829 International Society of Nephrology launched its 0by25 initiative, aimed at eliminating preventable deaths due to AKI by 2025 by increasing global awareness of AKI and using a need based approach[.]
43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents International Society of Nephrology launched its 0by25 initiative, aimed at eliminating preventable deaths due to AKI by 2025 by increasing global awareness of AKI and using a need-based approach to develop systems to achieve this goal [9] I ncidence and Short-Term Outcomes The AWARE study was a multinational prospective study of 4683 children from 32 ICUs [2]; AKI incidence was 27% This study showed that stage or worse AKI was associated with increased risk of 28-day mortality and longer mechanical ventilation The Kidney Intervention During Extracorporeal Membrane Oxygenation (KIDMO) group studied 834 patients receiving ECMO at six centers over years [10] AKI incidence was 74%, occurred early in the course of ECMO (93% within 48 h of ECMO initiation), and was associated with increased mortality and ECMO duration AKI in children undergoing cardiac surgery has been well studied and has shown highly variable AKI incidence (15– 70%) across studies [4, 11] The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study of 131 children from three centers over years [12] found that AKI occurred in 40% of children within the first 3 days after surgery and was associated with increased length of ICU stay and mechanical ventilation In 799 children from two centers in the Safe Pediatric Euglycemia after Cardiac Surgery (SPECS) trial, AKI developed in 36% of patients, with similar outcome associations [13] However, AKI incidence differed significantly between institutions (U. Michigan, 66%, vs Boston Children’s Hospital, 15%), suggesting that institutional differences impact the AKI development There is a relative paucity of AKI data in non-critically ill children, mostly from single-center studies In one center, of 13,914 noncritical pediatric admissions, AKI incidence was ≥5% [14] However, less than one-quarter of admissions had ≥2 SCr measures; when only patients with ≥2 SCr were considered, AKI incidence was 30% This study suggests a need for protocol SCr monitoring Other single-center work has identified other highrisk populations including nephrotic syndrome, 829 sickle cell disease, and those exposed to nephrotoxic medications Risk Factors Major non-modifiable risk factors for AKI in hospitalized children include underlying acute diseases (e.g., sepsis, circulatory disease, congenital cardiac anomalies) and acute illness severity (e.g., ventilation, shock, ECMO) These risks are important to appreciate to identify patients at highest AKI risk Risk factors for AKI after cardiac surgery have included younger age, lower weight, higher surgical complexity, cardiopulmonary bypass time, intraoperative practices, delayed sternal closure, perioperative comorbidities, and release of inflammatory mediators during bypass In recent years, there has been an increased focus on understanding AKI risk factors that may be potentially modifiable Nephrotoxic medication exposures (Table 43.2) are a modifiable risk where interventions to reduce exposure have led to reduced AKI incidence In a singlecenter study, the electronic health record was utilized to trigger healthcare providers to monitor kidney function in patients at high risk of nephrotoxic AKI (≥3 days of intravenous aminoglycoside or ≥3 simultaneous nephrotoxins) [15] This multidisciplinary approach to AKI prevention was feasible, associated with a 42% decrease in patient AKI days, and was sustainable over a 4-year period with a reduction in AKI rate due to nephrotoxins by over 60% [16] Long-Term Outcomes Observational studies in adults have demonstrated a consistent and high increased risk for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following AKI hospitalizations [17] Pre-existing CKD and worse AKI severity significantly increases ESRD risk in adults There is also extensive literature in adults showing a strong association between AKI and long-term cardiovascular events and death In children, studies of long-term AKI outcomes are limited Single-center observational studies have shown a higher incidence of long- term CKD and hypertension in children with AKI, relative to the general pediatric population 830 E H Ulrich et al Table 43.2 Non-exhaustive list of nephrotoxic medications administered to hospitalized children Mechanism of drug-induced Mechanism of drug-induced Medication AKI Medication AKI Analgesics Chemotherapy (continued) Gemcitabine Altered intraglomerular NSAIDs AIN, CIN, altered hemodynamics, TMA intraglomerular hemodynamics Selective COX-2 Altered intraglomerular Ifosfamide Tubular cell toxicity +/− inhibitors hemodynamics Fanconi syndrome Antiepileptics Interferon GN (MCD, FSGS), altered intraglomerular hemodynamics Topiramate Nephrolithiasis Methotrexate Crystal nephropathy Antimicrobials Mitomycin Altered intraglomerular hemodynamics Tubular cell toxicity Pentostatin Tubular cell toxicity Adefovir, cidofovir, tenofovir Aminoglycosides Tubular cell toxicity Vincristine SIADH Diuretics Amphotericin B Tubular cell toxicity Lipid/liposomal formulations are less toxic AIN, crystal nephropathy Loop diuretics, thiazides AIN; reduced intravascular Antivirals (acyclovir, ganciclovir) volume Beta-lactams AIN Drugs of abuse Foscarnet Crystal nephropathy Cocaine, heroin, ketamine, Rhabdomyolysis methadone, methamphetamine Indinavir AIN, crystal nephropathy Psychiatric medications Pentamidine Tubular cell toxicity Amitriptyline, fluoxetine Rhabdomyolysis Polymyxin antimicrobials Tubular cell toxicity Benzodiazepines Rhabdomyolysis Quinolones AIN, crystal nephropathy Haloperidol Rhabdomyolysis Rifampin AIN Lithium CIN, rhabdomyolysis Sulfadiazine Crystal nephropathy Proton pump inhibitors Sulfonamides AIN, crystal nephropathy Lansoprazole, omeprazole, AIN pantoprazole Vancomycin AIN, obstructive tubular Other cast formation Calcineurin inhibitors Allopurinol AIN Tacrolimus Altered intraglomerular Dextran, hydroxyethyl Osmotic nephropathy hemodynamics starch, sucrose Cardiovascular agents Gold GN ACEi, ARBs Altered intraglomerular Pamidronate GN (MCD, FSGS) hemodynamics Clopidogrel TMA Quinine TMA Statins Rhabdomyolysis Ranitidine AIN Chemotherapy SGL-2 inhibitors Altered intraglomerular hemodynamics Anti-VEGF Microvascular injury, Sodium phosphate Crystal nephropathy TMA Contrast dye Tubular cell toxicity Vitamin C Crystal nephropathy Zoledronate Tubular cell toxicity, GN Cisplatin CIN, tubular cell toxicity (FSGS) +/− Fanconi syndrome, TMA ACEi angiotensin-converting enzyme inhibitors, AIN acute interstitial nephritis, ARBs angiotensin II receptor blockers, CIN chronic interstitial nephritis, FSGS focal segmental glomerulosclerosis, GN glomerulonephritis, MCD minimal change disease, SIADH syndrome of inappropriate anti-diuretic hormone, TMA thrombotic microangiopathy, VEGF vascular endothelial growth factor [102–104] 43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents [18] A two-center study showed that ICU children with AKI have increased 5-year mortality and healthcare utilization [19, 20] There is evidence of long-term kidney risk in the child oncology literature, due to a number of mechanisms, including nephrotoxin exposure One study showed that 70% of hospitalized children exposed to nephrotoxins had evidence of CKD at 6-month follow-up [21] Literature on long-term kidney outcomes of AKI after cardiac surgery is controversial Two multicenter studies of children undergoing cardiac surgery showed that these patients have a high prevalence of hypertension and CKD 5 years after surgery (17% and 18%, respectively) but that post-operative AKI was not associated with 5–7-year kidney outcomes [12, 22] This finding may be due to the phenomenon of renal reserve and hyperfiltration mechanisms which may initially lead to increased GFR after kidney damage A large retrospective study conversely showed that 5-year post-cardiac surgery CKD incidence was 12% vs 3% in patients with vs without AKI [23] Regardless of the uncertain results on the long-term impact of AKI, children having cardiac surgery are at high risk for long- term kidney disease and hypertension Long-term kidney outcomes are difficult to study in children for several reasons AKI as a risk factor for poor clinical outcomes has only recently been appreciated; as a result, most children with AKI are not followed long term for kidney function monitoring, and little is known about their long-term health outcomes One study found that