Pattern and prognostic factors for kidney function progression in survivors of children with acute kidney injury: a cohort study.

OBJECTIVE: To examine the pattern of kidney function progression after acute kidney injury (AKI) and identify the associated risk factors. DESIGN: A prospective cohort study was conducted from June 2020 to June 2021 on children aged 1 month to <18 years admitted to the paediatric intensive care unit (PICU). Acute kidney disease (AKD) was defined as AKI persisting from 7 to 90 days after diagnosis. The natural history and prognostic factors of kidney function progression were determined. RESULTS: Among the 253 admissions with a median (IQR) age of 4.9 (9.7) years, the AKI and AKD incidence was 41.9% and 52.2% respectively. The incidence of estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 was 6.7% at 90 days and 11.9% at latest follow-up. Severe and prolonged AKI and higher degree of nephrotoxic medication exposure were associated with AKD development. The severity and duration of AKI and AKD significantly predicted kidney function non-recovery. Children with both entities exhibited a higher peak-to-baseline serum creatinine level ratio at 90 days (1.6 vs 1.0, p<0.001), and a more pronounced decline in eGFR (21% vs 19%, p=0.028) during the follow-up period compared with those without AKI/AKD. They also had an increased risk of having eGFR <90 mL/min/1.73 m2 at 90 days (HR 14.9 (95% CI 1.8 to 124.0)) and latest follow-up (HR 3.8 (95% CI 1.1 to 13.1)). CONCLUSIONS: AKI and AKD are prevalent among critically ill children and pose substantial risk for non-recovery of kidney function among PICU survivors. A structural follow-up visit for AKI survivors to monitor kidney function progression is advocated.

The impact of tubular dysfunction and its relationship with acute kidney injury in children.

BACKGROUND: Tubular dysfunction can cause electrolyte disturbances with potentially serious consequences. We studied the epidemiology and outcomes of electrolyte disturbances and tubular dysfunction among critically ill children and evaluated their relationships with acute kidney injury (AKI). METHODS: We conducted a prospective cohort study recruiting children aged 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (PICU) from 6/2020 to 6/2021. The serum levels of sodium, potassium, calcium, phosphate, and magnesium were reviewed and simultaneous urinary investigations for tubular function were performed among children with electrolyte disturbances. RESULTS: Altogether there were 253 episodes of admission. The median (interquartile) age was 4.9 (1.3-11.0) years and 58.1% were male. The median number of electrolyte disorders was 3 (2-4) types. Hypophosphatemia (74.2%), hypocalcemia (70.3%) and hypermagnesemia (52.9%) were the three commonest types of disturbances. Urinary electrolyte wasting was commonly observed among children with hypomagnesemia (70.6%), hypophosphatemia (67.4%) and hypokalemia (28.6%). Tubular dysfunction was detected in 82.6% of patients and urinary ß2-microglobulin level significantly correlated with the severity of tubular dysfunction (p < 0.001). The development of tubular dysfunction was independent of AKI status. Tubular dysfunction was associated with mortality (p < 0.001) and was an independent predictor of PICU length of stay (LOS) (p < 0.001). The incorporation of the tubular dysfunction severity into the AKI staging system improved the prediction of PICU LOS. CONCLUSIONS: Tubular dysfunction was associated with both morbidity and mortality in critically ill children and its assessment may help to capture a more comprehensive picture of acute kidney insult.

Risk factors for development of acute kidney injury and acute kidney disease in critically ill children.

BACKGROUND: Acute kidney injury (AKI) is common among critically ill children and these children are at risk of developing acute kidney disease (AKD). METHODS: A prospective cohort study was conducted on children aged > 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (ICU) of Hong Kong Children's Hospital from 6/2020 to 6/2021. The incidences and risk factors of both AKI and AKD were determined. RESULTS: There were 254 eligible admissions (58.3% in males, with a median age of 4.9 [9.7] years). The overall AKI incidence was 41.7% and 56% of children who remained hospitalized in the pediatric  ICU for ≥ 7 days after acquiring AKI developed AKD. Cardiac surgery, bone marrow transplantation and requirement of inotropes were risk factors for both AKI and AKD. The requirement of non-invasive ventilation [relative risk (RR): 2.625 (1.361, 5.064)], total medication dose [RR 1.006 (1.002, 1.010)] and maximal medication intensity [RR 1.154 (1.038, 1.283)] were additional determinants of AKI. Factors indicating more severe AKI and AKI progression were predictive of AKD development. The overall mortality in the pediatric ICU was 3.1%. AKI was significantly associated with mortality (p < 0.001), longer length of hospitalization in the pediatric ICU (p < 0.001) and hospital stay (p < 0.001). AKD was associated with a lower estimated glomerular filtration rate at discharge from the pediatric ICU (p = 0.036). CONCLUSION: AKI and AKD were common among critically ill children, and were associated with significant morbidity and mortality. Few modifiable risk factors, especially those related to nephrotoxic medication exposure, were associated with AKI development and AKD progression.

The Pitfall of Over-Sedation During Recovery From Acute Kidney Injury.

A 14-year-old boy with movement disorder and epilepsy developed status dystonicus leading to rhabdomyolysis and subsequent acute kidney injury requiring continuous renal replacement therapy (CRRT). He was given multiple intravenous sedatives and analgesics to control his dystonia and dyskinesia. 8 days after admission, his condition had improved and a trial termination of CRRT was carried out. The sedatives and analgesics were switched to oral diazepam, morphine, clonidine, and chloral hydrate. However, his renal function did not recover fully. There was rising trend of serum creatinine level with evolving hyperphosphatemia and metabolic acidosis. He also gradually developed hypoventilation, hypercapnia and pinpoint pupils after weaning CRRT. The clinical impression was over-sedation resulting in hypoventilation and respiratory failure, contributed by the deteriorating renal function. Non-invasive ventilatory support was then started and CRRT was resumed. His condition improved over the next 24 hours. Dexmedetomidine infusion was used during CRRT and he slowly required stepping up of sedatives again. A separate set of dosage for all his oral sedative agents was prepared for his subsequent CRRT weaning challenge and no more over-sedative episode was then encountered. Our case illustrated that patients at recovery phase of AKI are susceptible to medication overdose, especially during the period of CRRT weaning. Sedatives and analgesics including morphine and benzodiazepines should be used with caution during this period and alternatives may need to be considered. Advanced planning of medication dosage adjustment is advised to reduce the risk of medication overdose.

The application of hemoadsorption for hyperbilirubinemia and its impact on bilirubin removal kinetics in critically ill children.

Extracorporeal blood purification (EBP) is increasingly applied for bilirubin removal in critical care setting. We retrospectively reviewed the clinical features of children aged 1 month to 18 years old who received EBP for hyperbilirubinemia and explored the bilirubin removal kinetics by hemoadsorption (HA) in the pediatric intensive care unit of Hong Kong Children's Hospital from 3/2019 to 7/2022. Among the 14 episodes of EBP from six patients with a median age (interquartile range [IQR]) of 9.3(5.5) years old, 57.1% of them received HA, 33.3% received single-pass albumin dialysis (SPAD), and 7.1% received combined SPAD and HA. All HA episodes employed the Cytosorb® column. The median (IQR) pre-HA peak total bilirubin level was 406 (254) µmol/L. The saturation duration per HA episode was significantly shorter than the corresponding total treatment duration (8 vs 24 h, p = 0.012), and the median total and effective HA doses were 9.8(6.8) L/kg and 300.0 (163.4) mL/kg/h respectively. The overall bilirubin removal ratio by HA was 44.6 (14.5)%. A higher HA effective dose and a higher pre-HA bilirubin level were both associated with better bilirubin removal. No major EBP-specific complication was encountered. The liver enzymes showed improvement in all children. No patients required liver transplantation. There was no EBP-related mortality, but the overall PICU mortality of the cohort was 50%. HA was a safe and effective modality for bilirubin removal among children. Future studies should investigate the impact of bilirubin removal on clinical outcomes and explore the factors responsible for better removal efficacy.

The Sequential Use of Extracorporeal Cytokine Removal Devices in an Adolescent With COVID-19 Receiving Continuous Renal Replacement Therapy.

A 14-year-old male developed multisystem inflammatory syndrome in children (MIS-C) after acquiring the SARS-CoV-2 infection. He deteriorated rapidly requiring inotropic and ventilatory support as well as continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated acute kidney injury. A hemoadsoprtion column Cytosorb® was first incorporated into the CRRT circuit for myoglobin and cytokines removal, which was followed by sequential use of another type of cytokine-removing hemofilter (Oxiris®) (altogether 100 hours of extracorporeal blood purification [EBP] therapy). There was no major complication related to the EBP therapy. Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. His condition improved and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels. Our case demonstrated that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.

The successful application of hemoadsorption for extracorporeal liver support in a child with acute liver failure.

A 6-year-old boy developed acute liver failure with hepatic coma due to drug rash with eosinophilia and systemic symptoms (DRESS) after multiple antibiotics exposure. He had hyperbilirubinemia, elevated serum bile acids and hyperammonemia with peak serum levels of total bilirubin, direct bilirubin, bile acids and ammonia measuring 418, 328, 174, and 172 µmol/L respectively. In addition to the use of systemic steroid and other supportive therapy, he also received three sessions of hemoadsorption using the Cytosorb® column incorporated into the continuous renal replacement therapy circuit as extracorporeal liver support for a total duration of 75 h, which brought down his serum levels of total bilirubin to 119 µmol/L, bile acids to 58 µmol/L, and ammonia to 55 µmol/L. His conscious level gradually regained coupling an improvement of liver function. Except for mild thrombocytopenia and electrolyte disturbances, the therapy was well tolerated with no major complication encountered. Our case demonstrated that hemoadsorption can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure. The potential role and technical concerns of applying such technique in pediatric patients requires further evaluation in future studies.

Successful Treatment of Rhabdomyolysis-Associated Acute Kidney Injury with Haemoadsorption and Continuous Renal Replacement Therapy.

We report two children with rhabdomyolysis-associated acute kidney injury who were successfully treated with a haemoadsorption column CytoSorb® in addition to continuous renal replacement therapy (CRRT). A 14-year-old girl with multiorgan failure requiring extracorporeal membrane oxygenation developed rhabdomyolysis due to reperfusion injury. Her creatine kinase (CK) and lactate levels continued to escalate despite high-dose CRRT. A haemoadsorption column was therefore added post-CRRT filter, which brought down the CK level from 264,500 IU/L to 97,436 IU/L after 8 hours of therapy. Another 4-year-old boy with epilepsy and cerebral palsy who was admitted for gastroenteritis with dehydration developed acute kidney injury and rhabdomyolysis with a peak CK level of 946,060 IU/L. He was initially treated with CRRT for 40 hours, which reduced his CK level to 147,580 IU/L. Two sessions of haemoadsorption were then performed in addition to the CRRT, which further lowered his CK level to 32,306 IU/L in 48 hours. Both patients demonstrated enhanced reduction of CK levels when the haemoadsorption column was used in addition to the CRRT, and no specific complication related to the haemoadsorption therapy was reported. Our cases showed that haemoadsorption can be considered as an adjunctive therapy for children with severe rhabdomyolysis-associated acute kidney injury.

Staphylococcus aureus Infections in the Paediatric Intensive Care Unit: Illustrated Cases.

Staphylococcus aureus is known to be one of the most common gram-positive microorganisms and an important pathogen associated with sepsis and toxic shock. We present four anonymized consecutive cases in a paediatric intensive care unit (PICU) to illustrate the different clinical manifestations of staphylococcal infections, including local infection versus systemic infection, toxic shock versus septic shock, and osteomyelitis. Eczema, short gut syndrome, and scald injury may be associated. Haematologic and coagulopathic abnormalities may be present. Prompt diagnosis and use of appropriate antimicrobial treatments is essential to reducing mortality and morbidity associated with staphylococcal infections.