Predictive equations, oxidative and metabolic risk factors among Ghanaian patients presenting with chronic kidney disease
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Date
2010
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Abstract
Current recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients presenting with chronic kidney disease. The most widely used equations are the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulae. However, none of the predictive equations have been validated for the assessment of chronic kidney disease (CKD) cases in Ghana. The metabolic syndrome (MetS) is a common risk factor for cardiovascular and chronic kidney disease (CKD) in Western populations. The relationship between metabolic syndrome and risk of CKD in underdeveloped countries where genetic and environmental backgrounds differ from those in Western countries is not known. Anaemia, a complication of CKD is a potential nontraditional risk factor for cardiovascular disease (CVD). Dyslipidaemia and lipid peroxidation are both known risk factors for cardiovascular disease. This study assessed the lipid profile and oxidative stress/lipid peroxidation in patients presenting with Chronic Kidney Disease (CKD) using the oxidative stress marker; Malondialdehyde (MDA) and antioxidants; Vitamins A and C, Catalase and Uric Acid. Parathyroid hormone (PTH) has been identified as the main regulator of some electrolytes homeostasis, and thus this study set out to evaluate the relationship between PTH and these electrolytes as well as their ratios. The overall aim of this study was to evaluate the use of renal function equations in the assessment of renal function in CKD and to identify specific oxidative and metabolic risk factors in CKD. This is, therefore, the first study to specifically evaluate the predictive performance and accuracy of the seven renal function equations in patients presenting with CKD in our community. Furthermore, this study evaluated whether anaemia poses a cardiovascular risk and whether the risk is modified by the presence of CKD. In addition the present study sought to examine the association between the metabolic syndrome and risk of CKD among Ghanaian patients presenting with CKD. This study also assessed the lipid profile and oxidative stress/lipid peroxidation in patients presenting with CKD using the oxidative stress marker; Malondialdehyde (MDA) and antioxidants; Vitamins A and C, Catalase and Uric Acid. Finally, the relationship between PTH and electrolytes as well as their ratios was evaluated. Anaemia was defined as haemoglobin concentration ≤ 11.0 for both males and females whereas CKD was defined as an estimated GFR of ≥ 60 ml/min per 1.73 m2.
The study population included 146 individuals with various diagnosed chronic kidney diseases. Another 80 healthy subjects without any chronic kidney pathology but of similar age and sex distribution were used as controls.
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The results of these predictive equations for 146 patients using stage of CKD were compared with the recommended methods (4v-MDRD and CKD-EPI). The MetS was defined as the presence of three or more of the following risk factors according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria: elevated blood pressure, low high density lipoprotein cholesterol (HDL-C), high triglycerides, elevated plasma glucose and abdominal obesity. Anaemia was defined as haemoglobin concentration ≤ 11.0 for both males and females whereas CKD was defined as an estimated GFR of ≥ 60 ml/min per 1.73 m2.
The most accurate results were obtained with the reference equations (4v-MDRD and CKD-EPI) with CKD-EPI having a slight edge over 4v-MDRD equation. The sensitivity and specificity of the 4v-MDRD equation to detect glomerular filtration rate (GFR) values < 60 ml/min/1.73 m2 were 50.0% and 60.0% respectively; that of CKD-EPI was 66.6% and 70.0% respectively.
The prevalence of MetS among CKD subjects in this study was 30.1%. The CKD groups had significantly higher waist circumference (WC), were more hypertensive [based on systolic blood pressure (SBP) and diastolic blood pressure (DBP)], had more diabetics based on fasting blood glucose (FBG) and were more hypercholesterolaemic and hypertriglyceridaemic (i.e. TC and TG) as compared to the control. The CKD group are also about 9 times at risk of developing MetS as compared to the control group (OR = 8.8; 95% CI = 3.8-20.5). The female subjects with CKD are 2 times at risk of developing metabolic syndrome as compared to the male counterparts (OR = 1.9; 95% CI = 0.9-4.0). The CKD patients were about 9 fold at risk of developing hypertension (OR = 8.9; 95% CI = 3.1- 25.1) and diabetes (OR = 9.3; 95% CI = 4.7-18.2), about 2 times at risk of developing hypertriglyceridaemia (OR = 2.3; 95% CI = 1.3-4.2) and several folds at risk of developing proteinuria (OR = 409; 95% CI = 24.7-6759). There was a significant graded relationship between the number of MetS components present and risk of CKD. 58.9% of the subjects had CKD with an estimated GFR (eGFR) of < 60 ml/min/1.73 m2, estimated with the Modification of Diet in Renal Disease (MDRD) equation and were more likely to be anaemic and nondiabetic, with higher mean values for serum creatinine (CRT) lower values for haemoglobin (HGB), haematocrit (HCT), and red blood cells (RBC). CKD subjects with anaemia had a higher prevalence of several cardiovascular (CVD) risk factors; age, male sex, diabetes and hypertension and lower haematological parameters and estimated GFR. However they had higher total cholesterol (TC) and higher triglyceride (TG) level. With the exception of HDL-C, which showed no significant difference when CKD patients were compared with controls, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG) increased significantly in the CKD patients. Serum MDA increased significantly in the CKD patients as compared to the controls and increased with the severity of the condition. Vitamin A, Catalase and Uric Acid increased significantly in the CKD subjects as compared to controls, whilst vitamin C decreased significantly among the CKD subjects. For every mmol/l increase in the serum concentration of PO42- (r2 = 0.78, p < 0.0001), K+ (r2 = 0.28, p < 0.0001)
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and Mg2+ (r2 = 0.004, p = 0.0211) there was a corresponding increase in serum concentration of PTH with beta values of 0.005, 0.0007 and 0.001, respectively. However, there was no linear relationship between Na+ and PTH (r2 =0.001, p = 0.6687). The serum concentration of PTH decreased, for every mmol/l increase in the serum concentrations of Ca2+ (r=0.33, p < 0.0001).
These results suggest that measurement of GFR with predictive equations might be a prudent strategy for the assessment of renal function among the CKD population and that the metabolic syndrome might be an important factor in the cause and progression of chronic kidney disease among Ghanaian patients presenting with CKD. Furthermore, in persons with CKD, anaemia poses a further cardiovascular risk as it increases some of the traditional cardiovascular risk factors. Dyslipidaemia and increased oxidative stress with abnormal antioxidant levels are common in CKD patients. Therapeutic regimens aimed at strengthening the antioxidant defenses as well as normalizing lipid concentrations would be useful in protecting CKD patients against oxidative stress and any related complications. Excess PTH is linked with derangements in the metabolism of electrolytes like calcium, magnesium, phosphorus and potassium in CKD and contributes to a plethora of complications.
Description
A thesis submitted to the Department of Molecular Medicine, School of Medical Sciences in partial fulfillment of the requirements for the degree of
Doctor of Philosophy