Diagnostic accuracy of renal angina index alone or in combination with biomarkers for predicting acute kidney injury in children.

Early recognition of patients at risk for severe acute kidney injury (AKI) by renal angina index (RAI) may help in the early institution of preventive measures. Objective was to evaluate performance of RAI alone or in combination with biomarkers in predicting severe AKI (KDIGO stage 2 and 3 or equivalent) and receipt of kidney replacement therapy (KRT) in critically ill children. We searched PubMed, EMBASE, Web of Sciences, and CENTRAL for studies published till May 2021. Search terms included acute kidney injury, pediatrics, adolescent, renal angina index, and biomarker. Proceedings of relevant conferences and references of included studies were also scrutinized. Two reviewers independently assessed the study eligibility. Cohort and cross-sectional studies evaluating the diagnostic performance of RAI in predicting AKI or receipt of KRT in children were included. Eligible participants were the children less than 18 years with RAI assessment on day 0 ofadmission. We followed PRISMA-DTA guidelines and used the QUADAS-2 tool for quality assessment. A bivariate model for meta-analysis was used to calculate the summary estimates of diagnostic parameters. Major outcomes were the diagnostic accuracy of RAI (≥ 8) alone or with biomarkers in predicting severe AKI and KRT receipt. Diagnostic accuracy was reported using summary sensitivity, specificity, and area under the curve (AUC). Overall, 22 studies (24 reports, 14,001 participants) were included. RAI ≥ 8 on day 0 has summary sensitivity, specificity, and AUC of 0.86 (95% CI, 0.77-0.92), 0.77 (0.68-0.83), and 0.88 (0.85-0.91) respectively for prediction of severe AKI on day 3. In comparison, a combination of RAI and urinary neutrophil gelatinase-associated lipocalin (NGAL) showed summary sensitivity, specificity, and AUC of 0.76 (0.62-0.85), 0.89 (0.74-0.96), and 0.87 (0.84-0.90) respectively for predicting severe AKI. The sensitivity, specificity, and AUC of RAI for predicting receipt of KRT were 0.82 (0.71-0.90), 0.74 (0.66-0.81), and 0.85 (0.81-0.88) respectively. In meta-regression, only the study setting (sepsis vs. heterogenous) was associated with heterogeneity. We observed substantial heterogeneity among eligible studies. Five studies had concerns in patient selection, and seven studies also had applicability concerns in patient selection for this review. Moderate certainty evidence showed that RAI ≥ 8 has good predicting ability in recognizing children at risk of severe AKI and receipt of KRT. The combination of urinary NGAL and RAI further improves the predicting ability (low-certainty evidence). Further studies are required on the context-driven assessment of novel biomarkers in the early prediction of AKI in RAI-positive children. Systematic review registration number: CRD4202122268. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficacy of low-dose daily versus alternate-day prednisolone in frequently relapsing nephrotic syndrome: an open-label randomized controlled trial.

BACKGROUND: While patients with frequently relapsing nephrotic syndrome (FRNS) are initially treated with long-term alternate-day prednisolone, relapses and adverse effects are common. In an open-label randomized controlled trial, we compared the efficacy of therapy with low-dose daily to standard alternate-day prednisolone in reducing relapse rates over 12-month follow-up. METHODS: Consecutive patients, aged 2-18 years, with FRNS were included. Following therapy of relapse, prednisolone was tapered to 0.75 mg/kg on alternate days. Stratifying for steroid dependence, patients were randomly assigned to prednisolone at 0.2-0.3 mg/kg daily or 0.5-0.7 mg/kg alternate day for 12 months. Relapses were treated with daily prednisolone, followed by return to intervention. Primary outcome was the incidence of relapses. Proportion with therapy failure (≥ 2 relapses in any 6 months or significant steroid toxicity) and sustained remission, cumulative prednisolone intake and adverse events were evaluated. RESULTS: Patients receiving daily prednisolone (n = 30) showed significantly fewer relapses than those on alternate-day therapy (n = 31) (0.55 relapses/person-year versus 1.94 relapses/person-year; incidence rate ratio 0.28; 95% CI 0.15, 0.52). Daily therapy was associated with higher rates of sustained remission at 6 months (73.3 versus 48.4%) and 1 year (60 versus 31.6%; log rank p = 0.013), lower rates of treatment failure at 6 months (3.3 versus 32.8%) and 1 year (6.7 versus 57.4%; p < 0.0001), and lower prednisolone use (0.27 ± 0.07 versus 0.39 ± 0.19 mg/kg/day; p = 0.003). Three and two patients need to receive the study intervention to enable sustained remission and prevent treatment failure, respectively. CONCLUSIONS: In patients with FRNS, daily administration of low-dose prednisolone is more effective than standard-dose alternate day therapy in lowering relapse rates, sustaining remission, and enabling steroid sparing.

Factors Associated With Hypertension and Cardiovascular Parameters in Children With Infrequently Relapsing Nephrotic Syndrome.

OBJECTIVES: To assess the prevalence of hypertension in children with infrequently relapsing nephrotic syndrome (IRNS) and its association with dyslipidemia, and end organ damage including left ventricular hypertrophy (LVH), at relapse and after steroid induced remission. METHODS: Prospective observational study conducted in 83 children aged 1-12 years with IRNS, presenting in relapse. Blood pressure, fundus examination, blood and urine investigations were done at relapse and then at 4 weeks of therapy. Echocardiography at 4 weeks was performed for assessment of LVH and relative wall thickness (RWT) for concentric geo-metry (CG). RESULTS: 27 patients (32.5%) developed hypertension, out of which 21 patients (25.3%) had stage I hypertension. Hypertension in first episode (63.0%, P<0.01) and in previous relapses (87.5%, P<0.001) was significantly associated with hypertension in the current episode. 12 patients had a positive family history of hypertension, of which 8 (66.7%) were classified under the hypertensive group (P=0.016). Concentric geometry (CG) was found in 28% of hypertensive and 5.5% of non-hypertensive children (P=0.011). On regression analysis, a lower Up:Uc at the time of relapse was found to have a protective role for development of hypertension. CONCLUSION: One third children with IRNS had hypertension at relapse and a high proportion of hypertensive patients had CG pattern on echocardiography.

Feasibility and Efficacy of Sustained Low-Efficiency Dialysis in Critically Ill Children with Severe Acute Kidney Injury.

OBJECTIVES: To examine the feasibility, efficacy, and safety of sustained low-efficiency dialysis (SLED) in hemodynamically unstable, critically ill children. METHODS: Critically ill patients, 1-18 y old with hemodynamic instability (≥ 1 vasoactive drugs) and severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) in a tertiary care pediatric intensive care unit were prospectively enrolled. Patients weighing ≤ 8 kg or with mean arterial pressure < 5th percentile despite > 3 vasoactive drugs, were excluded. Patients underwent SLED until hemodynamically stable and off vasoactive drugs, or lack of need for dialysis. The primary outcome was the proportion of patients in whom the first session of SLED was initiated within 12 h of its indication and completed without premature (< 6 h) termination. Efficacy was estimated by ultrafiltration, urea reduction ratio (URR), and equilibrated Kt/V. Other outcomes included: changes in hemodynamic scores, circuit clotting, adverse events, and changes in indices on point-of-care ultrasonography and echocardiography. RESULTS: Between November 2018 and March 2020, 18 patients with median age 8.6 y and vasopressor dependency index of 83.2, underwent 41 sessions of SLED. In 16 patients, SLED was feasible within 12 h of indication. No session was terminated prematurely. Ultrafiltration achieved was 4.0 ± 2.2 mL/kg/h, while URR was 57.7 ± 16.2% and eKt/V 1.17 ± 0.56. Hemodynamic scores did not change significantly. Asymptomatic hypokalemia was the chief adverse effect. Sessions were associated with a significant improvement in indices on ultrasound and left ventricular function. Fourteen patients died. CONCLUSIONS: SLED is feasible, safe, and effective in enabling KRT in hemodynamically unstable children with severe AKI.

SARS-CoV-2 Infection in Children with Idiopathic Nephrotic Syndrome: A Multicentric Study.

A multicenter retrospective study was conducted to assess the clinical spectrum of 30 severe acute respiratory syndrome coronavirus (SARS-CoV-2)-positive children with idiopathic nephrotic syndrome. Difficult to treat nephrotic syndrome was found to be a high-risk group with a high incidence of acute kidney injury and mortality.

Electrically doped SiGe-heterojunction TFET based biosensor considering non-ideal hybridization issues: a simulation study.

Calibrated simulations are used to study a dielectric modulated, electrically doped, dual metal gate, SiGe heterojunction, double gate TFET biosensor in this work. Use of lower bandgap SiGe at the source side helps in improving the ON current of the biosensor. Electric doping is preferred over physical doping to overcome the random dopant fluctuations and high thermal budget problems. Non-ideal situations having partially and non-uniformly filled cavity regions are analyzed in this work. Partially filled cavity has fill factor less than 100% and is studied by considering 50%, 20%, and 10% fill factors. Different positions of biomolecules inside a partially filled cavity are also studied through extensive simulations and are found to affect the sensitivity largely. Four different non-uniform profiles, decreasing, increasing, convex and concave, are created in the cavity region and their sensitivity values are compared for different dielectric constants (k) and charge densities ( Q Bio ). Among the different non-uniform profiles considered, maximum sensitivity is obtained for decreasing profile and it improves with an increase in dielectric constant and positive charge density while it decreases when negative charge density increases.

Impaired Distal Tubular Acidification, Renal Cysts and Nephrocalcinosis in Monogenic Hypertension.

Monogenic defects in tubular sodium handling contribute a small proportion to hypertension in childhood. Presentation varies from severe hypertension manifesting at birth to asymptomatic hypertension and hypokalemic metabolic alkalosis detected incidentally in adulthood. A 12-y-old girl presenting with polyuria, polydipsia, severe hypertension and seizures, was found to have hypokalemia, renal medullary cysts and nephrocalcinosis. Clinical exome revealed a homozygous variation of unknown significance in exon 5 of the HSD11B2 gene, indicating the diagnosis of apparent mineralocorticoid excess. Therapy with spironolactone was associated with resolution of hypokalemia and normal blood pressure during two-year follow up.

Acute Myeloid Leukemia Presenting as a Central Nervous System Mass in a Child: A Case Report.

Extramedullary leukemia is common in pediatric acute myeloid leukemia (AML) and occurs as a solid tumor (myeloid sarcoma). We report a case of a child who presented with acute onset of paraparesis and found to have intracranial and paravertebral mass; subsequently, he was diagnosed as having AML on tissue biopsy. He was started on AML treatment protocol, and later he was in remission and myeloid sarcoma got cleared from intracranial and paravertebral region. Timely diagnosis and initiation of treatment are essential to improve survival in such cases.