The significance of enzymuria in assessing the nephrotoxicity of antitumor chemotherapy in children

Abstract

The significance of enzymuria in assessing the nephrotoxicity of cisplatin in a total dose of 100 mg/m 2 or iphosphamide in a total dose of 9 g/m 2 for children with solid malignant tumors (10 and 9 patients, respectively) was studied. Chemotherapy caused stable hyperenzymuria consisting in a significant increase in N-acetyl-lS-D-hexosaminidase, 7-glutamyltransferase, and alanine aminopeptidase activities in the urine during chelnotherapy in comparison with the initial values. The levels of enzyme excretion with the urine were higher in patients treated with iphosphamide than in those treated with cisplatin. The increase in serum creatinine and urea concentrations vs. the age-specific noru~ was obsen,ed in only 2 out of 9 children treated with iphosphamide. These results permit considering enzymuria as the most sensitive method for the diagnosis of nephrotoxicity. Key Words: chemotherapy; nephrotoxicity; urine enzymesThe therapeutic effect of antitumor drugs is often associated with toxic effects on various organs and systems. Nephrotoxicity characteristic of the platinum preparations, iphosphamide, and other cytostatics is a complication limiting the drug dose. Biochemical parameters routinely used for the diagnosis of toxic involvement of the kidneys, primarily nitrogen-containing serum compounds urea and creatinine, are not vein informative. Measurements of the urinary enzymes have been recently used for the diagnosis of renal involvement caused by toxic effects of antitumor, antibacterial, and other drugs [1,6,8,10]. Biochemical analysis of urine for early detection of nephrotoxicity of antitumor therapy is particularly ilnpoJtant in pediatric oncology, since the proposed method is noninvasive. The aim of this study was to assess the significance of biochemical parametel~ of blood serum and urine for timely diagnosis of nephrotoxicity in children with solid tumors receiving chelnotherapy. MATERIALS AND METHODSThe nephrotoxicity of chemotherapy protocols including iphosphalnide and cisplatin has been assessed by biochemical analysis of the blood and urine in :19 children (10 boys and 9 girls) aged 5-16 yeal~ before, during, and after chemotherapy. The children were followedup from 2 weeks to 3 months, during this period they were administered 1-3 5-day courses at 3-4-week hltervals. Nine children with nephroblastoma relapses (n=3), nephroblastoma (n=2), rhabdonayosarcoma (n=3), and disseminated Ewing's sarcoma (n=l) were treated by iphosphalnide-based protocols including iphosphamide in a total dose of 9 g/m 2 per course, vepeside (500 rag/m2), and carboplatin (450 1rig/m2). Ten children with osteogenic sarcoma (n=4)

Lysosomal exoglycosidases in the urine of children and adolescents

“…It is worth noting that HEX activity in the urine of children with early-stage diabetic nephropathy is 2-fold higher compared to healthy children (35) . Liubimova et al found HEX to be a more sensitive marker of cytotoxic drug-induced renal tubular damage than urea or albumin/creatinine ratio (36,37) . Urinary activity of HEX may help assess therapeutic outcomes in alcoholism (38) .…”

Complex Monitoring of Biochemical and Radionuclide Parameters in Patients with Metastatic Renal Cell Carcinoma during Immunotherapy

“…In this regard, the search for the most accurate biomarkers that would allow for early diagnosis of CKD and establishing the cause of its development is of current concern. At the moment, a number of biomarkers associated with nephrotoxicity are known, but FDA (Food and Drug Administration) and EMEA (European Medicines Agency) have approved only KIM-1 (kidney injury molecule-1), albumin, total protein, β 2-microglobulin, cystatin C, clusterin, and TFF3 (trefoil factor 3) for routine use in practice [ 10 , 11 ].…”

Nephrourological monitoring technology based on functional radionuclide tests: Functions of an automated workplace

“…In particular, these studies deal with the problem of early hydronephrotic transformation of the kidney [7,25], mechanisms of development of chronic and acute renal insufficiency [4,14,18], and the problem of nephrotoxic lesions caused by chemotherapy of malignant tumors [13,20,24,30,321.…”

“…This is a very considerable burden on the urinary system. Therefore, dysfunctions of the urinary system should be detected and corrected before applying intense oncological therapy [13,20,24,30,32,33].…”