Urinary Endothelin-1-Like Immunoreactivity in Young Male Patients with Testicular Cancer Treated by CIS-Platinum: Comparison with other Urinary Parameters

Abstract

1. Urinary excretion of endothelin-1-like immunoreactivity and urinary excretion of other parameters (beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase and microalbumin) were measured before, within 1 week after and 2 weeks after the administration of cis-platinum in five young male patients with testicular cancer (mean age 33.0 years) and were compared. 2. Urinary endothelin-1-like immunoreactivity/creatinine during, 1 week after, and 2 weeks after cis-platinum treatment was significantly higher than before cis-platinum. There was no difference in urinary endothelin-1-like immunoreactivity/creatinine during, 1 week after and 2 weeks after cis-platinum. 3. Among the four parameters, urinary endothelin-1-like immunoreactivity/creatinine showed the highest level after cis-platinum treatment. Urinary beta 2-microglobulin/creatinine most rapidly returned to normal levels after cis-platinum. 4. Although urinary endothelin-1-like immunoreactivity/creatinine did not show any significant correlations with urinary N-acetyl-beta-D-glucosaminidase (r = 0.291, not significant) or urinary microalbumin/creatinine (r = 0.076, not significant), it showed a significant correlation with urinary beta 2-microglobulin/creatinine (r = 0.475, P < 0.05). 5. These results suggest that endothelin-1 may be a sensitive urinary parameter in detecting cis-platinum-induced renal tubular injury.

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

“…21 Since urinary albumin excretion is also an indicator of glomerular injury, very large and/or delayed increases in urinary albumin may reflect more extensive damage to the entire nephron. 23,24,28 Nonetheless, the current data largely support maximal increases in urinary albumin concentrations within 4 to 10 days after cisplatin infusion in patients with clinical and subclinical AKI (Table 1).…”

“…41 Furthermore, another report suggested that urinary NAG concentrations may return to baseline as early as 2 weeks after cisplatin treatment. 23 Interestingly, there was no evidence of an increase in baseline NAG levels after additional courses of cisplatin treatment (up to 6). 22,32,34 NAG, similar to B2M, did not correlate with accumulated cisplatin dose.…”

“…After cisplatin infusion, urinary albumin concentrations were elevated as early as 4 h, 21 with a peak between 4 and 10 days and decline from the peak value around or before two weeks. [22][23][24] The magnitude of increases in albumin excretion from baseline varied greatly across clinical studies and populations of patients. In one set of patients (n ¼ 14) receiving cisplatin therapy at a dose of 20 mg/m 2 daily for 5 days, urinary albumin concentrations were elevated (2.9-fold) within 5 days after infusion compared to pretreatment levels and concentrations observed in healthy control subjects.…”

“…31,32,39 Nonetheless, increases in urinary B2M following cisplatin therapy occur as early as 12 h 32 and generally peak between 3 and 6 days (Table 2). 25,27,31,33,40 Urinary B2M levels decline about 1 to 2 weeks after cisplatin administration 23,25,29,40 and are in the normal range at least three months after cessation of cisplatin-containing chemotherapy (n ¼ 35). 41 The magnitude of B2M elevation is attenuated with successive cycles of chemotherapy, 27,32,34 although no significant correlations were observed between previous exposure to cisplatin, the dose of cisplatin, and urinary B2M levels.…”

Guidelines for treatment of renal injury during cancer chemotherapy 2016

“…Endothelin-1 is a 21-amino acid protein that possesses a vasoconstrictor effect; in the kidneys, it is expressed in mesangial cells and collecting ducts. Takeda et al [ 79 ] measured urinary endothelin-1-like immunoreactivity/Cr before and 1 and 2 weeks after cisplatin treatment; these authors reported that urinary endothelin-1-like immunoreactivity/Cr was significantly increased at 1 and 2 weeks after cisplatin treatment compared to pretreatment levels. Following cisplatin treatment, β2 microglobulin/Cr and endothelin-1-like immunoreactivity/Cr peaked on day 2 and subsequently declined, whereas NAG/Cr peaked on day 6.…”