Activin A: a marker of mineral bone disorder in children with chronic kidney disease?

BACKGROUND: Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD. METHODS: A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. RESULTS: The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). CONCLUSIONS: Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.

Urinary Apolipoprotein A1 and Neutrophil Gelatinase-associated Lipocalin in Children with Idiopathic Nephrotic Syndrome.

Urinary biomarkers are a promising diagnostic modality whose role was explored in nephrotic syndrome (NS). We estimated urinary apolipoprotein A1 (Apo A1) and neutrophil gelatinase-associated lipocalin (NGAL) in children with first-episode NS (FENS) and controls with a longitudinal follow-up to see the serial changes during remission. The study groups comprised 35 children with FENS and an equal number of age- and sex-matched controls. Patients were followed up at regular intervals, and 32 patients were classified as having steroid-sensitive NS (SSNS) and 3 as having steroid-resistant NS (SRNS). The mean follow-up period was 8.7 ± 4.2 months. Three patients in the SSNS group were labeled as having frequent relapses or steroid-dependent disease during follow-up. Of the three children with SRNS, two had minimal changes in the disease and one had idiopathic membranous nephropathy. The levels of Apo A1:creatinine, NGAL:creatinine, and spot urinary protein:urinary creatinine ratios were significantly higher in children with FENS compared with controls. The levels of the urine biomarkers decreased significantly at subsequent follow-up with remission. The Apo A1 and NGAL levels in SSNS patients were significantly high compared with both the controls and FENS patients. Urinary Apo A1 levels in SRNS patients were lower at initial presentation. This longitudinal study revealed changes in the urinary Apo A1 and NGAL in NS over the course of the disease.

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.

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.

Integration of Urinary Neutrophil Gelatinase-associated Lipocalin with the Renal Angina Index to Predict Subsequent Severe Acute Kidney Injury in Critically Ill Children: A Diagnostic Accuracy Study.

The primary objective of this study was to determine the performance of the renal angina index (RAI) in predicting subsequent severe acute kidney injury (AKI) on day 3 of admission and whether integrating urinary neutrophil gelatinase-associated lipocalin (NGAL) with RAI would lead to improved prediction of AKI. This was a prospective observational study conducted in the pediatric intensive care unit (PICU) of a tertiary care hospital involving 170 children meeting the inclusion criteria. The RAI was assessed within 24 h of admission to the PICU. Positivity for renal angina was considered RAI ≥8. Urine samples were collected for all enrolled patients within the first 24 h and on day 3 of the PICU stay. NGAL was assayed using human-specific enzyme-linked immunosorbent assay. The overall incidence of AKI was 18.2%. Out of 170 children, 31 (18.2%) were RAI-positive on day 0. A higher proportion of patients in the RAI-positive group developed AKI on day 3 compared with the RAI-negative group (83.9% vs. 3.6%, P <0.001). Those who were RAI-positive on day 0 had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 83.8%, 96.4%, 83.8%, and 96.4%, respectively, for predicting severe AKI on day 3. Incorporating urinary NGAL improved the specificity and PPV to 97.8% and 85.7%, respectively. Assessing the RAI is simple and useful for predicting severe AKI in critically ill children. The addition of urinary NGAL to the RAI optimizes its use for identifying patients at risk of subsequent severe AKI.

Predictors of mortality in children admitted with SARS-CoV-2 infection to a tertiary care hospital in North India.

AIM: To compare the demographic, clinical, laboratory and radiological parameters of patients with different clinical outcomes (death or discharge) and analyse them to find out the potential predictors for mortality in children hospitalised with SARS-CoV-2 infection. METHODS: Retrospective chart review of all patients less than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and requiring hospital admission between 16 April 2020 and 31 October 2020. RESULTS: Of 255 children with SARS-CoV-2 infection, 100 patients (median age 62.5 months, 59% males, 70% with moderate to severe disease) were hospitalised, of whom 27 died (median age 72 months, 59% males and 30% severely underweight). The subgroup with comorbidities (n = 14) was older (median age 126 months) and had longer duration of stay (median 10 days). Fever and respiratory symptoms were comparable while gastrointestinal symptoms were more common among non-survivors. Hypoxia at admission (odds ratio (OR) 5.48, P = 0.001), multiorgan dysfunction (OR 75.42, P = 0.001), presence of acute kidney injury (OR 11.66, P = 0.001), thrombocytopenia (OR 4.40, P = 0.003) and raised serum C-reactive protein (CRP) (OR 4.69, P = 0.02) were independently associated with mortality. The median time from hospitalisation to death was 3 days. The deceased group had significantly higher median levels of inflammatory parameters and a higher incidence of complications (myocarditis, encephalitis, acute respiratory distress syndrome and shock). CONCLUSIONS: Hypoxia at admission, involvement of three or more organ systems, presence of acute kidney injury, thrombocytopenia and raised serum C-reactive protein were found to be independently associated with increased odds of in-hospital mortality in children admitted with SARS-CoV-2 infection.

Comparison of clinical and laboratory profile of survivors and non-survivors of SARS-CoV-2-related multisystem inflammatory syndrome of childhood in India: An observational study.

AIM: The SARS-CoV-2 pandemic is characterised by multiple reports of paediatric multisystem inflammatory disease or multisystem inflammatory syndrome in children (MIS-C) with Kawasaki disease-like features often complicated by myocarditis, shock and macrophage activation syndrome. Certain clinical and laboratory markers may be used to identify high risk cases. METHODS: All sequentially admitted patients hospitalised between April 2020 and October 2020, who met the WHO case definition for MIS-C were included. Data included patient demographic information, presenting symptoms, organ dysfunction and laboratory parameters. SARS-CoV-2 infection was diagnosed by nasopharyngeal swab real-time reverse transcription-polymerase chain reaction and/or rapid antibody test for SARS-CoV-2 as recommended. The clinical and laboratory criteria were compared in the survival and non-survival groups. RESULTS: A total of 29 patients with MIS-C were treated during the study period. There were 21 survivors and 8 non-survivors. The non-survivors had more neurocognitive and respiratory symptoms along with increased incidence of myocarditis compared with survivors. The serum levels of CPK-MB, D-dimer, ferritin and triglyceride were significantly raised in non-survivors as compared to survivors. CONCLUSION: The non-survivor group had higher CPK and greater proportion of children with troponin-T elevation indicating higher incidence of myocardial injury and necrosis. The D-dimer, ferritin and triglyceride were also higher in the mortality group, indicating the greater extent of inflammatory damage in this group.

The 2021 Toolkit for Emergency Preparedness and Mitigation to Combat Surge of Pediatric COVID-19 Patients in India: The World Health Organization Collaborating Center for Emergency and Trauma in South East Asia Recommendations.

The authors of this toolkit focus on children under the age of 18 comprising approximately 41% of the total population in India. This toolkit has been created with an objective to prepare, mitigate the effects of any surge of COVID-19 in our communities, and help to optimally utilize the scarce resources. The toolkit design suggests the manpower, equipment, laboratory support, training, consumables, and drugs for a 10-bedded pediatric emergency room, 25-bedded COVID pediatric intensive care unit, and 75-bedded COVID pediatric high dependency unit/ward as defined for a 100-bedded facility. A dedicated and detailed chapter is included to address the psychological needs of the children. These data can be modified for other department sizes based on the facilities, needs, local environment, and resources available.

Acute Kidney Injury in Hospitalized Children with COVID19.

BACKGROUND: Acute kidney injury (AKI) has been recognized as a significant risk factor for mortality among adults with severe acute respiratory syndrome coronavirus infection. AIM: The aim of this study is to assess the prevalence and risk factors for AKI and mortality in children with coronavirus disease 2019 (COVID19) from a resource-limited setting. METHODS: Cross-sectional analysis of laboratory confirmed COVID19 children admitted from 1 March to 30 November 2020 in a tertiary care hospital in New Delhi, India was done. Clinical features and associated comorbidities of COVID19 were noted. Baseline serum creatinine (height-independent Hoste's equation) and peak serum creatinine were used for staging of AKI by the 2012 Kidney Disease Improving Global Outcomes serum creatinine criteria. Univariate analysis and Kaplan-Meier survival analysis were used to compare the overall outcome in the AKI vs. the non-AKI group. RESULTS: A total of 64 810 children between 1 month and 18 years visited the hospital; 3412 were tested for suspected COVID19, 295 tested positive and 105 (54% boys) were hospitalized. Twenty-four hospitalized children (22.8%) developed AKI; 8 in Stage 1 (33.3%), 7 in Stage 2 (29.2%) and 9 in Stage 3 (37.5%) respectively. Overall, three patients received KRT. Highest reported mortality was (66.6%) in AKI Stage 3. Risk factors for AKI included associated sepsis (OR 95% CI, 1.22-9.43, p < 0.01), nephrotic syndrome (OR 95% CI, 1.13-115.5, p < 0.01), vasopressor support (OR 3.59, 95% CI, 1.37-9.40, p value< 0.007), shock at presentation (OR 2.98, 95% CI, 1.16-7.60, p value 0.01) and mechanical ventilation (OR 2.64, 95% CI, 1.04-6.71, p value< 0.03). Mortality (25.71%) was higher in the AKI group (OR 95% CI, 1.14-8.35, p < 0.023) with shock (OR 45.92; 95% CI, 3.44-612.0, p value <0.004) and ventilation (OR 46.24; 95% CI, 1.6-1333.0 p value< 0.02) as significant risk factors for mortality. CONCLUSION: AKI is an important modifiable risk factor for mortality in children with COVID19 in a resource-limited setting. Our study supports the strengthening of kidney replacement therapy and its timely initiation to reduce the progression of AKI and thus mortality in children.

Clinical and Histopathological Profile of Adolescent onset Idiopathic Nephrotic Syndrome in North Indian Children.

Adolescent onset idiopathic nephrotic syndrome (INS) is marked by increased incidence atypical features and non-minimal change disease in histopathology. The objective of the study was to analyze the clinical features and histopathological spectrum of adolescent-onset INS. It was conducted in a Pediatric nephrology clinic of a tertiary care hospital in North India. We retrospectively evaluated clinical features, biochemical investigations and histopathology of 33 adolescents with idiopathic NS registered in pediatric nephrology clinic. Twenty-three (70.0%) adolescents had steroid resistant nephrotic syndrome. Hematuria was present in 39%, hypertension 36% and acute kidney injury (AKI) in 27%. Three-fourth of adolescents who underwent biopsy had non-minimal change disease in histopathology. Adolescent onset INS have increased incidence of AKI, hypertension, and non-minimal change disease.

Steroid Sensitive Nephrotic Syndrome: Revised Guidelines.

JUSTIFICATION: Steroid sensitive nephrotic syndrome (SSNS) is one of the most common chronic kidney diseases in children. These guidelines update the existing Indian Society of Pediatric Nephrology recommendations on its management. OBJECTIVE: To frame revised guidelines on diagnosis, evaluation, management and supportive care of patients with the illness. PROCESS: The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by review of literature and evaluation of evidence by experts in two face-to-face meetings. RECOMMENDATIONS: The initial statements provide advice for evaluation at onset and follow up and indications for kidney biopsy. Subsequent statements provide recommendations for management of the first episode of illness and of disease relapses. Recommendations on the use of immunosuppressive strategies in patients with frequent relapses and steroid dependence are accompanied by suggestions for step-wise approach and plan of monitoring. Guidance is also provided regarding the management of common complications including edema, hypovolemia and serious infections. Advice on immunization and transition of care is given. The revised guideline is intended to improve the management and outcomes of patients with SSNS, and provide directions for future research.

Peritoneal dialysis in children with sepsis-associated AKI (SA-AKI): an experience in a low- to middle-income country.

Background: In critically ill children, sepsis-associated acute kidney injury (SA-AKI) has significant morbidity and mortality.Aim: To estimate whether early initiation of peritoneal dialysis (PD) has a better short-term outcome than standard PD.Methods: Early PD (n = 25) was defined as a need for PD in Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 AKI, while those fulfilling the criteria for stage 3 KDIGO were categorised as a standard PD group (n = 25). The primary outcome measure was the estimated glomerular filtration rate (eGFR) at discharge or at 4 weeks after initiation of PD, whichever occurred earlier.Results: A prospective cohort of 50 children (32 boys) aged 2 months to 16 years with SA-AKI who underwent PD were recruited. The most frequent indication for PD was fluid overload (40%), followed by persistent metabolic acidosis (36%). Children in the early PD group had lower creatinine and higher eGFR at discharge/4-week follow-up (p < 0.001). The duration of PD was less if it was commenced early (p < 0.04); 24 of 25 (96%) children in the early PD group were off PD within 6 days of initiation compared with 13 of 25 (52%) in the standard PD group (p < 0.001).Conclusions: Compared with standard PD, early PD in SA-AKI resulted in a favourable renal outcome, decreased duration of PD and early discontinuation of dialysis.Abbreviations : AKI: acute kidney injury; CRRT: continuous renal replacement therapy; CS-AKI: cardiac surgery-associated acute kidney injury; eGFR: estimated glomerular filtration rate; ELAIN: early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury; ESCAPE: effect of strict blood pressure control and ACE inhibition on the progression of chronic kidney disease in paediatric patients; HIC: high-income countries; ISN: international society of nephrology; KDIGO: Kidney Disease: Improving Global Outcomes; LMIC: low- to middle-income countries; PD: peritoneal dialysis; PICU: paediatric intensive care unit; RRT: renal replacement therapy; SA-AKI: sepsis-associated acute kidney injury; SYL: Saving Young Lives; SOFA: sequential (sepsis-related) organ failure assessment score; STARRT-AKI: standard versus accelerated initiation of renal replacement therapy in acute kidney injury.

Peritoneal dialysis in critically ill children in resource-limited setting: A prospective cohort study.

BACKGROUND: Peritoneal dialysis (PD) is easily available and simple lifesaving procedure in children with renal impairment. There is paucity of reports on efficacy of PD in critically ill children in presence of shock and those requiring mechanical ventilation. METHODS: In this prospective observational study, efficacy and outcome of PD were evaluated in 50 critically ill children aged 1 month to 14 years admitted in pediatric intensive care unit of a tertiary care teaching hospital in India. RESULTS: Indication of PD was acute kidney injury (AKI) in 66% of patients followed by chronic kidney disease with acute deterioration due to infectious complications in 34%. Bacterial sepsis was the most common cause of AKI (22%), others being malaria (14%) and severe dengue (12%). At initiation of PD, 26% of patients were in shock and 46% were mechanically ventilated. PD was effective and improvement in pH, bicarbonate, and lactate started within hours, with consistent improvement in estimated glomerular filtration rate by 24 h, which continued till the end of procedure, including the subgroup of patients with shock and mechanical ventilation. Total complications were seen in 14% and of which peritonitis was present in 4.0% of patients. Mortality was seen in 14% (7/50) of patients. Shock at initiation of PD (odds ratio (OR), 5.03; 95% confidence interval (CI), 0.95-26.69; p < 0.04) and requirement of mechanical ventilation (OR, 9.17; 95% CI, 1.01-83.10; p < 0.02) were associated with mortality. CONCLUSIONS: Acute PD in critically ill children with renal impairment is a lifesaving procedure. Treatment of shock with resuscitative measures and respiratory failure with mechanical ventilation, along with PD, resulted in favorable renal outcome.