Comparison of darbepoetin alpha and recombinant human erythropoietin for treatment of anemia in pediatric chronic kidney disease: a non-inferiority trial from India.

To determine whether or not Darbepoetin alpha (DA) was non-inferior to recombinant human erythropoietin (rHuEPO) in the treatment of anemia in children with chronic kidney disease (CKD) stage 3-5 (on or not on dialysis). This was a randomized, open-label, two-arm, parallel group, active-controlled, non-inferiority trial conducted at a tertiary care center in New Delhi, India. Fifty patients of either gender (aged 1-18 years) with CKD stage 3-5 (on or not on dialysis) who had baseline hemoglobin (Hb) between 9 and 12 g/dL and were on stable erythropoietin therapy for at least 8 weeks were randomized (1:1) to either continue rHuEPO or switch to DA therapy for a period of 28 weeks. Doses were titrated in the initial 23 weeks to maintain the Hb between 11 and 12 g/dL, and efficacy was assessed between weeks 24 and 28. The primary efficacy outcome was the mean change in Hb between baseline and the evaluation period. In the intention-to-treat population (n = 50), the adjusted between-group difference in mean Hb change between the baseline and the evaluation period was 0.131 g/dL (95% CI: - 0.439 to 0.719, p = 0.629). The lower limit of the two-sided 95% CI for the difference in the mean change in Hb between the two treatment groups was well above the pre-specified non-inferiority margin of - 1.0 g/dL. Similar pattern of non-inferiority was seen for per protocol population. The safety profile of DA and rHuEPO was also comparable (injection site pain:rHuEPO-3, DA-7; p-0.296).   Conclusion: DA is non-inferior to rHuEPO for the treatment of anemia of CKD (stage 3-5) in pediatric population with a comparable safety profile.   Trial registration: ClinicalTrials.gov Identifier: NCT04959578 (retrospectively registered), Date: July 13, 2021. What is Known: • Limited studies showing darbepoetin alpha is effective in children as an erythropoiesis stimulating agent. • No RCT from Indian subcontinent addressing this topic. What is New: • Darbepoetin alpha is non inferior to recombinant human erythropoietin for treatment of anemia in children with CKD stage 3-5 (on or not on dialysis) with safety comparable to recombinant human erythropoietin. • A cost reduction of approximately 8.6% per patient by shifting to darbepoetin alpha.

Quality of life in children with nephrotic syndrome: a cross-sectional study using Hindi version of PedsQL 4.0 Generic Core Scales.

BACKGROUND: Worldwide, idiopathic nephrotic syndrome (INS) is the most common glomerular disorder in children. Limited studies are available on quality of life (QOL) in children with NS, especially from developing countries. The aim of the current study was to compare the QOL of children having INS with that of matched healthy controls and to evaluate the effects of sub-types on domain scores. METHODS: This single-center, cross-sectional analytical study was conducted in children between 2 and 18 years with primary INS, at a tertiary care center in India, from September 2018 to November 2018. QOL data were collected using PedsQL™4.0 Generic Core Scales "Hindi-for-India" version (child self-report and parent-report). A total of 102 cases with equal number of matched healthy controls were included. RESULTS: The mean total PedsQL scores were lower in NS children compared to healthy controls (p-0.0004). They had statistically lower scores in physical (p- < 0.0001), social (p-0.026), and school domains (p- < 0.0001); however, no such difference was noted in emotional functioning. School functioning was the most impacted domain overall, and also across all the clinical types. Worst scores were seen in children with steroid-resistant NS in all domains. Older age-at-enrolment, higher number of relapses, prevalent NS, steroid-resistant disease, calcineurin inhibitor (CNI) use, and higher number of immunosuppressant use were important predictors of poor total QOL scores. On multivariable regression, higher number of immunosuppressant use (p-0.015) and older age-at-enrolment (p-0.016) were main predictors of impaired total scores. Cases with edema and current/previous CNI use were more likely to have impaired emotional (p-0.028) and social (p-0.040) domain sub-scores, respectively. CONCLUSION: NS has a significant impact on the QOL of children in different domains of functioning, based on their as well as parents' perspective. TRIAL REGISTRATION NO: EC/08/18/1414; Date: 30/08/2018.

Continuous renal replacement therapy in children with severe sepsis and multiorgan dysfunction - A pilot study on timing of initiation.

OBJECTIVE: Scanty literature is available regarding continuous renal replacement therapy (CRRT) utility in severe sepsis with multiorgan dysfunction syndrome (MODS) from developing countries. Author unit's experience in pediatric CRRT is described and outcome of early initiation of CRRT with sepsis and MODS is assessed. MATERIALS AND METHODS: Children aged <16 years with sepsis and MODS who required CRRT from September 2010 to February 2015 were analyzed on demographic factors, timing of initiation of CRRT, mode of CRRT, effect of CRRT onhemodynamics, oxygenation parameters, and outcome. RESULTS: Twenty-seven children required CRRT (male - 16). The median age was 11 years (range 1.1-16). Twenty-one had severe sepsis with MODS. Eighteen patients were given CRRT within 48 h of admission to Intensive Care Unit (ICU). Statistically significant improvement in the P/F ratio, decrement in plateau pressure and vasoactive-inotropic score were noted in survivor group compared to nonsurvivor group (P = 0.022, 0.00, and 0.03, respectively). There was no statistically significant difference in duration of ICU stay, fluid overload, CRRT duration, PRISM score at 12 and 24 h, percentage of decrease in inotrope score, plateau pressure, and percentage of increase in P/F ratio in relation to timing of CRRT initiation. However, the survival rate was 61.1% (11/18) who received CRRT within 48 h of ICU admission compared to 33.3% (3/9) who received after 48 h (P = 0.0001). CONCLUSION: Our study emphasizes the CRRT role in improving the oxygenation status and hemodynamics. Survival benefit may be expected in those children who receive CRRT early in the course of sepsis. However, multicenter RCTs are required to prove mortality benefit.

Therapeutic Plasma Exchange in Children - Experience From a Tertiary Care Center.

OBJECTIVE: To assess the safety, efficacy and outcomes of therapeutic plasma exchange (TPE) in children. METHODS: Data were retrieved from hospital records for all children £18 years who underwent TPE between August, 2011 and July, 2018. RESULTS: 46 children [median (range) age 96 (8-204) months] underwent 293 sessions of TPE by membrane plasma separation technique. Renal disease was the commonest indication (24, 52.2%) followed by neurological illnesses (17; 36.9%). 36 (78.2%) patients belonged to American Society for Apheresis category I. Overall, the most common indication was atypical hemolytic uremic syndrome (aHUS) (16; 34.8%). Fresh frozen plasma plus albumin was used as replacement fluid in aHUS, while albumin was used in others. 40 (86.9%) patients had complete/partial recovery while six did not show any sign of recovery. Complications were seen in 21 (7.1%) sessions; majority of which were minor in the form of blood pressure fluctuations. CONCLUSION: TPE can be performed safely and effectively for renal and non-renal indications, even in small children.

Kawasaki disease with autoimmune hemolytic anemia.

BACKGROUND: Association of autoimmune haemolytic anaemia has been seldom reported with Kawasaki disease. CASE CHARACTERISTICS: A 7-month-old boy, presented with prolonged fever, erythematous rash, severe pallor and hepatosplenomegaly. OBSERVATIONS: Positive Direct Coombs test and coronary artery aneurysm on echocardiography. He was managed with steroids along with intravenous immunoglobulins and aspirin. OUTCOME: Early identification of the condition helped in the management. MESSAGE: Patients of autoimmune hemolytic anemia with unusual features such as prolonged fever, skin rash, and mixed antibody response in Coombs test should be evaluated for underlying Kawasaki disease as a possible etiology.

Nasopharyngeal carriage of Streptococcus pneumoniae.

OBJECTIVE: To determine nasopharyngeal carriage rate and prevalent serogroups/types (SGT) of S. pneumoniae in healthy children, assess their antimicrobial susceptibility and its implications over the heptavalent pneumococcal conjugate vaccine. METHODS: 200 healthy children aged between 3 months and 3 years attending Pediatric OPD at Sir Ganga Ram Hospital, New Delhi were studied. A nasopharyngeal swab was collected from each child which was processed to isolate Streptococcus pneumoniae. Serotyping was performed by the Quellung reaction. Antimicrobial susceptibility patterns were determined by disk diffusion and E test methods. RESULTS: S. pneumoniae carriage rate was 6.5%. Isolates belonged to serotypes 1, 6, 14 and 19, of which serotype 19 was the most common. None of the strains were totally resistant to penicillin though 2 (15.4%) were intermediately resistant. Overall, 84.6% of the isolates belonged to the strains covered by the heptavalent pneumococcal vaccine. CONCLUSION: The heptavalent conjugate vaccine covers most isolated strains, but since the number of strains is very small, it is suggested that there is need for further studies in different regions to assess the usefulness of this vaccine.

CT diagnosis of strangulated diaphragmatic hernia.

Strangulated diaphragmatic hernia is a surgical emergency which on occasions can be a diagnostic dilemma. We report of a 2-year-old-male child with strangulated diaphragmatic hernia in whom a correct preoperative diagnosis was made with progression of illness. CT depicted a curvilinear fat stripe in a fluid filled hemithorax.