Skip to main content
SpringerLink
Log in

Pharmacokinetics in Critically Ill Children with Acute Kidney Injury

  • Review Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Acute kidney injury (AKI) is a commonly encountered comorbidity in critically ill children. The coexistence of AKI disturbs drug pharmacokinetics and pharmacodynamics, leading to clinically significant consequences. This can complicate an already critical clinical scenario by causing potential underdosing or overdosing giving way to possible therapeutic failures and adverse reactions. Current available studies offer little guidance to help maneuver such complex dosing regimens and decision-making in pediatric patients as most of them are done on heterogeneous groups of adult populations. Though there are some studies on drug dosing during continuous renal replacement therapy (CRRT), their utility is in question because of the recent advances in CRRT technology. Our review aims to discuss the principles of pharmacokinetics pertinent for honing the existing practices of drug dosing in critically ill children with AKI, and the various complexities and intricate challenges involved. This in turn will provide a framework to help enable caretakers to tailor dosing regimens in complex clinical setups with further ease and precision.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Goldstein SL. Pediatric acute renal failure: demographics and treatment. Contrib Nephrol. 2004;144:284–90.

    PubMed  Google Scholar 

  2. Akcan-Arikan A, et al. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71(10):1028–35.

    CAS  PubMed  Google Scholar 

  3. Goldstein SL. Acute kidney injury biomarkers: renal angina and the need for a renal troponin I. BMC Med. 2011;9:135.

    PubMed  PubMed Central  Google Scholar 

  4. Fitzgerald JC, et al. Risk factors and inpatient outcomes associated with acute kidney injury at pediatric severe sepsis presentation. Pediatr Nephrol. 2018;33(10):1781–90.

    PubMed  Google Scholar 

  5. Slater MB, et al. Risk factors of acute kidney injury in critically ill children. Pediatr Crit Care Med. 2016;17(9):e391–8.

    PubMed  Google Scholar 

  6. Kari JA, et al. Outcome of pediatric acute kidney injury: a multicenter prospective cohort study. Pediatr Nephrol. 2018;33(2):335–40.

    PubMed  Google Scholar 

  7. Basu RK, et al. Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in critically ill children (AWARE): study protocol for a prospective observational study. BMC Nephrol. 2015;16:24.

    PubMed  PubMed Central  Google Scholar 

  8. Alkandari O, et al. Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit Care. 2011;15(3):R146.

    PubMed  PubMed Central  Google Scholar 

  9. Vaara S, Pettila V, Kaukonen KM. Quality of pharmacokinetic studies in critically ill patients receiving continuous renal replacement therapy. Acta Anaesthesiol Scand. 2012;56(2):147–57.

    CAS  PubMed  Google Scholar 

  10. Li AM, et al. A systematic review of antibiotic dosing regimens for septic patients receiving continuous renal replacement therapy: do current studies supply sufficient data? J Antimicrob Chemother. 2009;64(5):929–37.

    CAS  PubMed  Google Scholar 

  11. Kellum JA, Lameire N. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013;17(1):204.

    PubMed  PubMed Central  Google Scholar 

  12. For Children (Conventional Units) | NIDDK. 31 July 2022]; https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/kidney-disease/laboratory-evaluation/glomerular-filtration-rate-calculators/children-conventional-units. Accessed 31 July 2022.

  13. Levey AS. Measurement of renal function in chronic renal disease. Kidney Int. 1990;38(1):167–84.

    CAS  PubMed  Google Scholar 

  14. Perrone RD, et al. Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin The Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1990;16(3):224–35.

    CAS  PubMed  Google Scholar 

  15. van Acker BA, et al. Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate. Lancet. 1992;340(8831):1326–9.

    PubMed  Google Scholar 

  16. Shemesh O, et al. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 1985;28(5):830–8.

    CAS  PubMed  Google Scholar 

  17. Coresh J, et al. Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis. 2002;39(5):920–9.

    CAS  PubMed  Google Scholar 

  18. Cherry RA, et al. Accuracy of short-duration creatinine clearance determinations in predicting 24-hour creatinine clearance in critically ill and injured patients. J Trauma. 2002;53(2):267–71.

    CAS  PubMed  Google Scholar 

  19. Pong S, et al. 12-hour versus 24-hour creatinine clearance in critically ill pediatric patients. Pediatr Res. 2005;58(1):83–8.

    PubMed  Google Scholar 

  20. Wilson RF, Soullier G. The validity of two-hour creatinine clearance studies in critically ill patients. Crit Care Med. 1980;8(5):281–4.

    CAS  PubMed  Google Scholar 

  21. Holford NHG, Anderson BJ. Allometric size: The scientific theory and extension to normal fat mass. Eur J Pharm Sci. 2017;109S:S59–64.

    PubMed  Google Scholar 

  22. Sinha J, Duffull SB, Al-Sallami HS. A review of the methods and associated mathematical models used in the measurement of fat-free mass. Clin Pharmacokinet. 2018;57(7):781–95.

    PubMed  Google Scholar 

  23. McLeay SC, et al. The relationship between drug clearance and body size: systematic review and meta-analysis of the literature published from 2000 to 2007. Clin Pharmacokinet. 2012;51(5):319–30.

    CAS  PubMed  Google Scholar 

  24. O'Hanlon CJ et al. Consistent methods for fat free mass, creatinine clearance, and glomerular filtration rate to describe renal function from neonates to adults. CPT Pharmacometr Syst Pharmacol. 2023;12:401–12.

  25. Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ. 2019;364: k4891.

    PubMed  PubMed Central  Google Scholar 

  26. Downes KJ, et al. Urinary kidney injury biomarkers and tobramycin clearance among children and young adults with cystic fibrosis: a population pharmacokinetic analysis. J Antimicrob Chemother. 2017;72(1):254–60.

    CAS  PubMed  Google Scholar 

  27. Gist KM, et al. Acute kidney injury biomarkers predict an increase in serum milrinone concentration earlier than serum creatinine-defined acute kidney injury in infants after cardiac surgery. Ther Drug Monit. 2018;40(2):186–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Benoit SW, et al. A novel strategy for identifying early acute kidney injury in pediatric hematopoietic stem cell transplantation. Bone Marrow Transplant. 2019;54(9):1453–61.

    CAS  PubMed  Google Scholar 

  29. Finney H, et al. Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child. 2000;82(1):71–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Coll E, et al. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis. 2000;36(1):29–34.

    CAS  PubMed  Google Scholar 

  31. Fliser D, Ritz E. Serum cystatin C concentration as a marker of renal dysfunction in the elderly. Am J Kidney Dis. 2001;37(1):79–83.

    CAS  PubMed  Google Scholar 

  32. Mussap M, et al. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int. 2002;61(4):1453–61.

    CAS  PubMed  Google Scholar 

  33. Hoek FJ, Kemperman FA, Krediet RT. A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant. 2003;18(10):2024–31.

    CAS  PubMed  Google Scholar 

  34. Diao JA, et al. In search of a better equation—performance and equity in estimates of kidney function. N Engl J Med. 2021;384(5):396–9.

    PubMed  PubMed Central  Google Scholar 

  35. Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol. 2009;4(11):1832–43.

    PubMed  Google Scholar 

  36. Fong J, et al. Length/serum creatinine ratio does not predict measured creatinine clearance in critically ill children. Clin Pharmacol Ther. 1995;58(2):192–7.

    CAS  PubMed  Google Scholar 

  37. Kwong MB, et al. Lack of evidence that formula-derived creatinine clearance approximates glomerular filtration rate in pediatric intensive care population. Clin Nephrol. 1985;24(6):285–8.

    CAS  PubMed  Google Scholar 

  38. Suh-Lailam B. Pediatric estimation of glomerular filtration rate. 2015 [cited 2022 July 26 ]; https://www.aacc.org/cln/articles/2015/may/pediatric-estimation-of-glomerular-filtration-rate#:~:text=In%20children%2C%20the%20most%20frequently,with%20calibration%20traceable%20to%20IDMS. Accessed 26 July 2022.

  39. Counahan R, et al. Estimation of glomerular filtration rate from plasma creatinine concentration in children. Arch Dis Child. 1976;51(11):875–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Rabito CA, et al. Noninvasive, real-time monitoring of renal function during critical care. J Am Soc Nephrol. 1994;4(7):1421–8.

    CAS  PubMed  Google Scholar 

  41. Debreczeny MP, Dorshow RB. Transdermal optical renal function monitoring in humans: development, verification, and validation of a prototype device. J Biomed Opt. 2018;23(5):1–9.

    PubMed  Google Scholar 

  42. Shmarlouski A, et al. A novel analysis technique for transcutaneous measurement of glomerular filtration rate with ultralow dose marker concentrations. IEEE Trans Biomed Eng. 2016;63(8):1742–50.

    PubMed  Google Scholar 

  43. Bruns N, Dohna-Schwake C. Antibiotics in critically ill children-a narrative review on different aspects of a rational approach. Pediatr Res. 2022;91(2):440–6.

    PubMed  Google Scholar 

  44. Toutain PL, Bousquet-Mélou A. Volumes of distribution. J Vet Pharmacol Ther. 2004;27(6):441–53.

    CAS  PubMed  Google Scholar 

  45. Gonçalves-Pereira J, Póvoa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams. Crit Care. 2011;15(5):R206.

    PubMed  PubMed Central  Google Scholar 

  46. Tang GJ, et al. Factors affecting gentamicin pharmacokinetics in septic patients. Acta Anaesthesiol Scand. 1999;43(7):726–30.

    CAS  PubMed  Google Scholar 

  47. del Mar Fernández de Gatta Garcia M, et al. Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients. Intensive Care Med. 2007;33(2):279–85.

    PubMed  Google Scholar 

  48. Jamal JA, et al. Improving antibiotic dosing in special situations in the ICU: burns, renal replacement therapy and extracorporeal membrane oxygenation. Curr Opin Crit Care. 2012;18(5):460–71.

    PubMed  Google Scholar 

  49. Seyler L, et al. Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Crit Care. 2011;15(3):R137.

    PubMed  PubMed Central  Google Scholar 

  50. Matuszkiewicz-Rowińska J, et al. Dosing of antibiotics in critically ill patients: are we left to wander in the dark? Pol Arch Med Wewn. 2012;122(12):630–40.

    PubMed  Google Scholar 

  51. Ghiculescu R. Therapeutic drug monitoring: which drugs, why, when and how to do it. Aust Prescr 2008;31:42–4. https://doi.org/10.18773/austprescr.2008.025

  52. Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562–77.

    CAS  PubMed  Google Scholar 

  53. Matzke G, Millikin S. Influence of renal function and dialysis on drug disposition. In: Burton ME, Shaw LM, Schentag JJ, Evans WE, editors. Applied pharmacokinetics: principles of therapeutic drug monitoring, 3rd ed. Applied Therapeutics, Inc., Vancouver, Wash; 1992, p. 1-49.

  54. Jusko WJ, Szefler SJ, Goldfarb AL. Pharmacokinetic design of digoxin dosage regimens in relation to renal function. J Clin Pharmacol. 1974;14(10):525–35.

    CAS  PubMed  Google Scholar 

  55. Aronson JK, Grahame-Smith DG. Altered distribution of digoxin in renal failure—a cause of digoxin toxicity? Br J Clin Pharmacol. 1976;3(6):1045–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Blanco VE et al. Acute kidney injury pharmacokinetic changes and its impact on drug prescription. Healthcare (Basel). 2019;7(1):10.

  57. Vilay AM, Churchwell MD, Mueller BA. Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12(6):235.

    PubMed  PubMed Central  Google Scholar 

  58. Bagley CM Jr, Bostick FW, De Vita Jr. VT. Clinical pharmacology of cyclophosphamide. Cancer Res. 1973;33(2):226–33.

    PubMed  Google Scholar 

  59. Bauer TM, et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet. 1995;346(8968):145–7.

    CAS  PubMed  Google Scholar 

  60. Schmith VD, Foss JF. Effects of inflammation on pharmacokinetics/pharmacodynamics: increasing recognition of its contribution to variability in response. Clin Pharmacol Ther. 2008;83(6):809–11.

    CAS  PubMed  Google Scholar 

  61. Batchelor HK, Marriott JF. Paediatric pharmacokinetics: key considerations. Br J Clin Pharmacol. 2015;79(3):395–404.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Marsot A, et al. Population pharmacokinetic analysis during the first 2 years of life: an overview. Clin Pharmacokinet. 2012;51(12):787–98.

    CAS  PubMed  Google Scholar 

  63. Hirata S, Kadowaki D. Appropriate drug dosing in patients receiving peritoneal dialysis. Contrib Nephrol. 2012;177:30–7.

    PubMed  Google Scholar 

  64. Janknegt R, Nube M. A simple method for predicting drug clearances during CAPD. Perit Dial Int. 1985;5(4):254–254.

    Google Scholar 

  65. Maher JF. Influence of continuous ambulatory peritoneal dialysis on elimination of drugs. Perit Dial Int. 1987;7(3):159–65.

    Google Scholar 

  66. Manuel MA, Paton TW, Cornish WR. Drugs and peritoneal dialysis. Perit Dial Int. 1983;3(3):117–25.

    Google Scholar 

  67. Paton TW, et al. Drug therapy in patients undergoing peritoneal dialysis. Clinical pharmacokinetic considerations. Clin Pharmacokinet. 1985;10(5):404–25.

    CAS  PubMed  Google Scholar 

  68. Taylor CA 3rd, et al. Clinical pharmacokinetics during continuous ambulatory peritoneal dialysis. Clin Pharmacokinet. 1996;31(4):293–308.

    CAS  PubMed  Google Scholar 

  69. McIntosh ME, et al. Increased peritoneal permeability in patients with peritonitis undergoing continuous ambulatory peritoneal dialysis. Eur J Clin Pharmacol. 1985;28(2):187–91.

    CAS  PubMed  Google Scholar 

  70. Keller E. Peritoneal kinetics of different drugs. Clin Nephrol. 1988;30:S24–8.

    PubMed  Google Scholar 

  71. O’Brien MA, Mason NA. Systemic absorption of intraperitoneal antimicrobials in continuous ambulatory peritoneal dialysis. Clin Pharm. 1992;11(3):246–54.

    CAS  PubMed  Google Scholar 

  72. Elwell RJ, Frye RF, Bailie GR. Pharmacokinetics of intraperitoneal cefepime in automated peritoneal dialysis. Perit Dial Int. 2005;25(4):380–6.

    CAS  PubMed  Google Scholar 

  73. Guay DR, et al. Teicoplanin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis after intravenous and intraperitoneal dosing. Antimicrob Agents Chemother. 1989;33(11):2012–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Stamatiadis D, et al. Pharmacokinetics of teicoplanin in patients undergoing continuous ambulatory peritoneal dialysis. Perit Dial Int. 2003;23(2):127–31.

    CAS  PubMed  Google Scholar 

  75. Tomar A, Kumar V, Saha A. Peritoneal dialysis in children with sepsis-associated AKI (SA-AKI): an experience in a low- to middle-income country. Paediatr Int Child Health. 2021;41(2):137–44.

    PubMed  Google Scholar 

  76. Lorenzin A, et al. Solute and water kinetics in continuous therapies. In: Claudio Ronco RB, Kellum JA, Ricci Z, editors., et al., Critical care nephrology. Elsevier; 2019. p. 1000–5.

    Google Scholar 

  77. Daverio M, et al. Continuous kidney replacement therapy practices in pediatric intensive care units across Europe. JAMA Netw Open. 2022;5(12): e2246901.

    PubMed  PubMed Central  Google Scholar 

  78. Donagher J, Martin JH, Barras MA. Individualised medicine: why we need Bayesian dosing. Intern Med J. 2017;47(5):593–600.

    PubMed  Google Scholar 

  79. Holford N. Pharmacodynamic principles and target concentration intervention. Transl Clin Pharmacol. 2018;26(4):150–4.

    PubMed  PubMed Central  Google Scholar 

  80. Lainez J, et al. A variational Bayesian approach for dosage regimen individualization. In: Pistikopoulos EN, Georgiadis MC, Kokossis AC, editors. Computer aided chemical engineering. Elsevier; 2011. p. 1563–1567.

  81. Avent ML, et al. Vancomycin therapeutics and monitoring: a contemporary approach. Intern Med J. 2013;43(2):110–9.

    CAS  PubMed  Google Scholar 

  82. Darwich AS, et al. Model-informed precision dosing: background, requirements, validation, implementation, and forward trajectory of individualizing drug therapy. Annu Rev Pharmacol Toxicol. 2021;61:225–45.

    CAS  PubMed  Google Scholar 

  83. Bentley ML, Corwin HL, Dasta J. Drug-induced acute kidney injury in the critically ill adult: recognition and prevention strategies. Crit Care Med. 2010;38(6 Suppl):S169–74.

    CAS  PubMed  Google Scholar 

  84. Pannu N, Nadim MK. An overview of drug-induced acute kidney injury. Crit Care Med. 2008;36(4 Suppl):S216–23.

    CAS  PubMed  Google Scholar 

  85. Burgess LD, Drew RH. Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam. Pharmacotherapy. 2014;34(7):670–6.

    CAS  PubMed  Google Scholar 

  86. Luther MK, et al. Vancomycin plus piperacillin-tazobactam and acute kidney injury in adults: a systematic review and meta-analysis. Crit Care Med. 2018;46(1):12–20.

    CAS  PubMed  Google Scholar 

  87. Kang S, et al. Comparison of acute kidney injury and clinical prognosis of vancomycin monotherapy and combination therapy with beta-lactams in the intensive care unit. PLoS ONE. 2019;14(6): e0217908.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Miano TA, et al. Association of vancomycin plus piperacillin-tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study. Intensive Care Med. 2022;48(9):1144–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Goldstein SL, et al. Electronic health record identification of nephrotoxin exposure and associated acute kidney injury. Pediatrics. 2013;132(3):e756–67.

    PubMed  Google Scholar 

  90. Stoops C, et al. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action): reduction of nephrotoxic medication-associated acute kidney injury in the neonatal intensive care unit. J Pediatr. 2019;215:223-228.e6.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Preston S, Drusano G. Penicillins. http://www.antimicrobe.org/d24.asp#:~:text=Natural%20Penicillins,-Aqueous%20crystalline%20penicillin&text=The%20drug%20is%20widely%20distributed,)%20of%200.35%20L%2Fkg. Accessed 15 August 2022.

  92. Pacifici GM. Clinical pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate: a review. Pharmaceuticals (Basel). 2010;3(8):2568–91.

    CAS  PubMed  Google Scholar 

  93. Grucz TM, et al. Aminoglycoside dosing and volume of distribution in critically ill surgery patients. Surg Infect (Larchmt). 2020;21(10):859–64.

    PubMed  Google Scholar 

  94. Estes KS, Derendorf H. Comparison of the pharmacokinetic properties of vancomycin, linezolid, tigecyclin, and daptomycin. Eur J Med Res. 2010;15(12):533–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Drew R, Sakoulas G. Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults. https://www.uptodate.com/contents/vancomycin-parenteral-dosing-monitoring-and-adverse-effects-in-adults/print#:~:text=Tissue%20penetration%20%E2%80%94%20Following%20intravenous%20administration,L%2Fkg%20%5B11%5D. Accessed 15 August 2022.

  96. Turnidge J. Pharmacokinetics and pharmacodynamics of fluoroquinolones. Drugs. 1999;58(Suppl 2):29–36.

    CAS  PubMed  Google Scholar 

  97. Kobuchi S, et al. Pharmacokinetics of macrolide antibiotics and transport into the interstitial fluid: comparison among erythromycin, clarithromycin, and azithromycin. Antibiotics (Basel). 2020;9(4):199.

  98. Pistolesi V, Morabito S, Di Mario F, Regolisti G, Cantarelli C, Fiaccadori E. A guide to understanding antimicrobial drug dosing in critically Ill patients on renal replacement therapy. Antimicrob Agents Chemother. 2019, 63(8), pp. e00583–19. https://doi.org/10.1128/AAC.00583-19

  99. Kniffen TS, et al. Bioavailability, pharmacokinetics, and plasma concentration of tetracycline hydrochloride fed to swine. Am J Vet Res. 1989;50(4):518–21.

    CAS  PubMed  Google Scholar 

  100. Seng KY, et al. Population pharmacokinetics of rifampicin and 25-deacetyl-rifampicin in healthy Asian adults. J Antimicrob Chemother. 2015;70(12):3298–306.

    CAS  PubMed  Google Scholar 

  101. Mouton JW, van den Anker JN. Meropenem clinical pharmacokinetics. Clin Pharmacokinet. 1995;28(4):275–86.

    CAS  PubMed  Google Scholar 

  102. MacGowan AP. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. J Antimicrob Chemother. 2003;51 Suppl 2:ii17-25.

    PubMed  Google Scholar 

  103. Ahern JW, et al. Experience with vancomycin in patients receiving slow low-efficiency dialysis. Hosp Pharm. 2004;39(2):138–43.

    Google Scholar 

  104. Kielstein JT, et al. Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis. Crit Care Med. 2006;34(1):51–6.

    CAS  PubMed  Google Scholar 

  105. Burkhardt O, et al. Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis. Nephrol Dial Transplant. 2008;24(1):267–71.

    PubMed  Google Scholar 

  106. Fiaccadori E, et al. Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure. Crit Care Med. 2004;32(12):2437–42.

    CAS  PubMed  Google Scholar 

  107. Czock D, et al. Pharmacokinetics of moxifloxacin and levofloxacin in intensive care unit patients who have acute renal failure and undergo extended daily dialysis. Clin J Am Soc Nephrol. 2006;1(6):1263–8.

    CAS  PubMed  Google Scholar 

  108. König C, et al. Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis. J Antimicrob Chemother. 2017;72(5):1433–40.

    PubMed  Google Scholar 

  109. Kielstein JT, et al. Risk of underdosing of ampicillin/sulbactam in patients with acute kidney injury undergoing extended daily dialysis–a single case. Nephrol Dial Transplant. 2009;24(7):2283–5.

    CAS  PubMed  Google Scholar 

  110. Bridges BC, et al. Pediatric renal replacement therapy in the intensive care unit. Blood Purif. 2012;34(2):138–48.

    CAS  PubMed  Google Scholar 

  111. Tang Girdwood S, et al. Population pharmacokinetic modeling of total and free ceftriaxone in critically ill children and young adults and Monte Carlo simulations support twice daily dosing for target attainment. Antimicrob Agents Chemother. 2022;66(1): e0142721.

    PubMed  Google Scholar 

  112. Nehus EJ, et al. Meropenem in children receiving continuous renal replacement therapy: clinical trial simulations using realistic covariates. J Clin Pharmacol. 2014;54(12):1421–8.

    CAS  PubMed  Google Scholar 

  113. Stitt G, et al. Cefepime pharmacokinetics in critically ill pediatric patients receiving continuous renal replacement therapy. Antimicrob Agents Chemother. 2019;63(4):e02006–18.

  114. Yang M, et al. Population pharmacokinetics and dosage optimization of linezolid in critically ill pediatric patients. Antimicrob Agents Chemother. 2021;65(5):e02504–20.

  115. Butragueño-Laiseca, L., et al., Finding the dose for ceftolozane-tazobactam in critically ill children with and without acute kidney injury. Antibiotics (Basel). 2020;9(12):887.

  116. Jang SM, et al. Antibiotic exposure profiles in trials comparing intensity of continuous renal replacement therapy. Crit Care Med. 2019;47(11):e863–71.

    CAS  PubMed  Google Scholar 

  117. Gentamicin (Systemic). Pediatric and Neonatal Lexi-Drugs. [updated 2022 Jun 21; cited 2022 Jun 21] In Lexicomp Online [Internet]. UpToDate. Waltham, MA.

  118. Clindamycin (Systemic). Pediatric and Neonatal Lexi-Drugs. [updated 2022 Jun 10; cited 2022 Jun 21] In Lexicomp Online [Internet]. UpToDate. Waltham, MA.

  119. Levofloxacin (Systemic). Pediatric and Neonatal Lexi-Drugs. [updated 2022 Jun 10; cited 2022 Jun 21] In Lexicomp Online [Internet]. UpToDate. Waltham, MA.

  120. Fluconazole. Pediatric and Neonatal Lexi-Drugs. [updated 2022 Jun 18; cited 2022 Jun 21] In Lexicomp Online [Internet]. UpToDate. Waltham, MA.

  121. Acyclovir (Systemic). Pediatric and Neonatal Lexi-Drugs. [updated 2022 Jun 15; cited 2022 Jun 21] In Lexicomp Online [Internet]. UpToDate. Waltham, MA.

Download references

Author information

Author notes

  1. Manan Raina and Amani Ashraf contributed equally and shall be combined first authors.

Authors and Affiliations

  1. Hawken Upper School, Chesterland, OH, USA

    Manan Raina

  2. Northeast Ohio Medical University, Rootstown, OH, USA

    Amani Ashraf

  3. Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA

    Anvitha Soundararajan

  4. Bankura Sammilani Medical College and Hospital, Bankura, West Bengal, 722102, India

    Anusree Krishna Mandal

  5. Pediatric Nephrology, Kidney Institute, Medanta, The Medicity Hospital, Gurgaon, Haryana, 122001, India

    Sidharth Kumar Sethi

Authors
  1. Manan Raina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amani Ashraf
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anvitha Soundararajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anusree Krishna Mandal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sidharth Kumar Sethi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sidharth Kumar Sethi.

Ethics declarations

Funding

No funding was received for this work.

Conflicts of interest

Manan Raina, Amani Ashraf, Anvitha Soundararajan, Anusree Krishna Mandal, and Sidharth Kumar Sethi declare they have no competing interests in relation to this review article.

Ethics approval

Not applicable.

Informed consent for participation and publication

Not applicable.

Data availability

Not applicable.

Code availability

Not applicable.

Authors contributions

SKS and AA conceptualized the manuscript, MR, AA, AS, SKS and AKM wrote the manuscript. SKS critically reviewed the manuscript.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raina, M., Ashraf, A., Soundararajan, A. et al. Pharmacokinetics in Critically Ill Children with Acute Kidney Injury. Pediatr Drugs 25, 425–442 (2023). https://doi.org/10.1007/s40272-023-00572-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-023-00572-z

Search

Navigation