Development of clinical and laboratory biomarkers in an international cohort of 428 children with lupus nephritis.

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.

International cohort of 382 children with lupus nephritis - presentation, treatment and outcome at 24 months.

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.

An initiative to reduce medication errors in neonatal care unit of a tertiary care hospital, Kolkata, West Bengal: a quality improvement report.

BACKGROUND: Medication errors are an emerging problem in various hospital settings, especially in neonates. A study conducted in the neonatal care unit of a tertiary institute in Kolkata as baseline over 3 months, revealed total error to be around 71.1/100 prescriptions (median medication error percentage: 63%). PURPOSE: To assess the occurrences of medication errors and determine efficacy of Point-of-Care Quality improvement (POCQI) model in reducing the same from baseline 63% to less than 10%, in the above setting within next 9 months. MATERIALS AND METHODS: This quality improvement initiative of quasi-experimental design comprised randomly selected prescriptions and monitoring sheets of neonates admitted in the neonatal care unit, obeying inclusion and exclusion criteria. Medication errors were assessed and categorised using a predesigned and pretested checklist. Interventions were planned after forming a quality improvement team in four plan-do-study-act (PDSA) cycles spanning over 6 weeks each (including training of doctors and nurses, signature and countersignatures of respective healthcare personnel, computer-generated prescriptions and newly designed software-generated prescriptions) as per POCQI model of the WHO and results in post-intervention phase (3 months) were compared. RESULTS: A total of 552 prescriptions and monitoring sheets of 124 neonates were studied. Median medication error percentages in first, second, third and fourth PDSA cycle were, respectively, 48%, 42%, 30% and 14%. Total error reduced to 10.4/100 prescriptions (p<0.005), with significant reduction in erred dosage, timing, interval, preparation and rate of infusion of drugs in prescriptions of the post-intervention phase. CONCLUSION: Implementation of change ideas via PDSA cycles, as per the POCQI model with technological aid, significantly decreased the percentage of medication errors in neonates, which was also sustained in the post-intervention phase and facilitated error-free prescriptions.

New and Old Anti-CD20 Monoclonal Antibodies for Nephrotic Syndrome. Where We Are?

Nephrotic proteinuria is the hallmark of several glomerulonephritis determined by different pathogenetic mechanisms, including autoimmune, degenerative and inflammatory. Some conditions such as Minimal Change Nephropathy (MCN) and Focal Segmental Glomerulosclerosis (FSGS) are of uncertain pathogenesis. Chimeric anti-CD20 monoclonal antibodies have been used with success in a part of proteinuric conditions while some are resistant. New human and humanized monoclonal anti-CD 20 antibodies offer some advantages based on stronger effects on CD20 cell subtypes and have been already administered in hematology and oncology areas as substitutes of chimeric molecules. Here, we revised the literature on the use of human and humanized anti-CD 20 monoclonal antibodies in different proteinuric conditions, resulting effective in those conditions resistant to rituximab. Literature on the use of human anti-CD 20 monoclonal antibodies in different proteinuric diseases is mainly limited to ofatumumab, with several protocols and doses. Studies already performed with ofatumumab given in standard doses of 1,500 mg 1.73m2 suggest no superiority compared to rituximab in children and young adults with steroid dependent nephrotic syndrome. Ofatumumab given in very high doses (300 mg/1.73m2 followed by five infusion 2,000 mg/1.73 m2) seems more effective in patients who are not responsive to common therapies. The question of dose remains unresolved and the literature is not concordant on positive effects of high dose ofatumumab in patients with FSGS prior and after renal transplantation. Obinutuzumab may offer some advantages. In the unique study performed in patients with multidrug dependent nephrotic syndrome reporting positive effects, obinutuzumab was associated with the anti-CD38 monoclonal antibody daratumumab proposing the unexplored frontier of combined therapies. Obinutuzumab represent an evolution also in the treatment of autoimmune glomerulonephritis, such as membranous nephrotahy and lupus nephritis. Results of randomized trials, now in progress, are awaited to add new possibilities in those cases that are resistant to other drugs. The aim of the present review is to open a discussion among nephrologists, with the hope to achieve shared approaches in terms of type of antibodies and doses in the different proteinuric renal conditions.

Defining renal remission in an international cohort of 248 children and adolescents with lupus nephritis.

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.

Mortality in Children Treated With Maintenance Peritoneal Dialysis: Findings From the International Pediatric Peritoneal Dialysis Network Registry.

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.

Genotypes of glycoprotein B gene among the Indian symptomatic neonates with congenital CMV infection.

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.

Favourable renal survival in paediatric microscopic polyangiitis: efficacy of a novel treatment algorithm.

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.

Transient myeloproliferative disorder with trisomy 12.

The authors report the first case of transient myeloproliferative disorder (TMD) in a neonate with trisomy 12. The clinical course consisted of respiratory distress since birth with probability of transient tachypnea of newborn, but routine investigation revealed total leukocyte count of 56000/microL with 91% blasts, which returned to normal spontaneously during the subsequent 3 weeks. GTG-banded karyotype from peripheral blood was done to detect any mutation, specifically trisomy 21, but the proband revealed trisomy 12 and denaturing polyacrylamide gel electrophoresis (PAGE) detected mutation in exon 2 of GATA1. The condition has been described in association with Down syndrome (trisomy 21) but never with trisomy 12. This case demonstrates the importance of knowing this entity so that it is not erroneously diagnosed as a leukemic process. This is extremely important because most cases of TMD resolve spontaneously within a few weeks to months and do not require treatment other than supportive measures. A search of the literature did not reveal any similar case.

Retinal mass in a case of pediatric myelodysplastic syndrome (refractory anemia with excess of blasts).

PURPOSE: Myelodysplastic syndrome is a rare childhood clonal hematologic disorder characterized by dysplastic hematopoiesis and progression to leukemia. METHODS: Case report. RESULTS: An 8-year-old boy with low-grade fever, easy fatigability, and pallor of 3 months duration showed pancytopenia with 9% circulating blast cells. The bone marrow aspirate revealed striking trilineage dysplasia with 13% of blast cells. Cytogenetic analysis revealed 46, XY, del (20) (q11;q13). The findings were diagnostic of myelodysplastic syndrome with refractory anemia with excess of blasts in accordance with the World Health Organization criteria modified for pediatric age group. Fundus examination revealed a sickle-shaped hanging retinal mass of right eye. Biopsy/aspiration cytology of the retinal mass was not done in this case owing to risk of severe bleeding, a common feature in any hematologic malignancy. The child had been included in pediatric acute myeloid leukemia trials as the parents were not ready for stem cell transplantation, but he died after 3 months due to overwhelming infection. CONCLUSIONS: Myelodysplastic syndrome of childhood may present with retinal mass along with other hematologic features. Biopsy/aspiration cytology of the mass should not be attempted as it may cause intraocular hemorrhage.

The co-existence of CHARGE and myelodysplastic syndrome in a child.

We report the case of an 8-month-old female child with co-existence of CHARGE with myelodysplastic syndrome, which is not reported in the literature. The patient was treated with packed cell transfusion, laser photocoagulation for retinal detachment, and antimicrobials, and referred for bone marrow transplantation.