Early detection of acute cisplatin nephrotoxicity: interest of urinary monitoring of proximal tubular biomarkers

Abstract

BackgroundRenal toxicity induced by cisplatin (CisPt) is a clinical issue in patients with or without chronic kidney disease (CKD). Proximal tubular injury can result in acute kidney injury (AKI), which may compromise the course of chemotherapy and the prognosis. The purpose of this study was to investigate the time course of urinary markers of acute tubulotoxicity and to assess the usefulness of such monitoring in a routine clinical setting.MethodsThis work is an open prospective pilot study carried out among 23 patients receiving a platinum-based chemotherapy. Individual comorbidities, plasma parameters of kidney function (urea, creatinine) and estimated glomerular filtration rate were registered. Urinary excretion of leucine aminopeptidase, neutrophil gelatinase-associated lipocalin, cystatin C, liver fatty acid-binding protein and interleukin-18 were monitored during successive chemotherapy cycles. Episodes of AKI were identified according to KDIGO (Kidney Disease Improving Global Outcomes) 2012 guidelines.ResultsA total of 28 patients were recruited; among them 23 agreed to be part of the study, of whom 18 received CisPt and 5 carbo- or oxaliplatin. Of the 18 CisPt patients, 12 had a preexisting CKD. Sixteen AKI episodes were observed in 13 patients receiving CisPt with a pejorative evolution in seven cases (partial recovery of the renal function); a transient but dramatic increase in urinary biomarkers was observed 3 h after chemotherapy initiation, whereas plasma creatinine rise appeared 72 h after the end of CisPt treatment. Identified precipitating factors included: dehydration due to lack of fluid intake or diuretic use, exposure to high CisPt doses, regular use of nonsteroidal anti-inflammatory drugs and/or iodinated contrast agents and sepsis.ConclusionEven if numerous precipitating factors could be avoided, the monitoring of urinary markers seemed helpful for the early detection of subclinical AKI induced during CisPt chemotherapy.

Betterment of Diclofenac-Induced Nephrotoxicity by Pentoxifylline Through Modulation of Inflammatory Biomarkers

“…et al study showed that IL-18, NGAL, ITG, and VTN sera levels were significantly increased within a short period of renal injury (within h) and return to the normal levels within few days due to partial regeneration of damaged renal tubules [20]. This may explain the insignificant elevated levels of these biomarkers in the present study.…”

Ruthenium(II)/(III) DMSO-Based Complexes of 2-Aminophenyl Benzimidazole with In Vitro and In Vivo Anticancer Activity

“…As shown in Table 3 , the TI of compound ( 2 ) was approximately two-fold higher than the TI of ( 1 ), further suggesting that ( 2 ) has the greatest potential as a cancer-targeting treatment. However, the TI of cisplatin was found to be higher than either ( 1 ) or ( 2 ), despite the platinum drug having significant known side effects in vivo [ 68 , 69 ].…”

Histological, Biochemical, and Hematological Effects of Goniothalamin on Selective Internal Organs of Male Sprague-Dawley Rats

“…For instance, many previous studies reported that Cisplatin is nephrotoxic at the lower end doses of the therapeutic range for clinical use. Acute tubular necrosis, cystic tubular dilatation, tubular regeneration, and renal tissue inflammation were reported when Cisplatin was administered into rats at a dose 7.5 mg/kg of body weight [45]. Other researchers administered a low dose of Cisplatin (0.4 mg/kg) into rats daily for 8 weeks and it resulted in an irreversible kidney injury of acute tubular necrosis, a severe atrophy of glomerulus, and marked dilation of proximal convoluted tubules [46].…”