Emerging progressive atypical acute kidney injury in young children linked to ethylene glycol and diethylene glycol intoxication.

BACKGROUND: There had been a sudden surge of unusually severe and rapidly progressing acute kidney injury (AKI) incidence in Indonesia since August 2022 which did not correspond to the rise of COVID-19 incidence. We suspected this was related to ethylene glycol (EG) and diethylene glycol (DEG) intoxication. This study is aimed at describing the clinical and laboratory characteristics of AKI related to D(EG) intoxication in order to spread awareness of the possibility of intoxication in cases of rapidly progressing AKI with unknown etiology. METHODS: We conducted a cross-sectional study by collecting secondary data from the pediatric AKI registry at a national referral hospital in Jakarta, Indonesia. Data on children admitted from January to November 2022 with diagnosis of stage 3 AKI based on KDIGO criteria were included. Data regarding demographics, symptoms prior to anuria, laboratory results, infection panel including COVID-19 status, treatment administered, and mortality were analyzed. RESULTS: Sixteen patients tested positive for EG and DEG, all with history of consuming syrup-based medications. High anion gap metabolic acidosis was observed in majority of patients with mean pH 7.33 ± 0.07 and mean anion gap 15.6 ± 7.8 mEq/L. No patient had high osmolal gap (mean osmolal gap 3.46 ± 4.68). One deceased patient, who had kidney biopsy performed, showed severe damage and calcium oxalate crystals in the kidney tissue. Mortality was recorded in six patients (37.5%). CONCLUSION: Careful history taking of patient's clinical course, including consumption of syrup-based medications and laboratory findings, might aid clinicians to establish a working diagnosis of D(EG) intoxication without needing to wait for blood toxicology test. Early diagnosis and therapy are crucial to prevent substantial mortality.

Clinical Features of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 in Indonesia.

BACKGROUND: While the number of cases of multisystem inflammatory syndrome in children (MIS-C) is increasing, reported cases in Asian countries are still low, particularly in Indonesia. This study aimed to describe the characteristics of patients with MIS-C in a tertiary referral hospital in Indonesia. METHODS: This is a cross-sectional study with collected data of patients with MIS-C admitted to Dr. Cipto Mangunkusumo from March 2020 to April 2021. RESULTS: The first case of MIS-C was detected 5 months after the first reported coronavirus disease 2019 case in Indonesia. Thirteen patients out of 158 positive admitted patients for COVID-19 were diagnosed with MIS-C during the study period. Of these 13 patients, 2 patients (15%) had a fatal outcome. Subjects were predominantly male, and the median age was 7.58 years (IQR 12.3) years. Most patients required mechanical ventilation (7 out of 13 patients) and intubation (8 out of 13 patients). Patients who needed intubation usually needed mechanical ventilation. All inflammatory markers, white blood cells, neutrophil counts, and all coagulation factor parameters (except for normal prothrombin time and activated partial prothrombin time) were elevated. The median time to MIS-C diagnosis was 2 days in the survivor group (n = 11) compared to 8.5 days in the non-survivor group (n = 2). Compared to the non-survivor group, those who survived spent more days in the hospital, received vasopressors earlier, and did not require mechanical ventilation as early as the non-survivors. CONCLUSIONS: Our work highlights the differences in MIS-C clinical course, treatment, and clinical outcomes between the two groups.

Point-of-Care (POC) Urinary L-Type Fatty Acid-Binding Protein (u-LFABP) Use in Critically Ill, Very Preterm Neonates.

Preterm neonates are born with fewer functional nephrons, rendering them vulnerable to secondary insult. These insults are associated with acute kidney injury (AKI); thus, structural damage must be detected as early as possible. Urinary L-type fatty acid-binding protein (u-LFABP) has been proposed as a highly suitable kidney injury biomarker during prematurity. We aimed to analyze the use of POC u-LFABP in critically ill, very preterm neonates. This study was conducted at the neonatal intensive care unit (NICU), Dr. Cipto Mangunkusumo General Hospital, from November to December 2020. Baseline characteristics were recorded from electronic medical records. u-LFABP examination utilized stored urine samples from a previous study and was performed using a LFABP POC test kit. The proportion of abnormal u-LFABP (83.3%) was highest at 72 hours. Neonates with older gestational age (0-48 hours; p=0.017) and higher birth weight (0-48 hours; p=0.022, 72 hours; p=0.013) had normal u-LFABP levels. Neonates exposed to nephrotoxic agents showed higher proportion of abnormal u-LFABP (0-48 hours; p=0.006). Longer invasive mechanical ventilation (IMV) period was observed in neonates with abnormal u-LFABP levels at 0-48 hours (7.44 ± 7.9 vs. 1.50 ± 2.9 days; p=0.011). We found an association between complication rates and poorer disease outcome trends with abnormal u-LFABP; however, this relationship was not supported statistically. In conclusion, this study demonstrated that u-LFABP can be detected using bedside POC kit in critically ill very preterm neonates and those exposed to nephrotoxic agents may be at risk for kidney injury, confirmed by abnormal u-LFABP levels.

Silent Hypertensive Crisis in an Adolescent: First Case Report of Pediatric Pheochromocytoma from Indonesia.

Secondary hypertension in children, to the rare extent, can be caused by endocrine factors such as pheochromocytoma, an adrenal tumor that secretes catecholamine. Only a few cases have been reported in the past 3 decades. To the best of our knowledge, this is the first case report of pediatric pheochromocytoma from Indonesia. We reviewed a case of a 16-year-old Indonesian boy with history of silent hypertensive crisis who was referred from a remote area in an island to the pediatric nephrology clinic at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Despite medications, his symptoms persisted for 14 months. At the pediatric nephrology clinic, pheochromocytoma was suspected due to symptoms of catecholamine secretion presented, which was palpitation, diaphoresis, and weight loss. However, as the urine catecholamine test was unavailable in Indonesia, the urine sample was sent to a laboratory outside the country. The elevated level of urine metanephrine, focal pathological uptake in the right adrenal mass seen on 131I-MIBG, and histopathology examination confirmed the suspicion of pheochromocytoma. Following the tumor resection, he has been living with normal blood pressure without antihypertensive medications. This case highlights that pheochromocytoma should always be included in the differential diagnoses of any atypical presentation of hypertension. In limited resources setting, high clinical awareness of pheochromocytoma is required to facilitate prompt referral. Suspicion of pheochromocytoma should be followed by measurement of urine metanephrine levels. Early diagnosis of pheochromocytoma would fasten the optimal cure, alleviate the symptoms of catecholamine release, and reverse hypertension.

Mortality in children with positive SARS-CoV-2 polymerase chain reaction test: Lessons learned from a tertiary referral hospital in Indonesia.

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) is still increasing rapidly, but little is known about the prevalence and characteristics of fatal cases in children in Indonesia. This study aimed to describe the characteristics of children with COVID-19 with fatal outcomes in a tertiary referral hospital in Indonesia. METHODS: This cross-sectional study used data collected from the medical records of patients with COVID-19 admitted to Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia from March to October 2020. RESULTS: During the study period, 490 patients were admitted and diagnosed with suspected and probable COVID-19. Of these patients, 50 (10.2%) were confirmed to have COVID-19, and 20 (40%) had a fatal outcome. The fatality rate was higher in patients aged ≥10 years, categorized with severe disease upon admission, PaO2/FiO2 ratio ≤300 mmHg and chronic underlying diseases. The most common clinical manifestations were generalized symptoms, while acute respiratory distress syndrome (8/20) and septic shock (7/20) were the two most common causes of death. Increased procalcitonin, D-dimer, lactate dehydrogenase and presepsin levels were found in all fatal cases. One patient met the criteria of multisystem inflammatory syndrome in children. CONCLUSION: Our work highlights the high mortality rate in paediatric patients with positive SARS-CoV-2 polymerase chain reaction test. These findings might be related to or co-incided with COVID-19 infection. Further studies are needed to improve understanding of the role of severe acute respiratory syndrome coronavirus-2 in elaborating the mechanisms leading to death in children with comorbidities.

Cystatin C compared to serum creatinine as a marker of acute kidney injury in critically ill neonates.

BACKGROUND: Acute kidney injury (AKI) is one of the most common causes of neonatal morbidity and mortality. Diagnosing AKI in neonates is challenging as it lacks specific signs, symptoms, and biomarkers. However, detecting AKI in critically ill neonates is crucial to determine appropriate management and prevent complications. Cystatin C (CysC) has been recognized as a superior kidney biomarker reflecting kidney function in neonates. The objective of this study is to evaluate the diagnostic value of CysC as an AKI biomarker in critically ill neonates. METHODS: We performed a diagnostic test between cystatin C-based estimated glomerular filtration rate (eGFR-CysC) and serum creatinine-based estimated glomerular filtration rate (eGFR-SCr) as the gold standard to diagnose AKI in 135 critically ill neonates treated in Cipto Mangunkusumo National Hospital from July 2017 to January 2018. RESULTS: Prevalence of AKI was 23.7% predominantly in neonates with a very preterm gestational age, low birthweight, probable sepsis, and those receiving invasive oxygen therapy or nephrotoxic drugs. The proportion of AKI based on neonate RIFLE criteria was 72.7% risk, 18.9% injury, and 9% failure. eGFR-CysC had the following parameters: sensitivity, 84.8%; specificity, 61.8%; PPV, 41.8%; NPV, 89.7%; LR(+), 2.2; LR(-), 0.24; and accuracy, 67.4%. The AUROC for CysC was 84.9%. The optimal cut-off value for CysC was 1.605 mg/l. CONCLUSIONS: CysC may be used as a screening biomarker of AKI in critically ill neonates; yet, it was not superior to serum creatinine. Graphical abstract.

Experience of the first 6 years of pediatric kidney transplantation in Indonesia: A multicenter retrospective study.

BACKGROUND: Pediatric kidney transplantation was only introduced in Indonesia in 2013. We therefore aimed to assess the characteristics and outcomes of transplants performed from its inception to January 2019. METHOD: The study had a dual-center retrospective design. We examined the records of kidney transplant recipients and then calculated patient and graft survival rates by Kaplan-Meier survival analysis with 95% confidence intervals (95% CI). RESULTS: In total, 12 kidney transplantations were performed in eleven children during the study period; among these, ten were boys, and nine had renal failure caused by congenital anomaly of the kidney or urinary tract. All donors were living, and all recipients were on dialysis at the time of transplantation, when their median age was 14.5 years (range, 8-19 years). Three patients died of infection in the first year of follow-up and two lost their allograft by the time of their last follow-up (median, 13 months; range, 4-69 months). The 1-year patient survival rate was therefore 68.18% (95% CI, 29.72%-88.61%), which remained unchanged at 3 and 5 years. However, the non-death-censored graft survival rates at 1, 3, and 5 years were 68.18% (95% CI, 29.72%-88.61%), 51.14% (95% CI, 14.5%-79.46%), and 25.57% (95% CI, 1.38%-64.78%), respectively. CONCLUSION: Patient and graft survival rates after pediatric kidney transplantation in Indonesia are lower than those reported in other countries. Closer patient follow-up and stricter adherence to guidelines could improve transplant outcomes, but we must seek to improve the balance between infection and rejection.

Successful Treatment of Hepatitis C Virus Infection Using Direct-Acting Antiviral Agents (DAAs) in Adolescents with Kidney Transplantation: A Case Series.

INTRODUCTION: Hepatitis C virus (HCV) infection is common among end-stage renal disease patients undergoing hemodialysis. The standard treatment for HCV infection has been interferon-ribavirin combination prior to renal transplantation. However, compared to direct-acting antiviral agents (DAAs), the risk of graft rejection is higher with interferon therapy. Many recent studies have investigated the efficacy and safety of DAAs for treating HCV infection in kidney disease in adults; however, it has not been established in pediatric patients. To the best of our knowledge, this is the first report describing successful treatment using the DAAs sofosbuvir/daclatasvir in two pediatric kidney transplant recipients who had HCV genotype 1a infection without liver fibrosis. CASE PRESENTATION: Case 1 describes a 13-year-old Indonesian boy who had undergone hemodialysis since 2014 after being diagnosed with end-stage renal disease (ESRD) secondary to bilateral renal hypoplasia. Later, he had HCV infection and was treated with interferon-based therapy with ribavirin prior to living-related renal transplantation (LRRT). The HCV was undetected and his liver function normalized six months after treatment initiation. However, 10 months after treatment initiation, he had HCV virological breakthrough, leading to cessation of interferon therapy. Plans for LRRT were continued and HCV treatment using DAAs was set up to be given post LRRT. Case 2 describes a 14-year-old Indonesian girl who also had hemodialysis prior to LRRT after she was diagnosed with ESRD secondary to nephrotic syndrome. Later, she had HCV infection and was treated with interferon and ribavirin prior to the live-unrelated renal transplantation. HCV infection did not resolve, in addition, she experienced thrombocytopenia-which is a side effect of interferon-resulting in termination of interferon treatment. Both cases were treated with DAAs one year following renal transplantation after reaching stable graft function, leading to achievement of sustained virological response at 24 weeks. CONCLUSION: Post-transplantation treatment of chronic HCV is preferred in KTRs. The sofosbuvir/daclatasvir regimen as an interferon-free therapy is a safe, effective option for HCV infection in pediatric KTRs, who can tolerate sofosbuvir/daclatasvir well and respond favorably without significant adverse events.

Low-Dose Maintenance Intravenous Iron Therapy Can Prevent Anemia in Children with End-Stage Renal Disease Undergoing Chronic Hemodialysis.

Iron deficiency anemia is common in children with end-stage renal disease (ESRD) on long-term hemodialysis receiving erythropoiesis-stimulating agents. One approach to maintain the iron profile and hemoglobin levels is maintenance therapy with regular low doses of intravenous (IV) iron after initial iron repletion therapy; however, evidence for the benefits of this approach is lacking. This study evaluated the effect of IV iron maintenance therapy on anemia in children on regular hemodialysis. This retrospective cohort study included 41 pediatric ESRD patients with normal hemoglobin and iron status who underwent regular hemodialysis at the Pediatric Dialysis Unit of Cipto Mangunkusumo Hospital, Indonesia, between January 2015 and April 2019. Among these, 21 received IV iron maintenance therapy with two doses of 2 mg/kg of IV iron sucrose every 2 weeks (the treatment group) and 20 did not (the comparison group). Changes in hemoglobin and transferrin saturation were assessed after 6 weeks of observation and compared between the two groups. There was a significant reduction in the mean hemoglobin level compared with the baseline level in the comparison group (21 g/L; 95% CI, 9.3-33 g/L; p=0.001) but not in the treatment group (0.7 g/L; 95% CI, -6.6-8 g/L; p=0.84). The risk of anemia was lower in the treatment group (relative risk = 0.42; 95% CI, 0.22-0.79; p=0.003). Although majority of the patients had high baseline ferritin level, this study indicates that in our setting, ferritin may not be a reliable parameter to review the iron status, as it can be affected by chronic inflammation. Hence, the decision to start IV iron maintenance therapy in patients with hyperferritinemia should consider the patient's clinical condition and morbidity. To conclude, the coadministration of IV iron maintenance therapy is beneficial for maintaining hemoglobin levels and preventing anemia in children with ESRD who are undergoing regular hemodialysis, have achieved the target hemoglobin levels, and have normal iron status.