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e3 102 Bellomo R, Auriemma S, Fabbri A, et al The pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI) Int J Artif Organs 2008;31:166-178 103 Haase M, Haase-Fielitz A, Bagshaw SM, et al Cardiopulmonary bypass-associated acute kidney injury: a pigment nephropathy? Contrib Nephrol 2007;156:340-353 104 Borasino S, Wall KM, Crawford JH, et al Furosemide response predicts acute kidney injury after cardiac surgery in infants and neonates Pediatr Crit Care Med 2018;19(4):310-317 105 Joffe R, Al Aklabi M, Bhattacharya S, et al Cardiac surgery–associated kidney injury in children and renal oximetry Pediatr Crit Care Med 2018;19(9):839-845 106 Wijeysundera DN, Karkouti K, Rao V, et al N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery Crit Care Med 2009;37(6):1929-1934 107 Lam AQ, Humphreys BD Onco-nephrology: AKI in the cancer patient Clin J Am Soc Nephrol 2012;7:1692-1700 108 Goldman SC, Holcenberg JS, Finklestein JZ, et al A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis Blood 2001;97:2998-3003 109 Coiffier B, Altman A, Pui CH, Younes A, Cairo MS Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review J Clin Oncol 2008;26:2767-2778 110 Hobbs DJ, Steinke JM, Chung JY, Barletta GM, Bunchman TE Rasburicase improves hyperuricemia in infants with acute kidney injury Pediatr Nephrol 2010;25:305-309 111 Jones GL, Will A, Jackson GH, Webb NJ, Rule S, British Committee for Standards in Haematology Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology Br J Haematol 2015;169:661-671 112 Uchino S, Bellomo R, Morimatsu H, et al Continuous renal replacement therapy: a worldwide practice survey The beginning and ending supportive therapy for the kidney (B.E.S.T kidney) investigators Intensive Care Med 2007;33:1563-1570 113 Jeha S, Kantarjian H, Irwin D, et al Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the management of malignancy-associated hyperuricemia in pediatric and adult patients: final results of a multicenter compassionate use trial Leukemia 2005;19:34-38 114 Mannix R, Tan ML, Wright R, Baskin M Acute pediatric rhabdomyolysis: causes and rates of renal failure Pediatrics 2006;118: 2119-125 115 Cervellin G, Comelli I, Lippi G Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features Clin Chem Lab Med 2010;48:749-756 116 Huerta-Alardin AL, Varon J, Marik PE Bench-to-bedside review: Rhabdomyolysis: an overview for clinicians Crit Care 2005;9: 158-169 117 Bosch X, Poch E, Grau JM Rhabdomyolysis and acute kidney injury N Engl J Med 2009;361:62-72 118 Sever MS, Vanholder R, Lameire N Management of crush-related injuries after disasters N Engl J Med 2006;354:1052-1063 119 Patzer L Nephrotoxicity as a cause of acute kidney injury in children Pediatr Nephrol 2008;23:2159-2173 120 Oliveira JF, Silva CA, Barbieri CD, et al Prevalence and risk factors for aminoglycoside nephrotoxicity in intensive care units Antimicrob Agents Chemother 2009;53:2887-2891 121 McWilliam SJ, Antoine DJ, Smyth RL, Pirmohamed M Aminoglycoside-induced nephrotoxicity in children Pediatr Nephrol 2017;32(11):2015-2025 122 Servais H, Van Der Smissen P, Thirion G, et al Gentamicin-induced apoptosis in LLC-PK1 cells: involvement of lysosomes and mitochondria Toxicol Appl Pharmacol 2005;206(3):321-333 123 Ward DT, Maldonado-Pérez D, Hollins L, Riccardi D Aminoglycosides induce acute cell signaling and chronic cell death in renal cells that express the calcium-sensing receptor J Am Soc Nephrol 2005;16(5):1236-1244 124 Pannu N, Nadim MK An overview of drug-induced acute kidney injury Crit Care Med 2008;36:S216-S223 125 Houot M, Pilmis B, Thepot-Seegers V, et al Aminoglycoside use in a pediatric hospital: there is room for improvement-a before/after study Eur J Pediatr 2016;175(5): 659-665 126 Bertenshaw C, Watson AR, Lewis S, Smyth A Survey of acute renal failure in patients with cystic fibrosis in the UK Thorax 2007;62(6):541-545 127 Zarowitz BJ, Pilla AM, Popovich J Expanded gentamicin volume of distribution in patients with indicators of malnutrition Clin Pharm 1990;9(1):40-44 128 Vlasic-Matas J, Rumboldt Z, Karelovic D Renoprotective role of nifedipine during gentamicin therapy: randomized controlled trial Croat Med J 2000;41:417-422 129 Bloch R, Luft FC, Rankin LI, Sloan RS, Yum MN, Maxwell DR Protection from gentamicin nephrotoxicity by cephalothin and carbenicillin Antimicrob Agents Chemother 1979;15:46-49 130 Beauchamp D, Thériault G, Grenier L, et al Ceftriaxone protects against tobramycin nephrotoxicity Antimicrob Agents Chemother 1994;38:750-756 131 Kavutcu M, Canbolat O, Oztürk S, et al Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C Nephron 1996;72:269-274 132 Rybak MJ, Abate BJ, Kang SL, Ruffing MJ, Lerner SA, Drusano GL Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity Antimicrob Agents Chemother 1999;43:1549-1555 133 Prescott Jr WA National survey of extended-interval aminoglycoside dosing in pediatric cystic fibrosis pulmonary exacerbations J Pediatr Pharmacol Ther 2011;16(4):262-269 134 Prescott Jr WA, Nagel JL Extended-interval once-daily dosing of aminoglycosides in adult and pediatric patients with cystic fibrosis Pharmacotherapy 2010;30(1):95-108 135 Sonia SF, Hassan MS, Ara F, Hanif M Fractional excretion of magnesium, a marker of aminoglycoside induced nephrotoxicity in neonates Saudi J Kidney Dis Transpl.‚ÄØ2016;27(5):902-907 136 Anaissie EJ, Vartivarian SE, Abi-Said D, et al Fluconazole versus amphotericin B in the treatment of hematogenous candidiasis: a matched cohort study Am J Med 1996;101:170-176 137 Wu H, Huang J Drug-induced nephrotoxicity: pathogenic mechanisms, biomarkers and prevention strategies Curr Drug Metab 2018;19(7):559-567 138 Bagnis CI, Deray G Amphotericin B nephrotoxicity Saudi J Kidney Dis Transplant 2002;13(4):481-491 139 Sawaya BP, Briggs JP, Schnermann J Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties J Am Soc Nephrol 1995;6:154-164 140 Luber AD, Maa L, Lam M, Guglielmo BJ Risk factors for amphotericin B-induced nephrotoxicity J Antimicrob Chemother 1999;43:267-271 141 Dutta A, Palazzi DL Risk factors of amphotericin B toxicity in the nonneonatal pediatric population Pediatr Infect Dis J 2012;31(9): 910-914 142 Turcu R, Patterson MJ, Omar S Influence of sodium intake on amphotericin B-induced nephrotoxicity among extremely premature infants Pediatr Nephrol 2009;24(3): 497-505 143 Andrew EC, Curtis N, Coghlan B, Cranswick N, Gwee A Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations Br J Clin Pharmacol 2018;84(5):1006-1012 144 Yang C, Xue B , Song W, et al Reducing the toxicity of amphotericin B by encapsulation using methoxy poly(ethylene glycol)-bpoly(l-glutamic acid-co-l-phenylalanine) Biomater Sci 2018;6(8): 2189-2196 145 Goldman RD, Koren G Amphotericin B nephrotoxicity in children J Pediatr Hematol/Oncol 2004;26(7):421-426 146 Lake JG, Weiner LM, Milstone AM, Saiman L, Magill SS, See I Pathogen distribution and antimicrobial resistance among pediatric healthcare-associated infections reported to the National Health- e4 care Safety Network, 2011-2014 Infect Control Hosp Epidemiol 2018;39(1):1-11 147 Mellen CK, Ryba JE, Rindone JP Does piperacillin-tazobactam increase the risk of nephrotoxicity when used with vancomycin: a meta-analysis of observational trials Curr Drug Saf 2017;12(1): 62-66 148 Rybak MJ, Albrecht LM, Boike SC, Chandrasekar PH Nephrotoxicity of vancomycin, alone and with an aminoglycoside J Antimicrob Chemother 1990;25:679-687 149 Feiten HDS, Okumura LM, Martinbiancho JK, et al Vancomycinassociated nephrotoxicity and risk factors in critically ill children without preexisting renal injury Pediatr Infect Dis J 2019;38(9): 934-938 150 Cook KM, Gillon J, Grisso AG, et al Incidence of nephrotoxicity among pediatric patients receiving vancomycin with either piperacillin-tazobactam or cefepime: a cohort study J Pediatric Infect Dis Soc 2019;8(3):221-227 151 Hidayat LK, Hsu DI, Quist R High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity Arch Intern Med 2006;166:2138-2144 152 Elyasi S, Khalili H, Dashti-Khavidaki S, Mohammadpour A Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations a literature review Eur J Clin Pharmacol 2012;68(9):1243-1255 153 Alsultan A, Abouelkheir M, Alqahtani S, et al Optimizing vancomycin monitoring in pediatric patients Pediatr Infect Dis J 2018; 37(9):880-885 154 Campistol JM, Sacks SH Mechanisms of nephrotoxicity Transplantation 2000;69(suppl 12):SS5-SS10 155 Lanese DM, Conger JD Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles J Clin Invest 1993;91:2144-2149 156 Bobadilla NA, Tapia E, Franco M, et al Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity Kidney Int 1994;46:773-779 157 Perico N, Benigni A, Bosco E, et al Acute cyclosporine A nephrotoxicity in rats: which role for rennin-angiotensin system and glomerular prostaglandins? Clin Nephrol 1985;25(suppl 1): S83-S88 158 Kuypers DR, Neumayer HH, Fritsche L, et al Calcium channel blockage and preservation of renal graft function in cyclosporinetreated recipients: a prospective randomized placebo-controlled 2-year study Transplantation 2004;78:1204-1211 159 Whelton A Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications Am J Med 1999;106:13S-24S 160 Nash K, Hafeez A, Hou S Hospital-acquired renal insufficiency Am J Kidney Dis.‚ÄØ 2002;39(5):930-936 161 Brasch RC Contrast media toxicity in children Pediatr Radiol 2008;38(suppl 2):S281-S284 162 Margulies K, Schringer J, Burnett Jr J Radiocontrast-induced nephropathy: current status and future prospects Int Angiol 1992; 11:20-25 163 Andersen KJ, Christensen EI, Vik H Effects of iodinated x-ray contrast media on renal epithelial cells in culture Invest Radiol 1994;29:955-962 164 McCullough PA, Soman SS Contrast-induced nephropathy Crit Care Clin 2005;21:261-280 165 Denton KM, Shweta A, Anderson WP Preglomerular and postglomerular resistance responses to different levels of sympathetic activation by hypoxia J Am Soc Nephrol 2002;13:27-34 166 Uder M, Humke U, Pahl M, Jansen A, Utz J, Kramann B Nonionic contrast media iohexol and iomeprol decrease renal arterial tone: comparative studies on human and porcine isolated vascular segments Invest Radiol 2002;37:440-447 167 Marenzi G, Marana I, Lauri G, et al The prevention of radiocontrast-agent-induced nephropathy by hemofiltration N Engl J Med 2003;349:1333-1340 168 Tumlin J, Stacul F, Adam A, et al Pathophysiology of contrast-induced nephropathy Am J Cardiol 2006;98:14K-20K 169 Stacul F, Adam A, Becker CR, et al Strategies to reduce the risk of contrast-induced nephropathy Am J Cardiol 2006;98:59K-77K 170 Detaille T, Anslot C, de Clety SC Acute kidney injury in paediatric bone marrow patients Acta Clin Belg Suppl 2007;2:401-404 171 Thomas SE, Hutchinson RJ, DebRoy M, Magee JC Successful renal transplantation following prior bone marrow transplantation in pediatric patients Pediatr Transplant 2004;8:507-512 172 Kusumi E, Kami M, Hara S, et al Postmortem examination of the kidney in allogeneic hematopoietic stem cell transplantation recipients: possible involvement of graft-versus-host disease Int J Hematol 2008;87:225-230 173 Pinana JL, Valcárcel D, Martino R, et al Study of kidney function impairment after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation A single-center experience Biol Blood Marrow Transplant 2009;15:21-29 174 Morrison AR, Benabe EJ Prostaglandins and vascular tone in experimental obstructive nephropathy Kidney Int 1981;19:786 175 Badr KF, Brenner BM Kidney circulatory and nephron function in experimental obstruction of the urinary tract In: Brenner BM, Lazarus JM, eds Acute Kidney Failure New York: Churchill Livingstone; 1988 176 Klotman PE, Smith SR, Volpp BD, et al Thromboxane synthetase inhibition improves function of hydronephrotic rat kidneys Am J Physiol 1986;254:F282 177 Campbell HT, Bello-Reuss E, Klahr S Hydraulic water permeability and transepithelial voltage in the isolated perfused rabbit cortical collecting tubule following acute unilateral ureteral obstruction J Clin Invest 1985;75:219 178 Thirakomen K, Kozlov N, Arruda JA, et al Kidney hydrogen ion secretion after release of unilateral ureteral obstruction Am J Physiol 1976;231:1233 e5 Abstract: Renal dysfunction is common in nearly 30% of neonates and children in the pediatric intensive care unit, with varying degrees of clinical presentation The etiology of renal dysfunction and acute kidney injury (AKI) is important for looking at potentially reservable causes and interactions due to specific causes Because the causes of AKI are myriad, the clinician needs to have a logical approach to the evaluation and side effects (e.g., electrolyte dysfunction) and have a plan of action for intervention with the goal of minimizing additional damage as well as reversing AKI Key words: uric acid, AKI, acute kidney injury, electrolyte disturbances, hypertension, fluid overload 75 Pediatric Renal Replacement Therapy in the Intensive Care Unit RAJ MUNSHI AND JORDAN M SYMONS PEARLS • • • Patients receiving renal replacement therapy (RRT) require careful monitoring of fluid and electrolyte balance and nutritional needs Coordination between the critical care and nephrology staff is essential for the successful care of patients requiring RRT Avoiding delay of RRT may improve outcome Renal replacement therapy (RRT) has an established role in the pediatric intensive care unit (ICU).1 Indications for RRT include volume overload, azotemia, electrolyte and metabolic imbalance, intoxication, or inability to provide adequate nutrition due to renal compromise Acute kidney injury (AKI) is highly prevalent in the pediatric critical care setting; however severe, AKI is correlated with poor outcome in hospitalized adults and children.2–7 Studies demonstrate increased mortality in critically ill children with excessive fluid overload with concomitant AKI.8–12 These observations, coupled with advanced capabilities for RRT and concerns that delay in therapy may worsen outcomes, lead many clinicians to consider early initiation of renal support.13–15 Earlier intervention, either with RRT or perhaps through careful conservative management, may prevent complications associated with serious metabolic disarray and volume overload It may also permit vigorous nutritional and medical support Although all modalities of RRT can correct these abnormalities, certain modalities may be better suited for specific pediatric clinical situations To date, there is no evidence that the choice of RRT modality has an effect on mortality.16–19 However, growing evidence favors continuous RRT (CRRT) as compared with intermittent RRT for renal recovery.20,21 Basic Physiology of Dialysis and Ultrafiltration The physical principles of molecular movement across a semipermeable membrane underlie peritoneal dialysis, hemodialysis, and CRRT modalities The following brief review summarizes the basic mechanisms of particle and water removal for all forms of RRT • • • Peritoneal dialysis remains an excellent form of acute pediatric RRT Hemodialysis is the modality of choice for rapid correction of fluid or metabolic imbalance Continuous renal replacement therapy can establish and maintain fluid and metabolic control in unstable patients Diffusion describes the movement of dissolved particles across a semipermeable membrane from an area of high concentration to an area of low concentration (Fig 75.1) This physical principle operates in all renal replacement modalities in which dialysate is used Diffusion favors the movement of smaller particles and is most rapid when the concentration gradient across the semipermeable membrane is greatest Diffusion stops when the concentrations achieve equilibrium Convection occurs when dissolved particles pass across a semipermeable membrane due to a pressure gradient (Fig 75.2) Particles that are smaller than the pores of the membrane can pass freely; larger particles are restricted Because particles and water are moving together, the removed solution is isotonic to the original Ultrafiltration describes the movement of water across the semipermeable membrane due to pressure Convection occurs with ultrafiltration Peritoneal Dialysis Peritoneal dialysis (PD) has been successfully used as a therapy for AKI since 1946.22 It is a frequent choice for chronic dialysis support, especially in children There has been a shift in higher-resource countries toward hemodialysis and CRRT for RRT in AKI,23 although observational studies in children and systematic review in adults show no difference in mortality between PD and other methods.24–26 PD is the modality most often used in settings of limited resources, where its simplicity, effectiveness, and low cost make it attractive.27 PD is also a useful modality in patients with difficult vascular access and in those for whom the risk of complication from anticoagulation therapy is significant In 923 924 S E C T I O N V I I Pediatric Critical Care: Renal unstable, critically ill patients, the slow, steady ultrafiltration achieved with PD may be preferable to the rapid fluid removal that occurs in intermittent hemodialysis Similar to volume control, PD provides slow and relatively continuous metabolic control It is an effective method for correction of uremia Manipulation of the PD prescription can improve molecular clearance Technique • Fig 75.1 Diffusion Particles move across the semipermeable membrane from an area of higher concentration to an area of lower concentration Smaller particles diffuse more freely, whereas larger particles are relatively restricted • Fig 75.2 Convection Particles move across the semipermeable mem- brane, carried by ultrafiltered water, because of the effect of pressure All particles up to the cutoff size of the membrane move relatively equally The concentration of the effluent is equal to that of the original solution children, especially infants, who sustain AKI following cardiac surgery, early initiation of PD has been associated with improved outcomes.28–30 Physiology Instillation of dialysate into the peritoneal space permits diffusion of particles out of the blood and into the fluid across the peritoneum, which acts as a semipermeable membrane Hypertonic dialysate, causing an osmotic gradient, generates an ultrafiltrate Water movement will also tend to drag particles across the peritoneum by convection Indications PD can remove excess fluid and provide volume control in patients with oligoanuria Compared with fluid removal by intermittent hemodialysis, fluid removal with PD is much slower Manipulation of dialysis fluid osmolality and dwell time can adjust the quantity of volume removed In hemodynamically The technique for PD involves instilling a sterile dialysate into the peritoneal cavity and allowing it to dwell for a specified period, during which time diffusion and ultrafiltration occur At the end of the dwell time, the fluid drains from the peritoneal space and the process repeats Flexible, surgically placed catheters are most often used for chronic PD For acute PD, either this form of catheter or percutaneously inserted temporary PD catheters may be used Data suggest that fewer complications occur with surgically placed catheters.31 Catheters come in a variety of sizes, depending on the size of the patient Local practice often determines who will insert the catheters; the procedure requires expertise to ensure proper catheter function The International Society for Peritoneal Dialysis recommends a surgically placed Tenckhoff catheter, currently the most used flexible PD catheter.32 PD fluid comes in standardized, sterile bags with premixed formulations; pharmacy preparation is usually unnecessary The solutions consist of electrolytes (sodium, calcium, magnesium), dextrose as the primary osmotic agent, and base (either lactate or bicarbonate) Lactate absorption can lead to confusion in acid– base interpretation, especially in critically ill infants Bicarbonatebased dialysis fluid may avoid this issue,33 but premade bicarbonate-based solutions are not available in all countries, requiring extemporaneous preparation by the local pharmacy Ultrafiltration in PD occurs by osmotic pressure, usually through the presence of dextrose in the dialysis fluid Peritoneal dialysate contains standardized concentrations of dextrose; the choices vary somewhat between countries Dialysate with higher concentrations of dextrose yields greater ultrafiltration for each exchange of fluid Peritoneal dialysate should be warmed to body temperature before instillation This step is particularly important in small patients, in whom cold dialysate infusion can cause hypotension Initial exchanges with a new PD catheter should use relatively lower volumes of dialysate (10 to 20 mL/kg; ,500 mL/m2) to limit the chance of leakage from the catheter exit site Volumes may increase gradually to 30 to 40 mL/kg or 800 to 1100 mL/m2.34 Longer dwell periods between exchanges provide more time for diffusion and ultrafiltration Shorter dwell times may not maximize mass transfer for given dwell periods; they may permit more dialysis and ultrafiltration in a 24-hour period by allowing more exchanges per day Initial dwell periods of 30 to 60 minutes can be adjusted later based on clinical status PD fluid can be instilled by hand (manual PD) or with the use of a cycler (automated PD), a device that will automatically fill and empty the patient’s abdomen with dialysate on a preprogrammed schedule The cycler also contains a warmer for the fluid and monitoring systems to record effluent volumes Several brands of cyclers are available Programming limitations may prevent the use of a cycler for some patients who require very small fill volumes or very short dwell times ... Infect Dis Soc 2019;8(3):221-227 151 Hidayat LK, Hsu DI, Quist R High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity Arch Intern Med 2006;166:2138-2144... collecting tubule following acute unilateral ureteral obstruction J Clin Invest 1985;75:219 178 Thirakomen K, Kozlov N, Arruda JA, et al Kidney hydrogen ion secretion after release of unilateral... semipermeable membrane from an area of high concentration to an area of low concentration (Fig 75.1) This physical principle operates in all renal replacement modalities in which dialysate is used