Consenso colombiano de expertos sobre recomendaciones informadas en la evidencia para la prevención, diagnóstico y manejo de la infección por SARS-CoV-2/COVID-19 en paciente pediátrico con enfermedad renal crónica o lesión renal aguda asociada a COVID-19 / Colombian consensus of experts on evidence-informed recommendations for the prevention, diagnosis, and management of SARS-CoV-2 / COVID-19 infection in pediatric patients with chronic kidney disease or acute kidney injury associated with COVID-19

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Abstract Introduction: The numbers of SARS-CoV-2 infection in the pediatric population are low so far. There is limited information about the behavior of SARS-CoV-2 in a pediatric patient with chronic kidney disease. Objective: To formulate informed recommendations to the prevention, diagnosis, and management of SARS-CoV-2 infection in pediatric patients with kidney disease or acute kidney injury associated with COVID-19 in Colombia. Methodology: A rapid systematic review was performed in Embase and Pubmed databases and scientific societies, to answer questions prioritized by clinical experts in pediatric nephrology. The quality of the evidence was evaluated with validated tools according to the type of study. The preliminary recommendations were consulted by an expert group. The agreement was defined when approval was obtained from at least 70% of the experts consulted. Results: A response was obtained from ' 9 experts in pediatric nephrology in Colombia, who declared the conflict of interest before the consultation. The range of agreement for the recommendations ranged from 78.9% to '00%. The recommendations did not require a second consultation. Conclusion: The evidence-based recommendations for the management of a patient with kidney disease and COVID-19 in the Colombian context are presented.

Prevalence of Bladder and Bowel Dysfunction in the Outpatient Clinic of Pediatric Urology and Nephrology / Prevalencia de la disfunción de la vejiga y del intestino en la consulta ambulatoria de urología y nefrología pediátrica

Zoom Image Abstract Objective Bladder and bowel dysfunction (BBD) is defined as the presence of functional alterations in both organs. The correct diagnosis and treatment prevent the exposure of patients to multiple antibiotic treatments, invasive procedures and radiological studies. The aim of the present study was to estimate the prevalence of BBD in the outpatient clinic of pediatric urology and nephrology. Methods A prospective cohort composed of 334 patients aged between 5 and 18 years was evaluated. The Pediatric Lower Urinary Tract Symptom Score (PLUTSS) was applied. A score higher than 8 was considered as significant urinary symptomatology. Moreover, the Bristol Stool Scale and the Rome IV Criteria for functional constipation and fecal incontinence were used. Patients with organic pathologies were excluded. The risk factors were evaluated using logistic regression models. Results The median age was 9 years old (interquartile range [IQR]: 6­13). The PLUTSS questionnaire was significant in 16.5% of the kids, constipation was found in 31.9%, and fecal incontinence, in 4%. The prevalence of BBD was of 27.8%. The female gender (odds ratio [OR]: 2.47; p = 0.002) and psychological disorders (OR: 4.637; p = 0.024) were considered risk factors. The evaluation of the PLUTSS questionnaire showed relevance regarding incontinence (OR: 3.059; p = 0.038), enuresis (OR: 8.532; p < 0.001); intermittent flow (OR: 9.211; p = 0.004), frequency (OR: 6.73; p = 0.005), and constipation (OR: 34.46; p < 0.001). Conclusions The prevalence of BBD is of 27.8% in the outpatient clinic. It is important to prevent associated complications and the exposure to multiple antibiotic treatments, as well as invasive and imaging procedures, which also generate high costs to the health system.

Resumen Objetivo El síndrome de disfunción de la vejiga y del intestino (DVI) se define como la presencia de alteraciones funcionales en ambos órganos. El correcto diagnóstico y tratamiento previene la exposición de los pacientes a múltiples manejos antibióticos, procedimientos invasivos y estudios radiológicos. El objetivo de este estudio es estimar la prevalencia de DVI en la consulta ambulatoria de urología y nefrología pediátrica. Métodos Se evaluó una cohorte prospectiva de 334 pacientes de 5 a 18 años. Se aplicó el cuestionario de Puntuación de Síntomas del Tracto Urinario Inferior (Pediatric Lower Urinary Tract Symptom Score, PLUTSS), cuyo resultado mayor a 8 fue considerado significativo. Adicionalmente, se usó la Escala de Heces de Bristol (Bristol Stool Scale) y los Criterios Roma IV (Rome IV Criteria) para estreñimiento e incontinencia fecal. Los factores de riesgo se evaluaron bajo modelos de regresión logística. Resultados La edad mediana fue de 9 años (rango intercuartil [RIC]: 6­13). El cuestionario PLUTSS fue significativo en 16,5% de los niños, y se observó estreñimiento en 31,9%, e incontinencia fecal en 4%. La prevalencia de DVI fue de 27,8%. El sexo femenino (razón de probabilidades [RP]: 2.47; p = 0.002) y desordenes psicológicos (RP: 4.637; p = 0.024) fueron considerados factores de riesgo. La evaluación del cuestionario PLUTSS mostró relevancia en incontinencia (RP: 3.059; p = 0.038), enuresis (RP: 8.532; p < 0.001), flujo intermitente (RP: 9.211; p = 0.004), frecuencia (RP: 6.73; p = 0.005), y estreñimiento (RP: 34.46; p < 0.001). Conclusiones La prevalencia de DVI fue de 27.8% en la consulta ambulatoria. Es importante prevenir complicaciones asociadas y la exposición a múltiples tratamientos antibióticos, procedimientos invasivos e imagenológicos, que adicionalmente generan altos costos al sistema de salud.

Recomendaciones para el uso racional de la prueba 25-hidroxivitamina D Resumen de política

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The exponential increase in the request for laboratory tests of 25-Hydroxyvitamin D or [25 (OH) D has ignited the alarms and generated a strong call for attention, since it may reflect deficiencies in the standardization of clinical practice and in the use non-systematic scientific evidence for decision-making in real life, which allows to analyze the indications of the test, its frequency, interpretation and even to assess the impact for health systems, especially when contrasted with the minimum or almost. No effects of the strategy of screening or supplying indiscriminately to the general population, without considering a comprehensive clinical assessment of risks and needs of people. From a purely public health impact point of view, the consequence of massive and unspecified requests is affecting most of the health systems and institutions at the global level. The primary studies that determined average population intake values have been widely used in the formulation of recommendations in Clinical Practice Guidelines, but unfortunately misinterpreted as cut points to diagnose disease and allow the exaggerated prescription of nutritional substitution. The coefficient of variation in routine tests to measure blood levels of 25 (OH) D is high (28%), decreasing the overall accuracy of the test and simultaneously, increasing both the falsely high and falsely low values. The most recent scientific evidence analyzes and seriously questions the usefulness and the real effect of the massive and indiscriminate practice of prescribing vitamin D without an exhaustive risk analysis. The available evidence is insufficient to recommend a general substitution of vitamin D to prevent fractures, falls, changes in bone mineral density, incidence of cardiovascular diseases, cerebrovascular disease, neoplasms and also to modify the growth curve of mothers' children. They received vitamin D as a substitute during pregnancy. The recommendations presented in the document are based on the critical analysis of current evidence and the principles of good clinical practice and invite to consider a rational use of 25 (OH) D tests in the context of a clinical practice focused on people and a comprehensive assessment of needs and risks. The principles of good practice suggest that clinicians may be able to justify that the results of the 25 (OH) D test strongly influence and define clinical practice and modify the outcomes that interest people and impact their health and wellness. Currently there is no clarity on how to interpret the results, and the relationship between symptoms and 25 (OH) D levels, which may not be consistent with the high prevalence of vitamin D deficiency reported. For this reason, it is suggested to review the rationale of the request for tests for systematic monitoring of levels of 25 (OH) D or in all cases where substitution is performed. Consider the use of 25 (OH) D tests within the comprehensive evaluation of people with suspicion or confirmation of the following conditions: rickets, osteomalacia, osteoporosis, hyper or hypoparathyroidism, malabsorption syndromes, sarcopenia, metabolic bone disease.

Growth hormone improves growth retardation induced by rapamycin without blocking its antiproliferative and antiangiogenic effects on rat growth plate.

Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3ß, increase of glycogen deposits and stabilization of ß-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis.

Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: a case report.

Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal phosphate reabsorption that leads to hypophosphatemia, rickets, and bone pain; hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in hypercalciuria. Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum alkaline phosphatase levels, hypercalciuria and nephrocalcinosis. The other members of the family presented some of these alterations: the mother, hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son, hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline phosphatases; the father, high alkaline phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of hereditary hypophosphatemic rickets with hypercalciuria.

Decreased cyclosporine exposure during the remission of nephrotic syndrome.

In this paper, we report the pharmacokinetics changes observed in seven children with steroid-resistant nephrotic syndrome (SRNS). They received cyclosporine A (CsA) microemulsion 6 mg/kg/day and, one week later, they were admitted to perform a 12-h pharmacokinetic profile with eight time sample points. The pharmacokinetic profile was repeated at 24 weeks of treatment, when all patients achieved remission. Blood concentration against time curves were constructed for each patient at weeks 1 and 24 of CsA treatment. Peak concentrations (C (max)) and the time needed to reach peak concentrations (t (max)) were directly determined from these plots. The area under the curve (AUC) was estimated by the trapezoidal rule. There was a statistically significant difference of the AUC, trough levels, and t (max) between weeks 1 and 24, with a decrease of AUC from 5,211 ng*h/ml in week 1 to 3,289 ng*h/ml in week 24, the trough levels decreased from 157 ng/ml to 96 ng/ml, and the t (max) decreased from 1.85 h to 1.00 h. The higher CsA bioavailability during the nephrotic state has to be considered when managing patients, since the target AUC cannot be the same throughout the treatment.