ABSTRACT
Experimental evidence suggests that anthracyclines, widely used in cancer chemotherapy, may impair kidney function. We assessed kidney function by serum creatinine, urinary N-acetyl-beta-D-glucosaminidase activity indices (NAGi) and microalbuminuria (MA) in 160 serum and urine samples obtained from 66 children with cancer. The effect of dexrazoxane was analyzed in 6 children on dexrazoxane supportive therapy in conjunction with daunorubicin (DNR) treatment, as compared with 6 children not receiving this agent. NAGi was significantly (p<0.05) elevated after treatment by DNR, doxorubicin, epirubicin (EPI) and idarubicin (IDA). MA proved to be a less sensitive indicator of kidney damage than NAGi. DNR resulted in a progressive deterioration of proximal tubular function as determined by linear regression analysis. The mean NAGi in the dexrazoxanetreated group was significantly (p<0.005) lower than in children not receiving dexrazoxane prior to DNR treatment. In conclusion, our study demonstrated that DNR, EPI and IDA induced an acute renal tubular damage similar to known tubulotoxic agents as cisplatin, carboplatin, cyclophosphamide and ifosfamide. The damage was clinically mild and only a minor proportion of patients can be expected to develop long-lasting tubulopathy with negative impact on the quality of life.
Subject(s)
Anthracyclines/adverse effects , Antibiotics, Antineoplastic/adverse effects , Kidney Diseases/chemically induced , Lymphoma, Non-Hodgkin/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Acetylglucosaminidase/urine , Adolescent , Adult , Albuminuria/chemically induced , Albuminuria/metabolism , Albuminuria/prevention & control , Anthracyclines/therapeutic use , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Creatinine/blood , Daunorubicin/adverse effects , Daunorubicin/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Epirubicin/adverse effects , Epirubicin/therapeutic use , Female , Humans , Idarubicin/adverse effects , Idarubicin/therapeutic use , Infant , Kidney Diseases/metabolism , Kidney Diseases/prevention & control , Kidney Tubules, Proximal/drug effects , Male , Razoxane/therapeutic use , Retrospective StudiesABSTRACT
Antineoplastic chemotherapy is associated with nephrotoxic side effects. Data on nephrotoxicity in childhood cancer are scanty, in part because of the difficulties in obtaining reliable markers of glomerular function. We used serum cystatin C (cysC) to assess glomerular function. CysC was compared with serum creatinine concentration (S(Cr)), the endogenous creatinine clearence ( C(Cr)), and the calculated Counahan formula ( C(Counahan)) in children with leukemia and solid tumors. CysC was measured by particle-enhanced immunoturbidimetric assay. Serum and urinary creatinine concentrations were determined by the Jaffé method. Samples were obtained from 258 children, including 92 receiving anticancer chemotherapy, 108 long-term survivors, 40 children without any renal disease, and 18 patients with chronic renal insufficiency. CysC of patients on current chemotherapy was assessed both before and after treatment. Significant correlations were found between cysC and S(Cr) and between 1/cysC and C( Counahan). CysC increased significantly after cisplatin, methotrexate, cyclophosphamide, ifosfamide, and multimodality treatment. Our results suggest that cysC measurement can be used to characterize glomerular function in children with cancer.
