Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets

PLoS One. 2016 Feb 12;11(2):e0149013. doi: 10.1371/journal.pone.0149013. eCollection 2016.

Abstract

Objective: To design an experimental pediatric animal model of acute kidney injury induced by cisplatin.

Methods: Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study.

Results: 41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage.

Conclusions: a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury.

Publication types

  • Comparative Study

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / therapy
  • Animals
  • Antineoplastic Agents / toxicity*
  • Cisplatin / toxicity*
  • Disease Models, Animal
  • Female
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiopathology
  • Male
  • Prospective Studies
  • Renal Replacement Therapy
  • Sus scrofa

Substances

  • Antineoplastic Agents
  • Cisplatin

Grants and funding

This study was supported by grant PI12/0128 and PI11-01132 from Carlos III Institute of Health, Spain, and Comunidad Autónoma de Madrid (Consorcio para la Investigación del Fracaso Renal Agudo –CIFRA-) S2010/BMD-2378.