Detection of Early Cisplatin Induced Nephrotoxicity by Serial Estimation of Glomerular Filtration Rate: Comparison of Various Methods

Background and Aims:

Cisplatin is an effective agent for the treatment of solid tumors and nephrotoxicity isits serious side effect. This nephrotoxicity is dose dependent and results in debilitating renal failure. The aim of this study was to determine the early nephrotoxicity by serial estimation of glomerular filtration rate (GFR) using plasma two sample clearance method (PSC2) as the reference method and compared with other methods.

Methods:

Thirty three patients (26 males and 7 females; mean age 45 ±14 yrs) with different solid tumors whowere scheduled to receive cisplatin (mean dose of 114 ±23 mg/m2) in each cycle. GFR was determined simultaneously by 6 methods; (1) 24 Hours Creatinine Clearance (24HCrCl); (2) Gamma camera uptake method after 99mTc-diethylene triamine pentaacetic acid (DTPA) injection (Gates method); (3) Predicted creatinine clearance by Modification of Diet and Renal Diseases (MDRD); (4) Cockcroft-Gault's equation (CG's); (5) PSC 2; (6) Plasma one Sample Clearance method after 99mTc-DTPA injection (PSC 1). PSC 2 was chosen as reference method.

Results:

Three out of thirty three patients developed severe acute nephrotoxicity (GFR <50 ml/min). In remaining 30 patients, average fall in GFR after 6th cycle of cisplatin was 43.86 ± 16.10 ml/min/1.73 m2 (p <0.001) estimated by PSC2 which was more significant after 3rd cycle. Correlation coefficient (r) for PSC1, Gates, 24HCrCl, CG's and MDRD methods were 0.95, 0.91, 0.51, 0.59 and 0.67 respectively.

Conclusions:

GFR is the most sensitive indicator of early cisplatin induced nephrotoxicity and PSC1 andGates method are reliable substitute of PSC2 method. CG's, MDRD and 24 HCrCl methods are not reliable for detection of early nephrotoxicity. It is recommended that serial GFR should be estimated before and after every cisplatin dose, if not possible, than at least after the third cycle for precise detection of early nephrotoxicity.