In this study, the relationship between oxidative stress and hematological indices were investigated among chronic kidney disease (CKD) patients in Ghana. There were significant differences in age between CKD patients and control group (Table 1); this was in line with the observations made in earlier studies which reported that the risk of CKD increases as one grows older (11). As previously seen with (12), chronic kidney disease was more common in males (Table 1). A greater percentage of the patients studied had a clinical history of hypertension and diabetes. This agreed with a population-based study, which identified hypertension as an independent risk factor for CKD (13). In another study it was reported that hypertension was one of the leading causes of CKD, especially in black patients (14). Studies also support the high prevalence of diabetes in the CKD patients. In all, hypertension and diabetes are the most important risk factors for the development and progression of CKD (15).
In the studied population, body mass index (BMI) in CKD patients was statistically significant when compared to the control group (Table 1), supporting a previous study which found a similar increased BMI and high prevalence of obesity in CKD patients (16). The mean blood pressure difference between patients and controls were not significant (Table 2); most likely related to anti-hypertensive medication taken by patients.
White blood cell, neutrophil count as well as lymphocyte count (Table 2), were significantly higher in cases than controls. The higher lymphocyte count in this study contradicts with the findings of Tian et al (17). WBC and NEUT are markers of inflammation, which are used to predict a decrease in kidney function. In systemic inflammation, which is often associated with CKD, WBC and NEUT counts are thus elevated (18). On WBC differential counts, increased circulating neutrophils levels in patients is supported by a recent study, which suggests that these leukocytes when activated may be involved in renal arteriolar dysfunction, which could lead to glomerular hyperfiltration and CKD (17).
On another aspect, the CKD subjects had significantly reduced RBC, HB and HCT levels than in controls (Table 3). The reduction in red blood cell indices may be an indication of anaemia, a common complication of CKD. A normochromic, normocytic anaemia occurs early in the development of kidney disease and worsens with declining kidney function. The association between HGB concentration and kidney function has been demonstrated by several studies (19). The reduction in HGB and RBC occurs for a variety of reasons. Approximately 90% of the hormone erythropoietin is produced by the kidneys. Under normal physiological conditions, hypoxia in the kidney leads to an increase in the production of erythropoietin, which subsequently stimulates erythropoiesis (20). Nonetheless, as functional renal tissue declines in patients with CKD, the body is unable to produce adequate amounts of erythropoietin in response to hypoxia in the kidney. In effect, erythropoietic activity decreases and low levels of red blood cells and hemoglobin ensue (20). Another factor that may adversely affect HGB production is the use of medications such as metformin, fibrates, thiazolidinediones, and angiotensin-converting enzyme inhibitors (ACE-i) taken by these patients (21).
SOD activity was significantly reduced in patients with CKD compared to controls (Fig. 1). Decreased SOD activity is known to be associated with high oxidative stress levels (6). This reflects increased oxidative stress which has been evident in patients with renal impairment (22). Inflammation, typically present in CKD, further amplifies the oxidant generation process (22). SOD activity decreased with increasing total white blood cell and neutrophils (Table 4).
Oxidative stress together with leukotriene B4 activates the inflammatory pathway which attracts neutrophils to inflammatory sites leading to additional oxidative stress generation (23). Equally, neutrophils secrete a variety of inflammatory cytokines such as interleukin-6 which further trigger an increase in oxidative stress levels (24).
SOD activity correlated negatively with platelet count (Table 4). The negative correlation here means that as SOD activity decreases, platelet level increases. While platelets are well known mediators of hemostasis, there is significant knowledge that they play an equally important role in inflammation (25). Hemostasis and inflammation are linked pathologically, which is explained by the capacity for activated platelets to interact with leucocytes in a more robust reaction in the inflammatory process (25). It is therefore not surprising that platelet levels positively correlate with inflammatory cells (neutrophils) and subsequently oxidative stress in this study on CKD.
The positively significant correlation of SOD activity with lower RBC count, HGB concentration, and HCT (Table 5) was in line with a study, which also reported a direct correlation between HGB and antioxidant enzymes (such as extracellular SOD and catalase) (26). Oxidative stress is recognized to be a positive contributor for anaemia (27). Increased oxidative stress during anaemia is supported by a decrease in antioxidant defense enzymes, increased lipid peroxidation (27) and a greater susceptibility to the addition of pro-oxidants (28).
We also assessed the predictive ability of hematological indices and superoxide dismutase activity with chronic kidney disease using the sensitivity, specificity, accuracy, and area under the curve (Table 6, Figs. 2 (a) and 2(b)). In predicting CKD, SOD activity had sensitivity of 66% and specificity of 100% while WBC had higher sensitivity of 76% and comparable specificity of 90%. A previous ROC analysis by Costa et al, showed that lower erythrocyte SOD activity was associated with acute kidney injury (AKI) development, suggesting that SOD could play an early role as a biomarker for sepsis related AKI (29), however further validation study could ascertain whether it has a clinical role in the management of patients with chronic kidney disease. In resource-limited settings, hematological indices such as WBC could play a role in identifying and risk stratifying patients with CKD. The limitations of the study include small sample size and short duration of the study as well as non-estimation of glomerular filtration rate (eGFR) of patients.