Pretreatment cystatin C in children with malignancy: can it predict chemotherapy-induced glomerular filtration rate reduction during the induction phase?

J Pediatr Hematol Oncol. 2004 Jun;26(6):336-41. doi: 10.1097/00043426-200406000-00002.

Abstract

Background: Monitoring of kidney function is essential during chemotherapy. Serum creatinine is of limited value in early detection of renal insufficiency. The cystatin C level has been proved to be a good marker for detection of mild reduction in glomerular filtration rate.

Purpose: To evaluate the validity of the pretreatment serum cystatin C level in predicting significant reduction of the glomerular filtration rate during the induction phase of chemotherapy.

Patients and methods: Serum levels of cystatin C and creatinine and corrected creatinine clearance were assessed in 34 children with different types of malignancy just before the start of chemotherapy and again in 33 of them 1 month later. Patients were compared with 14 healthy controls of matched age and sex.

Results: Before chemotherapy, all patients when compared with controls had normal levels of cystatin C (P = 0.1) and creatinine (P = 0.62) and normal corrected creatinine clearance (P = 0.76). One month after chemotherapy, patients showed a significant increase in their cystatin C levels (P < 0.001) and a significant decrease in their corrected creatinine clearance (P < 0.001). However, creatinine levels did not change significantly (P = 0.65). Corrected creatinine clearance negatively correlated significantly with both cystatin C and creatinine levels (r = -0.622, P < 0.001; r = -0.346, P = 0.045, respectively) before chemotherapy and also 1 month after chemotherapy (r = -0.577, P < 0.001; r = -0.45, P = 0.009, respectively). When pretreatment levels of cystatin C and creatinine were used to predict patients who developed a reduction in corrected creatinine clearance of more than 20% after therapy, only the cystatin C level was statistically significant (P = 0.03). A cutoff point of 0.57 mg/L with sensitivity of 77.8%, specificity of 63%, and overall accuracy of 74% was suggested.

Conclusions: Children with malignant diseases develop significant reduction in their glomerular filtration rate during the induction phase of chemotherapy, although their serum creatinine level may not change significantly. Cystatin C, as a more sensitive marker than creatinine for the assessment of glomerular filtration rate, can be used to predict patients who would have a higher risk of renal impairment during the induction phase of chemotherapy and who thus would require more frequent renal function assessment to consider adjustment of the chemotherapy dose if indicated.

MeSH terms

  • Adolescent
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Creatinine / metabolism
  • Cystatin C
  • Cystatins / therapeutic use*
  • Cysteine Proteinase Inhibitors / therapeutic use
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Male
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • ROC Curve
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • CST3 protein, human
  • Cystatin C
  • Cystatins
  • Cysteine Proteinase Inhibitors
  • Creatinine