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.

Small vessel vasculitis, different renal outcomes in pediatric patients. Case reports

Vasculitis mainly affects the walls of the blood vessels, and is an uncommon disease in the pediatric population. In general, they are classified according to the EULAR / PreS consensus in children and in adults according to the Chapel-Hill consensus conference. ANCA-associated vasculitis (AAV) is part of small-vessel disease and is represented by granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and others. The representative renal histopathological findings are focal necrotizing glomerulonephritis with crescents, variable interstitial inflammation, absence of immune complexes, or small deposits of immunoglobulins. Clinically, AAV can manifest with hematuria, proteinuria, high blood pressure, and/or rapidly progressive glomerulonephritis. GPA can severely affect the kidney in 75% of cases. In MPA, renal involvement (75-90%) can be rapid and severe with the possibility of requiring renal replacement therapy in more than half of the patients. Furthermore, up to 25% of patients may have high blood pressure, and the mortality at one year can be up to 85%. In EGPA the renal involvement is usually mild. Three pediatric cases of AAV with different renal outcomes are presented, including the need for renal replacement therapy with the recovery of renal function, kidney transplantation, and death, followed in a fourth level of care institution in Colombia.

Las vasculitis, patologías cuyo hallazgo principal es la afectación de las paredes de los vasos sanguíneos, se presentan de forma infrecuente en la población pediátrica. En general, en niños se clasifican de acuerdo con el consenso de la EULAR/PReS, y en adultos, según la Conferencia de Consenso de Chapel-Hill. Las vasculitis asociadas con ANCA (VAA) hacen parte de las vasculitis de pequeños vasos y están representadas por la granulomatosis con poliangeítis (GPA), la granulomatosis eosinofílica con poliangeítis (EGPA) y la poliangeítis microscópica (PAM), entre otras. A nivel renal, los hallazgos histopatológicos representativos son la glomerulonefritis focal necrotizante con media luna, inflamación intersticial variable, ausencia de complejos inmunes o pequeños depósitos de inmunoglobulinas. Clínicamente, las VAA pueden manifestarse con hematuria, proteinuria, hipertensión arterial o glomerulonefritis rápidamente progresiva. La GPA puede afectar de forma severa el riñón en el 75% de los casos, mientras que, en la PAM, el compromiso renal (75-90%) puede ser rápido y severo con posibilidad de requerir terapia de reemplazo renal en más de la mitad de los pacientes. Además, hasta el 25% de los casos puede tener hipertensión arterial, con una mortalidad a un ario de 85%. En la EGPA, el compromiso renal suele ser leve. Se presentan 3 casos pediátricos de VAA con diferentes desenlaces renales, que incluyen necesidad de terapia de reemplazo renal con recuperación de función renal, trasplante renal y muerte, seguidas en una institución de IV nivel del suroccidente colombiano.

Agreement between biopsy and renal function in pediatric patients with lupus nephritis. A retrospective study / Acuerdo entre biopsia y función renal en pacientes pediátricos con nefritis lúpica. Un estudio retrospectivo

ABSTRACT Introduction: Lupus nephritis (LN) is a consequence of Systemic Lupus Erythematosus (SLE). Renal biopsy is a potential prognostic biomarker for renal function. Objective: To correlate histopathological findings and renal function in children with LN. Materials and methods: A retrospective observational study was conducted on children with a histopathological diagnosis of NL. Patients with no follow-up registered were excluded. The kidney biopsy at diagnosis was evaluated using the ISN/RPS scale. The Kappa index was used to determine the level of agreement between renal failure (Glomerular Filtration Rate [GFR] < 60 mL/min/1.73 m2) and presence or absence of each index on the modified ISN/RPS scale. Results: A total of 57 patients with NL were treated from 2011 to 2018 at the institution. Of these, 40 (70%) met inclusion criteria, and 10 (25%) were male. The median age of NL diagnosis was 12.9 years (IQR, 11.1-14.9). Follow-up time was 2.3 years (IQR, 1.0-5.16). At diagnosis, karyorrhexis was the characteristic with highest level of agreement with renal failure (k = 0.1873 SE = 0.0759 P = .0068) and at the last follow-up, it was global segmental sclerosis (k = 0.1481 SE = 0.078 P = .0287). There was no difference in the GFR at the last follow-up and the presence of proteinuria at diagnosis (P = .3936). Conclusion: Renal biopsy findings may be an insufficient tool to predict renal function. Treat ment and prognosis of patients with NL should be done using other biomarkers and clinical signs. Prospective studies should be performed to confirm this hypothesis.

RESUMEN Introducción: La nefritis lúpica (NL) es una consecuencia del lupus eritematoso sistémico (LES). La biopsia renal es un potencial biomarcador de pronóstico de función renal. Objetivo: Correlacionar hallazgos histopatológicos y la función renal de los pacientes pediátricos con la NL. Materiales y métodos: Estudio observacional retrospectivo. Se incluyeron pacientes pediátricos con diagnóstico histopatológico de NL. Se excluyeron pacientes sin seguimiento por la institución. Se evaluó la biopsia renal al diagnóstico con la escala modificada de la International Society of Nephrology and the Renal Pathology Society (ISN/RPS). Se usó el índice kappa para determinar el nivel de acuerdo entre la falla renal (tasa de filtración glomerular [TFG] < 60 mL/min/1,73 m2) y la presencia o ausencia de cada índice de la escala modificada de la ISN/RPS. Resultados: Entre el 2011 y el 2018, 57 pacientes con NL fueron atendidos en la institución, 40 cumplieron con los criterios de inclusión, 10 (25%) eran de sexo masculino. La mediana de edad de diagnóstico de NL fue 12,9 arios (IQR 11,1 a 14,9). El tiempo de seguimiento fue de 2,3 años (IQR 1,0 a 5,16). Al diagnóstico, la cariorexis fue la característica de la escala con mayor nivel de acuerdo con la falla renal (k = 0,1873, EE = 0,0759, p = 0,0068) y al último seguimiento lo fue la esclerosis segmentaria global (k = 0,1481, EE = 0,078, p = 0,0287). No hubo diferencia en la TFG al último seguimiento y presencia de proteinuria al diagnóstico (p = 0,3936). Conclusión: La biopsia renal puede ser insuficiente para evaluar la predicción de la función renal. El tratamiento de pacientes con NL debe realizarse utilizando otros biomarcadores y signos clínicos. Deben hacerse estudios prospectivos que puedan confirmar esta hipótesis.

New PAX2 Mutation Associated with Polycystic Kidney Disease: A Case Report.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage renal disease in children. Diagnosis by genetic testing has proven challenging due to its genetic and phenotypic heterogeneity, as well as incomplete penetrance. We report a case on a 16-months old female with a history of renal cysts and a PAX2 mutation. CASE PRESENTATION: The patient presented with a prenatal diagnosis of Potter sequence and a postnatal diagnosis of renal cysts. An ultrasound at 20 weeks gestation revealed right renal agenesis and possible left renal dysplasia. Post natal genetic analyses identified a novel mutation in PAX2. CONCLUSION: Cystic kidney disease is often underdiagnosed due to its variable expressivity and wide range of clinical manifestations; PAX2 genetic screening should be considered for all patients with CAKUT.

PHEX Gene Mutation in a Patient with X-Linked Hypophosphatemic Rickets in a Developing Country.

INTRODUCTION: X-linked hypophosphatemic rickets is part of a larger group of hereditary diseases characterized by renal phosphate loss, which causes growth disorders, rickets, and osteomalacia. These conditions are characterized by disorders in phosphate equilibrium, which is essential for bone formation. CASE REPORT: A female patient presented with bone deformities of the inferior extremities, prominent joints, and loss of teeth. She received initial management with oral calcium and orthotics in inferior extremities, with poor clinical outcome. PHEX gene sequencing revealed a pathogenic variant c.1601C>T (p.Pro534Leu). DISCUSSION: XLHR is caused by mutations in the PHEX gene; to date, more than 460 mutations have been associated with the disease. Clinically, it is characterized by bowing of the lower extremities, decreased growth, musculoskeletal complaints, dental abscesses, and other clinical signs and symptoms of rickets.

The prototoxin LYPD6B modulates heteromeric α3ß4-containing nicotinic acetylcholine receptors, but not α7 homomers.

Prototoxins are a diverse family of membrane-tethered molecules expressed in the nervous system that modulate nicotinic cholinergic signaling, but their functions and specificity have yet to be completely explored. We tested the selectivity and efficacy of leukocyte antigen, PLAUR (plasminogen activator, urokinase receptor) domain-containing (LYPD)-6B on α3ß4-, α3α5ß4-, and α7-containing nicotinic acetylcholine receptors (nAChRs). To constrain stoichiometry, fusion proteins encoding concatemers of human α3, ß4, and α5 (D and N variants) subunits were expressed in Xenopus laevis oocytes and tested with or without LYPD6B. We used the 2-electrode voltage-clamp method to quantify responses to acetylcholine (ACh): agonist sensitivity (EC50), maximal agonist-induced current (Imax), and time constant (τ) of desensitization. For ß4-α3-α3-ß4-α3 and ß4-α3-ß4-α3-α3, LYPD6B decreased EC50 from 631 to 79 µM, reduced Imax by at least 59%, and decreased τ. For ß4-α3-α5D-ß4-α3 and ß4-α3-ß4-α-α5D, LYPD6B decreased Imax by 63 and 32%, respectively. Thus, LYPD6B acted only on (α3)3(ß4)2 and (α3)2(α5D)(ß4)2 and did not affect the properties of (α3)2(ß4)3, α7, or (α3)2(α5N)(ß4)2 nAChRs. Therefore, LYPD6B acts as a mixed modulator that enhances the sensitivity of (α3)3(ß4)2 nAChRs to ACh while reducing ACh-induced whole-cell currents. LYPD6B also negatively modulates α3ß4 nAChRs that include the α5D common human variant, but not the N variant associated with nicotine dependence.

Emerging Role of the Cerebrospinal Fluid - Neuronal Interface in Neuropathology.

The choroid plexus and cerebrospinal fluid have recently begun to emerge as essential regulators of neural function. Factors produced by the choroid plexus are released into the ventricular environment and thus provide a rich source of extracellular signaling molecules throughout the central nervous system. Identified factors in the cerebrospinal fluid include growth factors, hormones, proteins, peptides, lipids, glucose, microRNAs (miRNAs), messenger RNA (mRNA), and enzymes. In addition to mediating neural function, these factors have the potential to serve as biomarkers of disease states. In this review, we highlight recent advances demonstrating the importance of extracellular signaling mechanisms in mediating neural function and provide recent evidence for their role in neuropathology.

Malnutrición en niños colombianos con infección por VIH/SIDA / Malnutrition in Colombian children with HIV/AIDS infection

Introducción: La desnutrición (DNT) es una de las complicaciones más tempranas que se presenta en niños con infección por VIH/SIDA, asociada a su morbimortalidad. Igualmente como consecuencia de la terapia antriretroviral y otros medicamentos utilizados, se han encontrado problemas de resistencia a la insulina y obesidad. Objetivo: Determinar la prevalencia de malnutrición (MNT) en niños con infección por VIH/SIDA por carga viral de la Clínica de VIH/SIDA del Hospital Universitario del Valle de Cali, Colombia (HUV) y su posible asociación con algunos factores de riesgo. Metodología: Estudio descriptivo, observacional de corte transversal, con análisis de casos y controles, a quienes se les tomaron datos como carga viral, %CD4, peso y talla. Se categorizó la carga viral (copias/ml) en: <400, ≥400-<300000, ≥30000-<1 millón y ≥1 millón; y el %CD4 en: <15%, ≥15%-<25% y ≥25%. Se consideró DNT global (déficit P/E≥10%), DNT crónica (déficit T/E≥5%), DNT aguda (déficit P/T≥10%) y sobrepeso (exceso P/T≥10%). Resultados: Fueron incluidos 111 niños entre 0 meses y 15 años de edad, con predominio del género masculino (51,3%), con modo de transmisión vertical en 91,8%. El 58.5% tenían entre ≥400-<300000 copias/ml de carga viral; y el 59% presentaron %CD4 ≥25%. La valoración nutricional evidenció DNT global en 64%, DNT aguda en 58%, DNT crónica en 22% y sobrepeso en 18%. Hubo riesgo de 1.7, 1.5 y 2.0 veces más de presentar DNT global, aguda y crónica, respectivamente, si la carga viral era ≥400 copias/ml. Conclusión: En niños con infección por VIH/SIDA por carga viral de la Clínica Pediátrica de VIH/SIDA del HUV de Cali, Colombia, la prevalencia de MNT fue superior al 18%, con una relación positiva superior a 1.5 veces entre carga viral y los diferentes tipos de DNT.

Introduction: Undernutrition (UNT) is a complication that occurs earlier in children with HIV/AIDS associated morbidity and mortality. Also as a result of anti-retroviral therapies and other drugs used, have encountered problems of insulin resistance and obesity. Objective: To determine the prevalence of malnutrition (MNT) in children diagnosed with HIV/AIDS by viral load in the Pediatric Clinic HIV/AIDS at the Hospital Universitario del Valle in Cali, Colombia (HUV) and its possible association with certain risk factors. Methodology: A descriptive cross-sectional study, with case-control analysis, whose data were taken as viral load, CD4%, weight and height. Were categorized viral load (copies / ml): <400, ≥ 400 - <300000, ≥ 30000 - <1 million and ≥ 1 million, and the %CD4 <15%, ≥ 15% - <25% ≥ 25%. UNT is considered global (low W/A≥10%), chronic (low H/A≥5%), acute (low W/H≥10%) and overweight (excess W/H≥10%). Results: We included 111 children from 0 months to 15 years old with male predominance (51.3%), mode of transmission in 91.8%. 58.5% were aged ≥ 400 - <300,000 copies/ml viral load, and 59% had CD4% ≥25%. Nutritional assessment showed 64% global UNT, 58% acute UNT, 22% chronic UNT and 18% overweight. Risk was 1.7, 1.5 and 2.0 times the present global, acute and chronic UNT, respectively, if the viral load was ≥ 400 copies / ml. Conclusion: In children diagnosed with HIV/AIDS by viral load of Pediatric Clinic HIV/AIDS at the HUV in Cali, Colombia, the prevalence of MNT was higher than 18%, with a positive relationship more than 1.5 times between viral load and the different types of UNT.

Mutational loss of Arabidopsis SLOW WALKER2 results in reduced endogenous spermine concomitant with increased aluminum sensitivity.

A previously-identified Arabidopsis mutant with hypersensitivity to aluminum, als7-1 was studied further to determine the nature of the mutation and subsequently establish the biochemical basis of the increase in Al sensitivity. Physiological analysis revealed that the Al hypersensitivity phenotype is correlated with increased Al uptake and Al-dependent gene expression, indicating that als7-1 has a defect in an Al-exclusion mechanism. Cloning of the als7-1 mutation showed that it negatively affects the gene encoding the putative nucleolar localised ribosomal biogenesis factor SLOW WALKER2, which is required for normal gametogenesis and mitotic progression. Molecular analysis indicated that Al hypersensitivity in als7-1 is correlated with loss of expression of a factor required for S-adenosylmethionine recycling and reduced levels of endogenous polyamines in the mutant. Further analysis shows that Al-dependent root growth inhibition is reversed by addition of exogenous spermine, which is correlated with a significant reduction in Al uptake by spermine treated roots. Endogenous spermine likely functions to compete with Al3+ for binding to extra- and intracellular anionic sites, which suggests that increased spermine levels may be an effective means to improve root growth in Al toxic acid soil environments.

Arabidopsis ALS1 encodes a root tip and stele localized half type ABC transporter required for root growth in an aluminum toxic environment.

Aluminum toxicity in acid soils severely limits crop productivity through inhibition of root growth and, consequently, shoot development. Several Arabidopsis mutants were previously identified as having roots with Al hypersensitivity, suggesting that these represent deleterious mutations affecting genes required for either Al tolerance or resistance mechanisms. For this report, the als1-1 mutant was chosen for further characterization. The phenotype of als1-1 is most obviously presented in Al challenged roots, as evidenced by exaggerated root growth inhibition in conjunction with increased expression of Al-responsive genes compared to wt. Using a map-based cloning approach, the als1-1 mutation was isolated and found to represent a deleterious amino acid substitution in a previously uncharacterized half type ABC transporter, At5g39040, which is expressed in a non-Al dependent manner in all organs tested. GUS-dependent analyses revealed that ALS1 expression is primarily localized to the root tip and the vasculature throughout the plant. Concomitant with this, an ALS1: GFP fusion accumulates at the vacuolar membrane of root cells, indicating that ALS1 may be important for intracellular movement of some substrate, possibly chelated Al, as part of a mechanism of Al sequestration.