Cis-diamminedichloroplatinum (II) has a marked anti-cancer effect on advanced urogenital neoplasm. However, its nephrotoxicity has been hindering the therapeutic usefulness of this drug. Reduction of acute nephrotoxicity has been achieved by use of pretreatment hydration and mannitol or furosemide diuresis. On the other hand, patients with urogenital neoplasm have many urinary tract complications, such as solitary kidney, various urinary diversion, hydronephrosis and pyelonephritis. Despite these hydration and diuresis, considerable deterioration of renal function occurs in those patients after CDDP treatment.
Renal function in 17 patients with advanced urogenital neoplasm treated with the regimens including CDDP was evaluated retrospectively. Four (23.5%) of the 17 patients showed renal dysfunction during the treatment.
Our study was designed to estimate the values urinary, β
2-microglobulin (β
2MG) and N-acetyl-β-glucosaminidase (NAG) excretion and the fractional excretion of sodium (FE
Na) as a sensitive indicator for prediction and early detection of CDDP nephrotoxicity.
In urogenital cancer patients, NAG and β
2MG excretions rose markedly in early stage of the CDDP treatment. In only one patient that fell into progressive renal insufficiency, extremely high levels of β
2MG and NAG excretions (β
2MG: 21090μg/day, NAG: 44.3unit/day) were noted compared with other patients.
Urinary excretion and renal tissue concentration of NAG were also studied in rat CDDP nephrotoxicity. Each of the rats that received CDDP at a dose of 2, 4 or 8mg/kg/day revealed significantly high urinary NAG excretion in comparison with the control (p<0.05). The NAG concentration in the renal tissue decreased contrarily to the CDDP concentration.
FE
Na is generally considered more helpful than other conventional methods in evaluating renal function in acute renal failure.
Both animal experiments and clinical studies showed that an elevated FE
Na was noted in CDDP induced acute tubular injury.
Furthermore, the patients with deterioration of renal function after the CDDP treatment revealed higher pretreatment levels of FE
Na compared with those showing no renal dysfunction.
It is concluded that the values of FE
Na and urinary N-acetyl-β-glucosaminidase and β
2-microglobulin excretions are sensitive indicators for the early detection of acute tubular damage induced by CDDP.
View full abstract