Browsing by Author "Cano, Francisco"
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Item Continuous EPO receptor activator therapy of anemia in children under peritoneal dialysis(2011) Cano, Francisco; Alarcón, Claudia; Azocar, Marta; Lizama, Carolina; Lillo, Ana María; Delucchi, Ángela; González, Mariluz; Arellano, Patricia; Delgado, Iris; Droguett, María TeresaThe short half-life of erythropoietin (rHuEPO) leads to repeated fluctuations in hemoglobin levels and the need for frequent administration. Continuous erythropoietin receptor activator (CERA) therapy has been approved for once or twice a month in adult dialysis patients. To evaluate the efficacy and safety of CERA therapy in the management of anemia in pediatric peritoneal dialysis (PD) stable PD children under twice-a-week EPO were converted to a subcutaneous CERA, scheduled every 2 weeks. The follow-up was 6 months. The primary efficacy parameter was hemoglobin > 11 g/dL. The exclusion criteria were ferritin < 100 ng/ml and Hb saturation < 20%. Sixteen children, aged 9.75 +/- 3.6 years, including 11 boys, participated in the study. Mean Hb level at month 0 was 10.8 +/- 1.9 g/dL. A decrease in hemoglobin to 10.38 +/- 1 g/dL at month 2 was observed. The CERA dose was increased from 0.86 +/- 0.33 to 1.67 +/- 0.4 mu g/kg at month 3. The target Hb level was reached by the 3rd month. The Hb level and CERA dose were 12.2 +/- 1.2 and 1.6 +/- 0.67 mu g/kg respectively at the end of the study. No adverse events were observed during the protocol. CERA is an effective and safe therapy for maintaining hemoglobin levels when administered twice, up to once a month, in PD children. Doses required to reach target Hb were higher than published experiences in adult populations.Item Free Water Transport and Its Association with Cardiovascular Status in Children on Peritoneal Dialysis(2019) Bolte, Lilian; Ibacache, María José; Delgado, Iris; Cano, FranciscoBackground:Volume overload is one of the most important factors associated with left ventricular hypertrophy (LVH) and cardiovascular disease in chronic peritoneal dialysis (PD) patients. MiniPET is a reliable tool to evaluate free water transport (FWT). In a clinical setting, the significance of FWT has not been evaluated in terms of outcome in children on PD. The objective was to define a FWT value of clinical significance in children on PD, fixing its relationship to left ventricular mass index (LVMI) as a well-known outcome parameter.Methods:MiniPET was performed with 3.86% glucose, 1-h long, to measure FWT in PD patients > 6 years old. An echocardiogram (ECG) was performed within 2 months of the MiniPET. Left ventricular hypertrophy was defined as LVMI ≥ 38.6 g/height2.7 (95th percentile). Receiver operating characteristic curve (ROC) analysis was used to determine the cut-off value of FWT searching the highest sensitivity and specificity to differentiate patients with normal/abnormal LVMI. A p < 0.05 was considered significant.Results:Forty-six studies were performed on 32 patients, 16 males; mean age 11.59 ± 3.07 years. Mean normalized FWT (nFWT) was 144.4 ± 84.8 mL/m2, corresponding to 46.7% of total ultrafiltration. Mean LVMI was 42 ± 11.3 g/m2.7 with a negative correlation to nFWT (p < 0.01). Eighteen out of 32 patients had LVH. The ROC analysis (nFWT vs LVMI) showed an area under the curve of 0.71 (95% confidence interval [CI], 0.53 - 0.89; p = 0.04), allowing a cut-off nFWT value of 110 mL/m2 to be defined, dividing the population into 2 groups of patients according to the LVMI cut-off value of 38,6 g/m2.7.Conclusions:The nFWT showed an inverse correlation to LVMI. A nFWT value < 110 mL/m2 was significantly associated with LVH. The negative relationship observed between nFWT and LVMI, and the cut-off level for nFWT according to the 95th percentile of LVMI, suggest that the regular evaluation of nFWT could become a useful tool in assessing the capacity of PD treatment to keep patients' volume status under control, avoiding cardiovascular impairment.Item Impaired phosphorylation of JAK2-STAT5b signaling in fibroblasts from uremic children.(IPNA2016 by Springer, 2016) Ugarte, Francisca; Irarrazabal, Carlos; Oh, Jun; Dettmar, Anne; Ceballos, María; Rojo, Angélica; Ibacache, María José; Suazo, Cristián; Lozano, Mauricio; Delgado, Iris; Cavada, Gabriel; Azócar, Marta; Delucchi, Ángela; Cano, FranciscoBACKGROUND: Chronic kidney disease (CKD) in children is characterized by severe growth failure. The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in uremic animals shows a post-receptor impaired phosphorylation of Janus kinase 2/signal transducer and activator of transcription (JAK-STAT) proteins. The objective of our study was to characterize the intracellular phosphorylation of JAK-STAT signaling in fibroblasts from children with CKD on chronic peritoneal dialysis (PD). METHODS: Serum GH-binding protein (GHBP), IGF-1 and IGFBP3 were measured in 15 prepubertal CKD stage-5 children on PD. Cytoplasmic JAK2, cytoplasmic/nuclear STAT5b and nuclear IGFBP3, acid-labile subunit (ALS) and IGF-1 mRNA expression were quantified in fibroblasts obtained from skin biopsies before and after stimulation with 200 ng/ml recombinant human growth hormone (rhGH). Phosphorylation activity at both the cytoplasmic and nuclear level was expressed as the ratio phosphorylated (p)/total (t) abundance of the product (p/t) at 30 and 60 min. Fifteen healthy children were recruited as the control group. Values were expressed in arbitrary units (AU) and normalized for comparison. Significance was defined as p < 0.05. RESULTS: Thirty minutes after rhGH stimulus, the cytoplasmic (p/t) JAK2 ratio was significantly lower in patients than in controls [median and interquartile range (IQR): 7.4 (4.56) vs. 20.5 (50.06) AU]. At 60 min after rhGH stimulation, median JAK2 phosphorylation activity was still significantly lower in the patients [7.14 (IQR 3.8) vs. 10.2 (IQR 29.8) AU; p < 0.05]. The increase in the cytoplasmic (p/t) STAT5b/β-actin ratio was lower at both measurement points in the patients compared to the controls, without reaching statistical significance between groups. Median IGFBP3 mRNA abundance was significantly decreased in fibroblasts from uremic patients 24 h after rhGH stimulation compared to the healthy controls [1.27 (IQR 0.83) vs. 2.37 (IQR 0.80) AU]. Median ALS and IGF-1 mRNA expression changed in response to rhGH stimuli at 24 and 48 h. CONCLUSION: In this study, children with CKD undergoing PD therapy showed an impaired phosphorylation of JAK2/STAT5b signaling in fibroblasts after GH stimulation, as well as impaired IGFBP3 mRNA abundance. Both impairments may be partially responsible for the observed resistance to the growth-promoting actions of GH in chronic kidney failure.Item Steroid withdrawal in pediatric kidney transplant allows better growth, lipids and body composition: a randomized controlled trial.(Karger, 2013) Mericq, Verónica; Salas, Paulina; Pinto, Viola; Cano, Francisco; Reyes, Loreto; Brown, Keenan; Gonzalez, Magdalena; Michea, Luis; Delgado, Iris; Delucchi, ÁngelaBACKGROUND: Glucocorticoid immunosuppressant therapy in pediatric kidney transplant (Tx) recipients does not allow the improvement of growth after Tx. OBJECTIVE: To determine the effect of early steroid withdrawal (SW) on longitudinal growth, insulin sensitivity (IS), and body composition (BC). METHODS: This was a prospective, randomized, multicenter study in Tx. Insulin-like growth factor (IGF)-I, IGF-binding protein 3 (IGFBP3), IS, and BC (DEXA/pQCT) were determined at baseline and up to 12 months after Tx. RESULTS: A total of 30 patients were examined; 14 patients were assigned to the SW group (7 male, 7 female; 12 in Tanner stage I) and 16 patients were assigned to the steroid control (SC) group (10 male, 6 female;12 in Tanner stage I). Their chronological age was 7.8 ± 4.3 years, height was -2.3 ± 0.99 SD scores (SDS), and body mass index -0.3 ± 1.2 SDS. After 1 year, the SW group showed an increase in height SDS (+1.2 ± 0.22 vs. +0.60 ± 0.13 SDS in the SC group, p < 0.02), lower IGFBP3 (p < 0.05), cholesterol (p < 0.05), and higher high-density lipoprotein cholesterol (p < 0.05). SW patients had lower trunk fat with no differences in IS. Only in prepubertal patients, the SW group had lower glycemia (p < 0.05), very low-density lipoprotein cholesterol (p < 0.01), triglycerides (p < 0.05), triglycerides/glycemia index (TyG; p < 0.02), and better lean mass. Both groups showed an improvement in lean mass after kidney Tx. CONCLUSIONS: SW improved longitudinal growth, lipid profile, and trunk and lean fat in Tx patients. In prepubertal recipients, the decrease in TyG suggests better IS.Item The mini-PET in pediatric peritoneal dialysis: a useful tool to predict volume overload?(Springer, 2013) Cano, Francisco; Rojo, Angélica; Azocar, Marta; Ibacache, María; Delucchi, Ángela; Ugarte, Francisca; Irarrazabal, Carlos; Delgado, IrisBACKGROUND: Cardiovascular disease (CVD) in patients on chronic peritoneal dialysis (PD) is a major cause of death and is closely linked to hypertension and volume overload. The mini-Pet has been proposed as a useful tool to evaluate free-water transport (FWT) and characterize ultrafiltration across the peritoneum. Knowledge regarding FWT could be of great value to predict volume overload in PD patients. Our objective in this study was to characterize FWT through the peritoneum in children on PD. METHODS: We studied clinically stable patients with >2 months on PD. Exclusion criteria were a peritonitis episode up to 2 months prior to entrance into the study and active nephrotic syndrome. A 1-h mini-peritoneal equilibration test (mini-PET) was performed with 3.86 % glucose. Calculations (see text for full definitions) were: Dip Na (Na dial min60 - Na dial min1), Dip D/PNa (D/PNa60 - D/PNa1), total Na removal (NaR = total Na dial60 - Na dial1), ultrafiltration small pores [(UFSP = NaR × 1,000)/Nap], and FWT (UF-UFSP). Peritoneal equilibration test (PET), left ventricular mass index (LVMI, g/m(2)), daily UF, and residual renal function were evaluated. Pearson's correlation coefficient was used to establish correlation between variables. RESULTS: Sixteen patients were included, with a mean age of 11.8 ± 3.8 years. Free water transport normalized to body surface area (BSA) (FWTn) was 133.9 ± 85.7 ml/m(2); creatinine dialysate-to-plasma (D/P) and glucose dialysate at X dwell time-to-0 dwell time (Dx/D0) ratios were 0.38 ± 0.1 and 0.65 ± 0.09, respectively. LVMI was 46.6 ± 14.8 g/m(2); 2-h creatinine D/P and glucose Dx/D0 showed no correlation with FWTn, UF, and LVMI. FWTn showed a significant inverse correlation with LVMI (r 0.58, p 0.02). CONCLUSIONS: This study characterized FWT in PD children through the mini-PET. Left ventricular hypertrophy showed a high prevalence in this group, and a significant correlation between LVMI and FWT was found. FWT could be a useful tool to evaluate UF in PD children.Item The short peritoneal equilibration test in pediatric peritoneal dialysis(2010) Cano, Francisco; Sanchez, Lorena; Rebori, Anabella; Quiroz, Lily; Delucchi, Angela; Delgado, Iris; Aguilar, Maria Alejandra; Azócar, Marta; Castro, Florencia; Ibacache, Maria José; Cuevas, Mónica; Esquivel, MariaLa prueba de equilibrio peritoneal (PET) es el método estándar de oro para definir la permeabilidad de la membrana peritoneal y para prescribir la terapia de diálisis peritoneal (DP) de forma individual. Sin embargo, es laborioso, consume tiempo de lactancia y requiere muchas horas para realizarse. Por ello, varios autores han intentado validar un protocolo PET corto, con resultados controvertidos. Para evaluar la concordancia entre la prueba de equilibrio peritoneal de 2 h (corta) y 4 h (clásica), se aplicó un protocolo observacional prospectivo en tres centros de DP (México, Chile y Uruguay) entre el 1 de julio de 2008 y el 31 de julio de 2009 Protocolo PET: la noche anterior a la prueba, cada paciente recibió cinco recambios, de 1 h cada uno, a la misma concentración de glucosa que se utilizó anteriormente. Posteriormente, se utilizó una solución de diálisis de glucosa al 2,5% durante un tiempo de permanencia de 4 h. El volumen de llenado de intercambio fue de 1.100 ml / m2 de superficie corporal. A la mañana siguiente, se drenó la permanencia de 4 h y se infundió Dianeal al 2,5%. Se obtuvieron tres muestras de dializado a las 0, 2 y 4 h. Se obtuvo una única muestra de sangre a los 120 min. Las proporciones de creatinina D / P y glucosa D / D0 se calcularon en las horas 0, 2 y 4. Los pacientes se clasificaron como transportadores bajo, promedio bajo, promedio alto o alto según los resultados de creat D / P y gluc D / D0. Se utilizaron las pruebas de Pearson y Kappa para las correlaciones numéricas y categóricas, respectivamente, y se consideró significativa una p <0,05. Se evaluaron 87 estudios de PET en 74 pacientes, 33 hombres, de 11,1 +/- 5,05 años. Se encontró una correlación lineal positiva del 92% entre 2 y 4 h creat D / P y del 80% entre 2 y 4 h gluc D / D0 (p <0,001). La prueba de Kappa mostró una concordancia significativa entre las categorías creat D / P y gluc D / D0 a las 2 y 4 h (p <0,001). Al analizar las categorías de valores de corte, se consideró que creat D / P era más bajo y gluc D / D0 más alto que otras experiencias. Este estudio prospectivo multicéntrico sugiere fuertemente que la PET obtenida a las 2 hy 4 h, basada en el transporte de creatinina o glucosa, proporciona una caracterización idéntica de la capacidad de transporte de la membrana peritoneal en niños con EP.Item Urinary Extracellular Vesicles as a Source of NGAL for Diabetic Kidney Disease Evaluation in Children and Adolescents With Type 1 Diabetes Mellitus(2021) Ugarte, Francisca; Santapau, Daniela; Gallardo, Vivian; Garfias, Carolina; Yizmeyián, Anahí; Villanueva, Soledad; Sepúlveda, Carolina; Rocco, Jocelyn; Pasten, Consuelo; Urquidi, Cinthya; Cavada, Gabriel; San Martin, Pamela; Cano, Francisco; Irarrázabal, Carlos E.Background: Tubular damage has a role in Diabetic Kidney Disease (DKD). We evaluated the early tubulointerstitial damage biomarkers in type-1 Diabetes Mellitus (T1DM) pediatric participants and studied the correlation with classical DKD parameters. Methods: Thirty-four T1DM and fifteen healthy participants were enrolled. Clinical and biochemical parameters [Glomerular filtration Rate (GFR), microalbuminuria (MAU), albumin/creatinine ratio (ACR), and glycated hemoglobin A1c (HbA1c)] were evaluated. Neutrophil gelatinase-associated lipocalin (NGAL), Hypoxia-inducible Factor-1a (HIF-1a), and Nuclear Factor of Activated T-cells-5 (NFAT5) levels were studied in the supernatant (S) and the exosome-like extracellular vesicles (E) fraction from urine samples. Results: In the T1DM, 12% had MAU >20 mg/L, 6% ACR >30 mg/g, and 88% had eGFR >140 ml/min/1.72 m2 . NGAL in the S (NGAL-S) or E (NGAL-E) fraction was not detectable in the control. The NGAL-E was more frequent (p = 0.040) and higher (p = 0.002) than NGAL-S in T1DM. The T1DM participants with positive NGAL had higher age (p = 0.03), T1DM evolution (p = 0.03), and serum creatinine (p = 0.003) than negative NGAL. The NGAL-E correlated positively with tanner stage (p = 0.0036), the median levels of HbA1c before enrollment (p = 0.045) and was independent of ACR, MAU, and HbA1c at the enrollment. NFAT5 and HIF-1a levels were not detectable in T1DM or control. Conclusion: Urinary exosome-like extracellular vesicles could be a new source of early detection of tubular injury biomarkers of DKD in T1DM patients.