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 Table of Contents  
Year : 2015  |  Volume : 40  |  Issue : 4  |  Page : 185-189

The utility of the CKD-EPI formula for determination of glomerular filtration rate in Nigerians with sickle cell disease

1 Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria
2 Department of Haematology, Obafemi Awolowo University, Ile-Ife, Nigeria
3 Department of Chemical Pathology, Obafemi Awolowo University, Ile-Ife, Nigeria
4 Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria

Date of Submission23-Jun-2015
Date of Acceptance08-Aug-2015
Date of Web Publication23-Nov-2015

Correspondence Address:
Anthony A Oyekunle
Department of Haematology and Immunology, Obafemi Awolowo University, 234-220005 Ile-Ife, Osun State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1110-1067.170217

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Background and objective Predictive formulae for the calculation of estimated glomerular filtration rate (eGFR) are increasingly being used in clinical practice for monitoring of renal function. We evaluated the usefulness of the CKD-EPI formula for eGFR in a population of Nigerian patients with sickle cell disease (SCD).
Patients and methods One hundred SCD patients were prospectively studied. Relevant information, including age, weight and sex, was obtained from the participants, whereas creatinine clearance was measured following a 24-h urine collection. The Cockcroft-Gault (C-G) and the CKD-EPI formulae were thereafter used to calculate the glomerular filtration rate (GFR) for all participants. SPSS (version 17) and Microsoft Excel 2007 computer software were used for all data collection and analyses. A P-value of less than 0.05 was considered significant.
Results The comparison of measured GFR versus eGFR by the C-G and CKD-EPI formulae in homozygous haemoglobin SS (HbSS) patients yielded correlation coefficients (r values) of 0.667 (P < 0.001) and 0.598 (P < 0.001), respectively. Correspondingly, among the heterozygous haemoglobin S + C (HbSC) patients, measured GFR versus eGFR resulted in r values of 0.819 (P < 0.001) and 0.848 (P < 0.001), respectively.
Conclusion The CKD-EPI formula is a good measure of eGFR in our population of SCD patients; however, it did not perform significantly better than the C-G formula.

Keywords: chronic kidney disease , CKD-EPI , estimated glomerular filtration rate, sickle cell disease

How to cite this article:
Aneke JC, Oyekunle AA, Adegoke AO, Sanusi AA, Okocha EC, Akinola NO, Durosinmi MA. The utility of the CKD-EPI formula for determination of glomerular filtration rate in Nigerians with sickle cell disease. Egypt J Haematol 2015;40:185-9

How to cite this URL:
Aneke JC, Oyekunle AA, Adegoke AO, Sanusi AA, Okocha EC, Akinola NO, Durosinmi MA. The utility of the CKD-EPI formula for determination of glomerular filtration rate in Nigerians with sickle cell disease. Egypt J Haematol [serial online] 2015 [cited 2020 Jan 23];40:185-9. Available from: http://www.ehj.eg.net/text.asp?2015/40/4/185/170217

  Introduction Top

Assessment of renal function is an integral component of the comprehensive care of patients with sickle cell disease (SCD). This is made even more important by the finding that renal dysfunction is a major determinant of survival in SCD [1] . Kidney dysfunction, with potential for progression to end-stage kidney disease, is a major contributor to the morbidity and mortality of patients with SCD [2],[3] . In fact, end-stage kidney disease has variously been documented in up to 11% of these patients [4],[5] . In monitoring for sickle cell nephropathy, evaluation of proteinuria is important as it has been shown to indicate early glomerular dysfunction. This makes it an important marker of kidney pathology [2] .

Glomerular filtration rate (GFR) is usually determined by measuring the creatinine clearance after a 24-h urine collection. This is time-consuming and laborious and cannot be easily measured in clinical practice. Consequently, predictive formulae have been developed to enable easier and faster calculation of GFR utilizing parameters such as serum creatinine, body size, age, race and sex [6],[7] . A number of predictive formulae are currently available that enable the determination of estimated glomerular filtration rate (eGFR) in different disease states with reasonable degrees of accuracy and precision. The Cockcroft-Gault (C-G) [8] formula has gained widespread acceptance and has equally been variously validated in cardiac [9] , renal [10] and recently in our population of SCD [11] patients.

Methods of GFR determination based on creatinine clearance are limited by the observation of renal tubular dysfunction in SCD, which leads to increased tubular secretion of creatinine and the consequent overestimation of GFR [12] . Indeed, Haymann et al. [13] reported some overestimation of true GFR when comparing the eGFR using the four-variable modification of diet in renal disease (MDRD) formula with 51 Cr-EDTA-based measured GFR, despite a good correlation. Moreover, Aparicio et al. [14] noted that a reduction in creatinine generation because of decreased muscle mass and changes in protein catabolism and hydration in SCD affects the results of creatinine clearance and also reported a poor correlation between measured GFR using 51 Cr-EDTA and values using creatinine clearance. Similarly, studies in children with SCD have shown a poor correlation between measured GFR by the 99m Tc-DTPA method and those utilizing urinary clearance of creatinine and cystatin C [15] . However, the use of radioisotopes for routine clinical assessment of GFR is yet to receive wide acceptance because they are largely labour intensive and hazardous [16] .

The shortcomings of creatinine-based methods of GFR estimation notwithstanding, they are still used widely on account of their convenience and safety. A number of studies have alluded to the accuracy, precision and clinical adequacy of the predictive formulae derived from GFR measurements in different disease states [9],[10],[11] . The unique pathophysiologic changes associated with sickle cell nephropathy have made it necessary that a disease-specific formula be developed for patients with this condition [17],[18] . The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) research group recently introduced a new equation [19] , which has been validated independently by several research groups [20],[21],[22] .

This study evaluated the performance of the CKD-EPI formula for eGFR in Nigerian patients with SCD.

  Patients and methods Top

The study was prospective, carried out over a 7-month period from January to July 2010. Ethical approval was obtained from the Hospital Ethics Committee and all participants provided informed consent; consent was provided by the parent or the guardian for patients younger than 18 years old. Patients were between 15 and 56 years of age, and were regular attendees of the Hematology Outpatient Clinic of our hospital; there were 100 confirmed (by cellulose acetate electrophoresis, at alkaline pH) patients with SCD [79 homozygous sickle cell anaemia (HbSS) and 21 compound heterozygous sickle cell disease (HbSC) patients, mainly from south-west Nigeria] in stable clinical conditions at least 2 weeks before recruitment and had not received blood transfusion in the last 3 months. Exclusion criteria included oedema or ketosis (which may be indicative of congestive cardiac failure or complicated diabetes mellitus) and those currently on drugs such as co-trimoxazole, probenecid or cephalosporins, which are known to interfere with the tubular excretion of creatinine and alkaline picrate assay (Jaffé reaction) for serum creatinine [23] .

Relevant clinical information was documented, and a 24-h urine collection was performed for each participant on an outpatient basis, using wide-bore 4-l containers to which boric acid had been added. On the morning of submission of the 24-h urine sample, 2.5 ml of venous blood was collected for serum creatinine estimation. Each participant was adequately and extensively counselled before commencement of urine collection to avoid errors. Both urinary and serum creatinine estimations were performed using Jaffe's reaction [24] . The eGFR calculations were performed using the following formulae: C-G [8] : [(140−age) × (weight, kg) × (0.85, if female)]/(72 × SCr) and CKD-EPI [19] : 141 × min(SCr/κ, 1)α × max(SCr/κ, 1)−1.209 × 0.993 age × 1.018 (if female) × 1.159 (if Black), where SCr is the serum creatinine (mg/dl), κ is 0.7 (female) or 0.9 (male), a is −0.329 (female) or −0.411 (male), min is the minimum of SCr/κ and 1 and max is the maximum of SCr/κ and 1. The measured and eGFR were both adjusted for body surface area (1.73 m 2 ), calculated using the Mosteller formula [25] : [height (cm) × weight (kg)/3600] 0.5 . SPSS (version 17; SPSS Inc., Chicago, Illinois, USA) and Microsoft Excel (2007) computer software were used for data collection and analysis. Pair-wise correlations were performed between measured and eGFR estimated using the two formulae. A P-value less than 0.05 was considered significant.

  Results Top

The patients (HbSS, n = 79; HbSC, n = 21) included 40 males and 60 females. The mean age of the HbSS and HbSC patients was 25.34 ± 6.77 years (range, 15-56 years) and 29.33 ± 8.97 years (range, 17-50 years), respectively.

The means of measured GFR in HbSS and HbSC were 66.28 ± 27.52 and 97.04 ± 17.47 ml/min/1.73 m 2 , respectively. Correspondingly, the mean eGFR were 56.26 ± 15.03 and 57.55 ± 17.46 ml/min/1.73 m 2 using the C-G formula and 115.44 ± 28.98 and 108.78 ± 30.78 ml/min/1.73 m 2 using the CKD-EPI formula in HbSS and HbSC, respectively ([Table 1]). Using the Kidney Disease: Improving Global Outcomes (KDIGO) classification [26] , the majority of the patients (75 and 62% HbSS and HbSC, respectively) had 'normal or high' kidney function ([Table 2]).
Table 1: Means and standard deviations of measured and calculated GFR in HbSS and HbSC

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Table 2: The distribution of estimated GFR of subjects using the KDIGO 2012* nomenclature

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Among the HbSS patients, measured GFR correlated significantly with the eGFR obtained by the C-G (r = 0.667, P < 0.001) and the CKD-EPI formulae (r = 0.598, P < 0.001). There was a better correlation between the measured GFR and the eGFR of the HbSC patients both by the C-G (r = 0.819, P < 0.001) and by the CKD-EPI formulae (r = 0.848, P < 0.001). shows the detailed comparisons between measured GFR and eGFR of the patients ([Table 3]).
Table 3: Correlation of Measured and calculated GFR in HbSS and HbSC

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Using a Bland-Altman analysis, there was a mean overestimation of GFR by 49.17 ± 25.36 and 35.03 ± 20.65 ml/min in the HbSS and HbSC patients, respectively, using the CKD-EPI formula, whereas correspondingly, the C-G was underestimated by a mean of 10.02 ± 21.17 and 11.83 ± 13.31 ml/min ([Figure 1]).
Figure 1 Bland-Altman analysis of measured versus estimated glomerular filtration rate (eGFR) using CKD-EPI and Cockcroft-Gault (C-G) formulae. The Bland-Altman plots for heterozygous haemoglobin SC (b, d) and homozygous haemoglobin SS (a, c) show overestimation of the measured GFR by the CKD-EPI formula (a, b), whereas the C-G formula underestimates the measured GFR (c, d).

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  Discussion Top

We had previously evaluated the utility of five predictive formulae for eGFR in our SCD patients, including the C-G, MDRD, Mawer, Gates and Hull. It was observed that eGFR by the C-G formula correlated best with measured GFR (using creatinine clearance) [11] . Similarly, several studies have also reported high correlations between the C-G formula and measured GFR in Nigerian patients with hypertension, congestive heart failure and chronic renal failure [9],[10] .

Following the introduction of the CKD-EPI formula, it has been shown to be a useful predictor of GFR in lean patients of sub-Saharan African descent [20] . It thus became imperative that this 'new' formula be tested in adult non-European, non-American SCD patients. Arlet et al. [21] reported eGFR by the CKD-EPI formula (in SCD patients aged between 18 and 67.5 years) as having the best correlation with measured GFR using the iohexol plasma clearance method, and thus recommended it be used for eGFR in SCD patients of non-Afro-American origin [21] . Similarly, Asnani et al. [22] compared eGFR derived from CKD-EPI, the C-G and the MDRD formulae with measured GFR using a 99m Tc-DTPA nuclear renal scan in a cohort of Jamaican sickle cell anaemia patients. They observed that eGFR based on the CKD-EPI formula showed a better correlation with measured GFR.

Our study showed that the CKD-EPI formula consistently overestimated GFR in HbSS and HbSC patients by an average of 49.19 and 11.7 ml/min, respectively. Interestingly, GFR overestimation was less in HbSC than in HbSS patients. Asnani et al. [22] had similarly noted GFR overestimation in HbSS patients using the CKD-EPI formula by a mean of 41.2 ml/min. In our HbSS patients, both formulae correlated significantly with measured creatinine clearance, even though the C-G formula performed better (r = 0.667 vs. 0.598). Similarly, both formulae correlated significantly with measured creatinine clearance in our HbSC patients, although the CKD-EPI formula seemed to be better (r = 0.848 vs. 0.819).

Our finding in HbSS patients is in contrast with the reports of Arlet et al. [21] and Asnani et al. [22] , both of which alluded to the superiority of the CKD-EPI formula in SCD patients. Although this discrepancy may reflect a true difference in patient populations as our patients were mainly from the Yoruba tribe of south-west Nigeria, the patients in the two studies alluded to above were mainly from the Caribbean. An increasing body of evidence has identified tribal (because of genetics) differences in GFR in health and disease [27],[28],[29] . In addition, it is important to note that different reference methods of GFR measurement were also used in these studies. Evaluation of tribal differences in GFR (and possibly its genetic determinants) among Nigerian patients could therefore be a subject of further research.

In conclusion, our study confirms that the CKD-EPI formula offers a good measure of GFR estimation in Nigerian SCD patients, although it slightly overestimates GFR measured by creatinine clearance. In addition, the CKD-EPI did not perform significantly better than the C-G formula in our cohort of patients. Some limitations of this study include the fact that reference markers such as inulin, 125 I-iothalamate, iohexol, technetium, diethylene triaminepentaacetic acid and chromium ethylene diaminetetraacetic acid, which are known to be superior to creatinine clearance, could not be used for GFR determination because of lack of facilities for them locally. Similarly, the diagnosis of SCD using haemoglobin electrophoresis alone could fail to detect patients with concurrent α-thalassaemia.

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Conflicts of interest

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  References Top

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  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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