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1.
Pediatr Nephrol ; 39(10): 2959-2968, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38802607

RESUMEN

BACKGROUND: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. METHODS: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. RESULTS: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. CONCLUSIONS: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission.


Asunto(s)
Biomarcadores , Tasa de Filtración Glomerular , Nefritis Lúpica , Humanos , Nefritis Lúpica/sangre , Nefritis Lúpica/diagnóstico , Niño , Femenino , Masculino , Estudios Retrospectivos , Biomarcadores/sangre , Adolescente , Sedimentación Sanguínea , Inducción de Remisión , Riñón/patología , Riñón/fisiopatología , Complemento C3/análisis , Complemento C3/metabolismo , Anticuerpos Antinucleares/sangre , Proteinuria/etiología , Proteinuria/orina , Proteinuria/sangre , Proteinuria/diagnóstico , Complemento C4/análisis , Complemento C4/metabolismo , Preescolar
2.
Kidney Int ; 103(5): 962-972, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36898413

RESUMEN

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.


Asunto(s)
Síndrome Nefrótico , Podocitos , Insuficiencia Renal , Niño , Humanos , Recién Nacido , Lactante , Preescolar , Adolescente , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/genética , Síndrome Nefrótico/patología , Inhibidores de la Calcineurina/efectos adversos , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Podocitos/patología , Insuficiencia Renal/inducido químicamente
3.
Pediatr Nephrol ; 38(11): 3699-3709, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37221349

RESUMEN

BACKGROUND: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. METHODS: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. RESULTS: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y-9y, 5m) (14y, 2m-18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. CONCLUSION: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Nefritis Lúpica , Adolescente , Niño , Femenino , Humanos , Masculino , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Riñón/patología , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Ácido Micofenólico/uso terapéutico , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento
4.
J Am Soc Nephrol ; 33(6): 1193-1207, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35354600

RESUMEN

BACKGROUND: Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. METHODS: A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. RESULTS: A total of 346 children (age, 9.8 years; IQR, 6.6-13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3-7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P<0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01 to 0.18; P<0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P=0.05), age at first rituximab treatment (8.0 versus 10.0 years; P=0.01), and history of steroid resistance (28% versus 18%; P=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. CONCLUSIONS: Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.


Asunto(s)
Agammaglobulinemia , Nefrosis Lipoidea , Síndrome Nefrótico , Neutropenia , Agammaglobulinemia/inducido químicamente , Agammaglobulinemia/tratamiento farmacológico , Niño , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Recurrencia , Estudios Retrospectivos , Rituximab/efectos adversos , Esteroides/uso terapéutico , Resultado del Tratamiento
5.
Rheumatology (Oxford) ; 61(6): 2563-2571, 2022 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-34626102

RESUMEN

OBJECTIVE: We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. METHODS: Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.


Asunto(s)
Fallo Renal Crónico , Nefritis Lúpica , Adolescente , Biopsia , Niño , Femenino , Humanos , Riñón/patología , Nefritis Lúpica/patología , Masculino , Inducción de Remisión , Estudios Retrospectivos
6.
Am J Kidney Dis ; 78(3): 380-390, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33549627

RESUMEN

RATIONALE & OBJECTIVE: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017. EXPOSURE: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied. OUTCOME: All-cause MPD mortality. ANALYTICAL APPROACH: Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates. RESULTS: A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%). LIMITATIONS: The interpretation of interregional survival differences as found in this study may be hampered by selection bias. CONCLUSIONS: This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival.


Asunto(s)
Fallo Renal Crónico/terapia , Diálisis Peritoneal/métodos , Adolescente , Factores de Edad , Asia/epidemiología , Causas de Muerte/tendencias , Niño , Preescolar , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/mortalidad , Masculino , América del Norte/epidemiología , Estudios Prospectivos , Sistema de Registros , Tasa de Supervivencia/tendencias , Factores de Tiempo
7.
Artículo en Inglés | MEDLINE | ID: mdl-33367818

RESUMEN

BACKGROUND: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. METHODS: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. RESULTS: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. CONCLUSION: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.

8.
Pediatr Nephrol ; 35(7): 1257-1266, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32170428

RESUMEN

BACKGROUND: Congenital nephrotic syndrome (CNS) is a rare but serious condition which affects neonates and is caused by monogenic defects of glomerular structural proteins or congenital viral infections. Several reports have established a causal relationship between human cytomegalovirus (HCMV) intrauterine infection and CNS, but thorough study assessing parameters has not yet been done. METHODS: This study aimed to ascertain significant demographic, biochemical, serological, inflammatory and etiological parameters with 12 months follow-up to clinically identify and monitor neonates with HCMV-associated CNS and sought to decipher the phylogenetic nature of infecting strains. Differences between four patient groups (neonates < 4 weeks old) with or without CNS and HCMV infection were compared by unpaired t testing and one-way analysis of variance (ANOVA). Linear regression was performed to assess statistical significance among individual groups. Maximum-likelihood-based phylogenetic analysis was performed with HCMV gH gene sequences to compare clinically isolated and referenced NCBI strains. This was further supported by analysis of effective number of codons (ENc), codon adaptation index (CAI) and mRNA structural variation. RESULTS: Patients with HCMV-associated CNS were found to have significant variations in many studied parameters compared with controls. The majority of clinical strains formed a separate phylogenetic cluster defining them as somewhat distinct from standard reference strains, which was supported by the other analyses. CONCLUSION: This study defined parameters for monitoring cases of HCMV-associated CNS, which suggest the possible existence of a selection force acting and rendering these HCMV strains able to infect selective host tissues and cause specific disease types.


Asunto(s)
Infecciones por Citomegalovirus/congénito , Síndrome Nefrótico/virología , Adulto , Estudios de Casos y Controles , Estudios Transversales , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/complicaciones , ADN Viral/sangre , Femenino , Humanos , Recién Nacido , Masculino , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/genética
9.
Clin Exp Nephrol ; 24(7): 622-629, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32201918

RESUMEN

BACKGROUND: Prednisolone dosing regimen based on body surface area (BSA) or body weight (BW) in managing uncomplicated nephrotic syndrome (NS) has been a matter of controversy. METHODS: In this parallel-arm randomized clinical trial, 60 children with uncomplicated NS in relapse were randomized to receive either of two regimens. Children of BW cohort received prednisolone (2 mg/kg/day) till remission (or 6 weeks for first episode); followed by 1.5 mg/kg on alternate days for 4 weeks (or 6 weeks for first episode). Children randomized for BSA cohort received prednisolone (60 mg/m2/day) till remission (or 6 week for first episode); followed by 40 mg/m2 on alternate days for 4 weeks (or 6 weeks for first episode). The primary endpoint was 6-month relapse-free survival in the intention-to-treat population (clinical trial registry of India CTRI/2015/03/005655). RESULTS: The 6-month relapse-free survival rates were similar for both BSA cohort 73.33% (22/30) and BW cohort 70% (21/30) (p = 1, OR 0.19, 95% CI 0.07-0.52). Requirement of cumulative steroid to achieve initial remission (96.1 ± 57.8 vs 63.58 ± 40.2 mg/kg, p = 0.014) and over 6-month study period (104.34 ± 50.82 vs 73.88 ± 42.95 mg/kg, p = 0.015) were significantly higher in BSA cohort in comparison to BW cohort. However, time taken in achieving remission during enrolment episode in both BSA and BW groups was comparable (7 ± 1.7 vs 6.9 ± 1.4 days, p = 0.81). While both treatments were well tolerated, the number of adverse events was one and half times as common in the BSA group than BW group (37 vs. 22 events). CONCLUSIONS: In treating children with uncomplicated NS, both BSA and BW regimens were equally effective in achieving initial remission and maintaining disease remission. Due to fewer adverse events and lesser cumulative steroid exposure with BW based regimen, it may be considered as better option over BSA regimen. CLINICAL TRIAL REGISTRY NAME: Clinical Trial Registry of India (CTRI/2015/03/005655).


Asunto(s)
Antiinflamatorios/administración & dosificación , Superficie Corporal , Peso Corporal , Síndrome Nefrótico/tratamiento farmacológico , Prednisolona/administración & dosificación , Antiinflamatorios/efectos adversos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Neumonía/inducido químicamente , Prednisolona/efectos adversos , Recurrencia , Inducción de Remisión , Infecciones del Sistema Respiratorio/inducido químicamente , Aumento de Peso
10.
BMC Nephrol ; 21(1): 520, 2020 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-33256621

RESUMEN

BACKGROUND: Approximately 30% of children with idiopathic nephrotic syndrome develop a complicated course with frequent relapses or steroid dependency. Rituximab, a B cell depleting monoclonal antibody, is a safe and effective alternative to steroids or other immunosuppressants for achieving and maintaining remission in this population at short term. Despite the good initial response relapses inevitably occur after regeneration of B lymphocytes, necessitating either repeat courses of rituximab or addition of another steroid-sparing immunosuppressant. METHODS: This is a prospective, single-center, open-label, two-parallel-arm randomized controlled phase III study among children with steroid dependent nephrotic syndrome who are maintained in remission with oral steroids. One hundred children will be randomized to either Rituximab and maintenance Mycophenolate mofetil (A) or repeated courses of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200 mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will be administered at 0, 8 and 16 months if B cell count normalize at the given time points. Prednisolone will be discontinued in both groups 2 weeks following first course of rituximab. Primary aim is to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, frequency of relapses and changes in anthropometry. Circulating B lymphocyte populations will be studied as biomarkers or predictors of rituximab responsiveness and adverse events will be analysed. DISCUSSION: The study will provide evidence as to the comparative safety and efficacy of two alternative steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results obtained with the alternative treatment protocols. TRIAL REGISTRATION: This trial was prospectively registered to the Clinicaltrial.gov ( NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/ ) and Clinical Trials Registry of India ( CTRI/2019/04/018517 dated 09/04/2019).


Asunto(s)
Glucocorticoides/uso terapéutico , Factores Inmunológicos/uso terapéutico , Ácido Micofenólico/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Rituximab/administración & dosificación , Adolescente , Niño , Preescolar , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Quimioterapia de Mantención , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Resultado del Tratamiento
12.
Nephrol Dial Transplant ; 34(6): 981-991, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30773598

RESUMEN

BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (±1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.


Asunto(s)
Acidosis Tubular Renal/terapia , Pérdida Auditiva Sensorineural/terapia , Acidosis Tubular Renal/complicaciones , Acidosis Tubular Renal/genética , Adolescente , Adulto , Anciano , Bicarbonatos/sangre , Calcio/orina , Niño , Preescolar , Estudios de Cohortes , Análisis Mutacional de ADN , Sordera/complicaciones , Sordera/genética , Sordera/terapia , Femenino , Estudios de Asociación Genética , Tasa de Filtración Glomerular , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/genética , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mutación , Nefrocalcinosis/complicaciones , Nefrocalcinosis/genética , Nefrocalcinosis/terapia , Enfermedades Raras/complicaciones , ATPasas de Translocación de Protón Vacuolares/genética , Adulto Joven
13.
BMC Pediatr ; 19(1): 291, 2019 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-31438890

RESUMEN

BACKGROUND: Cytomegalovirus [CMV] is a causative agent of congenital infection worldwide and often leads to neurological deficits and hearing loss in newborns. Infants born with symptomatic congenital Cytomegalovirus infection [cCMV] are at significant high risk for developing adverse long-term outcomes. In this study, we look into the sequence variability of surface glycoprotein B [gB] encoding region in newborns with symptomatic CMV infection for the first time in Eastern region of India. METHODS: 576 suspected newborns from seropositive mothers were subjected to the study and ELISA was used to confirm CMV infection. Different genotypes and their subtypes were determined using multiplex nested-PCR. Viral load of different glycoprotein B [gB] genotypes was measured using RT-PCR. Sequencing and phylogenetic analysis was then performed using Bayesian interference. RESULTS: The overall frequency of cCMV infection was 18.4%, where 16.0% neonates were symptomatic. Among the different gB genotypes, gB1 had the highest frequency [23.5%] and gB4 showed the lowest occurrence [5.8%]. 23.5% of symptomatic neonates had mixed genotypes of gB, probably indicating matrenal reinfection with CMV strains in Indian population. Significant genotypic clades [gB1-gB2-gB3-gB5] were grouped closely based on gene sequences, but the gB4 sequence was in the outlier region of the phylogenetic tree indicating the genetic polymorphism. CONCLUSION: This is the first study on cCMV genotyping and its phylogenetic analysis from Eastern Indian neonatal population. The study holds importance in the assessment of cCMV seroprevalence in global perspective. gB protein can be used as a potential therapeutic target against CMV infection.


Asunto(s)
Infecciones por Citomegalovirus/congénito , Genotipo , Proteínas del Envoltorio Viral/genética , Secuencia de Bases , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/genética , Cartilla de ADN/genética , Femenino , Humanos , India/epidemiología , Recién Nacido , Masculino , Reacción en Cadena de la Polimerasa Multiplex , Filogenia , Análisis de Secuencia de ADN
15.
Indian J Crit Care Med ; 22(1): 30-33, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29422730

RESUMEN

AIMS: Dengue is currently one of the most important mosquito-borne viral infections. Acute renal failure (ARF) is a serious complication among children suffering from dengue infection. SUBJECTS AND METHODS: A retrospective cohort review of baseline characteristics, disease outcomes, and risk factors of dengue-infected patients, with and without renal failure (RF), were compared. RESULTS: Among 97 children with dengue, 13.4% had RF (estimated glomerular filtration rate <60 ml/min/1.73 m2) at presentation. In comparison to all children (100%) of RF cohort, only 32% children of non-RF cohort (P < 0.0001) were suffering either from dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The 7-day survival rate was 61.5% (8/13) among RF group as compared to 96.4% (81/84) in non-RF group (P < 0.001). When a fraction of patients who needed vasopressor support were significantly higher in RF cohort (70% vs. 14% for RF and non-RF, respectively, P < 0.001), requirement of mechanical ventilation (15% vs. 11%, P = 0.67) was comparable in both cohorts. CONCLUSIONS: DHF/DSS is an independent risk factor for the development of ARF in patients with dengue infection. Mortality rate is high once RF develops in these children.

16.
Pediatr Nephrol ; 32(6): 1013-1021, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28191596

RESUMEN

BACKGROUND: Childhood-onset lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). Despite treatment-related toxicities, cyclophosphamide (CYC) and glucocorticoid-based treatment protocols are still considered standard therapy in managing this multisystem disorder. An effective and safe alternative induction regimen is needed. METHODS: Forty-four pediatric patients with active LN aged 3.5-13.8 (median 8.4) years, of whom 32 entered the study at diagnosis of SLE, were followed over 36 months. Induction therapy consisted of methylprednisolone pulses followed by either rituximab (RTX) (n = 17), mycophenolate mofetil (MMF) (n = 12) or pulse-CYC (n = 15), with tapering dose of prednisolone orally. MMF was added as maintenance immunosuppressant (800 mg/m2 daily) in all children from the third month onward. RESULTS: Flare-free survival was significantly higher at 36 months with RTX compared with MMF and CYC (100% for RTX vs. 83% for MMF. and 53% for CYC, p = 0·006). Twelve patients (76.5%) achieved complete remission with RTX compared with five (41.7%) and seven (46.7%) with MMF and CYC, respectively, at last follow-up. Requirement of mean daily dosage of prednisone was significantly lower in RTX group [p = 0.005 (RTX vs MMF); 0.0001 (RTX vs CYC) at 36 months] compared with other groups after the 3-month follow-up. In comparison with few minor adverse events in the other two cohorts, several serious adverse events occurred in the CYC group. CONCLUSIONS: Efficacy and medium-term safety of RTX induction followed by MMF maintenance therapy in inducing and maintaining remission among children with LN were evident in this study.


Asunto(s)
Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/mortalidad , Rituximab/uso terapéutico , Niño , Preescolar , Protocolos Clínicos , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Metilprednisolona/uso terapéutico , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéutico , Inducción de Remisión/métodos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
17.
Clin Exp Nephrol ; 21(1): 143-151, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27108294

RESUMEN

BACKGROUND: Calcineurin inhibitors (CNI), mycophenolate mofetil (MMF), and levamisole are common treatment choices for patients with frequently relapsing (FRNS) and steroid-dependent nephrotic syndrome (SDNS). METHODS: In this retrospective cohort study, we analyzed the relative efficacy and safety of tacrolimus, MMF, and levamisole over a period of 30 months, in treating 340 children with idiopathic FRNS/SDNS. The children received either MMF 1200 mg/m2 daily, or levamisole 2.5 mg/kg on alternate days, or tacrolimus 0.1-0.2 mg/kg daily along with tapering doses of alternate-day prednisolone. RESULTS: Tacrolimus was associated with a higher rate of 30-month relapse-free survival when compared to MMF (61.7 vs. 38.5 %, p < 0.001), or levamisole (61.7 vs. 24 %, p < 0.001). However, relapse rate increased almost threefold once tacrolimus was stopped, resulting in a higher relapse rate per patient-year when compared to the MMF group (2.0 vs. 1.5, p = 0.013). The cumulative prednisolone dose per patient during the last year of the study period was also increased among tacrolimus group in comparison with MMF group (96.4 vs. 74.4 mg/kg/year, p = 0.004). Independent of the impact of drug choice, the relapse risk was higher in patients with steroid dependency at baseline (HR 2.14, 95 %CI 1.79-2.96, p < 0.0001). In comparison with few minor adverse events in other two cohorts, several serious adverse events were documented in the tacrolimus group. CONCLUSIONS: Although there are serious safety concerns regarding tacrolimus, it is more effective than MMF or levamisole in maintaining relapse-free survival. However, unlike MMF, the relative efficacy of tacrolimus in preventing further relapses is seen only when the patient is on the drug. Taking together the long-term efficacy and safety data observed, MMF appears as a safe and effective alternative to tacrolimus in managing pediatric FRNS/SDNS.


Asunto(s)
Inhibidores de la Calcineurina/administración & dosificación , Glucocorticoides/administración & dosificación , Inmunosupresores/administración & dosificación , Levamisol/administración & dosificación , Ácido Micofenólico/administración & dosificación , Síndrome Nefrótico/terapia , Prednisolona/administración & dosificación , Tacrolimus/administración & dosificación , Adolescente , Inhibidores de la Calcineurina/efectos adversos , Niño , Preescolar , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Lactante , Levamisol/efectos adversos , Masculino , Ácido Micofenólico/efectos adversos , Síndrome Nefrótico/diagnóstico , Prednisolona/efectos adversos , Recurrencia , Estudios Retrospectivos , Tacrolimus/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
18.
Pediatr Nephrol ; 31(10): 1681-9, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27180178

RESUMEN

BACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high patient morbidity and mortality. There is no consensus on the best RRT modality for pediatric AKI. METHODS: The efficacy and safety of continuous peritoneal dialysis (cPD) and daily intermittent hemodialysis (dHD) were compared in 136 children aged 1 month to 16 years requiring RRT for AKI. Mortality, risk factors and causes of death, 1-month and 3-month renal recovery rates, and technique-related complications were assessed. RESULTS: Uremia control and the rate of catheter-related complications were comparable in the groups. Thirty-day survival was 60.7 % (51 out of 84) with cPD and 36.5 % (19 out of 52) with dHD (p = 0.019). Although age <1 year, extended time lag from disease onset to RRT initiation, mechanical ventilation, and extended vasopressor dependence independently predicted death, adjusted mortality was higher with dHD relative to cPD (hazard ratio [HR] 1.75, 95%CI 1.18-2.84, p = 0.022). Almost all fatalities in the dHD group (94 %) occurred during or within an hour of a HD session. Renal function normalized in 27 % of survivors after 4 weeks and in 51 % after 3 months. The risk of permanent end-stage renal disease was increased in patients with an intrinsic renal cause of AKI (HR 2.72; 95 % CI 1.37-3.83; p = 0.029) and in those with delayed RRT initiation (HR 2.17; 95 % CI 123-2.93; p = 0.015), but did not differ between patients treated with dHD and cPD. CONCLUSIONS: Favorable patient survival with cPD compared with dHD in children treated for AKI was evident in this study.


Asunto(s)
Lesión Renal Aguda/terapia , Diálisis Peritoneal Ambulatoria Continua/métodos , Diálisis Renal/métodos , Lesión Renal Aguda/mortalidad , Adolescente , Causas de Muerte , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Estimación de Kaplan-Meier , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Pruebas de Función Renal , Masculino , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/mortalidad , Recuperación de la Función , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Terapia de Reemplazo Renal , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Uremia/terapia , Uremia/orina , Cateterismo Urinario/efectos adversos
19.
Am J Kidney Dis ; 2015 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-26071057

RESUMEN

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

20.
Nephrol Dial Transplant ; 30 Suppl 1: i113-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25758433

RESUMEN

BACKGROUND: Microscopic polyangiitis (MPA) is one of the most common forms of antineutrophil cytoplasm autoantibodies (ANCA)-associated vasculitis in children. Cyclophospamide and glucocorticoid-based treatment protocols are still considered gold standard in managing this multi-system disorder. But treatment-related toxicity is a major cause of chronic morbidity and early mortality in MPA. Hence, the search for an effective and safe alternative immunosuppressant is essential. METHODS: A retrospective analysis of baseline clinico-pathological presentation and treatment-outcome was performed among 11 paediatric MPA patients. All of whom were treated with a pre-specified cyclophosphamide free, rituximab- and mycophenolate mofetil (MMF)-based management protocol as per centre practice. RESULTS: We describe the clinical course of 11 children with MPA over a median follow-up period of 20.9 months. Both patient survival and renal survival at 1 year follow-up were 100%. In spite of the varying degree of renal involvement at presentation, kidney function was recovered in all patients with a median estimated glomerular filtration rate (eGFR) of 79.5 mL/min/1.73 m(2). At last follow-up, 91% (10/11) of patients were in complete remission and one (9%) child continued partial remission state. There was no treatment failure. In total, 73% (8/11) of patients were off steroids at last follow-up and 82% (9/11) of patients never relapsed during follow-up period. CONCLUSIONS: Efficacy and medium-term safety of rituximab- and MMF-based protocol in managing children with MPA was evident in this study.


Asunto(s)
Algoritmos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Enfermedades Renales/prevención & control , Poliangitis Microscópica/mortalidad , Ácido Micofenólico/análogos & derivados , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Antineoplásicos/uso terapéutico , Niño , Preescolar , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Renales/mortalidad , Masculino , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/patología , Ácido Micofenólico/uso terapéutico , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento
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