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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 8  |  Page : 56-59

A prospective study to compare the measured glomerular filtration rate compared to estimated glomerular filtration rate in patients undergoing definitive chemoradiation, with platinum agents for various malignancies


Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Date of Web Publication22-Mar-2019

Correspondence Address:
Dr. Vikas Asati
Room No. 214, PG Mens Hostel, Kidwai Memorial Institute of Oncology, Near NIMHANS, Bengaluru - 560 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.204881

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 > Abstract 


Context: Renal function assessment is of paramount importance before using the platinum agents especially cisplatin. Glomerular filtration rate (GFR) estimation by diethyl-triamine-penta-acetic acid (DTPA) scan (measured GFR [mGFR]) is considered gold standard.
Aims: The aim of this study is to know if we can replace the mGFR with the GFR estimation with Cockcroft–Gault formula (eGFR) in patients undergoing chemoradiation.
Settings and Design: This is a prospective, descriptive study.
Subjects and Methods: Patients who are planned for definitive chemoradiation will be eligible for the study. Renal function will be measured DTPA scan and Cockcroft–Gault (CG) formula. Subgroup analysis based on the weight, age, and sex will be done.
Statistical Analysis Used: Demographic and renal function parameters were analyzed using summary measures. To test the significance of the difference between mGFR and cGFR, a paired t-test will be used; to look for an association between various estimates of renal function, the Pearson's correlation coefficient will be calculated using a two-tailed test.
Results: Median mGFR of patients was 82.7 (range: 65–125 ml/min, standard deviation [SD] =14.0 ml/min) while the median eGFR as per the CG formula was 83.9 ml/min (range: 37–137 ml/min, SD = 24.4 ml/min). The median mGFR was only 1.2 ml/min lesser when measures by the CG formula with no significance difference between them (P = 0.66, 95% confidence interval: −4.5–6.3).
Conclusions: We concluded that in resource-limited setting eGFR using CG formula can replace mGFR, especially in patients with age <60 years. Although weight did not showed a significant difference by two methods, a study with large sample is needed to confirm the result.

Keywords: Chemoradiation, cisplatin, Cockcroft–Gault formula, estimated glomerular filtration rate, measured glomerular filtration rate


How to cite this article:
Rudresh A, Asati V, Lakshmaiah K, Lokanatha D, Babu S, Rajeev L, Lokesh K, Babu G. A prospective study to compare the measured glomerular filtration rate compared to estimated glomerular filtration rate in patients undergoing definitive chemoradiation, with platinum agents for various malignancies. J Can Res Ther 2019;15, Suppl S1:56-9

How to cite this URL:
Rudresh A, Asati V, Lakshmaiah K, Lokanatha D, Babu S, Rajeev L, Lokesh K, Babu G. A prospective study to compare the measured glomerular filtration rate compared to estimated glomerular filtration rate in patients undergoing definitive chemoradiation, with platinum agents for various malignancies. J Can Res Ther [serial online] 2019 [cited 2020 Nov 28];15:56-9. Available from: https://www.cancerjournal.net/text.asp?2019/15/8/56/204881




 > Introduction Top


Platinum agents (cisplatin and carboplatin) are commonly used as a radiosensitizer in the treatment of carcinoma cervix as well as head and neck cancer patients receiving the concurrent chemoradiotherapy as definitive treatment. Nephrotoxicity[1] is an important side effect of platinum agents and hence renal function assessment is of paramount importance before using them. Renal function can be measured directly by measuring the measured glomerular filtration rate (mGFR) using radioisotope and indirectly by estimated GFR (eGFR) using mathematical formulae “abbreviated modification of diet in renal disease (aMDRD)” and “Cockcroft–Gault (CG).” eGFR based on serum creatinine is now widely reported by clinical laboratories and is available in most clinical encounters as a “ first line” test of kidney function. mGFR using urinary or plasma clearance of exogenous filtration markers is considered the gold standard for evaluation of kidney function but is not routinely available because of the complexity of measurement protocols.

In the present study, our aims are to prospectively compare the renal function as measured by mGFR using technetium-99m diethyl-triamine-penta-acetic acid (Tc-99m DTPA) scan, with the eGFR calculated by CG formula in patients planned for definitive concurrent chemoradiation and to find out the appropriate subgroup of patients where we can substitute the cGFR with mGFR.


 > Subjects and Methods Top


Study

This is a prospective observation study carried out at Kidwai Memorial Institute of Oncology Bengaluru, India from July 2015 to July 2016. The patients of gynecological malignancy (carcinoma cervix, carcinoma vault, etc.) and head and neck cancer who are planned for definitive concurrent chemoradiation are enrolled in the study. Written consent taken from all patients before starting any chemotherapy.

Exclusion criteria: patients with the following characteristics are excluded from the study:

  1. Baseline deranged renal function (as measured by serum creatinine >1.5 mg/dl)
  2. Abnormal renal imaging (as assessed by ultrasonography [USG] or computed tomography [CT] scan)
  3. Patients with history of diabetes and systemic hypertension or any other comorbidity which can affect renal function.


Method

The relevant clinical history and examination were done on all the patients. All patients underwent all routine blood investigations (complete blood count, serum urea, creatinine, and liver function test). Imaging USG abdomen or CT scan was performed for as the clinical situation and any baseline renal abnormality detected by imaging is ruled out in all patients. mGFR is measured in all patients by plasma clearance of radioisotope Tc-99m DTPA scan. eGFR is measured using CG formula ([140 − age] × weight/serum creatinine × 72), multiply with 0.85 if female.

Chemotherapy is administered weekly at dose of cisplatin 40 mg/m2 or carboplatin area under the curve 2 along with radiotherapy. Radiotherapy is given 5 days a week from Monday to Friday.

As the weight, age, and sex are the three important parameters to calculate GFR as per the CG formula, subgroup analysis based on these factors will be analyzed.

Statistical analysis

Demographic and renal function parameters were analyzed using summary measures. To test the significance of difference between mGFR and cGFR, a paired t-test will be used; to look for association between various estimates of renal function, the Pearson's correlation coefficient will be calculated using a two-tailed test.


 > Results Top


One hundred patients were enrolled in the study and considered evaluable in study. The median age of the patients was 51.9 years (range: 31–80 years, standard deviation [SD] =10.4 years). Fifty-nine patients were female while 41 patients were male. Median weight of the patients was 49.6 kg (range: 30–72 kg, SD = 9.9 years). Median mGFR of patients was 82.7 (range: 65–125 ml/min, SD = 14.0 ml/min) while the median eGFR as per the CG formula was 83.9 ml/min (range: 37–137 ml/min, SD = 24.4 ml/min). The median mGFR was only 1.2 ml/min lesser when measures by the CG formula with no significance difference between them (P = 0.66, 95% confidence interval [CI]: −4.5–6.3).

Subgroup analysis based on age, weight, and sex is done into two ways. Both the methods are compared separately and then with each other. We find that the mGFR does not vary significantly with age, weight, and sex as shown in [Table 1]. The eGFR clearly underestimates GFR when the age is more than 60 years (69.6 ± 19.4 vs. 89.5 ± 24.1 ml/min, P = 0.001). eGFR overestimates the GFR in patients having weight more than 50 kg (90.1 ± 23.6 vs. 77.2 ± 23.9 ml/min, P = 0.015).
Table 1: Estimated glomerular filtration rate and measured glomerular filtration rate based on patient's age, sex, and weight

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Although the mGFR and eGFR did not have significant difference, it is not same in all subgroups [Table 2].
Table 2: Correlation between estimated glomerular filtration rate and measured glomerular filtration rate based on patient's age, sex, and weight

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Patients with age <60 years mGFR and eGRF do not have significant difference with mean mGFR 83.3 ± 14.3 ml/min and mean eGFR 89.5 ± 24.1 ml/min (P = 0.063 95% CI: −0.33–12.62). While in the patients with age ≥60 years, there is a significant difference between the two methods with mean mGFR of 81.25 ± 13.4 ml/min and eGFR 69.6 ± 19.4 ml/min (P = 0.001, 95% CI: −18.36 to −4.98).

Patients with weight less than 50 kg mGFR and eGRF do not have a significant difference with mean mGFR 81.2 ± 11.4 ml/min and mean eGFR 77.2 ± 23.9 ml/min (P = 0.283 95% CI: −11.41–3.40). Same in the patients with weight equal to or more than 50 kg, there is no significant difference between the two methods with mean mGFR 84.2 ± 16.0 ml/min and eGFR 90.1 ± 23.6 ml/min (P = 0.111, 95% CI −1040–13.24).


 > Discussion Top


Platinum compound, especially cisplatin, is a well-known nephrotoxic agent used in clinical oncology during chemoradiation; hence, the calculation of GFR is single most important factor for renal toxicity prevention. The mechanism of cisplatin nephrotoxicity is thought to be renal tubular damage by uptake into the S3 segment of the proximal tubule through the organic cation transporter-2 and the copper transporter 1. For widespread clinical application, the assessment of renal function needs to be accurate, convenient, and inexpensive. An accurate, noninvasive formula-based method that does not require multiple blood samples or tedious urine collection would be ideal.

Creatinine-based estimating equations include age, gender, race, or weight as surrogates for differences in creatinine generation from muscle mass.[2] The dose reduction of nephrotoxic drugs was historically calculated from serum creatinine according to the CG formula.[2] Because DTPA scan is not available frequently, this study is a small step to find out the ideal patients where eGFR can be the surrogate for the mGFR. We find that the most important factor affecting the GFR is age where eGFR cannot assess the accurate renal function; hence, DTPA scan needs to done in this age group of patients. To our surprise, weight does not affect the GFR significantly as seen above. The mean weight in our study was just 49.6 ± 9.9 kg which is significantly less as compared to standard Indian male (65 kg) or female weight (55 kg). There can be many reasons for this difference such as cancer cachexia, and poor nutrition.

An Indian study done by Dr. Gupta et al.[3] also find that the both CG and aMDRD correlated with mGFR measurement. Between the two mathematical formulae, aMDRD correlates more with mGFR measurement.[4],[5] In reality, aMDRD needs a scientific calculator so may be a less practical tool. K/DOQ guidelines also recommend the use of either aMDRD or CG equations to predict GFR.[6] In case the CG and the aMDRD estimates differ, it may be useful to consider a measure of the actual mGFR (if possible). However, in elderly population, Launay-Vacher et al. have recommended the use of aMDRD formula over CG.[7],[8]

Another study from Denmark by Lauritsen et al.[9] compared the mGFR and various formulas to estimate GFR by patients of Germ cell tumors planed for cisplatin-based chemotherapy. They also confirmed that no equation had sufficient accuracy to be recommended during and after chemotherapy where exact GFR measurements are most important, the Wright and CG equations offered acceptable results before chemotherapy and in follow-up. This is in line with earlier studies on oncology patients with measurements before chemotherapy.[10],[11],[12]


 > Conclusions Top


In resource-limited setting, eGFR using CG formula can replace mGFR, especially in patients with age <60 years. Although weight did not showed a significant difference by two methods a study with large sample is needed to confirm the result.

Acknowledgment

We would like to thank Mr. Vijay C R for helping us during statistical analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel) 2010;2:2490-518.  Back to cited text no. 1
    
2.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41.  Back to cited text no. 2
    
3.
Gupta PK, Kumar P, Lal P, Barai S, Prasad N, Jain S, et al. Estimation of prevalence of pretreatment renal insufficiency and use of mathematical formulae to assess the renal dysfunction in patients of head and neck cancers undergoing concurrent chemoradiotherapy in Northern India. Clin Cancer Investig J 2016;5:151-8.  Back to cited text no. 3
  [Full text]  
4.
Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16:763-73.  Back to cited text no. 4
    
5.
Jafar TH, Schmid CH, Levey AS. Serum creatinine as marker of kidney function in South Asians: A study of reduced GFR in adults in Pakistan. J Am Soc Nephrol 2005;16:1413-9.  Back to cited text no. 5
    
6.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med 2003;139:137-47.  Back to cited text no. 6
    
7.
Launay-Vacher V, Chatelut E, Lichtman SM, Wildiers H, Steer C, Aapro M; International Society of Geriatric Oncology. Renal insufficiency in elderly cancer patients: International Society of Geriatric Oncology clinical practice recommendations. Ann Oncol 2007;18:1314-21.  Back to cited text no. 7
    
8.
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.  Back to cited text no. 8
    
9.
Lauritsen J, Gundgaard MG, Mortensen MS, Oturai PS, Feldt-Rasmussen B, Daugaard G. Reliability of estimated glomerular filtration rate in patients treated with platinum containing therapy. Int J Cancer 2014;135:1733-9.  Back to cited text no. 9
    
10.
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.  Back to cited text no. 10
    
11.
Ainsworth NL, Marshall A, Hatcher H, Whitehead L, Whitfield GA, Earl HM. Evaluation of glomerular filtration rate estimation by Cockcroft-Gault, Jelliffe, Wright and modification of diet in renal disease (MDRD) formulae in oncology patients. Ann Oncol 2012;23:1845-53.  Back to cited text no. 11
    
12.
Barraclough LH, Field C, Wieringa G, Swindell R, Livsey JE, Davidson SE. Estimation of renal function – What is appropriate in cancer patients? Clin Oncol (R Coll Radiol) 2008;20:721-6.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2]



 

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