud.

Introduction: This article summarizes the clinical practice guideline (CPG) for the management of stage 3b, 4, and 5 chronic kidney disease (CKD) in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the management of stage 3b, 4, and 5 CKD in EsSalud. Methods: A guideline development group (GDG) was formed, including specialists and methodologists. The GDG formulated 9 clinical questions. Systematic searches for systematic reviews and primary studies were conducted in PubMed from December 2020 to August 2021. Evidence was selected to answer the clinical questions posed. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The GDG used the GRADE methodology to review the evidence and formulate recommendations, points of good clinical practice (GPC), and management flowcharts. Finally, the CPG was approved with Resolution No. 88-IETSI-ESSALUD-2021. Results: This CPG addressed 9 clinical questions. Based on these questions, 17 recommendations (7 strong and 10 conditional), 28 GPC points, and 4 management flowcharts were formulated. Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the management of stage 3b, 4, and 5 CKD in EsSalud.

Hiperaldosteronismo primario asociado a neoplasia adrenal. Reporte de caso

Se describe el caso de un varón de 68 años con antecedente de hipertensión arterial no tratada, diagnosticada un año antes, que ingresó con un cuadro de anasarca, debilidad muscular y disnea al reposo. Los primeros exámenes realizados mostraron hipopotasemia severa, alcalosis metabólica, litiasis renal y vesical y enfermedad renal crónica. La tomografía abdominal reveló una tumoración suprarrenal derecha, hidronefrosis bilateral y litiasis renal y vesical. Con la sospecha de hiperaldosteronismo primario se completó el estudio, con la determinación de relación aldosterona/concentración de renina directa, que resultó alta. El estudio metabólico arrojó hipercalciuria e hiperuricosuria y la gradiente transtubular de potasio mayor de 7. El paciente fue sometido a tratamiento quirúrgico con nefrectomía derecha, sin embargo, falleció en el postoperatorio inmediato, por shock hipovolémico e insuficiencia respiratoria.

SUMMARY We report the case of a 68-year-old male with a history of non-treated arterial hypertension diagnosed the previous year that was admitted with anasarca, muscle weakness and dyspnea at rest. The first laboratory exams showed severe hypopotassemia, metabolic alkalosis, renal and gallbladder lithiasis and chronic renal disease. The abdominal tomography revealed a right suprarenal tumor, bilateral hydronephrosis and renal and gallbladder lithiasis. Under the suspicion of primary hyperaldosteronism, the diagnosis was confirmed with the determination of the relationship between aldosterone/direct renin concentration, which was high. The metabolic study showed hypercalciuria and hyperuricosuria and the potassium trans tubular gradient was above 7. The patient underwent right nephrectomy, nonetheless, died at the immediate post-operatory period due to a hypovolemic shock and respiratory failure.

Neonatal apneic phenotype in a murine congenital central hypoventilation syndrome model is induced through non-cell autonomous developmental mechanisms.

Congenital central hypoventilation syndrome (CCHS) represents a rare genetic disorder usually caused by mutations in the homeodomain transcription factor PHOX2B. Some CCHS patients suffer mainly from deficiencies in CO2 and/or O2 respiratory chemoreflex, whereas other patients present with full apnea shortly after birth. Our goal was to identify the neuropathological mechanisms of apneic presentations in CCHS. In the developing murine neuroepithelium, Phox2b is expressed in three discrete progenitor domains across the dorsal-ventral axis, with different domains responsible for producing unique autonomic or visceral motor neurons. Restricting the expression of mutant Phox2b to the ventral visceral motor neuron domain induces marked newborn apnea together with a significant loss of visceral motor neurons, RTN ablation, and preBötzinger complex dysfunction. This finding suggests that the observed apnea develops through non-cell autonomous developmental mechanisms. Mutant Phox2b expression in dorsal rhombencephalic neurons did not generate significant respiratory dysfunction, but did result in subtle metabolic thermoregulatory deficiencies. We confirm the expression of a novel murine Phox2b splice variant which shares exons 1 and 2 with the more widely studied Phox2b splice variant, but which differs in exon 3 where most CCHS mutations occur. We also show that mutant Phox2b expression in the visceral motor neuron progenitor domain increases cell proliferation at the expense of visceral motor neuron development. We propose that visceral motor neurons may function as organizers of brainstem respiratory neuron development, and that disruptions in their development result in secondary/non-cell autonomous maldevelopment of key brainstem respiratory neurons.

Guía de práctica clínica para el tamizaje, diagnóstico y manejo de la enfermedad renal crónica en estadios 1 al 3 en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for the screening, diagnosis, and management of chronic kidney disease stages 1-3 for the Peruvian Social Security (EsSalud)

RESUMEN El presente artículo resume la guía de práctica clínica (GPC) para tamizaje, diagnóstico y manejo de los pacientes con enfermedad renal crónica (ERC) en los estadios 1 al 3 en el Seguro Social del Perú (EsSalud). Para el desarrollo de esta GPC, se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas clínicos y metodólogos, el cual formuló ocho preguntas clínicas. Para responder cada pregunta se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando fue considerado pertinente, de estudios primarios; y se seleccionó la evidencia pertinente. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones periódicas, el GEG usó la metodología GRADE para revisar la evidencia y emitir las recomendaciones. Se emitieron ocho recomendaciones (cuatro fuertes y cuatro condicionales), 29 puntos de buena práctica clínica, y tres flujogramas.

ABSTRACT This paper summarizes the clinical practice guidelines (CPG) for the screening, diagnosis, and management of patients with chronic kidney disease (CKD) stages 1-3 in the Social Security of Peru (EsSalud). A guideline development group (GDG) was established for develop this CPG, which included clinical and methodology specialists, who formulated 08 clinical questions. Systematic searches of systematic reviews and, when considered necessary, primary studies were conducted to answer each question; and relevant evidence was selected. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GDG used the GRADE methodology for reviewing the evidence and for developing recommendations. At the end, this CPG formulated 08 recommendations (04 strong and 04 conditional), 29 points of good clinical practice, and 03 flowcharts were formulated.

Effectiveness of adherence to a renal health program in a health network in Peru.

OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.

Effectiveness of adherence to a renal health program in a health network in Peru / Efectividad de la adherencia a un programa de salud renal en una red sanitaria de Perú

ABSTRACT OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.

RESUMEN OBJETIVO Evaluar la efectividad de la adherencia a un programa de salud renal en la reducción de mortalidad y progresión a hemodiálisis. MÉTODOS Utilizamos una base de datos que condensaba el seguimiento de los pacientes (2013-2017), los ingresos a diálisis de los mismos y la mortalidad por todas las causas en Perú. La adherencia al programa se estableció con el cumplimiento de visitas mínimas durante su primer año de seguimiento. La efectividad de la adherencia al programa se midió en términos de debut a hemodiálisis o muerte por todas las causas. Se utilizaron curvas de Kaplan-Meier, test de diferencias en la distribución (Log-Rank test) y métodos de análisis de supervivencia. Los análisis se realizaron utilizando R estudio 3.5.0 RESULTADOS Fueron evaluados 20.354 participantes, 54,1% varones, edad media de 72,1 años, con un seguimiento medio de 2,2 años; 15.279 (75.1%) tuvieron ERC en estadios tempranos (estadio 1 al 3a). La adherencia disminuyó en un 41,0% el riesgo de terapia de reemplazo renal (HR = 0,59; IC95% 0,41-0,85) en el grupo de bajo riesgo y en un 31,0% (HR = 0,69; IC95% 0,57-0,83) la mortalidad en el grupo de alto riesgo. CONCLUSIONES La estrategia de cuidado multidisciplinario con evaluaciones estandarizadas según estadio es efectiva en reducir el ingreso a terapia de reemplazo renal cuando se identifica al paciente en estadios tempranos y en reducir la mortalidad en estadios avanzados.

Early detection of chronic renal disease: coordinated work between primary and specialized care in an ambulatory renal network of Peru / Detecção precoce de doença renal crônica: trabalho coordenado entre atenção primária e especializada em uma rede peruana de atenção renal ambulatorial

Abstract Introduction: The aim of the study was to report the implementation of a functional network for the early diagnosis of chronic kidney disease (CKD) in patients with risk factors and the coordinated work between primary and specialized care in social security in Perú. Material and methods: A cross-sectional analysis of the data of patients evaluated in a health network in the city of Lima (2013 to 2016), older than 18 years, with risk factors for CKD, evaluated with serum creatinine and creatine albumin ratio in random urine (ACR). A multivariate logistic regression analysis was performed to evaluate the factors associated with the finding of CKD. Results: The implementation included training in renal health, installation of a digital database, organization of laboratories, and empowerment of primary care. We evaluated 42,746 patients of which 41.8% were men, with median age 69.2 years. The most frequent cause of detection was hypertension (HBP): 23,921 (55.9%). The prevalence of CKD was 12,132 (28.4%), the most frequent stage of CKD was 3a: 4735 (39.0%). Of the total, 6214 (14.5%) patients had microalbuminuria and 1335 (3.1%), macroalbuminuria. The risk of CKD increased 2.5 times (95% CI: 2.3-2.7) in patients with diabetes (DM) and HBP, in men (OR 1.2, 95% CI: 1.2-1.3) and as age increased (> 77 years: OR 2.7, 95% CI: 2.5-2.8). The identification of the disease in the primary care setting is 60% less likely than in specialized care. Conclusions: One of every four patients are diagnosed with CKD, and the simultaneous diagnosis of DM and HBP and old age are the most important factors.

Resumo Introdução: O objetivo do presente estudo foi descrever a implementação de uma rede funcional para o diagnóstico precoce de doença renal crônica (DRC) em pacientes com fatores de risco e o coordenar os trabalhos entre atenção primária e especializada no sistema de seguridade social peruano. Material e métodos: Análise transversal dos dados de pacientes maiores de 18 anos com fatores de risco para DRC avaliados em uma rede de saúde na cidade de Lima (2013 a 2016) por meio de creatinina sérica e relação albumina/creatinina (RAC) em amostra aleatória de urina. Análise de regressão logística multivariada foi executada para avaliar os fatores associados à presença de DRC. Resultados: A implementação incluiu treinamento em saúde renal, instalação de um banco de dados digital, organização de laboratórios e empoderamento da atenção primária. Foram avaliados 42.746 pacientes, dos quais 41,8% eram homens, com idade mediana de 69,2 anos. A causa mais comum de detecção foi hipertensão, observada em 23.921 indivíduos (55,9%). A prevalência de DRC foi de 12.132 (28,4%), com estágio 3A sendo o mais frequente com 4735 casos (39,0%). Do total, 6214 (14,5%) pacientes apresentavam microalbuminúria e 1335 (3,1%) macroalbuminúria. O risco de DRC foi 2,5 vezes maior (IC 95%: 2,3-2,7) nos pacientes com diabetes e hipertensão, em homens (OR 1,2, IC 95%: 1,2-1,3) e idosos (> 77 anos: OR 2,7, IC 95%: 2,5-2,8). A identificação da doença no cenário da atenção primária é 60% menos provável do que na atenção especializada. Conclusões: Um em cada quatro pacientes é diagnosticado com DRC. Idade avançada e diagnóstico simultâneo de DM e hipertensão são os fatores mais relevantes.

Early detection of chronic renal disease: coordinated work between primary and specialized care in an ambulatory renal network of Peru.

INTRODUCTION: The aim of the study was to report the implementation of a functional network for the early diagnosis of chronic kidney disease (CKD) in patients with risk factors and the coordinated work between primary and specialized care in social security in Perú. MATERIAL AND METHODS: A cross-sectional analysis of the data of patients evaluated in a health network in the city of Lima (2013 to 2016), older than 18 years, with risk factors for CKD, evaluated with serum creatinine and creatine albumin ratio in random urine (ACR). A multivariate logistic regression analysis was performed to evaluate the factors associated with the finding of CKD. RESULTS: The implementation included training in renal health, installation of a digital database, organization of laboratories, and empowerment of primary care. We evaluated 42,746 patients of which 41.8% were men, with median age 69.2 years. The most frequent cause of detection was hypertension (HBP): 23,921 (55.9%). The prevalence of CKD was 12,132 (28.4%), the most frequent stage of CKD was 3a: 4735 (39.0%). Of the total, 6214 (14.5%) patients had microalbuminuria and 1335 (3.1%), macroalbuminuria. The risk of CKD increased 2.5 times (95% CI: 2.3-2.7) in patients with diabetes (DM) and HBP, in men (OR 1.2, 95% CI: 1.2-1.3) and as age increased (> 77 years: OR 2.7, 95% CI: 2.5-2.8). The identification of the disease in the primary care setting is 60% less likely than in specialized care. CONCLUSIONS: One of every four patients are diagnosed with CKD, and the simultaneous diagnosis of DM and HBP and old age are the most important factors.

Development of a Novel FIJI-Based Method to Investigate Neuronal Circuitry in Neonatal Mice.

The emergence of systems neuroscience tools requires parallel generation of objective analytical workflows for experimental neuropathology. We developed an objective analytical workflow that we used to determine how specific autonomic neural lineages change during postnatal development. While a wealth of knowledge exists regarding postnatal alterations in respiratory neural function, how these neural circuits change and develop in the weeks following birth remains less clear. In this study, we developed our workflow by combining genetic mouse modeling and quantitative immunofluorescent confocal microscopy and used this to examine the postnatal development of neural circuits derived from the transcription factors NKX2.2 and OLIG3 into three medullary respiratory nuclei. Our automated FIJI-based image analysis workflow rapidly and objectively quantified synaptic puncta in user-defined anatomic regions. Using our objective workflow, we found that the density and estimated total number of Nkx2.2-derived afferents into the pre-Bötzinger Complex significantly decreased with postnatal age during the first three weeks of postnatal life. These data indicate that Nkx2.2-derived structures differentially influence pre-Bötzinger Complex respiratory oscillations at different stages of postnatal development.

[Progression of chronic renal disease in a reference hospital of social security of Peru 2012-2015]. / Progresión de enfermedad renal crónica en un hospital de referencia de la seguridad social de Perú 2012-2015.

OBJECTIVES.: To describe the characteristics of the population with chronic kidney disease (CKD) stage 3 and 4, to determine the factors associated with CKD progression and admission to renal replacement therapy (RRT), as well as renal survival. MATERIALS AND METHODS.: Longitudinal retrospective study of patients referred between January 2012 and December 2015 to the Renal Health Unit of the Hospital Nacional Edgardo Rebagliati Martins (HNERM), who were evaluated and followed by a multidisciplinary team. The clinical and laboratory data for each query were recorded in a software created specifically for the program. A multivariate logistic regression analysis was performed to assess the factors associated with the progression of CKD, a Cox regression model to predict the risk of entering RRT and the Kaplan-Meier method for renal survival analysis. RESULTS.: We assessed 1248 patients in stage 3A: 248 (20%), stage 3B: 548 (44%) and stage 4: 452 (36%). 352 (28%) progressed, being proteinuria the most important progression factor (OR: 3.2; CI 95%: 2,2-4.6). Proteinuria increases the risk of admission to RRT in four times and having a glomerular filtration rate < 30% in 3.6 times. Median follow-up was 12 months (RIC 5-27 months). 92 patients (7%) required to initiate RRT. Renal survival at 12 months of follow-up was 96% and at 24 months was 90%. CONCLUSIONS.: Our study shows that in a specialized center a significant proportion of patients with CKD does not progress in their disease and that the factor that is most associated with progression of disease and at the onset of RRT is proteinuria.

OBJETIVOS.: Describir las características de la población con enfermedad renal crónica (ERC) estadio 3 y 4, determinar los factores asociados a progresión de ERC y a ingreso a terapia de reemplazo renal (TRR), así como la sobrevida renal. MATERIALES Y MÉTODOS.: Estudio retrospectivo longitudinal de pacientes remitidos entre enero de 2012 y diciembre de 2015 a la Unidad de Salud Renal del Hospital Nacional de Edgardo Rebagliati Martins (HNERM), quienes fueron evaluados y seguidos por un equipo multidisciplinario. Los datos clínicos y de laboratorio de cada consulta se registraron en un software creado específicamente para el programa. Se realizó un análisis de regresión logística multivariado para evaluar los factores asociados con la progresión de la ERC, un modelo de regresión de Cox para predecir el riesgo de ingresar al TRR y el método de Kaplan-Meier para el análisis de supervivencia renal. RESULTADOS.: Se evaluó a 1248 pacientes en estadio 3A: 248 (20%), estadio 3b: 548 (44%) y estadio 4: 452 (36%). 352 (28%) progresaron, siendo la proteinuria el factor de progresión más importante (OR: 3,2; IC95%: 2,2-4,6). La proteinuria incrementa el riesgo de ingreso a la TRR en cuatro veces y el tener una tasa de filtración glomerular <30% en 3,6 veces. La mediana de seguimiento fue de 12 meses (RIC 5-27 meses). 92 pacientes (7%) requirieron iniciar TRR. La supervivencia renal a los 12 meses de seguimiento fue del 96% y a los 24 meses de 90%. CONCLUSIONES.: Nuestro estudio muestra que en un centro especializado una proporción significativa de pacientes con ERC no progresa en su enfermedad y que el factor que más se asocia a progresión de enfermedad y a inicio de TRR es la proteinuria.

Progresión de enfermedad renal crónica en un hospital de referencia de la seguridad social de Perú 2012-2015 / Progression of chronic renal disease in a reference hospital of social security of Peru 2012-2015

RESUMEN Objetivos. Describir las características de la población con enfermedad renal crónica (ERC) estadio 3 y 4, determinar los factores asociados a progresión de ERC y a ingreso a terapia de reemplazo renal (TRR), así como la sobrevida renal. Materiales y métodos. Estudio retrospectivo longitudinal de pacientes remitidos entre enero de 2012 y diciembre de 2015 a la Unidad de Salud Renal del Hospital Nacional de Edgardo Rebagliati Martins (HNERM), quienes fueron evaluados y seguidos por un equipo multidisciplinario. Los datos clínicos y de laboratorio de cada consulta se registraron en un software creado específicamente para el programa. Se realizó un análisis de regresión logística multivariado para evaluar los factores asociados con la progresión de la ERC, un modelo de regresión de Cox para predecir el riesgo de ingresar al TRR y el método de Kaplan-Meier para el análisis de supervivencia renal. Resultados. Se evaluó a 1248 pacientes en estadio 3A: 248 (20%), estadio 3b: 548 (44%) y estadio 4: 452 (36%). 352 (28%) progresaron, siendo la proteinuria el factor de progresión más importante (OR: 3,2; IC95%: 2,2-4,6). La proteinuria incrementa el riesgo de ingreso a la TRR en cuatro veces y el tener una tasa de filtración glomerular <30% en 3,6 veces. La mediana de seguimiento fue de 12 meses (RIC 5-27 meses). 92 pacientes (7%) requirieron iniciar TRR. La supervivencia renal a los 12 meses de seguimiento fue del 96% y a los 24 meses de 90%. Conclusiones. Nuestro estudio muestra que en un centro especializado una proporción significativa de pacientes con ERC no progresa en su enfermedad y que el factor que más se asocia a progresión de enfermedad y a inicio de TRR es la proteinuria.

ABSTRACT Objectives. To describe the characteristics of the population with chronic kidney disease (CKD) stage 3 and 4, to determine the factors associated with CKD progression and admission to renal replacement therapy (RRT), as well as renal survival. Materials and methods. Longitudinal retrospective study of patients referred between January 2012 and December 2015 to the Renal Health Unit of the Hospital Nacional Edgardo Rebagliati Martins (HNERM), who were evaluated and followed by a multidisciplinary team. The clinical and laboratory data for each query were recorded in a software created specifically for the program. A multivariate logistic regression analysis was performed to assess the factors associated with the progression of CKD, a Cox regression model to predict the risk of entering RRT and the Kaplan-Meier method for renal survival analysis. Results. We assessed 1248 patients in stage 3A: 248 (20%), stage 3B: 548 (44%) and stage 4: 452 (36%). 352 (28%) progressed, being proteinuria the most important progression factor (OR: 3.2; CI 95%: 2,2-4.6). Proteinuria increases the risk of admission to RRT in four times and having a glomerular filtration rate < 30% in 3.6 times. Median follow-up was 12 months (RIC 5-27 months). 92 patients (7%) required to initiate RRT. Renal survival at 12 months of follow-up was 96% and at 24 months was 90%. Conclusions. Our study shows that in a specialized center a significant proportion of patients with CKD does not progress in their disease and that the factor that is most associated with progression of disease and at the onset of RRT is proteinuria.

Isolation as a strategy for controlling the transmission of hepatitis C virus (HCV) infection in haemodialysis units.

BACKGROUND: The hepatitis C virus (HCV) infection affects about 2% of the world's population and can cause chronic liver infection and persistent long-term sequelae such as cirrhosis and liver cancer.The prevalence of HCV infection among people on haemodialysis is often higher than the general population. The virus is easily transmitted parenterally, and blood transfusions have previously played a significant role in transmission; however, erythropoietin therapy has reduced the need for transfusions, and coupled with improved screening of donated blood, has significantly decreased transmission by transfusion. Although control of hospital-acquired infection has improved with the advent of biosafety measures, stopping HCV transmission in haemodialysis units remains challenging.Isolating people infected with HCV involves physical separation from others to limit direct or indirect transmission and includes a number of strategies during dialysis. The evidence for isolating people infected with HCV during haemodialysis is sparse with some inconsistencies. OBJECTIVES: To evaluate the benefits and harms of isolation of HCV-infected patients during haemodialysis on the transmission of HCV to other patients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 26 November 2015 through contact with the Information Specialist using search terms relevant to this review. We also searched the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 2015), Web of Science Conference Proceedings Citation Index-Science (CPCI-S, 1990 to 2015), ProQuest Dissertations & Theses Database (1990 to 2015), and Open Grey (1990 to 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and cluster RCTs evaluating the clinical benefits and harms of isolating HCV-infected patients during haemodialysis on the transmission of HCV to other patients. We considered incidence of dialysis-acquired HCV infection, all-cause mortality, and adverse effects associated with isolation as the primary outcomes. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. MAIN RESULTS: Only one study, which included 12 centres was identified: four centres used dedicated haemodialysis machines for HCV-infected patients and eight centres used non-dedicated machines. The total number of patients enrolled was 593. One centre was excluded after randomisation. Random sequence generation was not described and allocation concealment was not performed. Participants and personnel were not blinded and blinding of outcome assessors was not reported. Only 74.5% of the patients were followed for 9 months; and 47.3% were followed for an additional 9 months. The authors only reported one outcome, measuring the difference in the incidence of HCV in both groups. The authors did not consider the exposure time, to determine the adjusted rate of seroconversion risk/patient-year. The study reported that the incidence of HCV infection during the first follow-up period (9 months) was 1.6% in the dedicated group, and 4.7% in the non-dedicated one (446 patients analysed out of 593 randomised; RR 0.34, 95% CI 0.11 to 1.07). During the second follow-up period (18 months) the incidence was 1.3% in the dedicated group and 5.8% in the control (281 patients analysed out of 593 randomised; RR 0.22, 95% CI 0.05 to 1.02). Therefore, we found no differences in terms of the number of participants developing HCV infection when comparing the dedicated group with the usual care. Moreover, the evidence was of very low quality, which means that we have very little confidence in the effect estimate. AUTHORS' CONCLUSIONS: The benefits and harms of isolation of HCV-infected patients during haemodialysis on the transmission of HCV to other patients are uncertain. Evidence from one short-duration cluster-randomised study with a high risk of bias did not find differences in terms of the number of participants developing HCV infection when comparing the use of dedicated haemodialysis machines for HCV infected patients with the use of non-dedicated machines.

[CONSUMPTION OF READY-TO-EAT CEREAL IS INVERSELY ASSOCIATED WITH BODY MASS INDEX IN 6-13 YEARS OLD CHILEAN SCHOOLCHILDREN].

BACKGROUND AND AIMS: childhood obesity in Chile is a serious problem with the prevalence continuing to increase over the last decade, despite all governmental efforts to diminish it. Studies indicate that the consumption of certain foods may help to control body weight. The objective of this study was to evaluate the relationship between ready-to-eat cereals (RTEC), body mass index and nutritional intake of macronutrients and micronutrients in school children from Santiago, Chile. METHODS AND RESULTS: the study included 1 477 children aged 6-13 years who were evaluated by trained nutritionists. Weight, height and waist circumference were measured and a 24-hour recall questionnaire was administered in which the hours spent watching TV were also recorded. Overall, 32% of boys and 28 % of girls were overweight but the difference between them was not significant. All children, regardless of sex, showed a significant inverse relationship between amounts of RTEC consumed and body mass index (BMI). Those girls that consumed higher amount of RTEC had a reduced waist circumference than those that had a lower intake. A high consumption of RTEC in all children was related to a higher intake of calories, proteins, carbohydrates, calcium and zinc and to a lower intake of calories from fat. RTEC consumption was also associated with lower risk of being overweight/obese. CONCLUSION: this study identifies RTEC intake as a potential indicator of a healthy diet. Controlled interventions are necessary to isolate the effect of RTEC consumption from other participating factors.

Introducción y objetivos: la obesidad infantil en Chile es un problema serio de salud, con una prevalencia que ha ido en aumento durante las últimas décadas, a pesar de todos los esfuerzos gubernamentales por combatirla. Algunos estudios indican que el consumo de ciertos alimentos puede ayudar en el control del peso corporal. El objetivo de este estudio fue evaluar la relación entre los cereales listos para comer (CLC), el índice de masa corporal y la ingesta de macro y micronutrientes en escolares de Santiago de Chile. Métodos y resultados: el estudio incluyó 1.477 niños con edades entre los 6-13 años que fueron evaluados por nutricionistas entrenados. Se midieron peso, talla y circunferencia de la cintura, además se aplicó una encuesta alimentaria por recordatorio de 24 horas y se preguntó por el número de horas que veían TV. Del total, el 32% de los niños y el 28% de las niñas presentaron exceso de peso, diferencia que no fue significativa. Todos los niños, independientemente del género, mostraron una asociación inversa significativa entre el consumo de CLC y el índice de masa corporal. Aquellas niñas que consumían mayores cantidades de CLC tenían menor circunferencia de cintura que aquellas que consumían menos. Un mayor consumo de CLC en todos los niños estuvo relacionado con mayor ingesta de calorías, proteínas, carbohidratos, calcio y zinc, además de con un menor consumo de calorías provenientes de las grasas. El consumo de CLC también estuvo asociado con menor riesgo de ser obeso o padecer sobrepeso. Conclusión: este estudio muestra que la ingesta de CLC es un indicador potencial de una dieta saludable. Son necesarias intervenciones más controladas para evaluar el efecto aislado de los CLC en comparación con otros factores.

Consumption of ready-to-eat cereal is inversely associated with body mass index in 6-13 years old Chilean schoolchildren / El consumo de cereales listos para comer está inversamente asociado con el índice de masa corporal en escolares chilenos de 6 a 13 años

Background and aims: childhood obesity in Chile is a serious problem with the prevalence continuing to increase over the last decade, despite all governmental efforts to diminish it. Studies indicate that the consumption of certain foods may help to control body weight. The objective of this study was to evaluate the relationship between ready-to-eat cereals (RTEC), body mass index and nutritional intake of macronutrients and micronutrients in school children from Santiago, Chile. Methods and results: the study included 1 477 children aged 6-13 years who were evaluated by trained nutritionists. Weight, height and waist circumference were measured and a 24-hour recall questionnaire was administered in which the hours spent watching TV were also recorded. Overall, 32% of boys and 28 % of girls were overweight but the difference between them was not significant. All children, regardless of sex, showed a significant inverse relationship between amounts of RTEC consumed and body mass index (BMI). Those girls that consumed higher amount of RTEC had a reduced waist circumference than those that had a lower intake. A high consumption of RTEC in all children was related to a higher intake of calories, proteins, carbohydrates, calcium and zinc and to a lower intake of calories from fat. RTEC consumption was also associated with lower risk of being overweight/obese. Conclusion: this study identifies RTEC intake as a potential indicator of a healthy diet. Controlled interventions are necessary to isolate the effect of RTEC consumption from other participating factors (AU)

Introducción y objetivos: la obesidad infantil en Chile es un problema serio de salud, con una prevalencia que ha ido en aumento durante las últimas décadas, a pesar de todos los esfuerzos gubernamentales por combatirla. Algunos estudios indican que el consumo de ciertos alimentos puede ayudar en el control del peso corporal. El objetivo de este estudio fue evaluar la relación entre los cereales listos para comer (CLC), el índice de masa corporal y la ingesta de macro y micronutrientes en escolares de Santiago de Chile. Métodos y resultados: el estudio incluyó 1.477 niños con edades entre los 6-13 años que fueron evaluados por nutricionistas entrenados. Se midieron peso, talla y circunferencia de la cintura, además se aplicó una encuesta alimentaria por recordatorio de 24 horas y se preguntó por el número de horas que veían TV. Del total, el 32% de los niños y el 28% de las niñas presentaron exceso de peso, diferencia que no fue significativa. Todos los niños, independientemente del género, mostraron una asociación inversa significativa entre el consumo de CLC y el índice de masa corporal. Aquellas niñas que consumían mayores cantidades de CLC tenían menor circunferencia de cintura que aquellas que consumían menos. Un mayor consumo de CLC en todos los niños estuvo relacionado con mayor ingesta de calorías, proteínas, carbohidratos, calcio y zinc, además de con un menor consumo de calorías provenientes de las grasas. El consumo de CLC también estuvo asociado con menor riesgo de ser obeso o padecer sobrepeso. Conclusión: este estudio muestra que la ingesta de CLC es un indicador potencial de una dieta saludable. Son necesarias intervenciones más controladas para evaluar el efecto aislado de los CLC en comparación con otros factores (AU)