Schimke immuno-osseous dysplasia. A case report in Colombia.

Background: Schimke immune-osseous dysplasia (SIOD) is an ultra-rare multisystemic, monogenic, and autosomal recessive inherited disease caused by biallelic mutations in the SMARCAL1 gene. Approximately 100 cases have been reported worldwide. The disease is characterized by skeletal, renal, and immunological abnormalities. Case description: This is a 6-year-old female patient who debuted with nephrotic syndrome at five years of age, with a switch to corticosteroid resistance and poor response to immunosuppressive treatment received. The patient was admitted and referred to our institution due to convulsive status. During her hospitalization, thrombosis was found in the left renal vein, and a renal biopsy report of Collapsing Focal and Segmental Glomerulosclerosis (FSGS) was obtained. The patient had multiple infections during hospitalization, with T lymphocyte lymphopenia and severe IgG hypogammaglobulinemia. Additionally, given dysmorphic facies, delayed weight-height development, and spondyloepiphyseal dysplasia, exome sequencing was performed, finding an homozygous pathogenic variant c.1933C > T p.Arg645Cys in SMARCAL1, compatible with the diagnosis of SIOD. Discussion: We present the case of a patient that exhibited a severe phenotype of the disease, with skeletal, renal, severe combined immunological compromise and cerebrovascular involvement during follow-up, and the available proposed mechanisms of the disease focused on the clinical manifestations of this patient. It is the first case of SIOD reported in Colombia and the first comprehensive characterization reported in the literature of a patient with homozygosity of the known variant c.1933C > T p.Arg645Cys. Conclusion: A severe phenotype of the disease with cerebrovascular involvement by homozygosity of the known variant c.1933C > T p.Arg645Cys in the SMARCAL1 gene can be expected.

Proteinuria en la infancia: a propósito de un caso de enfermedad de Dent

Introducción: la proteinuria en la edad pediátrica es una entidad relativamente frecuente, la cual puede ser fisiológica o patológica. La segunda, por una alteración a nivel glomerular con pérdida de proteínas de gran tamaño o a nivel tubular, caracterizada por pérdida de proteínas de bajo peso molecular y alteraciones en la excreción de iones. Entre las enfermedades hereditarias que cursan con proteinuria tubular, se ha descrito la enfermedad de Dent, una patología ligada al cromosoma X. Esta enfermedad se manifiesta principalmente en varones, pero las mujeres pueden ser portadoras y tener manifestaciones clínicas leves de la enfermedad. La primera descripción de esta enfermedad fue hecha por Dent y Friedman en 1964. La mayoría de los casos recientemente reportados han sido en China y Alemania. Objetivo: realizar una revisión general de la enfermedad de Dent y del enfoque diagnóstico de la proteinuria en la infancia con base en nuestro caso, para así, sospechar de esta enfermedad. Descripción del caso: se presenta el caso de un paciente masculino sin antecedentes prenatales ni personales de importancia, quien presenta proteinuria persistente desde los primeros meses de vida y a quien, a los 7 años de edad, se le documenta la presencia de una variante ya conocida en el gen CLCN5, causante de la enfermedad de Dent tipo 1. Discusión: la proteinuria persistente patológica en la infancia debe ser estudiada debido a su posible relación con patologías que pueden afectar la función renal. Además de la diferenciación de la proteinuria persistente, de origen glomerular y tubular, la evaluación de alteraciones en la excreción de electrolitos, puede guiarnos hacia la realización de estudios genéticos y, por ende, al diagnóstico de patologías infrecuentes como la enfermedad de Dent. Conclusión: el enfoque diagnóstico de causas poco frecuentes de proteinuria tubular en la infancia, como la enfermedad de Dent, requiere de la valoración conjunta entre nefrología pediátrica y genética clínica.

Background: In pediatric patients, proteinuria is a relatively frequent entity that can be physiological or pathological. The second one, due to an alteration at the glomerular level with the loss of large proteins or at the tubular level, characterized mainly by the loss of low molecular weight proteins and changes in the excretion of ions. Among the hereditary diseases that present with tubular proteinuria, Dent disease is a disease linked to the X chromosome. Therefore, it manifests essentially in males, but women can be carriers and have minor clinical manifestations of the disease. Dent and Friedman made the first description of this disease in 1964. Recently, most of the cases have been reported in China and Germany. Objective: To perform a revision of Dent disease, as well as the diagnostic approach of childhood proteinuria based in our case in order to suspect this disease. Case description: This is the case of a masculine patient, without relevant prenatal and personal antecedents, the son of a father with polycystic renal disease, who presents persistent proteinuria from the first months of life, and who, at seven years old, the presence of a variant in the CLCN5 gene -causing of type 1 Dent disease- was documented. Discussion: The persistent pathological proteinuria in childhood must be studied due to its possible relation with pathologies that could affect renal function. Moreover, the differentiation among glomerular and tubular proteinuria can guide us to perform additional studies, including genetic tests to diagnose infrequent pathologies like Dent disease. Conclusion: The diagnostic approach to rare causes of tubular proteinuria in childhood, such as Dent's disease, requires joint assessment between pediatric nephrology and clinical genetics.

Urinary KIM-1 is not correlated with gestational age among 5-year-old children born prematurely.

Background: Preterm birth is associated with decreased nephron endowment. Currently, there is no reliable non-invasive biomarker to identify or monitor decreased nephron number in at-risk patients. Urinary Kidney Injury Molecule-1 (KIM-1) is a biomarker of acute and chronic renal injury. We measured urinary KIM-1 among a wide array of other potential biomarkers. Methods: We conducted an ambispective cohort study of 5-years-old children born prematurely and healthy controls identified from city schools. Detailed anthropometrics, renal ultrasound dimensions, and biochemical parameters were measured. Urinary KIM-1 was measured using Luminex® technology. Age independent z-scores were calculated and compared. Spearman correlations were used for estimating the association between measures and KIM-1. Results: We enrolled 129 children, 97 (75.2%) born pre-term and 32 (24.8%) healthy controls born at full-term. Pre-term patients had significantly lower weight and body surface area than controls. Pre-term patients and controls did not differ in current age, sex, race, height, blood pressure, urinary sodium, fractional sodium excretion, serum creatinine and estimated GFR. All spearman correlation between KIM-1 and gestational age, renal and serum measurements were weak without statistical significance. Conclusion: In 5-year-old children born prematurely, KIM-1 was not correlated with gestational age. Further prospective studies need to confirm this finding.

B-cell activating factor (BAFF) and its receptors' expression in pediatric nephrotic syndrome is associated with worse prognosis.

AIM: Immune pathogenesis of nephrotic syndrome (NS) is not completely understood. We aimed to evaluate the expression of B-cell activating factor (BAFF) and its receptors in renal samples from pediatric NS patients and its relationship with renal function survival. MATERIALS AND METHODS: We conducted an ambispective study on 33 patients with pediatric NS. Immunohistochemistry for BAFF, TACI, BCMA and BR3 was performed. Markers were evaluated on podocytes and interstitial inflammatory infiltrates (III). We performed Kaplan-Meier curves to describe renal function survival according to markers' expression. RESULTS: Thirty-three NS patients were included. Minimal change disease was seen in 21 (63.6%) patients, and focal segmental glomerulosclerosis in 12 (36.4%). BAFF was found in podocytes (18.2% of samples) and III (36.4% of samples), BAFF-R in one sample, TACI in 4 (podocytes and III), and BCMA in 5 samples of podocytes and 7 of III. BAFF on podocytes and III was associated with worst renal function at follow-up; those patients had 25% probability of having GFR >90 mL/min/1.73m2, versus 84.9% when absent (p = 0.0067). Patients with BAFF in III had 42.9% probability of having GFR>90 mL/min/1.73 m2, versus 94.1% when absent (p = 0.0063). CONCLUSION: BAFF expression in renal biopsies could be a prognostic factor for renal function.

Renal volume of five-year-old preterm children are not different than full-term controls

Abstract Objective: In previous studies, smaller renal volumes were reported in prematurely born infants, however, these renal volumes were not corrected for body surface area, the main determinant of renal size. Given the rapid growth of the renal cortex after premature birth, the authors hypothesized that corrected volumes would not differ from healthy controls. Methods: Ambispective cohort study with prospective follow-up of prematurely born babies in a large specialized center and retrospectively recruited healthy control group. Children were assessed for renal length and renal volumes at age 5 by three independent ultrasonographers. Detailed anthropometry, blood pressure and renal function were also obtained. Age independent z-scores were calculated for all parameters and compared using descriptive statistics. Results: Eighty-nine premature study participants (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age) were studied. Study participants did not differ in age, sex, Afro-Colombian descent, height, blood pressure, serum creatinine, or new Schwartz eGFR. Premature study participants had a significantly lower weight (17.65 ± 2.93 kg) than controls (19.05 ± 2.81 kg, p = 0.0072) and lower body surface area. The right renal volumes were significantly smaller (39.4 vs 43.4 mL), but after correction for body surface area, the renal volume and renal length z-scores were identical for both kidneys (mean right kidney -0.707 vs -0.507; mean left kidney -0.498 vs -0.524, respectively). Conclusion: Renal volumes need to be corrected to body surface area. After correction for body surface area, 5-year-old healthy and prematurely born children have comparable renal volumes.

Treatment of post-transplant recurrent FSGS in children using plasmapheresis and augmentation of immunosuppression.

BACKGROUND: Up to 60% of pediatric renal transplant recipients with end-stage renal disease due to primary focal and segmental glomerulosclerosis (FSGS) may develop recurrent disease. Such recurrence is associated with poor prognosis if no remission is achieved. We report a single center experience with a protocol based on plasmapheresis and increased immunosuppression that resulted in a high long-lived remission rate. METHODS: This retrospective cohort study included consecutive pediatric renal transplant patients with recurrent FSGS treated with a standardized protocol using plasmapheresis and cyclophosphamide to supplement usual post-transplant immunosuppression with calcineurin inhibitors and steroids. Relapse was defined as urinary protein/creatinine ratio > 1.0 g/g and remission as < 0.5 g/g. RESULTS: Seventeen patients with FSGS recurrence post-transplant were treated. All had therapy resistant FSGS in native kidneys and had been on dialysis from 4 to 10 years. Of the 17, one died perioperatively from a pulmonary thromboembolism. Fifteen others achieved a complete remission within 3 months of treatment for FSGS recurrence. After a median follow-up period of 4 years, there were no recurrences of significant proteinuria. One patient achieved remission with rituximab. CONCLUSION: The addition of plasmapheresis and cyclophosphamide to a calcineurin- and steroid-based immunosuppression regime was highly successful in inducing high remission rates with recurrent FSGS. Prospective trials are needed to evaluate further the efficacy of increased immunosuppression along with plasmapheresis in this setting.

Renal volume of five-year-old preterm children are not different than full-term controls.

OBJECTIVE: In previous studies, smaller renal volumes were reported in prematurely born infants, however, these renal volumes were not corrected for body surface area, the main determinant of renal size. Given the rapid growth of the renal cortex after premature birth, the authors hypothesized that corrected volumes would not differ from healthy controls. METHODS: Ambispective cohort study with prospective follow-up of prematurely born babies in a large specialized center and retrospectively recruited healthy control group. Children were assessed for renal length and renal volumes at age 5 by three independent ultrasonographers. Detailed anthropometry, blood pressure and renal function were also obtained. Age independent z-scores were calculated for all parameters and compared using descriptive statistics. RESULTS: Eighty-nine premature study participants (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age) were studied. Study participants did not differ in age, sex, Afro-Colombian descent, height, blood pressure, serum creatinine, or new Schwartz eGFR. Premature study participants had a significantly lower weight (17.65 ± 2.93 kg) than controls (19.05 ± 2.81 kg, p = 0.0072) and lower body surface area. The right renal volumes were significantly smaller (39.4 vs 43.4 mL), but after correction for body surface area, the renal volume and renal length z-scores were identical for both kidneys (mean right kidney -0.707 vs -0.507; mean left kidney -0.498 vs -0.524, respectively). CONCLUSION: Renal volumes need to be corrected to body surface area. After correction for body surface area, 5-year-old healthy and prematurely born children have comparable renal volumes.

Low agreement between kidney volume and kidney length z-scores.

BACKGROUND: Pediatric nephrologists use kidney length and kidney volume z-scores to longitudinally assess normal nephron endowment. However, most radiologists only report kidney length. Agreement between kidney length and kidney volume z-scores in children has been understudied. This study aims to assess agreement between kidney length and kidney volume z-scores in children. METHODS: This novel cross-sectional cohort study prospectively followed prematurely born babies from a large specialized prematurity follow-up center. A healthy control group matched the cases by age and sex and was recruited from schools. Children were assessed for kidney length and kidney volumes at age 5 by three independent ultrasonographers. All measurements were performed in triplicate. Detailed anthropometry, blood pressure, and kidney function were also obtained. Age-independent z-scores were calculated for all parameters according to Scholbach and Weitzel and compared using descriptive statistics. RESULTS: We studied 89 premature patients (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age). There were 732 determinations of kidney length, width, and thickness. The mean z-score of the right kidney length was 0.65 ± 0.08 (SEM) compared with 0.88 ± 0.08 of the left kidney length (p = 0.0003, two-sided paired t test). The squared correlation coefficient for kidney volume to kidney length was 0.32 (p < 0.0001). Bland and Altman analysis revealed considerable bias with - 1.36 ± 0.76 standard deviations and 95% limits of agreement from - 2.83 to - 0.16. CONCLUSION: Reporting only kidney length results in significant overestimation of age-independent z-scores. Based on our findings, consideration to measuring all kidney dimensions may be more appropriate.

Low Birthweight as a Risk Factor for Non-communicable Diseases in Adults.

According to studies undertaken over the past 40 years, low birthweight (LBW) is not only a significant predictor of perinatal death and morbidity, but also increases the risk of chronic non-communicable diseases (NCDs) in adulthood. The purpose of this paper is to summarize the research on LBW as a risk factor for NCDs in adults. The Barker hypothesis was based on the finding that adults with an LBW or an unhealthy intrauterine environment, as well as a rapid catch-up, die due to NCDs. Over the last few decades, terminology such as thrifty genes, fetal programming, developmental origins of health and disease (DOHaD), and epigenetic factors have been coined. The most common NCDs include cardiovascular disease, diabetes mellitus type 2 (DMT2), hypertension (HT), dyslipidemia, proteinuria, and chronic kidney disease (CKD). Studies in mothers who experienced famine and those that solely reported birth weight as a risk factor for mortality support the concept. Although the etiology of NCD is unknown, Barry Brenner explained the notion of a low glomerular number (nGlom) in LBW children, followed by the progression to hyperfiltration as the physiopathologic etiology of HT and CKD in adults based on Guyton's renal physiology work. Autopsies of several ethnic groups have revealed anatomopathologic evidence in fetuses and adult kidneys. Because of the renal reserve, demonstrating renal function in proportion to renal volume in vivo is more difficult in adults. The greatest impact of these theories can be seen in pediatrics and obstetrics practice.

Renal length z-score for the detection of dysfunction in children with solitary functioning kidney.

AIM: To evaluate whether renal length z-scores predict renal dysfunction in children with a solitary functioning kidney (SFK). METHODS: In a single-centre retrospective cohort of children with SFK, we correlated body mass index z-scores, extracellular volume and lean body mass to renal length z-scores. We grouped these z-scores to other markers of renal dysfunction (proteinuria, hypertension, extracellular volume and abnormal estimated glomerular function rate [eGFR]) and analysed renal length z-score with multivariate analysis, receiver-operated characteristics (ROC) plots and Youden's index to determine an appropriate cut-off. RESULTS: 111 children had a median follow-up 5.08 years, eGFR 80.8 mL/min/1.73 m2 , and age at last follow-up 7.4 (3.8-13.4 years). The median renal length z-scores of those without any renal dysfunction (n = 37, 25.1%) were greater (+3.66, interquartile range 3.02-4.47) than those with renal dysfunction (median 3.11, interquartile range 1.76-4.11, P = .0107, Mann-Whitney test). Using a cut-off of z-score of >+1.911, the odds ratio for having no renal dysfunction was 0.07 (95% CI 0.002-0.459, P = .0010). However, accuracy of the renal length z-score was poor (ROC curve 0.6488). CONCLUSION: In this cohort of children with SKF, using the renal length z-score as a biomarker of renal dysfunction at 7 years of age is not recommended.

Acute renal failure in children. Multicenter prospective cohort study in medium-complexity intensive care units from the Colombian southeast.

BACKGROUND: Acute kidney injury is frequent in critically ill children; however, it varies in causality and epidemiology according to the level of patient care complexity. A multicenter prospective cohort study was conducted in four medium-complexity pediatric intensive care units from the Colombian southeast aimed to estimate the clinical prognosis of patients with diagnosis of acute kidney injury. METHODS: We included children >28 days and <18 years of age, who were admitted with diagnosis of acute kidney injury classified by Kidney Disease Improving Global Outcomes (KDIGO), during the period from January to December 2017. Severe acute kidney injury was defined as stage 2 and stage 3 classifications. Maximum KDIGO was evaluated during the hospital stay and follow up. Length of hospital stay, use of mechanical ventilation and vasoactive drugs, use of renal replacement therapy, and mortality were assessed until discharge. RESULTS: Prevalence at admission of acute kidney injury was 5.2% (95%CI 4.3% to 6.2%). It was found that 71% of the patients had their maximum KDIGO on day one; an increment in the maximum stage of acute kidney injury increased the pediatric intensive care unit stay. Patients with maximum KDIGO 3 were associated with greater use of mechanical ventilation (47%), compared with maximum KDIGO 2 (37%) and maximum KDIGO 1 (16%). Eight patients with maximum KDIGO 2 and 14 with maximum KDIGO 3 required renal replacement therapy. Mortality was at 11.8% (95%CI 6.4% to 19.4%). CONCLUSION: Acute kidney injury, established and classified according to KDIGO as severe and its maximum stage, was associated with worse clinical outcomes; early therapeutic efforts should focus on preventing the progression to severe stages.

Hematuria en la niñez: revisión sistemática cualitativa / Hematuria in the childhood A systematic cualitative review

Introducción: la hematuria aislada en niños es un hallazgo frecuente en la práctica clínica diaria del médico general y el pediatra, y un reto diagnóstico para averiguar su etiología y manejo. Objetivo: describir las pautas básicas para el diagnóstico y manejo de la hematuria aislada en menores de 18 años por el médico general y el pediatra. Materiales y métodos: se realizó una búsqueda bibliográfica sistemática en las bases de datos PubMed, ScienceDirect, LILACS y Embase, utilizando palabras claves del DeCS (español) y MeSH (inglés), mediante las combinaciones con la conjunción «AND¼ o la disyunción «OR¼, de manuscritos tipo estudios observacionales, ensayos clínicos, guías de práctica clínica y revisiones sistemáticas, publicados entre 1995 y 2017, que describieran el diagnóstico y el manejo básico de la hematuria. La calidad de los artículos fue evaluada por medio de los instrumentos PRISMA, CONSORT y STROBE, según correspondiera. Resultados: se identificaron 402 publicaciones, de las cuales 34 cumplieron con los criterios y 28 fueron seleccionadas para realizar esta revisión. Conclusiones: la hematuria aislada se define por el hallazgo de cinco eritrocitos por campo de alto poder en orina fresca centrifugada o más de cinco eritrocitos por microlitro en orina fresca no centrifugada. El diagnóstico y tratamiento se realiza por pasos: a) historia clínica y b) confirmación por microscopía óptica de alta resolución. Diferenciar la hematuria benigna de las que requieren paraclínicos de extensión es primordial para confirmarla más tempranamente, evitar procedimientos invasivos, disminuir el gasto en salud y hacer un seguimiento predictivo. (AU)

Introduction: Isolated hematuria in children is a frequent finding in the daily clinical practice of the general physician and pediatrician, being a diagnostic challenge to find out its etiology and management. Objective: To describe the basic guidelines for the diagnosis and management of isolated hematuria in children under 18 years of age by the general physician and the pediatrician. Materials and methods: A systematic bibliographic search was carried out in the databases PubMed, ScienceDirect, LILACS and Embase, using key words from DeCS (Spanish) and MeSH (English) through combinations with the conjunction "AND" or the disjunction " OR ", of manuscripts such as observational studies, clinical trials, clinical practice guidelines and systematic reviews, published between 1995 and 2017 that described the basic diagnosis and management of hematuria. The quality of the articles was evaluated through the PRISMA, CONSORT and STROBE instruments, as was appropriate. Results: 402 publications were identified, of which 34 met the criteria and 28 were selected to carry out this review. Conclusions: Isolated hematuria is defined by the finding of five erythrocytes per high power field in centrifuged fresh urine or more than five erythrocytes per microliter in fresh non-centrifuged urine Diagnosis and treatment are carried out in steps: a) clinical history, and b) confirmation by high resolution optical microscopy. Differentiating benign hematuria from those requiring paraclinical extension is essential to confirm it earlier, avoid invasive procedures, decrease health expenditure and make predictive follow-up. (AU)

Diagnóstico prenatal de hidronefrosis y seguimiento postnatal en la ciudad de Cali entre 1987 y 1995

Se presenta la revisión retrospectiva de 90 pacientes con hidronefrosis prenatal captados en el Hospital Universitario del Valle Evaristo García, Clínica Rafael Uribe Uribe del instituto de Seguros Sociales, Hospital Infantil Club Noel y en los consultorios particulares de tres nefrólogos pediatras de la ciudadde Cali entre el 1o. de enero de 1987 y el 30 de junio de 1995. Se revisaron las historias clínicas y los estudios imagenológicos durante el período prenatal y el seguimiento postnatal. Resultados: se estudiaron 90 pacientes con 127 unidades renales comprometidas. El promedio de edad materna es de 28 años y el 50 por ciento de ellas son primigestantes. La edad media en que se hizo el diagnóstico fue a las 30 mas o menos 5 semanas de gestación (20-40 semanas). Hubo predominio del sexo masculino en el 78 por ciento de los casos. Los diagnósticos prenatales más frecuentes fueron hidronefrosis unilateral (58 por ciento), hidronefrosis bilateral (26 por ciento) y riñón displásico multiquístico (14 por ciento). Luego de la evaluación postnatal con ecografía y cistouretrografía miccional cíclica, y estudios complementarios cuando se consideró necesario, los diagnósticos finales fueron hidronefrosis no obstructiva (43 por ciento), reflujo vesicoureteral (22 por ciento), hidronefrosis obstructiva (13 por ciento), riñón displásico multiquístico (8 por ciento), doble sistema colector (5 por ciento), otros (megauréter, secuencia de Potter, ectopia renal cruzada, ureterocele y divertículo paraureteral) (6 por ciento) y valvas de uretra posterior (3 por ciento). Los pacientes fueron discutidos en la Clínica de Nefro-Urología para definir conducta. Veintinueve pacientes (32 por ciento) requirieron corrección quirúrgica (12 pieloplastias, 11 reimplantes ureterales, tres polectomías, una fulguración de valvas, una vesicostomía y una nefrectomía). La función renal de los pacientes con hidronefrosis obstructiva se normalizó después de la cirugía. En el 23.3 por ciento de los casos (21 pacientes) se presentó infección urinaria en la fase inicial del estudio. En 70 pacientes se evaluó la función renal en el momento de entrada al estudio, siendo normal en el 96 por ciento; estaba disminuida en los dos pacientes con valvas de uretra posterior y en un paciente con reflujo vésico-ureteral grado IV bilateral.