ABSTRACT
BACKGROUND AND OBJECTIVES: We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1.73 m2 were included. Patients with BK virus active nephritis, recurrence of renal disease, GFR decline in previous 3 months, or treated with calcium antagonists or antifungal drugs were excluded. They were randomized to receive placebo (n=10) or eplerenone 25 mg/d for 24 months (n=13). Visits were scheduled at baseline, 6, 12, and 24 months. At each period, a complete clinical examination was performed and blood and urine samples were taken. Urine creatinine, 8-hydroxylated-guanosine, heat shock protein 72 (HSP72), and kidney injury molecule (KIM-1) levels were also assessed. In kidney biopsy samples, the tubulo-interstitial area affected by fibrosis (TIF) and glomerulosclerosis were measured at baseline and after 24 months. RESULTS: The baseline eGFR was 80±6 in the placebo and 86±6 ml/min per 1.73 m2 in the eplerenone group; at 24 months it was 66±8 and 81±7 ml/min per 1.73 m2, respectively (P=0.33; 95% confidence intervals, -18 to 33 at baseline, and -11 to 40 after 24 months). The albumin-to-creatinine ratio was 110±74 in the placebo, and 265±140 mg/g in the eplerenone group; and after 24 months it was 276±140 and 228±88 mg/g, respectively (P=0.15; 95% confidence intervals, -283 to 593, and -485 to 391, respectively). In addition, the placebo exhibited a greater TIF, glomerulosclerosis, and urinary HSP72 compared with the eplerenone group. CONCLUSIONS: Although this study was underpowered to provide definitive evidence that long-term eplerenone administration attenuates the progression of CAN in pediatric transplant patients, it encourages testing the potential benefit of MRB in this pediatric population.
Subject(s)
Glomerulonephritis/drug therapy , Kidney Transplantation/adverse effects , Kidney/drug effects , Mineralocorticoid Receptor Antagonists/administration & dosage , Spironolactone/analogs & derivatives , Adolescent , Age Factors , Albuminuria/diagnosis , Albuminuria/drug therapy , Albuminuria/etiology , Allografts , Biomarkers/urine , Biopsy , Child , Disease Progression , Drug Administration Schedule , Eplerenone , Female , Fibrosis , Glomerular Filtration Rate/drug effects , Glomerulonephritis/diagnosis , Glomerulonephritis/etiology , Guanosine/analogs & derivatives , Guanosine/urine , HSP72 Heat-Shock Proteins/urine , Hepatitis A Virus Cellular Receptor 1/metabolism , Humans , Kidney/metabolism , Kidney/physiopathology , Male , Mexico , Mineralocorticoid Receptor Antagonists/adverse effects , Prospective Studies , Single-Blind Method , Spironolactone/administration & dosage , Spironolactone/adverse effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Although tacrolimus therapy is not the first-line therapy for childhood nephrotic syndrome, it is often used instead of cyclosporine to ameliorate the side effects. The pharmacokinetics (PK) of tacrolimus (Tac) can be influenced by many conditions, and it has a high plasma protein binding. The Tac PK during relapse and remission of childhood nephrotic syndrome has not been well described. METHODS: We performed 14 PK profiles (with measurements before intake and 0.5, 1, 2, 4, and 12 hours postintake) in 7 children with steroid-resistant nephrotic syndrome at week 1 (all nephrotic) and week 16 after Tac therapy (all in remission). These data were compared with historical PK data of 161 PK profiles in 87 pediatric renal transplant recipients with measurements before intake and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postintake. Tac levels were measured using the Abbott Tacro II assay. We used descriptive statistics to generate percentiles and compared these with those of patients with steroid-resistant nephrotic syndrome. RESULTS: The median age of patients with nephrotic syndrome was 3.2 years (range 2.5, 17.2), male gender 71.4%, significantly younger than the control group. Median Tac dose was similar during both PK profiles (0.11 mg·kg·d at week 1 versus 0.13 mg·kg·d at week 16, P = 0.81). There were no statistically significant differences in median dose-normalized area-under-the-time-concentration profiles, peak concentration, time to reach peak concentration, and Tac trough levels. Individual dose-normalized Tac levels for each time point during the PK profile were also not different (P = 0.81). CONCLUSIONS: We conclude that Tac PK profiles are unaltered during relapse of nephrotic syndrome.
Subject(s)
Immunosuppressive Agents/pharmacokinetics , Nephrotic Syndrome/drug therapy , Tacrolimus/pharmacokinetics , Adolescent , Area Under Curve , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Immunosuppressive Agents/administration & dosage , Male , Nephrotic Syndrome/physiopathology , Recurrence , Tacrolimus/administration & dosage , Time FactorsABSTRACT
PTE is defined as hematocrit >51% or hemoglobin >17 g/dL after renal transplantation. Risk factors include native kidneys with adequate erythropoiesis pretransplant, smoking, renal artery stenosis, and cyclosporine treatment. We report the case of a 14-yr-old female kidney transplant patient, with triple therapy immunosuppression and stable graft function who developed PTE at 12 months post-transplant with hemoglobin 17.3 g/dL, hematocrit 54.2%, stable graft function, and normotensive with normal cardiac echocardiogram and erythropoietin levels. The only risk factor found was tobacco use. As she had no spontaneous improvement, enalapril treatment was started at 19 months post-transplant with a hemoglobin level of 17.5 g/dL and hematocrit 53%; by 23 months post-transplant, hemoglobin lowered to 15 g/dL and hematocrit to 44.5% and continued to be in normal range thereafter. PTE is a rare condition in childhood and can be successfully treated with enalapril.
Subject(s)
Kidney Transplantation/adverse effects , Polycythemia/etiology , Adolescent , Female , HumansABSTRACT
BACKGROUND: Monocyte chemotactic protein-1 (MCP-1) plays a direct role in the infiltration of macrophages and monocytes during the early stages of Henoch-Schönlein purpura (HSP) nephritis. The aim of this study was to compare the urinary MCP-1/creatinine levels in children with and without HSP nephritis and determine if they are associated with the severity of renal lesions. METHODS: We included 77 patients with HSP and 25 healthy control children. Levels of serum creatinine, urinalysis, and 12-h proteinuria assessments were performed. Urinary MCP-1 levels were determined by ELISA. RESULTS: Fifty-seven patients had nephritis (74 %). Urinary MCP-1/creatinine levels were significantly higher in patients with HSP nephritis (median, 653 pg/mg) compared to those with HSP without nephritis (median, 269 pg/mg) or healthy children (191 pg/mg). In addition, higher MCP-1/creatinine levels were observed in HSP patients who had renal biopsy (median, 1,412 pg/mg) in comparison to HSP patients without renal biopsy (median, 302 pg/mg). The urinary MCP-1 cut-off value of 530 pg/mg could be used to distinguish patients who undergo renal biopsy with a sensitivity of 81 % and specificity of 77 %. CONCLUSIONS: Urinary MCP-1/creatinine levels are elevated in the early stages of severe HSP nephritis and can be used as a biomarker for HSP nephritis.
Subject(s)
Chemokine CCL2/urine , Creatinine/urine , IgA Vasculitis/complications , IgA Vasculitis/urine , Nephritis/urine , Adolescent , Area Under Curve , Biomarkers/urine , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , IgA Vasculitis/pathology , Infant , Male , Nephritis/etiology , Nephritis/pathology , ROC CurveABSTRACT
Introducción. Actualmente, la enfermedad renal crónica es un padecimiento con un gran impacto en la población infantil mexicana, con consecuencias limitantes y graves a corto plazo. La pobreza y la falta de justicia social del entorno influyen en la atención oportuna y rehabilitación a largo plazo. El objetivo de este estudio fue documentar las diferencias relacionadas con las características sociodemográficas de los pacientes que recibieron tratamiento en el Hospital Infantil de México Federico Gómez en un periodo de seis años. Métodos. Se realizó un estudio comparativo retrospectivo de los pacientes con enfermedad renal crónica terminal que fueron diagnosticados en 2003 y en 2009. La información fue proporcionada por el Departamento de Archivo Clínico y Bioestadística. Se registraron los datos de edad, sexo, etiología de la enfermedad renal, nivel socioeconómico, tipo de financiamiento, lugar de origen e ingreso a un programa de rehabilitación (diálisis o trasplante). Resultados. En el 2003 se recibieron 69 pacientes con enfermedad renal crónica terminal, mientras que en el 2009 se recibieron 50 pacientes. No hubo diferencias de edad ni de sexo. Pudo conocerse la etiología de la uremia en 40% de los niños diagnosticados en 2003 y en 54% de los diagnosticados en 2009. La mayoría de los pacientes provinieron de los niveles socioeconómicos más bajos. Hubo una tendencia a la disminución en el número de pacientes de otros estados del país, siendo 30% en 2003 y 16% en 2009. Pudieron ingresar a programa de rehabilitación 23 pacientes en 2003 (33%) y 29 pacientes en 2009 (58%), p = 0.007. Conclusiones. Hubo una disminución de 28% en el número de casos atendidos, del 2003 al 2009. La atención se ha concentrado en pacientes provenientes del Estado de México y el Distrito Federal. A pesar de que, aparentemente, el nivel socioeconómico es similar en ambos grupos, la proporción de niños que ingresaron al programa de rehabilitación a largo plazo aumentó en forma significativa, de 33% en 2003 a 58% en 2009.
Background. Chronic renal disease (CRD) is a disease with a strong impact on the childhood Mexican population with short-range limiting and serious consequences. Poverty and a social environment devoid of social justice hinder timely medical attention and long-range rehabilitation. The aim of this study was to determine the differences regarding sociodemographic features in patients under treatment at Hospital Infantil de México Federico Gómez, with a 6-year difference: patients diagnosed in 2003 as compared to those diagnosed in 2009. Methods. A retrospective comparative study was carried out with end-stage chronic renal disease (ESRD) patients with information obtained from the clinical files. Data were obtained on age, gender, renal insufficiency etiology, socioeconomic level, type of financing, place of origin, and whether patient entered a rehabilitation program (dialysis or transplant). Results. In 2003, 69 patients with ESRD were received, whereas 50 patients were received in 2009. There were no differences in age or gender between dates. Etiology of uremia was determined in 40% of the children in 2003 and 50% in 2009. Most patients in the assessed years belong to the lowest socioeconomic levels, coming from the State of Mexico and metropolitan Mexico City. There was a decreasing trend in the number of patients coming from other states of the country: 30% in 2003 and 16% in 2009. Twenty-three patients (33%) entered the rehabilitation program in 2003 and 29 patients (58%) in 2009 (p = 0.007). Conclusions. There was a 28% decrease between 2003 and 2009 in the number of cases being managed. Attention has been focused on the State of Mexico and metropolitan Mexico City area. In spite of socioeconomic level being apparently similar in the studied years, there was a significant increase in the proportion of children entering a long-range rehabilitation program (from 33% in 2003 to 58% in 2009).
ABSTRACT
Introducción. A pesar de que las nuevas terapias inmunosupresoras han mejorado notablemente la evolución clínica de los trasplantes renales, los rechazos agudo y crónico siguen limitando la sobrevida a largo plazo del injerto. En base a lo anterior, el objetivo de este estudio fue determinar la presencia de anticuerpos séricos contra antígenos de histocompatibilidad (HLA) clase I y clase II en niños con rechazo agudo del injerto renal. Métodos. Se realizó un estudio clínico prospectivo en pacientes con trasplante renal que presentaron rechazo agudo del injerto. Se les tomó muestra de suero al momento de la biopsia renal, misma que fue utilizada para la detección de anticuerpos contra antígenos HLA de clase I y II por ensayo basado en equipo fuoroanalizador (Luminex) y microperlas cubiertas con antígenos clase I y clase II de One Lambda. Resultados. De 21 pacientes estudiados, 17 pacientes (81%), fueron diagnosticados con rechazo celular y cuatro (19%) con rechazo agudo mediado por anticuerpos. El tiempo post-trasplante promedio de presentación del rechazo humoral agudo fue de 18.7 meses y para el rechazo celular de 36.7 meses. Once pacientes (52.3%) presentaron anticuerpos específicos contra el donador. Los anticuerpos contra antígenos HLA clase I donador específicos se encontraron en seis pacientes, siendo más frecuente el rechazo agudo mediado por anticuerpos (humoral), donde todos los pacientes tuvieron anti HLA clase I con Chi cuadrada (P =0.004). En cuanto a los anticuerpos inespecíficos, el 95.2% de los pacientes desarrollaron este tipo de anticuerpos. Conclusiones. El 95% de los niños con rechazo del injerto renal presentan anticuerpos anti HLA, específicos y/o no específicos contra el donador. Los anticuerpos anti HLA donador específicos clase I se presentan con mayor frecuencia en el rechazo humoral.
Background. Although new immunosuppressive therapies have signifcantly improved the clinical progression of kidney transplants, acute and chronic rejection continue to limit long-term graft survival. Despite this, the aim of the study was to determine the presence of human leukocyte antigen (HLA) antibodies class I and class II in children with acute renal graft rejection. Methods. Patients with graft rejection were included in the study. A serum sample for anti-HLA antibody measurement class I and II by Luminex was taken at the time of renal biopsy. Results. Seventeen patients (81%) had cellular rejection and four (19%) antibody-mediated rejection. Mean post-transplant time of rejection was 18.7 months and 36.7 months for humoral rejection and cellular rejection, respectively. Eleven patients (52.3%) had donor specific (DS) antibodies. Anti-HLA class I DS was found in six patients including the four patients with humoral rejection (Fisher exact test p =0.004); 95.2% had non-DS antibodies. Conclusions. Of the children with acute renal graft rejection, 95% have anti HLA antibodies (DS and/or non-DS). Anti-HLA DS class I are more frequent in humoral rejection.
