Cisplatin Induced Renal Insufficiency Measured by Glomerular Filtration Rate with 99 mTc-DTPA and by using Serum Creatinine based Formulae: A Prospective Study

IntrOductIOnCisplatin also known as Cis-Diammine-Dichloroplatinum (CDDP) is a chemotherapeutic alkylating nephrotoxic agent.Cisplatin is used as standard chemotherapy in concurrent setting in different sites like head and neck cancer, cervical cancer and other cancers [1,2].Coughlin CT and Richmon RC and Douple EB suggested treatment efficacy of cisplatin by two mechanisms [3,4].In cells, binding of platinum to DNA inhibits repair of sublethal damage as well as transcription of cytoplasmic proteins thus causing cytotoxic effects.In kidney, cisplatin is freely filtered as well as secreted by tubular cells.Acute toxicity is mainly reflected by proximal tubular dysfunction [5,6].However, cisplatin induced acute nephrotoxicity is dose limited, but can be prevented with adequate hydration.There is a little doubt that repeated infusion of cisplatin may lead to chronic RI.However, according to the literature, kidney function seems to stabilize on a lower func tional level with no or very little further deterioration after completion of chemotherapy [7][8][9].Renal function may worsen with increasing age, co-morbities like diabetes and hypertension, acute loss of weight and muscle mass, dehydration and long term use of non-steroidal inflammatory drugs and after some malignancies like multiple myeloma [10,11].Therefore renal function assessment is important and can be done by glomerular filtration rate using dGFR.Such a method uses technetium-99 m-diethyl-triamine-penta-acetic acid ( 99 mTc-DTPA).In dGFR method 99 mTc-DTPA is injected into the patient.It emits X-rays which are picked up by gamma camera and converted into electronic signals.These signals reflect renal functional status.Other methods are SCR levels and eGFR.The eGFR is calculated by indirect mathematical formulae such as CG [12][13][14] and aMDRD [15] which are based on SCR levels and patient's body weight, height, age and ethnicity.Cockcroft-Gault (CG) formula: CrCl (mL/min) = k x {(140 -age) x weight (kg)} / SCR (μ mol/L), Where k = 1.23 (male) or 1.04 (female).aMDRD formula: GFR (mL/min/1.73m 2 ) = k x 186 x (SCR)-1.154x (age)-0.203,Where k = 1 (men) or 0.742 (women), GFR indicated glomerular filtration rate and SCR is measured in mg/dl.In India, to the best of our knowledge, there is no prospective study that documents the incidence of RI before and after cisplatin infusion [16][17][18][19][20]. Therefore, we conducted a prospective study in patients who were planned to receive cisplatin with the aim to study the incidence of RI before and after CDDP and to correlate dGFR and eGFR. MAterIAls And MethOdsThis prospective study was done in the Department of Radiotherapy and Nuclear Medicine at a tertiary care hospital between August 2013 to November 2015.Clearance was sought from the institutional ethics committee and all patients were required to sign informed consent form.We included histopathologically proven previously untreated 64 consecutive patients of locally advanced stage (III or IV) head and neck or uterine cervix cancers.Cisplatin based