pp 1-21 | Cite as

Understanding the Effects of Kidney Disease and Dialysis Treatment on Pharmacotherapy in Children

  • Verena GottaEmail author
  • Olivera Marsenic
  • Marc Pfister
Part of the Handbook of Experimental Pharmacology book series


Chronic kidney disease (CKD) and acute kidney injury (AKI) requiring renal replacement therapy (RRT) by dialysis are rare conditions in pediatric patients. In pediatric patients with CKD, dialysis is mainly performed using peritoneal dialysis (PD) or intermittent hemodialysis (HD). In patients with AKI, continuous renal replacement therapy (CRRT) using hemofiltration, hemodialysis, or both techniques can be used. This chapter reviews (1) physiology and epidemiology of kidney disease and dialysis in children and (2) pharmacokinetic principles to be considered for developing pediatric dose recommendations under different dialysis modalities. Methods for both calculating and predicting dialysis drug clearance are reviewed; scaling approaches for predicting dialysis clearance in pediatric patients from data obtained in adults are discussed.


Acute kidney injury Chronic kidney disease Modeling Pediatrics Pharmacokinetics Pharmacometrics Renal dialysis 


  1. Akcan-Arikan A, Zappitelli M, Loftis LL et al (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71:1028–1035Google Scholar
  2. Andreoli S (2004) Acute renal failure: clinical evaluation and management. In: Avner E, Harmon W, Niaudet P (eds) Pediatric nephrology. Lippincott Williams & Wilkins, Philadelphia, pp 1233–1251Google Scholar
  3. Andreoli SP (2009) Acute kidney injury in children. Pediatr Nephrol 24:253–263Google Scholar
  4. Atkinson AJ, Susla GM (2012) Pharmacokinetics in patients requiring renal replacement therapy. In: Huang S-M, Lertora J, Atkinson A (eds) Principles of clinical pharmacology, 3rd edn. Elsevier, San Diego, pp 65–79Google Scholar
  5. Atkinson AJ, Umans JG (2009) Pharmacokinetic studies in hemodialysis patients. Clin Pharmacol Ther 86:548–552Google Scholar
  6. Auron A, Brophy PD (2012) Hyperammonemia in review: pathophysiology, diagnosis, and treatment. Pediatr Nephrol 27:207–222Google Scholar
  7. Benfield M, Bunchman T (2004) Management of acute renal failure. In: Pediatric nephrology. Lippincott Williams & Wilkins, Philadelphia, pp 1253–1266Google Scholar
  8. Blowey D (2004) Principles of drug administration in children receiving renal replacement therapy. In: Warady B, Schaefer F, Fine R, Alexander S (eds) Pediatric dialysis. Springer, Dordrecht, pp 545–565Google Scholar
  9. Brophy PD (2008) Renal supportive therapy for pediatric acute kidney injury in the setting of multiorgan dysfunction syndrome/sepsis. Semin Nephrol 28:457–469Google Scholar
  10. Brou NA, Jacqz-Aigrain E, Zhao W (2015) Cystatin C as a potential biomarker for dosing of renally excreted drugs. Br J Clin Pharmacol 80:20–27Google Scholar
  11. Bunchman TE, Ferris ME (2011) Management of toxic ingestions with the use of renal replacement therapy. Pediatr Nephrol 26:535–541Google Scholar
  12. Cella M, Knibbe C, Danhof M, Della Pasqua O (2010) What is the right dose for children? Br J Clin Pharmacol 70:597–603Google Scholar
  13. Center for Drug Evaluation and Research (CDER) (2010) Guidance for industry pharmacokinetics in patients with impaired renal function – study design, data analysis, and impact on dosing and labeling. CDER, RockvilleGoogle Scholar
  14. Chua AN, Warady BA (2017) Care of the pediatric patient on chronic dialysis. Adv Chronic Kidney Dis 24:388–397Google Scholar
  15. Clarkson M, Magee C, Brenner B (2010) Peritoneal dialysis. In: Clarkson M, Magee C, Brenner B (eds) Pocket companion to Brenner & Rector’s the kidney. Elsevier, Philadelphia, pp 730–752Google Scholar
  16. Committee for Medicinal Products for Human use (CHMP) (2015) Guideline on the evaluation of the pharmacokinetics of medicinal products in patients with decreased renal function. CHMP, LondonGoogle Scholar
  17. Dao K, Chtioui H, Lu Y et al (2017) Pharmacokinetics of pomalidomide in a patient receiving hemodialysis using a high-cutoff filter. Am J Kidney Dis 69:553–554Google Scholar
  18. Depner TA, Greene T, Daugirdas JT et al (2004) Dialyzer performance in the HEMO study: in vivo K0A and true blood flow determined from a model of cross-dialyzer urea extraction. ASAIO J 50:85–93Google Scholar
  19. Dettli L (1976) Drug dosage in renal disease. Clin Pharmacokinet 1:126–134Google Scholar
  20. Downes KJ, Dong M, Fukuda T et al (2017) Urinary kidney injury biomarkers and tobramycin clearance among children and young adults with cystic fibrosis: a population pharmacokinetic analysis. J Antimicrob Chemother 72:254–260Google Scholar
  21. Duranton F, Cohen G, De Smet R et al (2012) Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol 23:1258–1270Google Scholar
  22. Golper TA, Fissell R, Fissell WH et al (2014) Hemodialysis: core curriculum 2014. Am J Kidney Dis 63:153–163Google Scholar
  23. Gotta V, Dao K, Rodieux F et al (2017) Guidance to develop individual dose recommendations for patients on chronic hemodialysis. Expert Rev Clin Pharmacol 10:737–752Google Scholar
  24. Gotta V, Marsenic O, Pfister M (2018) Age- and weight-based differences in haemodialysis prescription and delivery in children, adolescents and young adults. Nephrol Dial Transplant 33:1649–1660Google Scholar
  25. Gotta V, Marsenic O, Pfister M (2019a) Understanding urea kinetic factors that enhance personalized hemodialysis prescription in children. ASAIO J.
  26. Gotta V, Pfister M, Marsenic O (2019b) Ultrafiltration rates in children on chronic hemodialysis routinely exceed weight based adult limit. Hemodial Int 23:126–128Google Scholar
  27. Griffin BR, Faubel S, Edelstein CL (2018) Biomarkers of drug-induced kidney toxicity. Ther Drug Monit 41:213–226Google Scholar
  28. KDIGO (Kidney Disease: Improving Global Outcomes) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease – Kidney International Supplements. J Int Soc Nephrol 3:1–150Google Scholar
  29. Keller E, Reetze P, Schollmeyer P (1990) Drug therapy in patients undergoing continuous ambulatory peritoneal dialysis. Clin Pharmacokinet 18:104–117Google Scholar
  30. Khanal A, Castelino RL, Peterson GM, Jose MD (2014) Dose adjustment guidelines for medications in patients with renal impairment: how consistent are drug information sources? Intern Med J 44:77–85Google Scholar
  31. Knoderer CA, Leiser JD, Nailescu C et al (2008) Fenoldopam for acute kidney injury in children. Pediatr Nephrol 23:495–498Google Scholar
  32. Kwiatkowski DM, Sutherland SM (2017) Acute kidney injury in pediatric patients. Best Pract Res Clin Anaesthesiol 31:427–439Google Scholar
  33. Lavergne V, Ouellet G, Bouchard J et al (2014) Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology. Semin Dial 27:407–414Google Scholar
  34. Liesenfeld KH, Staab A, Härtter S et al (2013) Pharmacometric characterization of dabigatran hemodialysis. Clin Pharmacokinet 52:453–462Google Scholar
  35. Madhukar M, Ramesh K (2018) Mechanisms of solute clearance and ultrafiltration in peritoneal dialysis. Accessed 1 Feb 2019
  36. Marsenic O, Baluarte H (2011) Acute and chronic renal failure. In: Florin T, Ludwig S, Aronson P, Werner H (eds) Netter’s pediatrics. Elsevier, Philadelphia, pp 397–407Google Scholar
  37. Matzke GR, Aronoff GR, Atkinson AJ et al (2011) Drug dosing consideration in patients with acute and chronic kidney disease – a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 80:1122–1137Google Scholar
  38. Matzke GR, Dowling TC, Marks SA, Murphy JE (2016) Influence of kidney disease on drug disposition: an assessment of industry studies submitted to the FDA for new chemical entities 1999-2010. J Clin Pharmacol 56:390–398Google Scholar
  39. Mehta RL (1999) Supportive therapies: intermittent hemodialysis, continuous renal replacement therapies, and peritoneal dialysis. In: Schrier RW (ed) Atlas of diseases of the kidney, vol 1, online edn. Wiley-Blackwell, Philadelphia, pp 19.1–19.16. Google Scholar
  40. Metsvaht T, Nellis G, Varendi H et al (2015) High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination. BMC Pediatr 15:14Google Scholar
  41. Michaels AS (1966) Operating parameters and performance criteria for hemodialyzers and other membrane-separation devices. Trans Am Soc Artif Intern Organs 12:387–392Google Scholar
  42. Mueller BA, Golper TA (2019) Drug removal in continuous renal replacement therapy. In: UpToDate. Accessed 1 Feb 2019
  43. Mueller BA, Smoyer WE (2009) Challenges in developing evidence-based drug dosing guidelines for adults and children receiving renal replacement therapy. Clin Pharmacol Ther 86:479–482Google Scholar
  44. Murray P, Liu K (2011) Management of renal replacement therapy in acute kidney injury. Nephrol Self Assess Program 10:242–246Google Scholar
  45. Nolin TD, Naud J, Leblond FA, Pichette V (2008) Emerging evidence of the impact of kidney disease on drug metabolism and transport. Clin Pharmacol Ther 83:898–903Google Scholar
  46. Nolin TD, Aronoff GR, Fissell WH et al (2015) Pharmacokinetic assessment in patients receiving continuous RRT: perspectives from the kidney health initiative. Clin J Am Soc Nephrol 10:159–164Google Scholar
  47. Odeh YK, Wang Z, Ruo TI et al (1993) Simultaneous analysis of inulin and 15N2-urea kinetics in humans. Clin Pharmacol Ther 53:419–425Google Scholar
  48. Paton TW, Cornish WR, Manuel MA, Hardy BG (1985) Drug therapy in patients undergoing peritoneal dialysis clinical pharmacokinetic considerations. Clin Pharmacokinet 10:404–426Google Scholar
  49. Pea F, Viale P, Pavan F, Furlanut M (2007) Pharmacokinetic considerations for antimicrobial therapy in patients receiving renal replacement therapy. Clin Pharmacokinet 46:997–1038Google Scholar
  50. Rees L, Schaefer F, Schmitt CP et al (2017) Chronic dialysis in children and adolescents: challenges and outcomes. Lancet Child Adolesc Health 1:68–77Google Scholar
  51. Rodieux F, Wilbaux M, van den Anker JN, Pfister M (2015) Effect of kidney function on drug kinetics and dosing in neonates, infants, and children. Clin Pharmacokinet 54:1183–1204Google Scholar
  52. Roychowdhury S, Talpaz M (2011) Managing resistance in chronic myeloid leukemia. Blood Rev 25:279–290Google Scholar
  53. Shiraishi Y, Okajima M, Sai Y et al (2012) Elimination of teicoplanin by adsorption to the filter membrane during haemodiafiltration: screening experiments for linezolid, teicoplanin and vancomycin followed by in vitro haemodiafiltration models for teicoplanin. Anaesth Intensive Care 40:442–449Google Scholar
  54. Sutherland SM, Alexander SR (2012) Continuous renal replacement therapy in children. Pediatr Nephrol 27:2007–2016Google Scholar
  55. Ulinski T, Sellier-Leclerc A-L, Tudorache E et al (2012) Acute tubulointerstitial nephritis. Pediatr Nephrol 27:1051–1057Google Scholar
  56. Veltri MA, Neu AM, Fivush BA et al (2004) Drug dosing during intermittent hemodialysis and continuous renal replacement therapy: special considerations in pediatric patients. Paediatr Drugs 6:45–65Google Scholar
  57. Verrina E, Cappelli V, Perfumo F (2009) Selection of modalities, prescription, and technical issues in children on peritoneal dialysis. Pediatr Nephrol 24:1453–1464Google Scholar
  58. Vidal L, Shavit M, Fraser A et al (2005) Systematic comparison of four sources of drug information regarding adjustment of dose for renal function. Br Med J 331:263–266Google Scholar
  59. Vilay AM, Churchwell MD, Mueller BA (2008) Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care 12:235Google Scholar
  60. Walters S, Porter C, Brophy PD (2009) Dialysis and pediatric acute kidney injury: choice of renal support modality. Pediatr Nephrol 24:37–48Google Scholar
  61. Warady B, Morgenstern B, Alexander S (2004) Peritoneal dialysis. In: Avner E, Harmon W, Niaudet P (eds) Pediatric nephrology. Lippincott Williams & Wilkins, Philadelphia, pp 1375–1394Google Scholar
  62. Zepeda-Orozco D, Quigley R (2012) Dialysis disequilibrium syndrome. Pediatr Nephrol 27:2205–2211Google Scholar
  63. Zhang L, Boulton DW, Pfister M (2012) A pharmacometric approach to quantify the impact of chronic kidney disease and hemodialysis on systemic drug exposure: application to saxagliptin. J Clin Pharmacol 52:126S–133SGoogle Scholar
  64. Zhang L, Roy A, Pfister M (2014) Pharmacometrics in chronic kidney disease. In: Crommelin DJA, Lipper RA (eds) Applied pharmacometrics. American Association of Pharmaceutical Scientists 2014. Springer, New York, pp 109–137Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Pediatric Pharmacology and PharmacometricsUniversity of Basel Children’s HospitalBaselSwitzerland
  2. 2.Pediatric NephrologyYale University School of MedicineNew HavenUSA

Personalised recommendations