|Year : 2014 | Volume
| Issue : 3 | Page : 157-161
A comparison between estimates of glomerular filtration rate using technetium-99m-diethylene-triamine-pentaacetic acid clearance and modification of diet in renal disease equation
Amrah Javaid1, Iqbal Munir2, Saghir A Jaffri3, Muhammad H Qazi3, Muhammad K Nawaz2
1 Department of Basic Sciences, College of Medicine, Princess Noura Bint Abdul Rehman University, Riyadh, Saudi Arabia
2 Department of Nuclear Meicine, Shaukat Khanam Memorial Cancer Hospital & Research Center, Lahore, Pakistan
3 Departments of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
|Date of Web Publication||11-Oct-2014|
Department of Basic Sciences, College of Medicine, Princess Noura Bint Abdul Rehman University, Riyadh
Background: More than half of cancer patients have unrecognized renal insufficiency, which is a reduced glomerular filtration rate (GFR) and is a disease complication factor.
Aims and Objectives: The objective of the present study is to compare the accuracy of GFR with two methods, i.e., GFR by Gates' method (gamma camera uptake method with technetium-99m-diethylene-triamine-pentaacetic acid (Tc-99m-DTPA) and GFR by modification of diet in renal disease (MDRD) equation in cancer patients.
Materials and Methods: A total of 50 cancer patients with abnormal serum creatinine were included in the study. 50 age matched cancer patients with normal creatinine, blood urea nitrogen (BUN) and serum albumin were taken as controls. History of patients including site of cancer, chemotherapy regime and dose of chemotherapy was recorded. Serum creatinine was estimated by auto analyzer using Jaffe's method. Glomerular filtration rate (GFR) was calculated using camera based modified gates method with (99mTc-DPTA) and MDRD equation.
Results: Mean age of patients was 50 year. Level of serum creatinine and BUN were significantly increased (P < 0.001) in patients when compared to controls. Level of serum albumin was non-significantly (P > 0.05) decreased in cancer patients and body surface area also increased, but differences were non-significant (P > 0.05) in cancer patients when compared to controls. Mean GFR was estimated by camera based modified gates method which increased in cancer patients as compared to GFR by MDRD equation but differences were not significant (P > 0.05). Cost, time duration and time for reagent preparation was very high using Renogram (Gate's method) as compared to the cost and other factors involved in estimation of GFR by MDRD equation.
Conclusion: It is concluded that the MDRD equation is more suitable, economical and time saving for the estimation of GFR as compared to Renogram using Tc-99m-DPTA. However future prospective studies are required to the estimation of GFR in those tumors, which may cause kidney damage such as cisplatin or carboplatin, methotrexate.
ملخص البحث :
تهدف هذه الدراسة إلى مقارنة دقة معدل الترشيح الكبيبى باستخدام طريقتين ، أحداهما طريقة قيتس(Gates) والأخرى بوصفة تعديل النظام الغذائي لدى مرضى الكلى المصابين بالسرطان. وخلصت الدراسة إلى أن وصفة تعديل النظام الغذائي كانت الأنسب والأرخص كما أنها توفر الزمن لقياس معدل الترشيح الكبيبى مقارنة بالطريقة الأخرى. هناك حاجة لدراسات مستقبلية لقياس معدل الترشيح الكبيبى لدى مرضى السرطان الذين قد تسبب أدوية سيسبلاتين(Cisplatin) وكاربوبلاتين(Carboplatin) وميثوتركسيت(Methotrixate) ضررًا للكلية.
Keywords: Creatinine, glomerular filtration rate, modification of diet in renal disease equation, reno gram, technetium-99m-diethylene-triamine-pentaacetic acid
|How to cite this article:|
Javaid A, Munir I, Jaffri SA, Qazi MH, Nawaz MK. A comparison between estimates of glomerular filtration rate using technetium-99m-diethylene-triamine-pentaacetic acid clearance and modification of diet in renal disease equation. Saudi J Med Med Sci 2014;2:157-61
|How to cite this URL:|
Javaid A, Munir I, Jaffri SA, Qazi MH, Nawaz MK. A comparison between estimates of glomerular filtration rate using technetium-99m-diethylene-triamine-pentaacetic acid clearance and modification of diet in renal disease equation. Saudi J Med Med Sci [serial online] 2014 [cited 2019 Jun 19];2:157-61. Available from: http://www.sjmms.net/text.asp?2014/2/3/157/142504
| Introduction|| |
In cancer patients the spectrum of disease includes acute renal failure, chronic renal failure and tubular disorders. Many solid and hematologic cancers may involve the renal parenchyma resulting in stage IV disease. 
More than half of cancer patients have unrecognized renal insufficiency (RI), which is observed by reduced GFR with normal serum creatinine. Unrecognized RI is associated with an increased risk for chemotherapy associated adverse events in such patients. 
Renal impairment due to nephrotoxic chemotherapeutic agents can result in altered excretion and metabolism of antineoplastic drugs resulting in increased systemic toxicity.  Chemoradiotherapy induced tumor cell lysis with release of intracellular constituents, including potassium, phosphate and nucleic acids. In tumor lysis syndrome, increased level of uric acid may accumulate, leading to intratubular crystallization and renal failure. 
The use of nephrotoxic drugs such as cisplatin is one of the chemotherapeutic agents in the treatment of a variety of solid tumors, however, it has a side effect of nephrotoxicity.  In addition, methotrexate is primarily excreted by the kidneys and estimate of renal function is essential before the use of high-dose therapy.  Carboplatin is eliminated almost entirely by glomerular filtration. The dose can be calculated effectively based on a patient's renal function as defined by the GFR.  Ifosfamide is an alkylating agent known to cause renal tubular dysfunction and acute renal failure. 
There is a need to estimate the renal function of cancer patients invariably. Inadequate dosing may compromise efficacy while overestimation of renal function may impair safety.  Many drugs used in treating cancer are, at least in part, excreted via kidneys, so that renal impairment may not only lead to impaired drug elimination but also potential lethal toxicity. 
Doses of chemotherapeutic drugs are adjusted according to the GFR, i.e., the more reduced the GFR, the lower the treatment dose. GFR can also be estimated using an algorithm that converts plasma creatinine concentration to GFR, e.g., the modification of diet in renal disease (MDRD) equation. 
GFR indicates creatinine clearance (CrCl), i.e., a ratio of the concentration of creatinine in serum and urine. Serum creatinine and CrCl have the leading role in the early diagnosis, monitoring and classification of chronic RI. 
MDRD equation may be used for the estimation of GFR, which is accepted due to its simplicity, economic viability and acceptable performance.  The most commonly used formula is the "4-varibale MDRD," which estimates GFR using four variables: Serum creatinine, age, race and gender.  However a study found that the MDRD equation performed poorly as compared with the reference standard radionuclide GFR using technetium-99m-diethylene-triamine-pentaacetic acid (Tc-99m-DTPA),  where as another study declared renography method not suitable for routine GFR estimation. 
Tc-99m-DTPA is simple but more time consuming for the determination of the glomerular ﬁltration rate (GFR). The technique may allow an accurate monitoring of GFR in cancer patients receiving chemotherapy. Height, actual body weight and serum creatinine were measured and GFR and CrCl is calculated. Nevertheless, it is stated that the Gates' method in Tc-99m-DTPA renography is not suitable for the estimation of GFR in routine practice. Its diagnostic accuracy is debated. Scans by this technique may be challenging and are associated with some radiation exposure. 
Purpose of study
To compare GFR estimation with two methods, i.e., GFR by Gates' method (gamma camera uptake method with Tc-99m-DTPA) and GFR by MDRD equation in cancer patients considering cost, time duration, any effect of radiation and equipment or laboratory availability.
| Materials and methods|| |
A total of 100 cancer patients, 50 with deranged and 50 with normal renal function (based on serum creatinine), receiving nephrotoxic drugs (cisplatin, ifosfamide, carboplatin and methotrexate) and no previous history of renal failure were included in the study. Patients were referred from the Department of Oncology undergoing chemotherapy who were referred to the Department of Nuclear Medicine Shaukat Khanum Memorial Hospital and Research Center, Lahore, Pakistan. All patients gave informed consent. History of patients including site of cancer, chemotherapy regime and dose of chemotherapy was noted. Serum creatinine was estimated by auto analyzer using Jaffe's method. Ultra sound report was also considered for any change in echogenicity of renal parenchyma. GFR was estimated by renography using Tc-99m-DTPA and diet modification using MDRD equation.
Renography using Tc-99m-DTPA
Tc-99m-DTPA was prepared using a commercially available freeze-dried kit (Amersham Health, United Kingdom). The patient was hydrated with 300 ml of water 20 min prior to the examination and laid down on a bed in the supine position. About 180-220 MBq 99mTc-DPTA was given via an antecubital vein and followed by infusion of 20 ml of normal saline. Frames of 128 × 128 matrix were recorded with an online-computer, initially at 2 s for 1 min and then at 30 s for 20 min. The post-injection empty syringe was again counted by the two devices in the same way as pre-injection.
Region of interest (ROI) over each kidney was assigned manually on the frame added from 1 to 3 min following injection. The semilunar background ROI around each kidney was deﬁned and was modiﬁed for the inferior ROIs in the original Gates. The background corrected time-activity curve was generated and the renal uptake of individual kidney for 1 min from 2 to 3 min after the injection was calculated. The GFR (GFR gates) was automatically estimated by a commercially available computer (GMS-5500A/P, Toshiba, Tokyo, Japan) according to the Gates' algorithm. 
For MDRD study diet of all those patients was modified who had abnormal serum creatinine level with decreased GFR (<90 ml/min). In MDRD the protein was restricted to <60 g/day for a person with body weight 70 kg. Modified diet plan included salt, dry fruit and nuts restriction, 2-3 servings or 8 ounces of good quality protein food (fish, lean meat and eggs) daily, cup of milk, yogurt and ice cream/day, used 3 fruits and vegetables 3 servings with low potassium/day, limit for fluids including water, coffee, tea, lemonade, carbonated beverages was to take 6 cups or 48 ounces/day. No restriction for margarine used for cooking. The total calorie intake of patients was restricted to 40-45 kcal/kg/day. GFR was calculated by formula. 
GFR (mL/min/1.73 m 2 ) = 186 × Serum creatinine−1.154 × Age−0.203
Data was entered and analyzed by using Statistical Package for the Social Sciences IBM SPSS-14.0. All quantitative variables were expressed as mean ± standard deviation. Data was compared by using Student t-test. P < 0.05 was considered to be statistically significant.
| Results|| |
Age and kidney function related parameters in cancer patients are tabulated in [Table 1]. It was observed that the mean age of patients was 50 year and of control was 42 year. Level of serum creatinine and blood urea nitrogen were significantly increased (P < 0.001) in patients as compared to controls. Level of serum albumin decreased non significantly (P > 0.05) in cancer patients and body surface area (BSA) also increased non significantly (P > 0.05) in cancer patients as compared to the controls.
Comparison of Renogram (Gate's method) and MDRD equation are presented in [Table 2]. Mean GFR by Renogram using Tc-99m-DTPA increased in cancer patients as compared to GFR by MDRD equation, but no significant differences were observed. Cost, time duration and time for reagent preparation was very high for Renogram (Gate's method) as compared to the cost and other estimates of MDRD equation.
| Discussion|| |
As an increasing number of patients are treated with curative chemotherapy, there are more long-term survivors in the general population.  Follow-up of these long-term survivors of cancer patients is done with several intended endpoints, which tend to vary. Broadly, they include detection of recurrence with the intention of offering early salvage therapy, recognition and management of treatment induced complications, the somewhat more difficult to measure psychological benefits of continued medical involvement from the patients prospective.  In this study, calculating GFR with 99mTc-DTPA in adult patients has assessed the nephrotoxic effects of chemotherapy.  The main nephrotoxic chemotherapeutic agents used in adult are cisplatin, carboplatin, ifosfamide and methotrexate. Acute nephrotoxicity is a major side effect of these chemotherapeutic drugs chronic nephrotoxicity appears to be a relatively rare complication except in patients with pre-existing renal disease.  Monitoring such, patients with serial urinalysis, serum creatinine concentrations and calculation of GFR is the most reliable way to screen for nephrotoxicity. 
From our results after applying statistical tests on the data, we found that in control group (Group C) who has 50 patients with normal value of serum creatinine the mean estimated GFR (eGFR) by renogram using 99mTc DTPA is 86.87 ± 21.07 ml/min/1.73 m 2 . While the mean eGFR of the same patient's group when calculated by using MDRD equation was 87.30 ± 20.58 ml/min/1.73 m 2 . After applying multiple comparison tests on data we found that difference between the eGFR by 99mTc DTPA and MDRD method the significance difference is 0.905 (P > 0.05) which means there is no significant statistical difference in both methods to calculate eGFR in normal healthy population with normal value of serum creatinine [Graph 1] [Additional file 1].
After plotting the graph [Graph 1] we can clearly appreciate that the MDRD equation tends to slightly overestimate the eGFR at higher value. The cut-off of eGFR value from which onwards tends to overestimate the eGFR is 80 ml/min/1.73 m 2 as reported in the literature as well.  However when we looked at our raw data we found that there is not more than 11 ml/min/1.73 m 2 which is of patient no 5 who's eGFR by renogram is 120 ml/min/1.73 m 2 but by MDRD equation it is 131 ml/min/1.73 m 2 .
In the experimental group (Group E) 50 patients, most of these were in stage 3 and 4 according to abnormal value of serum creatinine the mean eGFR by renogram using 99mTc DTPA is 38.26 ± 14.79 ml/min/1.73 m 2 . Although the mean eGFR of the same patient's group when calculated by using MDRD equation was 36.58 ± 14.57 ml/min/1.73 m 2 . After applying multiple comparison tests on data we found that difference between the eGFR by 99mTc DTPA and MDRD method the significance difference is 0.642 (P > 0.05) which means there is no significant statistical difference in both methods to calculate eGFR in diseased population with abnormal value of serum creatinine [Graph 2] [Additional file 2].
In the experimental group [Graph 2] we can interpret that the value of eGFR is the almost the same either estimated using MDRD Eq. or renogram using 99mTc DTPA. From the graph we can see how well GFR by MDRD equation matches the GFR value of renogram. This clearly indicates that MDRD equation for calculating GFR value in the group of patients with abnormal serum creatinine is as good, though the value of P is lower in the experimental group than the control group which in other words supports the hypothesis that the MDRD equation is more accurate in calculating the eGFR in disease patients with abnormal serum creatinine rather than healthy subjects with normal creatinine levels. But still MDRD can accurately measure the eGFR in healthy subjects. ,
Furthermore the factors associated with creatinine excretion, such as age, sex and BSA, are also well-addressed in the MDRD equations. The MDRD equation is not only accurately measures the GFR in the population with normal serum creatinine as mentioned in the Graph 1, but also measures it accurately in the experimental group [Graph 2] as good as renogram with 99mTc-DTPA.
| Conclusion|| |
It is therefore concluded that the MDRD equation is more suitable for the estimation of GFR as compared to Renogram using Tc-99m-DPTA. However future prospective studies are required for the estimation of GFR in those tumors, which may cause kidney damage such as cisplatin or carboplatin, methotrexate or other drugs.
| References|| |
Humphreys BD, Soiffer RJ, Magee CC. Renal failure associated with cancer and its treatment: An update. J Am Soc Nephrol 2005;16:151-61.
Lotan E, Leader A, Lishner M, Gottfried M, Pereg D. Unrecognized renal insufficiency and chemotherapy-associated adverse effects among breast cancer patients. Anticancer Drugs 2012;23:991-5.
Ronald JH, Susan FU, Kevin V, Ronold PO, George SC. National Kidney Foundation's Kidney disease out comes quality initiative clinical practice guideline for chronic kidney disease in children and adolescence: Evaluation, Classification and Stratification. Am J Kidney Dis2009;39:S1-266.
Ronco C, Bellomo R, Inguaggiato P, Bonello M, Bordoni V, Salvatori G, et al
. Rasburicase therapy in acute hyperuricemic renal dysfunction. Contrib Nephrol 2004;144:158-65.
Mohamed HE, El-Swefy SE, Mohamed RH, Ghanim AM. Effect of erythropoietin therapy on the progression of cisplatin induced renal injury in rats. Exp Toxicol Pathol 2013;65:197-203.
Amin A, Effat D, Goher N, Ramadan B. Tc-99m diethylenetriamine-pentaacetic acid (DTPA): Is it reliable for assessment of methotrexate-induced cumulative effect on renal filtration in rheumatoid arthritis patients? Rheumatol Int 2013;33:3059-63.
Collins IM, Roberts-Thomson R, Faulkner D, Rischin D, Friedlander M, Mileshkin L. Carboplatin dosing in ovarian cancer: Problems and pitfalls. Int J Gynecol Cancer 2011;21:1213-8.
Berns JS, Haghighat A, Staddon A, Cohen RM, Schmidt R, Fisher S, et al
. Severe, irreversible renal failure after ifosfamide treatment. A clinicopathologic report of two patients. Cancer 1995;76:497-500.
Marx GM, Blake GM, Galani E, Steer CB, Harper SE, Adamson KL, et al
. Evaluation of the Cockroft-Gault, Jelliffe and Wright formulae in estimating renal function in elderly cancer patients. Ann Oncol 2004;15:291-5.
Wright JG, Boddy AV, Highley M, Fenwick J, McGill A, Calvert AH. Estimation of glomerular filtration rate in cancer patients. Br J Cancer 2001;84:452-9.
Hartlev LB, Boeje CR, Bluhme H, Palshof T, Rehling M. Monitoring renal function during chemotherapy. Eur J Nucl Med Mol Imaging 2012;39:1478-82.
Soldo F, Brzak M, Vrkić N. Compensated creatinine method and glomerular filtration rate estimation in a heterogeneous population of patients. Acta Med Croatica 2012;66:179-91.
Woods LL. Intrarenal mechanisms of renal reserve. Semin Nephrol 1995;15:386-95.
Craig AJ, Samol J, Heenan SD, Irwin AG, Britten A. Overestimation of carboplatin doses is avoided by radionuclide GFR measurement. Br J Cancer 2012;107:1310-6.
Itoh K. Comparison of methods for determination of glomerular filtration rate: Tc-99m-DTPA renography, predicted creatinine clearance method and plasma sample method. Ann Nucl Med 2003;17:561-5.
Gibson P, Shammas A, Cada M, Licht C, Gupta AA. The role of Tc-99m-DTPA nuclear medicine GFR studies in pediatric solid tumor patients. J Pediatr Hematol Oncol 2013;35:108-11.
Thrall JH, Jains PO, Harvey AZ. Practical Nuclear Medicine. 3 rd
ed. : Springer USA ; 2005. p. 205-20.
Li Y, Tang X, Zhang J, Wu T. Nutritional support for acute kidney injury. Cochrane Database Syst Rev 2012;8:CD005426.
Launay-Vacher V, Oudard S, Janus N, Gligorov J, Pourrat X, Rixe O, et al
. Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: The renal insufficiency and anticancer medications (IRMA) study. Cancer 2007;110:1376-84.
Luo CW, DU X, Weng JY, Wu SJ, Guo R, Lu ZS, et al
. A retrospective study of kidney insufficiency in adult patients after myeloablative allogeneic hematopoietic stem cell transplantation. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2012;20:671-5.
Cochran M, St John A. A comparison between estimates of GFR using [99mTc]DTPA clearance and the approximation of Cockcroft and Gault. Aust N Z J Med 1993;23:494-7.
Gupta SK, Singla S, Bal C. Renal and hematological toxicity in patients of neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-DOTATATE. Cancer Biother Radiopharm 2012;27:593-9.
Poole SG, Dooley MJ, Rischin D. A comparison of bedside renal function estimates and measured glomerular filtration rate (Tc99mDTPA clearance) in cancer patients. Ann Oncol 2002;13:949-55.
Kletzel M, Pirich L, Haut P, Cohn RA. Comparison of Tc-99 measurement of glomerular filtration rate vs. calculated creatinine clearance to assess renal function pretransplant in pediatric patients undergoing hematopoietic stem cell transplantation. Pediatr Transplant 2005;9:584-8.
Buron F, Hadj-Aissa A, Dubourg L, Morelon E, Steghens JP, Ducher M, et al
. Estimating glomerular filtration rate in kidney transplant recipients: Performance over time of four creatinine-based formulas. Transplantation 2011;92:1005-11.
[Table 1], [Table 2]