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BACKGROUND: The outbreak of the COVID-19 pandemic has had a profound impact on the circulation of seasonal respiratory viruses. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in adults hospitalized with severe acute respiratory infection (SARI) during the COVID-19 pandemic. METHODS: This population-based cohort study included patients aged > 18 years hospitalized for SARI in Brazil between February 2020 and February 2023. The primary outcome was in-hospital mortality. A competing risk analysis was used to account for competing events. RESULTS: In total, 2,159,171 patients were included in the study. SARS-CoV-2 was the predominant virus (98.7%). The cumulative incidence of in-hospital mortality was 33.1%, 31.5%, 21.0%, 18.7%, and 18.6%, for patients positive for SARS-CoV-2, adenovirus, RSV, influenza, and other viruses, respectively. SARS-CoV-2 accounted for 99.3% of the deaths. Older age, male sex, comorbidities, hospitalization in the northern region, and oxygen saturation <95% were the common risk factors for death among all viruses. CONCLUSIONS: In this large cohort study, individuals infected with SARS-CoV-2 or adenovirus had the highest risk of mortality. Irrespective of the virus type, older age, male sex, comorbidities, hospitalization in vulnerable regions, and low oxygen saturation were associated with an increased risk of fatality.
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OBJECTIVE: The objective of this study was to estimate the vaccine effectiveness (VE) against hospitalization and severe illness in adolescents due to infection with SARS-CoV-2 variants (gamma, delta, and omicron). STUDY DESIGN: A test-negative, case-control analysis was conducted in Brazil from July 2021 to March 2022. We enrolled 8458 eligible individuals (12-19 years of age) hospitalized with an acute respiratory syndrome, including 3075 cases with laboratory-proven COVID-19 and 4753 controls with negative tests for COVID-19. The primary exposure of interest was vaccination status. The primary outcome was SARS-CoV-2 infection during gamma/delta vs omicron-predominant periods. The aOR for the association of prior vaccination and outcomes was used to estimate VE. RESULTS: In the pre-omicron period, VE against COVID-19 hospitalization was 88% (95% CI, 83%-92%) and has dropped to 59% (95% CI, 49%-66%) during the omicron period. For hospitalized cases of COVID-19, considering the entire period of the analysis, 2-dose schedule was moderately effective against intensive care unit admission (46%, [95% CI, 27-60]), need of mechanical ventilation (49%, [95% CI, 32-70]), severe COVID-19 (42%, [95% CI, 17-60]), and death (46%, [95% CI, 8-67]). There was a substantial reduction of about 40% in the VE against all end points, except for death, during the omicron-predominant period. Among cases, 240 (6.6%) adolescents died; of fatal cases, 224 (93.3%) were not fully vaccinated. CONCLUSION: Among adolescents, the VE against all end points was substantially reduced during the omicron-predominant period. Our findings suggest that the 2-dose regimen may be insufficient for SARS-CoV-2 variants and support the need for updated vaccines to provide better protection against severe COVID-19.
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COVID-19 , SARS-CoV-2 , Adolescente , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Eficacia de las Vacunas , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Patients with kidney diseases (KD) appear to be at particularly high risk for severe COVID-19. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with KD. METHODS: We performed an analysis of all pediatric patients with KD and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 16, 2020, and May 29, 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized patients with COVID-19, 290 cases (1.3%) had KD. Of these, 59 (20.8%) had a fatal outcome compared with 7.5% of the non-KD cohort (P < 0.001). Pediatric patients with KD had an increased hazard of death compared with the non-KD cohort (Hazard ratio [HR] = 2.85, 95% CI 2.21-3.68, P < 0.0001). After adjustment, the factors associated with the death among KD patients were living in Northeast (HR 2.16, 95% CI 1.13-4.31) or North regions (HR 3.50, 95% CI 1.57-7.80), oxygen saturation < 95% at presentation (HR 2.31, 95% CI 1.30-4.10), and presence of two or more associated comorbidities (HR 2.10, 95% CI 1.08-4.04). CONCLUSIONS: Children and adolescents with KD had a higher risk of death compared with the non-KD cohort. The higher risk was associated with low oxygen saturation at admission, living in socioeconomically disadvantaged regions, and presence of other pre-existing comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary information.
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COVID-19 , Enfermedades Renales , Humanos , Adolescente , Niño , COVID-19/epidemiología , SARS-CoV-2 , Niño Hospitalizado , Factores de Riesgo , Enfermedades Renales/epidemiologíaRESUMEN
This study aimed to evaluate the risk factors for COVID-19-related death in a large cohort of hospitalized children with hematological disorders. We performed an analysis of all pediatric patients with COVID-19 registered in a Brazilian nationwide surveillance database between February 2020 and May 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using the cumulative incidence function. Among 21,591 hospitalized pediatric patients with COVID-19, 596 cases (2.8%) had hematological diseases. Sixty-one children (27.4%) with malignant hematological diseases had a fatal outcome as compared with 4.2% and 7.4% of nonmalignant hematological and nonhematological cohorts, respectively ( P <0.0001). Children with hematological diseases had a significant increased hazard of death compared with those without these conditions (hazard ratio [HR],=2.40, 95% confidence interval, 1.98 - 2.91). In multivariable analysis, the factors associated with death were the presence of malignant hematological disease (HR, 2.22, 95% CI 1.47 - 3.36), age >10 years (HR 2.19, 95% CI 1.46 - 3.19), male (HR 1.52, 95% CI 1.02 - 2.27), oxygen saturation <95% (HR 2.02, 95% CI 1.38 - 2.96), and abdominal pain at admission (HR 2.75, 95% CI 1.76 - 4.27). Children with malignant hematological diseases had a higher risk of death compared with those without these disorders.
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COVID-19 , Enfermedades Hematológicas , Humanos , Masculino , Adolescente , Niño , COVID-19/epidemiología , Niño Hospitalizado , Estudios Retrospectivos , Mortalidad Hospitalaria , Factores de Riesgo , Enfermedades Hematológicas/complicacionesRESUMEN
The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes and Pediatric Renal Nutrition Taskforce are opinion-based rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.
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Nefrología , Diálisis Peritoneal , Insuficiencia Renal Crónica , Niño , Humanos , Estado Nutricional , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Riñón , Diálisis Renal , Estudios Observacionales como AsuntoRESUMEN
OBJECTIVE: To evaluate the severity and clinical outcomes of the SARS-CoV-2 gamma variant in children and adolescents hospitalized with COVID-19 in Brazil. STUDY DESIGN: In this observational retrospective cohort study, we performed an analysis of all 21 591 hospitalized patients aged <20 years with confirmed SARS-CoV-2 infection registered in a national database in Brazil. The cohort was divided into 2 groups according to the predominance of SARS-CoV-2 lineages (WAVE1, n = 11 574; WAVE2, n = 10 017). The characteristics of interest were age, sex, geographic region, ethnicity, clinical presentation, and comorbidities. The primary outcome was time to death, which was evaluated by competing-risks analysis, using cumulative incidence functions. A predictive Fine and Gray competing-risks model was developed based on the WAVE1 cohort with temporal validation in the WAVE2 cohort. RESULTS: Compared with children and adolescents admitted during the first wave, those admitted during the second wave had significantly more hypoxemia (52.5% vs 41.1%; P < .0001) and intensive care unit admissions (28.3% vs 24.9%; P < .0001) and needed more noninvasive ventilatory support (37.3% vs 31.6%; P < .0001). In-hospital deaths and death rates were 896 (7.7%) in the first wave and 765 (7.6%) in the second wave (P = .07). The prediction model of death included age, ethnicity, region, respiratory symptoms, and comorbidities. In the validation set (WAVE2), the C statistic was 0.750 (95% CI, 0.741-0.758; P < .0001). CONCLUSIONS: This large national study found a more severe spectrum of risk for pediatric patients with COVID-19 caused by the gamma variant. However, there was no difference regarding the probability of death between the waves.
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COVID-19 , SARS-CoV-2 , Adolescente , COVID-19/epidemiología , Niño , Hospitalización , Humanos , Pandemias , Estudios RetrospectivosRESUMEN
BACKGROUND: Diabetes has been recognized as a major comorbidity for COVID-19 severity in adults. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with diabetes. METHODS: We performed an analysis of all pediatric patients with diabetes and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 2020 and May 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized pediatric patients with COVID-19, 379 (1.8%) had diabetes. Overall, children and adolescents with diabetes had a higher prevalence of ICU admission (46.6% vs. 26%), invasive ventilation (16.9% vs. 10.3%), and death (15% vs. 7.6%) (all P < 0.0001). Children with diabetes had twice the hazard of death compared with pediatric patients without diabetes (Hazard ratio [HR] = 2.0, 95% CI, 1.58-2.66). Among children with diabetes, four covariates were independently associated with the primary outcome, living in the poorest regions of the country (Northeast, HR, 2.17, 95% CI 1.18-4.01, and North, (HR 4.0, 95% CI 1.79-8.94), oxygen saturation < 95% at admission (HR 2.97, 95% CI 1.64-5.36), presence of kidney disorders (HR 3.39, 95% CI 1.42-8.09), and presence of obesity (HR 3.77, 95% CI 1.83-7.76). CONCLUSION: Children and adolescents with diabetes had a higher risk of death compared with patients without diabetes. The higher risk of death was associated with clinical and socioeconomic factors.
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COVID-19 , Diabetes Mellitus , Adolescente , Adulto , COVID-19/complicaciones , Niño , Niño Hospitalizado , Comorbilidad , Diabetes Mellitus/epidemiología , Hospitalización , Humanos , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: The grading of urinary tract dilatation (UTD) on postnatal sonography is a fundamental step to establish rational management for infants with antenatal hydronephrosis (ANH). The aim of this study was to compare the prediction accuracy of UTD grading systems for relevant clinical outcomes. In addition, we propose a refinement of the UTD classification by adding quantitative measurements and evaluate its impact on accuracy. METHODS: Between 1989 and 2019, 447 infants diagnosed with isolated AHN were prospectively followed. The events of interest were surgical interventions and kidney injury. Comparison of performance of the grading systems and the impact on the accuracy of a modified UTD classification (including the size of the kidney parenchyma) was assessed by the area under the receiver-operating characteristic curve (AUC). RESULTS: Of 447 infants, 131 (29%) underwent surgical intervention and 26 (5.8%) had developed kidney injury. The median follow-up time was 9 years (IQ range, 7-12 years). The performance for detecting the need for surgical intervention was excellent for all grading systems (AUC > 0.90). However, for predicting kidney injury, the modified UTD classification exhibited significant improvement in accuracy (AUC = 0.913, 95%CI, 0.883-0.937) as compared with UTD classification (AUC = 0.887, 95%CI, 0.854-0.915) (P = 0.027). CONCLUSIONS: Our study confirms that the hydronephrosis grading systems provide excellent accuracy in discriminating patients who need surgical intervention among infants with AHN. Our findings suggest that the inclusion of kidney parenchymal thickness to UTD classification might increase the accuracy for predicting infants who may develop kidney injury. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Hidronefrosis , Sistema Urinario , Dilatación , Femenino , Humanos , Hidronefrosis/diagnóstico por imagen , Hidronefrosis/etiología , Lactante , Riñón/diagnóstico por imagen , Masculino , Embarazo , Estudios Retrospectivos , Ultrasonografía Prenatal , Sistema Urinario/diagnóstico por imagenRESUMEN
Cachexia associated with chronic kidney disease (CKD) has been linked to GH resistance. In CKD, GH treatment enhances muscular performance. We investigated the impact of GH on cachexia brought on by CKD. CKD was induced by 5/6 nephrectomy in c57BL/6J mice. After receiving GH (10 mg/kg/day) or saline treatment for six weeks, CKD mice were compared to sham-operated controls. GH normalized metabolic rate, increased food intake and weight growth, and improved in vivo muscular function (rotarod and grip strength) in CKD mice. GH decreased uncoupling proteins (UCP)s and increased muscle and adipose tissue ATP content in CKD mice. GH decreased lipolysis of adipose tissue by attenuating expression and protein content of adipose triglyceride lipase and protein content of phosphorylated hormone-sensitive lipase in CKD mice. GH reversed the increased expression of beige adipocyte markers (UCP-1, CD137, Tmem26, Tbx1, Prdm16, Pgc1α, and Cidea) and molecules implicated in adipose tissue browning (Cox2/Pgf2α, Tlr2, Myd88, and Traf6) in CKD mice. Additionally, GH normalized the molecular markers of processes connected to muscle wasting in CKD, such as myogenesis and muscle regeneration. By using RNAseq, we previously determined the top 12 skeletal muscle genes differentially expressed between mice with CKD and control animals. These 12 genes' aberrant expression has been linked to increased muscle thermogenesis, fibrosis, and poor muscle and neuron regeneration. In this study, we demonstrated that GH restored 7 of the top 12 differentially elevated muscle genes in CKD mice. In conclusion, GH might be an effective treatment for muscular atrophy and browning of adipose tissue in CKD-related cachexia.
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Hormona de Crecimiento Humana , Insuficiencia Renal Crónica , Ratones , Animales , Hormona del Crecimiento/metabolismo , Caquexia/etiología , Caquexia/complicaciones , Tejido Adiposo/metabolismo , Atrofia Muscular/etiología , Atrofia Muscular/complicaciones , Ratones Endogámicos C57BL , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Músculo Esquelético/metabolismo , Hormona de Crecimiento Humana/metabolismoRESUMEN
PURPOSE: The aim of this study was to evaluate the performance of the new classification of urinary tract dilatation (UTD) to predict long-term clinical outcomes in infants with isolated antenatal hydronephrosis (ANH). MATERIALS AND METHODS: Between 1989 and 2019, 447 infants diagnosed with isolated severe ANH and were prospectively followed. The main predictive variable for the analysis was the new UTD classification system. The events of interest were surgical interventions, urinary tract infections, chronic kidney disease stage II or higher, hypertension and proteinuria. The primary end-point was time until the occurrence of a composite event of renal injury, including proteinuria, hypertension and chronic kidney disease. RESULTS: Among 447 infants with ANH included in the analysis, 255 (57%) had UTD P1, 93 (20.8%) UTD P2 and 99 (22.2%) UTD P3. Median followup time was 9 years (IQR 7-12 years). Of 447 patients included in the analysis, 11 (2.5%) had hypertension, 13 (2.9%) exhibited persistent mild proteinuria, 14 (3%) developed chronic kidney disease Stage 2 and 26 (5.8%) had the composite outcome of renal injury. By survival analysis, the UTD system predicted accurately all events of interest. According to the Kaplan-Meier survival analysis, the probability of renal injury at 20 years of age was estimated at about 0%, 14% and 56% for patients assigned to UTD P1, UTD P2 and UTD P3, respectively (p <0.001). CONCLUSIONS: Our findings provide insights that the new UTD classification has a good performance for discriminating not only mid-term, but also long-term clinical outcomes, including renal injury.
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Dilatación Patológica/clasificación , Hidronefrosis/clasificación , Estudios de Cohortes , Dilatación Patológica/complicaciones , Dilatación Patológica/diagnóstico por imagen , Humanos , Hidronefrosis/complicaciones , Hidronefrosis/diagnóstico por imagen , Lactante , Recién Nacido , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía Prenatal , Sistema Urinario/diagnóstico por imagenRESUMEN
Chronic kidney disease (CKD) is a relentlessly progressive disease with a very high mortality mainly due to cardiovascular complications. Endothelial dysfunction is well documented in CKD and permanent loss of endothelial homeostasis leads to progressive organ damage. Most of the vast endothelial surface area is part of the microcirculation, but most research in CKD-related cardiovascular disease (CVD) has been devoted to macrovascular complications. We have reviewed all publications evaluating structure and function of the microcirculation in humans with CKD and animals with experimental CKD. Microvascular rarefaction, defined as a loss of perfused microvessels resulting in a significant decrease in microvascular density, is a quintessential finding in these studies. The median microvascular density was reduced by 29% in skeletal muscle and 24% in the heart in animal models of CKD and by 32% in human biopsy, autopsy and imaging studies. CKD induces rarefaction due to the loss of coherent vessel systems distal to the level of smaller arterioles, generating a typical heterogeneous pattern with avascular patches, resulting in a dysfunctional endothelium with diminished perfusion, shunting and tissue hypoxia. Endothelial cell apoptosis, hypertension, multiple metabolic, endocrine and immune disturbances of the uremic milieu and specifically, a dysregulated angiogenesis, all contribute to the multifactorial pathogenesis. By setting the stage for the development of tissue fibrosis and end organ failure, microvascular rarefaction is a principal pathogenic factor in the development of severe organ dysfunction in CKD patients, especially CVD, cerebrovascular dysfunction, muscular atrophy, cachexia, and progression of kidney disease. Treatment strategies for microvascular disease are urgently needed.
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Enfermedades Cardiovasculares/epidemiología , Microvasos/patología , Insuficiencia Renal Crónica/epidemiología , Animales , Enfermedades Cardiovasculares/fisiopatología , Comorbilidad , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Microcirculación , Microvasos/fisiopatología , Insuficiencia Renal Crónica/fisiopatologíaRESUMEN
Inflammation is involved in the pathogenesis of many disorders. However, the underlying mechanisms are often unknown. Here, we test whether cystinosin, the protein involved in cystinosis, is a critical regulator of galectin-3, a member of the ß-galactosidase binding protein family, during inflammation. Cystinosis is a lysosomal storage disorder and, despite ubiquitous expression of cystinosin, the kidney is the primary organ impacted by the disease. Cystinosin was found to enhance lysosomal localization and degradation of galectin-3. In Ctns-/- mice, a mouse model of cystinosis, galectin-3 is overexpressed in the kidney. The absence of galectin-3 in cystinotic mice ameliorates pathologic renal function and structure and decreases macrophage/monocyte infiltration in the kidney of the Ctns-/-Gal3-/- mice compared to Ctns-/- mice. These data strongly suggest that galectin-3 mediates inflammation involved in kidney disease progression in cystinosis. Furthermore, galectin-3 was found to interact with the pro-inflammatory cytokine Monocyte Chemoattractant Protein-1, which stimulates the recruitment of monocytes/macrophages, and proved to be significantly increased in the serum of Ctns-/- mice and also patients with cystinosis. Thus, our findings highlight a new role for cystinosin and galectin-3 interaction in inflammation and provide an additional mechanistic explanation for the kidney disease of cystinosis. This may lead to the identification of new drug targets to delay cystinosis progression.
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Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Cistinosis/complicaciones , Síndrome de Fanconi/inmunología , Galectina 3/metabolismo , Inflamación/inmunología , Sistemas de Transporte de Aminoácidos Neutros/genética , Animales , Quimiocina CCL2/inmunología , Quimiocina CCL2/metabolismo , Cistina/metabolismo , Cistinosis/inmunología , Cistinosis/metabolismo , Cistinosis/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Síndrome de Fanconi/metabolismo , Síndrome de Fanconi/patología , Femenino , Galectina 3/genética , Humanos , Inflamación/metabolismo , Inflamación/patología , Túbulos Renales Proximales/inmunología , Túbulos Renales Proximales/patología , Lisosomas/metabolismo , Macrófagos/inmunología , Masculino , Ratones , Ratones Noqueados , Monocitos/inmunología , ProteolisisRESUMEN
Cachexia is a multifactorial syndrome defined by significant body weight loss, fat and muscle mass reduction, and increased protein catabolism. Protein energy wasting (PEW) is characterized as a syndrome of adverse changes in nutrition and body composition being highly prevalent in patients with CKD, especially in those undergoing dialysis, and it is associated with high morbidity and mortality in this population. Multiple mechanisms are involved in the genesis of these adverse nutritional changes in CKD patients. There is no obvious distinction between PEW and cachexia from a pathophysiologic standpoint and should be considered as part of the spectrum of the same nutritional disorder in CKD with similar management approaches for prevention and treatment based on current understanding. A plethora of factors can affect the nutritional status of CKD patients requiring a combination of therapeutic approaches to prevent or reverse protein and energy depletion. At present, there is no effective pharmacologic intervention that prevents or attenuates muscle atrophy in catabolic conditions like CKD. Prevention and treatment of uremic muscle wasting involve optimal nutritional support, correction of acidosis, and physical exercise. There has been emerging consistent evidence that active treatment, perhaps by combining nutritional interventions and resistance exercise, may be able to improve but not totally reverse or prevent the supervening muscle wasting and weakness. Active research into more direct pharmacological treatment based on basic mechanistic research is much needed for this unmet medical need in patients with CKD.
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Caquexia/etiología , Suplementos Dietéticos , Fallo Renal Crónico/terapia , Apoyo Nutricional/métodos , Desnutrición Proteico-Calórica/etiología , Diálisis Renal/efectos adversos , Caquexia/fisiopatología , Caquexia/terapia , Terapia Combinada , Ejercicio Físico/fisiología , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Masculino , Debilidad Muscular/fisiopatología , Necesidades Nutricionales , Pronóstico , Desnutrición Proteico-Calórica/fisiopatología , Desnutrición Proteico-Calórica/terapia , Diálisis Renal/métodosRESUMEN
BACKGROUND: Posterior urethral valves (PUVs) are associated with severe consequences to the urinary tract and are a common cause of chronic kidney disease (CKD). The aim of this study was to develop clinical predictive model of CKD in a cohort of patients with PUVs. METHODS: In this retrospective cohort study, 173 patients with PUVs were systematically followed up at a single tertiary unit. The primary endpoint was CKD ≥ stage 3. Survival analyses were performed by Cox regression proportional hazard models with time-fixed and time-dependent covariables. RESULTS: Mean follow-up time was 83 months (SD, 70 months). Sixty-five children (37.6%) developed CKD stage ≥ 3. After adjustment by the time-dependent Cox model, baseline creatinine, nadir creatinine, hypertension, and proteinuria remained as predictors of the endpoint. After adjustment by time-fixed model, three variables were predictors of CKD ≥ stage 3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk score was divided into three categories: low-risk (69 children, 39.9%), medium-risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD ≥ stage 3 at 10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main limitation was the preclusion of some relevant variables, especially bladder dysfunction, that might contribute to a more accurate prediction of renal outcome. CONCLUSION: The model accurately predicts the risk of CKD in PUVs patients. This model could be clinically useful in applying timely intervention and in preventing the impairment of renal function.
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Modelos Biológicos , Insuficiencia Renal Crónica/epidemiología , Uretra/anomalías , Obstrucción Uretral/complicaciones , Preescolar , Progresión de la Enfermedad , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/etiología , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Análisis de Supervivencia , Obstrucción Uretral/congénito , Obstrucción Uretral/mortalidadRESUMEN
BACKGROUND: Solitary functioning kidney (SFK) is an important condition in the spectrum of congenital anomalies of the kidney and urinary tract. The aim of this study was to describe the risk factors for renal injury in a cohort of patients with congenital SFK. METHODS: In this retrospective cohort study, 162 patients with SFK were systematically followed up (median, 8.5 years). The primary endpoint was time until the occurrence of a composite event of renal injury, which includes proteinuria, hypertension, and chronic kidney disease (CKD). A predictive model was developed using Cox proportional hazards model and evaluated by c statistics. RESULTS: Among 162 children with SFK included in the analysis, 132 (81.5%) presented multicystic dysplastic kidney, 20 (12.3%) renal hypodysplasia, and 10 (6.2%) unilateral renal agenesis. Of 162 patients included in the analysis, 10 (6.2%) presented persistent proteinuria, 11 (6.8%) had hypertension, 9 (5.6%) developed CKD stage ≥ 3, and 18 (11%) developed the composite outcome. After adjustment by the Cox model, three variables remained as independent predictors of the composite event: creatinine (HR, 3.93; P < 0.001), recurrent urinary tract infection (UTI) (HR, 5.05; P = 0.002), and contralateral renal length at admission (HR, 0.974; P = 0.002). The probability of the composite event at 10 years of age was estimated as 3%, 11%, and 56% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). CONCLUSION: Our findings have shown an overall low risk of renal injury for most of infants with congenital SFK. Nevertheless, our prediction model enabled the identification of a subgroup of patients with an increased risk of renal injury over time.
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Modelos Biológicos , Nomogramas , Proteinuria/diagnóstico , Insuficiencia Renal Crónica/diagnóstico , Riñón Único/complicaciones , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Humanos , Incidencia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Proteinuria/epidemiología , Proteinuria/etiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Riñón Único/congénito , Riñón Único/mortalidad , Riñón Único/fisiopatologíaRESUMEN
BACKGROUND: Anorexia and malnutrition are associated with poor outcomes in children with chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: We assessed changes in body mass index (BMI) as kidney function declines and its association with risk for end-stage renal disease (ESRD) among 854 participants followed between 2005 to 2013 in the CKD in Children (CKiD) Study. PREDICTORS: Repeated measurements of estimated glomerular filtration rate (eGFR) by serum creatinine concentration in our trajectory analysis using mixed models; change in BMI z score (per year) after eGFR decreased to <35mL/min/1.73m2 in logistic regression models. OUTCOMES: Repeated measurements of BMI z score (as a reflection of weight status) in our trajectory analysis; ESRD in logistic regression models. RESULTS: During a mean longitudinal follow-up of 3.4 years, BMI z scores remained stable until eGFR decreased to <35mL/min/1.73m2. When eGFR decreased to <35mL/min/1.73m2, a mean decline in BMI z score of 0.13 (95% CI, 0.09-0.17) was noted with each 10-mL/min/1.73m2 further decline in eGFR. This was statistically significantly different from the weight trajectory when eGFR was ≥35mL/min/1.73 m2 (P<0.001). Among children and adolescents with significant weight loss (defined as decline in BMI z score > 0.2 per year) after eGFR decreased to <35mL/min/1.73m2, the odds of ESRD was 3.28 (95% CI, 1.53-7.05) times greater compared with participants with stable BMI z scores (BMI z score change per year of 0-0.1). LIMITATIONS: Observational nature of our study, lack of longitudinal assessments of inflammatory markers. CONCLUSIONS: In children and adolescents with CKD, weight loss mostly occurs when eGFR decreases to <35mL/min/1.73m2, and this weight loss was associated with higher risk for ESRD. Further studies are needed to define the reasons for the association between weight loss and more rapid progression to ESRD in children and adolescents.
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Índice de Masa Corporal , Progresión de la Enfermedad , Fallo Renal Crónico/etiología , Insuficiencia Renal Crónica/complicaciones , Pérdida de Peso , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/fisiopatología , Pruebas de Función Renal , Modelos Lineales , Masculino , Pronóstico , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Factores SexualesRESUMEN
PURPOSE OF REVIEW: The aim of this review is to provide an overview of the current advances in the understanding of the mechanisms involved in the progression of chronic kidney disease (CKD) with emphasis on the role of glomerular hemodynamics and tubulointerstitial fibrosis. RECENT FINDINGS: Despite the varied causes of CKD, the progressive destruction of renal tissue processes through a complex common pathway. Current studies have highlighted both the role of the abnormal intrarenal hemodynamics and of the activation of fibrogenic biochemical pathway in the replacement of normal renal structure by extracellular matrix and ultimately by fibrosis. Molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney has been identified. SUMMARY: There is a clear need to understand and elucidate the mechanisms of progression of CKD to develop efficient therapeutic strategies to halt decline of renal function in children.
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Progresión de la Enfermedad , Hemodinámica , Glomérulos Renales/fisiopatología , Túbulos Renales/patología , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/fisiopatología , Niño , Fibrosis , Humanos , Glomérulos Renales/patología , Túbulos Renales/fisiopatología , Insuficiencia Renal Crónica/diagnósticoRESUMEN
Loss of lean body mass is a relevant component of the cachexia, or protein energy wasting (PEW), syndrome. Reduced muscle mass seems to be the most solid criterion for the presence of cachexia/PEW in patients with chronic kidney disease (CKD), and those with greater muscle mass loss have a higher risk of death. Children with CKD have many risk factors for lean mass and muscle wasting, including poor appetite, inflammation, growth hormone resistance, and metabolic acidosis. Mortality risks in patients with CKD increases as body mass index (BMI) and weight decreases. However, data regarding cachexia/PEW and muscle wasting in children with CKD is scarce due to lack of consensus in diagnostic criteria and an appropriate investigative methodology. Further research is urgently needed to address this important complication in the pediatric CKD setting, which may have fundamental impact on clinical outcomes.