Skip to main content

Advertisement

Log in

Drugs in treating paediatric acute kidney injury

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Acute kidney injury (AKI) is a complex syndrome which affects a significant proportion of hospitalized children. The breadth and impact of AKI on health outcomes in both adults and children have come to the fore in recent years with increasing awareness encouraging research advancement. Despite this, management strategies for most types of AKI remain heavily reliant on fluid and electrolyte management, hemodynamic optimization, nephrotoxin avoidance and appropriate initiation of kidney replacement therapy. Specific drugs targeting the mechanisms involved in AKI remain elusive. Recent improvement in appreciation of the complexity of AKI pathophysiology has allowed for greater opportunity to consider novel therapeutic agents. A number of drugs specifically targeting AKI are in various stages of development. This review will consider some novel and repurposed agents; interrogate the plausibility of the proposed mechanisms of action, as they relate to what we know about the pathophysiology of AKI; and review the level of existing literature supporting their efficacy. The evidence base, particularly in children, is limited.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. McGregor TL, Jones DP, Wang L, Danciu I et al (2016) Acute kidney injury incidence in noncritically ill hospitalized children, adolescents, and young adults: a retrospective observational study. Am J Kidney Dis 67:384–390

    PubMed  Google Scholar 

  2. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL et al (2017) Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med 376:11–20

    PubMed  Google Scholar 

  3. Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120:c179-184

    PubMed  Google Scholar 

  4. Hessey E, Melhem N, Alobaidi R, Ulrich E et al (2021) Acute kidney injury in critically ill children is not all acute: lessons over the last 5 years. Front Pediatr 9:648587

    PubMed  PubMed Central  Google Scholar 

  5. Devarajan P (2022) Pathogenesis of intrinsic acute kidney injury. Curr Opin Pediatr 35:234–238

    PubMed  Google Scholar 

  6. Benoit SW, Devarajan P (2018) Acute kidney injury: emerging pharmacotherapies in current clinical trials. Pediatr Nephrol 33:779–787

    PubMed  Google Scholar 

  7. Castaneda MP, Swiatecka-Urban A, Mitsnefes MM, Feuerstein D et al (2003) Activation of mitochondrial apoptotic pathways in human renal allografts after ischemiareperfusion injury. Transplantation 76:50–54

    CAS  PubMed  Google Scholar 

  8. Baliga R, Ueda N, Walker PD, Shah SV (1999) Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev 31:971–997

    CAS  PubMed  Google Scholar 

  9. Vallon V (2003) Tubuloglomerular feedback and the control of glomerular filtration rate. News Physiol Sci 18:169–174

    CAS  PubMed  Google Scholar 

  10. Schmidt C, Hocherl K, Schweda F, Bucher M (2007) Proinflammatory cytokines cause down-regulation of renal chloride entry pathways during sepsis. Crit Care Med 35:2110–2119

    CAS  PubMed  Google Scholar 

  11. Venkatachalam MA, Weinberg JM, Kriz W, Bidani AK (2015) Failed tubule recovery, AKI-CKD transition, and kidney disease progression. J Am Soc Nephrol 26:1765–1776

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Brocklebank V, Wood KM, Kavanagh D (2018) Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol 13:300–317

    CAS  PubMed  Google Scholar 

  13. Raghavan R, Eknoyan G (2014) Acute interstitial nephritis - a reappraisal and update. Clin Nephrol 82:149–162

    PubMed  PubMed Central  Google Scholar 

  14. Davidson JA, Khailova L, Treece A, Robison J et al (2019) Alkaline phosphatase treatment of acute kidney injury in an infant piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest. Sci Rep 9:14175

    PubMed  PubMed Central  Google Scholar 

  15. Peters E, Geraci S, Heemskerk S, Wilmer MJ et al (2015) Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate. Br J Pharmacol 172:4932–4945

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Heemskerk S, Masereeuw R, Moesker O, Bouw MP et al (2009) Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients. Crit Care Med 37:417 423-e411

    Google Scholar 

  17. Pickkers P, Heemskerk S, Schouten J, Laterre PF et al (2012) Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. Crit Care 16:R14

    PubMed  PubMed Central  Google Scholar 

  18. Pickkers P, Mehta RL, Murray PT, Joannidis M et al (2018) Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in patients with sepsis-associated acute kidney injury: a randomized clinical trial. JAMA 320:1998–2009

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Kohda Y, Chiao H, Star RA (1998) alpha-Melanocyte-stimulating hormone and acute renal failure. Curr Opin Nephrol Hypertens 7:413–417

    CAS  PubMed  Google Scholar 

  20. Simmons MN, Subramanian V, Crouzet S, Haber GP et al (2010) Alpha-melanocyte stimulating hormone analogue AP214 protects against ischemia induced acute kidney injury in a porcine surgical model. J Urol 183:1625–1629

    CAS  PubMed  Google Scholar 

  21. McCullough PA, Bennett-Guerrero E, Chawla LS, Beaver T et al (2016) ABT-719 for the prevention of acute kidney injury in patients undergoing high-risk cardiac surgery: a randomized phase 2b clinical trial. J Am Heart Assoc 5:e003549

    PubMed  PubMed Central  Google Scholar 

  22. Zhuo M, Paik JM, Wexler DJ, Bonventre JV et al (2022) SGLT2 inhibitors and the risk of acute kidney injury in older adults with type 2 diabetes. Am J Kidney Dis 79:858-867-e851

    Google Scholar 

  23. Higashijima Y, Tanaka T, Yamaguchi J, Tanaka S et al (2015) Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury. Am J Physiol Renal Physiol 308:F878-887

    CAS  PubMed  Google Scholar 

  24. Katagiri D, Hamasaki Y, Doi K, Okamoto K et al (2013) Protection of glucagon-like peptide-1 in cisplatin-induced renal injury elucidates gut-kidney connection. J Am Soc Nephrol 24:2034–2043

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Thielmann M, Corteville D, Szabo G, Swaminathan M et al (2021) Teprasiran, a small interfering RNA, for the prevention of acute kidney injury in high-risk patients undergoing cardiac surgery: a randomized clinical study. Circulation 144:1133–1144

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Kaushal GP, Shah SV (2016) Autophagy in acute kidney injury. Kidney Int 89:779–791

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Andrianova NV, Zorova LD, Babenko VA, Pevzner IB et al (2019) Rapamycin is not protective against ischemic and cisplatin-induced kidney injury. Biochemistry (Mosc) 84:1502–1512

    CAS  PubMed  Google Scholar 

  28. Su Y, Lu J, Gong P, Chen X et al (2018) Rapamycin induces autophagy to alleviate acute kidney injury following cerebral ischemia and reperfusion via the mTORC1/ATG13/ULK1 signaling pathway. Mol Med Rep 18:5445–5454

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Maremonti F, Meyer C, Linkermann A (2022) Mechanisms and models of kidney tubular necrosis and nephron loss. J Am Soc Nephrol 33:472–486

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Devisscher L, Van Coillie S, Hofmans S, Van Rompaey D et al (2018) Discovery of novel, drug-like ferroptosis inhibitors with in vivo efficacy. J Med Chem 61:10126–10140

    CAS  PubMed  Google Scholar 

  32. Sharma S, Leaf DE (2019) Iron chelation as a potential therapeutic strategy for AKI prevention. J Am Soc Nephrol 30:2060–2071

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Mishra OP, Pooniya V, Ali Z, Upadhyay RS et al (2008) Antioxidant status of children with acute renal failure. Pediatr Nephrol 23:2047–2051

    PubMed  Google Scholar 

  34. Bolisetty S, Zarjou A, Agarwal A (2017) Heme oxygenase 1 as a therapeutic target in acute kidney injury. Am J Kidney Dis 69:531–545

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Carlson WD, Keck PC, Bosukonda D, Carlson FR Jr (2022) A process for the design and development of novel bone morphogenetic protein-7 (BMP-7) mimetics with an example: THR-184. Front Pharmacol 13:864509

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Wetzel P, Haag J, Campean V, Goldschmeding R et al (2006) Bone morphogenetic protein-7 expression and activity in the human adult normal kidney is predominantly localized to the distal nephron. Kidney Int 70:717–723

    CAS  PubMed  Google Scholar 

  37. Himmelfarb J, Chertow GM, McCullough PA, Mesana T et al (2018) Perioperative THR-184 and AKI after cardiac surgery. J Am Soc Nephrol 29:670–679

    CAS  PubMed  Google Scholar 

  38. Vincenti F, Kim J, Gouveia D, Pelle G et al (2021) Phase 3 trial design of the hepatocyte growth factor mimetic ANG-3777 in renal transplant recipients with delayed graft function. Kidney Int Rep 6:296–303

    PubMed  Google Scholar 

  39. Swaminathan M, Stafford-Smith M, Chertow GM, Warnock DG et al (2018) Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. J Am Soc Nephrol 29:260–267

    PubMed  Google Scholar 

  40. Bove T, Zangrillo A, Guarracino F, Alvaro G et al (2014) Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA 312:2244–2253

    PubMed  Google Scholar 

  41. Noce A, Marrone G, Rovella V, Busca A et al (2019) Fenoldopam mesylate: a narrative review of its use in acute kidney injury. Curr Pharm Biotechnol 20:366–375

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Gillies MA, Kakar V, Parker RJ, Honore PM et al (2015) Fenoldopam to prevent acute kidney injury after major surgery-a systematic review and meta-analysis. Crit Care 19:449

    PubMed  PubMed Central  Google Scholar 

  43. Ricci Z, Luciano R, Favia I, Garisto C et al (2011) High-dose fenoldopam reduces postoperative neutrophil gelatinase-associated lipocaline and cystatin C levels in pediatric cardiac surgery. Crit Care 15:R160

    PubMed  PubMed Central  Google Scholar 

  44. Nakagawa Y, Nishikimi T, Kuwahara K (2019) Atrial and brain natriuretic peptides: Hormones secreted from the heart. Peptides 111:18–25

    CAS  PubMed  Google Scholar 

  45. Zeidel ML (1990) Renal actions of atrial natriuretic peptide: regulation of collecting duct sodium and water transport. Annu Rev Physiol 52:747–759

    CAS  PubMed  Google Scholar 

  46. Nigwekar SU, Navaneethan SD, Parikh CR, Hix JK (2009) Atrial natriuretic peptide for management of acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol 4:261–272

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Yamada H, Doi K, Tsukamoto T, Kiyomoto H et al (2019) Low-dose atrial natriuretic peptide for prevention or treatment of acute kidney injury: a systematic review and meta-analysis. Crit Care 23:41

    PubMed  PubMed Central  Google Scholar 

  48. Sackner-Bernstein JD, Skopicki HA, Aaronson KD (2005) Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111:1487–1491

    CAS  PubMed  Google Scholar 

  49. van Deursen VM, Hernandez AF, Stebbins A, Hasselblad V et al (2014) Nesiritide, renal function, and associated outcomes during hospitalization for acute decompensated heart failure: results from the Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure (ASCEND-HF). Circulation 130:958–965

    PubMed  Google Scholar 

  50. Ejaz AA, Martin TD, Johnson RJ, Winterstein AG et al (2009) Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery. J Thorac Cardiovasc Surg 138:959–964

    CAS  PubMed  Google Scholar 

  51. Bronicki RA, Domico M, Checchia PA, Kennedy CE et al (2017) The use of nesiritide in children with congenital heart disease. Pediatr Crit Care Med 18:151–158

    PubMed  Google Scholar 

  52. Campbell DJ (2017) Long-term neprilysin inhibition - implications for ARNIs. Nat Rev Cardiol 14:171–186

    CAS  PubMed  Google Scholar 

  53. Packer M, Claggett B, Lefkowitz MP, McMurray JJV et al (2018) Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial. Lancet Diabetes Endocrinol 6:547–554

    CAS  PubMed  Google Scholar 

  54. Voors AA, Gori M, Liu LC, Claggett B et al (2015) Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 17:510–517

    CAS  PubMed  Google Scholar 

  55. Kemna M, Hong B, Friedland-Little J, Albers E, Law YM (2020) Valsartan/sacubitril in pediatric heart failure. J Heart Lung Transplant 39:S450

    Google Scholar 

  56. Bhatt GC, Gogia P, Bitzan M, Das RR (2019) Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review. Arch Dis Child 104:670–679

    PubMed  Google Scholar 

  57. Alsaadoun S, Rustom F, Hassan HA, Alkhurais H et al (2020) Aminophylline for improving acute kidney injury in pediatric patients: a systematic review and meta-analysis. Int J Health Sci (Qassim) 14:44–51

    PubMed  Google Scholar 

  58. Gordon AC, Perkins GD, Singer M, McAuley DF et al (2016) Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med 375:1638–1648

    CAS  PubMed  Google Scholar 

  59. Joannidis M, Druml W, Forni LG, Groeneveld ABJ et al (2017) Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017: Expert opinion of the Working Group on Prevention, AKI section, European Society of Intensive Care Medicine. Intensive Care Med 43:730–749

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Thorlacius EM, Suominen PK, Wahlander H, Keski-Nisula J et al (2019) The effect of levosimendan versus milrinone on the occurrence rate of acute kidney injury following congenital heart surgery in infants: a randomized clinical trial. Pediatr Crit Care Med 20:947–956

    PubMed  Google Scholar 

  61. Grisaru S, Xie J, Samuel S, Hartling L et al (2017) Associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli: a systematic review and meta-analysis. JAMA Pediatr 171:68–76

    PubMed  Google Scholar 

  62. Legendre CM, Licht C, Muus P, Greenbaum LA et al (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181

    CAS  PubMed  Google Scholar 

  63. Schoettler M, Carreras E, Cho B, Dandoy CE et al (2022) Harmonizing definitions for diagnostic criteria and prognostic assessment of transplantation-associated thrombotic microangiopathy: a report on behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research. Transplant Cell Ther 29:151–163

    PubMed  PubMed Central  Google Scholar 

  64. Barbour T, Scully M, Ariceta G, Cataland S et al (2021) Long-term efficacy and safety of the long-acting complement C5 inhibitor ravulizumab for the treatment of atypical hemolytic uremic syndrome in adults. Kidney Int Rep 6:1603–1613

    PubMed  PubMed Central  Google Scholar 

  65. Tanaka K, Adams B, Aris AM, Fujita N et al (2021) The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Pediatr Nephrol 36:889–898

    PubMed  Google Scholar 

  66. Goodship TH, Cook HT, Fakhouri F, Fervenza FC et al (2017) Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 91:539–551

    CAS  PubMed  Google Scholar 

  67. Andrianova NV, Zorov DB, Plotnikov EY (2020) Targeting inflammation and oxidative stress as a therapy for ischemic kidney injury. Biochemistry (Mosc) 85:1591–1602

    CAS  PubMed  Google Scholar 

  68. Clave S, Rousset-Rouviere C, Daniel L, Tsimaratos M (2019) The invisible threat of non-steroidal anti-inflammatory drugs for kidneys. Front Pediatr 7:520

    PubMed  PubMed Central  Google Scholar 

  69. Saran R, Robinson B, Abbott KC, Bragg-Gresham J et al (2020) US Renal Data System 2019 Annual Data Report: epidemiology of kidney disease in the United States. Am J Kidney Dis 75:A6–A7

    PubMed  Google Scholar 

  70. Raza MN, Hadid M, Keen CE, Bingham C et al (2012) Acute tubulointerstitial nephritis, treatment with steroid and impact on renal outcomes. Nephrology (Carlton) 17:748–753

    PubMed  Google Scholar 

  71. Ulinski T, Sellier-Leclerc AL, Tudorache E, Bensman A et al (2012) Acute tubulointerstitial nephritis. Pediatr Nephrol 27:1051–1057

    PubMed  Google Scholar 

  72. Jahnukainen T, Saarela V, Arikoski P, Ylinen E et al (2013) Prednisone in the treatment of tubulointerstitial nephritis in children. Pediatr Nephrol 28:1253–1260

    PubMed  Google Scholar 

  73. Fernandez-Juarez G, Perez JV, Caravaca-Fontan F, Quintana L et al (2018) Duration of treatment with corticosteroids and recovery of kidney function in acute interstitial nephritis. Clin J Am Soc Nephrol 13:1851–1858

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Wente-Schulz S, Aksenova M, Awan A, Ambarsari CG et al (2021) Aetiology, course and treatment of acute tubulointerstitial nephritis in paediatric patients: a cross-sectional web-based survey. BMJ Open 11:e047059

    PubMed  PubMed Central  Google Scholar 

  75. Tirelli F, Shafer BM, Davidson SL, Lerman MA (2021) Immunomodulation and TNF-alpha inhibition for tubulointerstitial nephritis and uveitis syndrome: a case series. J AAPOS 25:267.e1-267.e6

    PubMed  Google Scholar 

  76. Moledina DG, Wilson FP, Kukova L, Obeid W et al (2021) Urine interleukin-9 and tumor necrosis factor-alpha for prognosis of human acute interstitial nephritis. Nephrol Dial Transplant 36:1851–1858

    PubMed  Google Scholar 

  77. Hulse M, Rosner MH (2019) Drugs in development for acute kidney injury. Drugs 79:811–821

    CAS  PubMed  Google Scholar 

  78. Kalantari K, Rosner MH (2021) Recent advances in the pharmacological management of sepsis-associated acute kidney injury. Expert Rev Clin Pharmacol 14:1401–1411

    CAS  PubMed  Google Scholar 

  79. Pickkers P, Darmon M, Hoste E, Joannidis M et al (2021) Acute kidney injury in the critically ill: an updated review on pathophysiology and management. Intensive Care Med 47:835–850

    PubMed  PubMed Central  Google Scholar 

  80. Xu Y, Zou P, Cao X (2022) Advances in pharmacotherapy for acute kidney injury. Expert Opin Pharmacother 23:713–726

    CAS  PubMed  Google Scholar 

  81. Endre ZH, Kellum JA, Di Somma S, Doi K et al (2013) Differential diagnosis of AKI in clinical practice by functional and damage biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative Consensus Conference. Contrib Nephrol 182:30–44

    PubMed  Google Scholar 

  82. Goldstein SL, Akcan-Arikan A, Alobaidi R, Askenazi DJ et al (2022) Consensus-based recommendations on priority activities to address acute kidney injury in children: a modified Delphi consensus statement. JAMA Netw Open 5:e2229442

    PubMed  PubMed Central  Google Scholar 

  83. Iwakura T, Fukasawa H, Kitamura A, Ishibuchi K et al (2020) Effect of dipeptidyl peptidase-4 inhibitors on cisplatin-induced acute nephrotoxicity in cancer patients with diabetes mellitus: a retrospective study. PLoS One 15:e0229377

  84. Ambrosi N, Arrosagaray V, Guerrieri D, Uva PD et al (2016) alpha-lipoic acid protects against ischemia-reperfusion injury in simultaneous kidney-pancreas transplantation. Transplantation 100:908–915

    CAS  PubMed  Google Scholar 

  85. Suh SH, Lee KE, Kim IJ, Kim O et al (2015) Alpha-lipoic acid attenuates lipopolysaccharide-induced kidney injury. Clin Exp Nephrol 19:82–91

    CAS  PubMed  Google Scholar 

  86. Du J, Jiang S, Hu Z, Tang S et al (2019) Vitamin D receptor activation protects against lipopolysaccharide-induced acute kidney injury through suppression of tubular cell apoptosis. Am J Physiol Renal Physiol 316:F1068–F1077

    CAS  PubMed  Google Scholar 

  87. Bulger EM, May AK, Robinson BRH, Evans DC et al (2020) A novel immune modulator for patients with necrotizing soft tissue infections (NSTI): results of a multicenter, phase 3 randomized controlled trial of reltecimod (AB 103). Ann Surg 272:469–478

    PubMed  Google Scholar 

  88. Garg AX, Devereaux PJ, Hill A, Sood M et al (2018) Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial. CMAJ 190:E1273–E1280

    PubMed  PubMed Central  Google Scholar 

  89. Correa TD, Takala J, Jakob SM (2015) Angiotensin II in septic shock. Crit Care 19:98

    PubMed  PubMed Central  Google Scholar 

  90. Wan L, Langenberg C, Bellomo R, May CN (2009) Angiotensin II in experimental hyperdynamic sepsis. Crit Care 13:R190

    PubMed  PubMed Central  Google Scholar 

  91. Friedrich JO, Adhikari N, Herridge MS, Beyene J (2005) Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med 142:510–524

    CAS  PubMed  Google Scholar 

  92. Baysal A, Yanartas M, Dogukan M, Gundogus N et al (2014) Levosimendan improves renal outcome in cardiac surgery: a randomized trial. J Cardiothorac Vasc Anesth 28:586–594

    CAS  PubMed  Google Scholar 

  93. Zhou C, Gong J, Chen D, Wang W et al (2016) Levosimendan for prevention of acute kidney injury after cardiac surgery: a meta-analysis of randomized controlled trials. Am J Kidney Dis 67:408–416

    CAS  PubMed  Google Scholar 

  94. Loomba RS, Villarreal EG, Dhargalkar J, Rausa J et al (2022) The effect of dexmedetomidine on renal function after surgery: a systematic review and meta-analysis. J Clin Pharm Ther 47:287–297

    CAS  PubMed  Google Scholar 

  95. Ma S, Evans RG, Iguchi N, Tare M et al (2019) Sepsis-induced acute kidney injury: a disease of the microcirculation. Microcirculation 26:e12483

    PubMed  Google Scholar 

  96. Peng K, McIlroy DR, Bollen BA, Billings FTt, et al (2022) Society of cardiovascular anesthesiologists clinical practice update for management of acute kidney injury associated with cardiac surgery. Anesth Analg 135:744–756

    PubMed  Google Scholar 

  97. Xie Y, Jiang W, Cao J, Xie H (2021) Dexmedetomidine attenuates acute kidney injury in children undergoing congenital heart surgery with cardiopulmonary bypass by inhibiting the TLR3/NF-kappaB signaling pathway. Am J Transl Res 13:2763–2773

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Poyan Mehr A, Tran MT, Ralto KM, Leaf DE et al (2018) De novo NAD(+) biosynthetic impairment in acute kidney injury in humans. Nat Med 24:1351–1359

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Zappitelli.

Ethics declarations

Conflict of interest

MZ receives consultant remuneration from Bioporto Inc. to adjudicate AKI for a study on NGAL; however, this did not impact the conduct or content of this work.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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

Costigan, C., Balgobin, S. & Zappitelli, M. Drugs in treating paediatric acute kidney injury. Pediatr Nephrol 38, 3923–3936 (2023). https://doi.org/10.1007/s00467-023-05956-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-023-05956-4

Keywords

Navigation