

ORIGINAL ARTICLE 

Year : 2019  Volume
: 19
 Issue : 3  Page : 8085 

Validity of current equations to estimated glomerular filtration rate in geriatric population
Osama El Minshawy^{1}, Elham Ahmed^{2}, Eman El Bassuoni^{3}
^{1} Professor of Internal Medicine, MD, Minia University, Minia, Egypt ^{2} Lecturer of Internal Medicine, MD, Minia University, Minia, Egypt ^{3} Assistant Professor of Physiology, MD, Minia University, Minia, Egypt
Date of Submission  05Mar2019 
Date of Acceptance  19Jun2019 
Date of Web Publication  2Aug2019 
Correspondence Address: MD Elham Ahmed Internal Medicine department, MD, Minia University, Minia, 61111 Egypt
Source of Support: None, Conflict of Interest: None  Check 
DOI: 10.4103/jesnt.jesnt_11_19
Background Despite the estimation of glomerular filtration rate (GFR) being the best index of kidney function, and estimated glomerular filtration rate (eGFR) being limited by differences in creatinine generation among different age groups, the data regarding the accuracy of serum creatininebased formulae on the geriatric population is still scarce. Aim Our aim is to investigate the accuracy of the eGFR equations to predict renal function in geriatric population versus the measurement of true GFR by diethylenetriaminepentaacetic acid (^{99m}TcDTPA). Patients and methods The study included 160 elderly persons, with 93 (58%) females. All persons were from Minia Governorate, Egypt. GFR was estimated using Modification of Diet in Renal Disease, abbreviated Modification of Diet in Renal Disease, Walser, Nankivell, Cockcroft–Gault, Mayo Clinic, and Chronic Kidney Disease Epidemiology Collaboration. The true GFR was determined for all participants with ^{99m}TcDTPA. Results All the seven eGFR estimations correlated with ^{99m}TcDTPA clearance (P<0.05), but their r^{2} was low, ranging from 0.69 to 0.54. Their respective r^{2} values were as follows: Modification of Diet in Renal Disease 0.69, Chronic Kidney Disease Epidemiology Collaboration 0.63, abbreviated Modification of Diet in Renal Disease 0.62, Cockcroft–Gault 0.58, Mayo Clinic 0.55, Walser 0.55, and Nankivell 0.54. Conclusion In the geriatric population, the overall performance of these seven prediction equations did not give a precise assessment of kidney function, that is, all analyzed formulae lacked the precision to estimate true GFR.
Keywords: diethylenetriaminepentaacetic acid, estimated glomerular filtration rate, geriatric population
How to cite this article: El Minshawy O, Ahmed E, El Bassuoni E. Validity of current equations to estimated glomerular filtration rate in geriatric population. J Egypt Soc Nephrol Transplant 2019;19:805 
How to cite this URL: El Minshawy O, Ahmed E, El Bassuoni E. Validity of current equations to estimated glomerular filtration rate in geriatric population. J Egypt Soc Nephrol Transplant [serial online] 2019 [cited 2019 Nov 16];19:805. Available from: http://www.jesnt.eg.net/text.asp?2019/19/3/80/263896 
Introduction   
The aging process leads to significant alterations in many organ systems, with the kidney being particularly susceptible to agerelated changes. Within the kidney, aging leads to ultrastructural changes such as glomerular and tubular hypertrophy, glomerulosclerosis, and tubulointerstitial fibrosis, which may compromise renal plasma flow and glomerular filtration rate (GFR) [1]. Aging is nearly a universal phenomenon in biology, only partially controlled by genetic endowment. Individuals and their organs age at varying rates. The kidneys manifest the aging process by gradual loss of nephrons and a corresponding decrease in GFR [2]. The lack of accuracy of serum creatinine (SCr) to estimate renal function has led to the development of a number of formulae for estimation of GFR, such as Cockcroft–Gault, Modification of Diet in Renal Disease (MDRD), abbreviated Modification of Diet in Renal Disease (aMDRD), Walser, Nankivell, Mayo Clinic equation, and Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) [3],[4],[5],[6],[7],[8],[9],[10]. Estimating GFR in elderly patients is a problem, as they are poorly represented in studies [11].
Measurement of true GFR requires the determination of renal clearance of a marker freely filtered by the kidney without undergoing any metabolism, tubular secretion, or reabsorption and thus rapidly secreted in the urine by glomerular filtration only. Inulin fulfills these criteria, since its introduction in 1935 [12]. Renal clearance of inulin is the gold standard for the measurement of GFR [13].
One of the most available and routinely used method nowadays is diethylenetriaminepentaacetic acid (^{99m}TcDTPA) isotopic clearance. This method was compared with the inulin clearance, based on the singleinjection technique, and the correlation was 0.97, which is nevertheless impressive [10]. So, the radionuclidic methods in patients with chronic renal failure are reliable and reproducible, closely resembling those of inulin clearance. Among all radionuclidic methods, ^{99m}TcDTPA shows the best results [14].
Accurate assessment of renal function is important in geriatric to determine the degree of renal dysfunction, in CKD [11].
Aim   
Our aim is to determine the accuracy of currently available GFR prediction equations in geriatric population by comparing them versus measurement of true GFR by ^{99m}TcDTPA.
Patients and methods   
Ethicsrelated statement
The study protocol was approved by Ethical Research Board of Minia School of Medicine, Egypt. Informed consent was obtained from all patients who participated in this study. The study was conducted in accordance with the guidelines of 1975 Declaration of Helsinki.
The study included 160 elderly persons, comprising 93 (58%) female geriatric individuals. Patients were from the outpatient clinic, ElMinia University Hospital, ElMina, Egypt. Age, body weight, height, BMI, serum albumin, blood urea nitrogen (BUN), and SCr were reported on the same day of the study. The age of the study group ranged from 61 to 93 years, with mean age of 67±7 years and mean body weight of 71±0.1 kg. Body surface area (BSA) average was 1.3±0.2 m^{2} and BMI was 26.8±1.2 kg/m^{2}. All geriatric populations had glomerular filtration rate (iGFR) determined with ^{99m}TcDTPA clearance by the following technique: the patients were hydrated orally at 10 ml water/kg body weight before the start of the study. ^{99m}TcDTPA dosed at 50 µCi/kg was injected intravenously. Initial rapid sequences of dynamic images were acquired to assess renal perfusion every four seconds for 30 min and Nd time activity curve was generated using computer software. Sequential static images were also acquired 3 h after intravenous injection of ^{99m}TcDTPA to evaluate renal cortical uptake [15].
For each determined GFR, the following seven formulae were performed from data recorded on the day of measurement of true GFR.
 MDRD (equation 7: demographic and serum variables only) [5].
Estimated glomerular filtration rate (eGFR) (ml/min/1.73 m^{2})=170×SCr0.999×age–0.176×BUN−0.170×serum albumin concentration+0.318. ×0.762 (if woman). ×1.180 (if the patient is African–American).
 aMDRD [6].
eGFR (ml/min/1.73 m^{2})=186×(SCr)−1.154× (age)−0.203. ×0.742(for woman). ×1.212 (for African–American).
 Walser [7]
eGFR (ml/min)=7.57×(SCr×0.0884)−1−0.103×age+0.096×weight−6.66 for man=6.05×(SCr×0.0884)−1−0.080×age+0.080×weight–4.81 for woman (ml/min/ m^{2}).  Nankivell [8].
eGFR(ml/min)=6700/(SCr×88.4)+(body weight/4)−(BUN×0.357/2)−(100/m^{2})+35 (for males) or 25 (for females).  Cockcroft–Gault [4]
eGFR (ml/min)=(140–age)×body weight/(72×SCr) (×0.85 for women).  Mayo Clinic formula [9] eGFR (ml/min/1.73 m^{2})=EXP(1.911+(5.249/SCr)−(2.114/SCr2)−0.00686×age–0.205 (if female), if SCr less than 0.8 use 0.8 for SCr.
In these formulae, SCr is in mg/dl, age in years, BUN in mg/dl, and serum albumin in g/dl.  CKDEPI [10]
In white males, eGFR (ml/min/1.73 m^{2})=141×(SCr/0.9)−1.209× (0.993) age.
In white females, eGFR (ml/min/1.73 m2)=141×(SCr/0.7)−1.209× (0.993) age×1.018.
eGFR values given by Cockcroft–Gault and Nankivell were corrected for 1.73 m^{2} of BSA (have been multiplied by 1.73/BSA); thus, all the Estimated GFR values are normalized to 1.73 m^{2} BSA, except Wasler return results, which were normalized to 3 m^{2}/(height)^{2}. BSA was estimated according to the Mosteller formula [BSA (m^{2})=([height (cm)×weight (kg)]/3600)½] [15],[16].
Statistical analysis
Results are shown as mean±SD. Correlation between variables was performed using commercially available statistical software (minatab 15). The percent error in GFR prediction was calculated as follows: % prediction error=(predicted value−measured value)/(measured value)×100. Accuracy for each eGFR formula was assessed as the proportion of GFR estimates within 10, 30, and 50% deviation of the true GFR. Precision was determined as the root mean square error, where root mean square error=SD of the mean difference between real GFR and eGFR. Bland–Altman recommendations were used to compare the GFR calculated with prediction equations compared with a renal clearance of ^{99m}TcDTPA (the reference method). Measures of accuracy (i.e. nearness of the reduced major axis of the data to the line of perfect concordance) and precision (i.e. tightness of the data around their reduced major axis) determine whether data observed significantly diverge from the line of perfect concordance, which occurs at 45°. The Bland–Altman limits of agreement procedure use data scale assessment in analyzing both the accuracy (i.e. bias) and amount of variation or precision between any two measured values when the range of data is sufficiently limited [15],[17].
Results   
The clinical and anthropometric data of our population are described in [Table 1]. The mean age was 67±7 years, with range of 61–93 years. Mean body weight was 71±8 kg, height was 1.7±0.1 m, BSA average was 1.73±0.2 m^{2}, BMI was 26±1.2 kg/m^{2}, and mean SCr and BUN were 0.9±0.2 and 19±3 mg/dl, respectively. The serum albumin was 4±1 g/dl. The correlation between measured GFR by ^{99m}TcDTPA and eGFR by seven equations in all patients is showed in [Figure 1] and [Table 2]. Percentages of prediction errors in different equations are shown in [Table 3]. MDRD gave the best performance with 36% of eGFR within an error between ±10%. Considering the error range between ±30% and ±50%, the MDRD still performed the best. Both Nankivell and Walser formulae gave the worst performance with 25% only of eGFR within an error between ±10%. Considering the error range between ±30 and ±50%, Walser equation gave slightly superior results than Nankivell equation.  Figure 1 (A) Correlation between measured GFR by 99mTc DTPA and estimated GFR by Modification of Diet in Renal Disease (MDRD)Equation. (B) Correlation between measured GFR by 99mTc DTPA and estimated GFR by CKDEPI Equation. (C) Correlation between measured GFR by 99mTc DTPA and estimated GFR by Abbreviated MDRD (aMDRD) Equation. (D) Correlation between measured GFR by 99mTc DTPA and estimated GFR by CockcroftGault Equation. (E) Correlation between measured GFR by 99mTc DTPA and estimated GFR by  Mayo Clinic Formula Equation. (F) Correlation between measured GFR by 99mTc DTPA and estimated GFR by Walser Equation. (G) Correlation between measured GFR by 99mTc DTPA and estimated GFR by Nankivell Equation.
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 Table 2 True diethylenetriaminepentaacetic acid glomerular filtration rate and estimated glomerular filtration rate by different equations
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We have tried to evaluate the degree of concordance between true measured GFR and eGFR by a graphical method that demonstrates the differences between estimated and measured GFR values and draw the line of equality on which all points would lie if the two values, estimation and measurement, gave exactly the same reading every time. This helps the eye in detecting the degree of concordance between measurements. Data again indicated the poor concordance of each GFR estimation equation with ^{99m}TcDTPA GFR measurement.
Discussion   
In the current study, we have evaluated seven presently used equations for estimation of GFR in the geriatric population and compare this estimation with true measured GFR by ^{99m}TcDTPA to decide which of these formulae will verify superior performance. eGFR values by all the seven equations tested here based on biochemical, demographic, and anthropometric data correlated well with the measured GFR by ^{99m}TcDTPA.
The K/DOQI guidelines recommend the use of the MDRD, its abbreviated version aMDRD, and Cockcroft–Gault formulae as useful estimates of GFR in adult patients. The K/DOQI bases their recommendation on 30% accuracy of 75 and 90% for Cockcroft–Gault and MDRD equations, respectively [3],[4],[5],[6].
In the current study, we found that this recommendation can be extended only to geriatric population by using the MDRD as our results show it giving the best performance and accuracy in Geriatric population, r^{2}=0.69, but our results illustrated that Cockcroft–Gault formulae did not give a good performance, r^{2}=0.58, for geriatric population.
Bevc and colleagues reported that all equations lacked precision in estimating GFR in geriatric population, and this is in agreement with our results. However, in contrast to our results, Bevc et al. [11] reported that all equations are equal for estimating GFR in elderly white patients with CKD, as our results illustrated that despite all equations are far from being ideal, eGFR MDRD was superior to other equations in precision and accuracy.Each of the estimation formula has dissimilar genesis that may assist to clarify findings in the current study population. The Cockcroft–Gault equation was derived from an investigation of 249 men with creatinine in a steady state, and it is well known that SCr concentration are influenced by muscle mass, dietary protein intake, sex, and age, thus limiting the precision of creatininebased equations; these results are in agreement with our results [4],[18].
MDRD equation was developed as an estimation of ^{125}Iiothalamate renal clearancebased GFR measured in 1628 patients with CKD. The mean GFR in this population was 39.8±21.2 ml/min/1.73 m^{2}, and the mean age of the cohort was 50.6±12.7 years. When the error in GFR prediction was calculated, the MDRD formula performed gave better results than the other tested equations. Nevertheless, only 36% of the predicted GFR values were estimated within ±10% error as compared with the reference measurement by ^{99m}TcDTPA [5].
Nevertheless, our finding indicates that none of the seven tested formulae can be a valid alternative to the direct measurement of GFR and prediction equations may not be sufficient for properly estimating GFR, stating that when careful GFR measurement is needed, precise GFR measurement needs to be considered. However, the application of the MDRD equation should be sufficient for routine clinical practice.
On the measurement of GFR using a modified renal clearance of ^{125}Iiothalamate (iGFR) as described by Israelit et al. [19], they found the MDRD equation was better than Nankivell and Cockcroft–Gault formulae (53% of eGFR were within 20% of iGFR and 90% were within 50%).
Conclusion   
In geriatric population, the overall performance of these seven prediction equations does not give a precise assessment of kidney function, that is, all analyzed formulae lacked the precision to estimate true GFR. So we may conclude that none of these GFR prediction equations seem to safely substitute for measurement of true GFR.
Acknowledgements
The authors acknowledge all members of Clinical Pathology Department and Minia Oncology Center for performance of the investigations of this study.
Minia University, Egypt, helped us in the performance of the investigation.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3]
