Antineutrophil cytoplasmic antibody in children with nephrotic syndrome treated with levamisole: a cross-sectional cohort study.

BACKGROUND: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning. METHODS: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA. RESULTS: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months. CONCLUSIONS: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication.

Presentation and outcome of pediatric lupus nephritis from a large single centre contemporary cohort in Eastern India.

BACKGROUND: We present clinical, biochemical, and histopathological characteristics and treatment outcomes of biopsy proven childhood lupus nephritis (LN) from a low/middle income setting treated in the current era of increased use of Mycophenolate Mofetil (MMF) and biologics. METHODS: Retrospective observational study of children (1-18 years) with biopsy proven LN treated from 01.01.2010 to 31.01.2020. RESULTS: 60 children met our inclusion criteria (80%, n = 48 were females). The median age at diagnosis was 11 (IQR: 9-12) years. The most common extra-renal manifestation was mucocutaneous (n = 54, 90%) and the most common kidney manifestation was edema (n = 50, 83.3%). The median 24-h urinary protein excretion was 1117.8 (IQR: 795.4-1941.7) mg/m2/day with 67% (n = 40) having nephrotic range proteinuria (>1000 mg/m2/day). 75% (n = 45) children had eGFR <90 mL/min/1.73 m2 (median eGFR = 71; IQR: 56-90 mL/min/1.73 m2). Anti-Nuclear Antibody was positive in all, both complement three and four were low in 82% (n = 49) and anti-double stranded DNA antibodies were positive in 63% (n = 38). 85% (n = 51) had proliferative LN with majority being class IV (57%, n = 34). All children received steroids for induction therapy. MMF was given as the sole induction agent in 48% (n = 29) and cyclophosphamide in 27% (n = 16). Rituximab was added in 17% (n = 10) as a rescue agent. Median follow up duration was 50 (IQR: 28-82) months. Six children (10%) died as a result of serious infections and none of them had shown complete response (CR). Out of the 52 children who had a follow up duration of at least 2 years, CR was achieved in 46 children (88%) and partial response (PR) or no response (NR) in three children (6%) each. Although children who were in CR/PR at last follow up had lower proteinuria, higher eGFR, and lower histopathology activity index at onset; low numbers in the NR group precluded us from subjecting them to any statistical correlation tests. 36% (n = 22) of children developed 36 episodes of renal flares with overall incidence of 0.14/person-year. CONCLUSION: Our study on a contemporary cohort of childhood LN highlights the importance of achieving CR and its feasibility.

Incidence and risk factors of acute kidney injury among childhood nephrotic syndrome: a prospective cohort study.

Acute kidney injury (AKI) is a known independent risk factor for morbidity/mortality but there is scarcity of robust data on it among childhood nephrotic syndrome (NS). We assessed the incidence of AKI among hospitalized children with NS as well as looked for any significant risk factors. Prospective observational study conducted across two tertiary pediatric hospitals in Eastern India from September 2020 to August 2021. Children aged 1-18 years admitted with NS and without any nephritic features or pre-existing chronic kidney disease (CKD) were included. In 200 admissions (n = 176; 63% female, median age 4 years [IQR: 3-7]), AKI occurred in 36 (18%; 95% CI 13 to 36%). Two children required kidney replacement therapy and one death was recorded. In 27/36 (75%), AKI resolved within 48 h, 4 had persistent AKI, 3 acute kidney disease, and two progressed to CKD. On multivariate regression analysis: fractional excretion of sodium ≤ 0.2% (OR 12.77; 95% CI 3.5-46.4), male gender (OR 6.38; 95% CI 2.76-14.74), underlying infection (OR 5.44; 95% CI 2.4-11.86), nephrotoxic drugs (OR 4.83; 95% CI 2.21-10.54), and albumin ≤ 1.4 g/dl (OR 4.35; 95% CI 1.55-12.8) were associated with AKI. A predictive equation using these five variables on admission had high AUC (0.86) in correctly identifying 17 children who subsequently developed AKI.   Conclusion: In a low resource setting, AKI is common among hospitalized children with NS. Larger multi-center prospective studies are needed to refine prediction equations and test its utility in preventing AKI development. What is Known: • Acute Kidney Injury is a known independent risk factor for increased morbidity and mortality. • There are few studies to assess the incidence of Acute kidney injury in hospitalised cases of childhood nephrotic syndrome.. What is New: • This is the largest prospective cohort of children suffering from nephrotic syndrome, in India, proposing a novel algorithm for predicting the risk of AKI among hospitalised cases of childhood nephrotic syndrome.

Improving acute peritoneal dialysis outcome with use of soft peritoneal dialysis catheter (Cook Mac-Loc Multipurpose Drainage catheter®) among infants < 1500 g in a low resource setting.

BACKGROUND: Despite its utility, uncertainty exists on the feasibility of acute peritoneal dialysis (PD) and optimal PD catheter type for very low birth weight (VLBW < 1500 g) and extremely low birth weight (ELBW < 1000 g) infants. We hereby report our experience of acute PD among these high-risk infants and compare the outcome between stylet-based rigid catheter (SRC) and Cook Mac-Loc Multipurpose Drainage catheters® (CMMDC). METHODS: Case notes of infants < 1500 g undergoing PD between 2012 and 2021 in a network of five participating neonatal units supported by a tertiary paediatric nephrology centre in Kolkata, India, were retrospectively reviewed. PD was conducted either with SRC or after 2018 with CMMDC. Outcome parameters included complications, survival during PD, and survival to discharge. RESULTS: 24 infants (VLBW: n = 13 and ELBW: n = 11) underwent PD at median age 4.5 days (IQR 3-6) with either CMMDC (n = 14) or SRC (n = 10). Significant improvement in biochemical parameters and fluid removal was seen in both ELBW and VLBW infants. CMMDC was associated with significantly fewer PD-related complications 7/14 (50%) vs. 9/10 (90%) (p = 0.04) and higher survival during PD 13/14 (93%) vs. 5/10 (50%) (p = 0.02), without significant difference in survival to hospital discharge 8/14 (57%) vs. 3/10 (30%) (p = 0.25). CMMDC also enabled longer duration of PD, higher ultrafiltration, and better control of acidosis. Consumable cost was higher for CMMDC (USD$60) than SRC (USD$14). CONCLUSIONS: In a low resource setting, CMMDC had lower PD complications and superior short-term survival among ELBW/VLBW infants. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evaluation of a simulation training programme for geriatric medicine.

BACKGROUND: geriatrics encompasses diverse medical, social and ethical challenges requiring a multidimensional, interdisciplinary approach. Recent reports have highlighted failings in the care of older people. It is therefore vital that trainees in geriatrics are afforded opportunities to develop skills in managing this complex population. Simulation has been adopted as a teaching tool in medicine; however, evidence for its use in geriatrics has been limited to small, single-site studies primarily involving role-play or discrete clinical skills training. METHODS: a standardised, two centre, multimodal, interprofessional, geriatrics simulation training programme was developed using curriculum-mapped scenarios in which the patient perspective was central. Simulation techniques used included high-fidelity patient manikins, actors with integrated clinical skills using part-task trainers and role-play exercises. A mixed-methods evaluation was used to analyse data from participants before and after training. RESULTS: eighty-nine candidates attended 12 similar courses over 2 years. Thematic analysis of candidate feedback was supportive of simulation as a useful tool, with benefits for both technical and non-technical skills. Candidates commented that simulation was a valuable training modality addressing curriculum areas rarely taught formally including continence assessment, end-of-life decisions and multidisciplinary situations. Quantitative analysis of pre- and post-course questionnaires revealed a significant improvement of self-reported confidence in managing geriatric scenarios (mean improvement 11.5%; P < 0.001). DISCUSSION: this study demonstrated the feasibility of a standardised simulation training programme across two sites in geriatrics. Simulation training affords situational learning without compromising patient safety and is an exciting and novel method of delivering teaching for geriatrics that could be integrated into national training curricula.