Francois et al[70] noted a mean age of 47.6±14.3 amongst patients with CKD in Cameroon. The majority of subjects were between 40 and 49 years, with a peak age of between 45 and 49 years. This observation has also been corroborated by other researchers in Nigeria[35,71] and other developing countries,[72,73,75] but this contrasts with the observations in developed countries, where patients are usually elderly.[74]
There was a male preponderance in this study, with M:F percentages as 66.3%:36.7%. Ulasi and Ijoma also recorded male preponderance in South-East of Nigeria of 65.3%:34.7%.[71]
Yaw and colleagues, reported a similar observation in their study amongst 203 participants with CKD in Ghana with M:F percentages of 64.5%:35.5%. This is comparable to studies done in Spain,[76] and United States of America,[77] which also reported a male predominance of 60.9%:39.1% and 61.2%:38.8%
respectively in patients with CKD. The male predominance might be a reflection of the fact that CKD and its risk factors such as hypertension are commoner in males than females. Differences in the health seeking behaviors of males and females might also play a role in the observed differences in CKD prevalence in the two sexes.[75]
Relationship of the risk factors and CKD stages
Three leading risk factors for CKD were observed amongst the 120 participants recruited into this study: hypertension (30.8%), diabetes mellitus (25.0%), and glomerulonephritis (20.8%). Of these, 3.3% of the participants had both HTN and DM.
Available literature from other studies done in Nigeria[35] and Ghana [73,78,79]
have identified chronic glomerulonephritis and hypertension as the commonest causes of CKD with diabetic nephropathy ranking third. In developed countries DM is the commonest cause of CKD. [74]
Francois et al, in their own study of 95 patients with CKD in Cameroon observed hypertension, diabetes and HIV infection as the most common causes of CKD in their study population.[70] Yaw and his colleagues in Ghana described chronic glomerulonephritis (33.0%), hypertension (21.2%) and diabetes mellitus (22.2%) as the common causes of chronic kidney disease in their study.[75]
In this study, the majority of the 120 subjects were in advanced stages of kidney disease, 108 (90%) were in stage 5 CKD, 8 (6.67%) were in stage 4, and 4 (3.33%) were between stages 1 and 3 disease. This is similar to the findings of Abdu at the Muhimbili National Hospital in Dar es Salaam, he
recruited 100 subjects with CKD into his study. 78% were in stage 5 CKD, 13% in stage 4, with stage 4 and stage 5 both accounting for 91% of the study population. Few patients (9%) were in early CKD (stage 1-3).[ 83] This is similar to finding in other developing countries,[ 71, 75] unlike the situation in developed countries. This late presentation might be due to a host of factors which include: lack of regular screening programmes for kidney function, late referral to specialist centers from primary healthcare providers, inadequate education on the risk factors/ clinical symptoms of CKD. The lack of health care insurance coupled with the high cost of health care services as well as the use of alternative consultations like spiritualists and traditional healers; may also contribute to the late presentation of patients.
Haematological Profile
This study shows a significant difference in all the haematological parameters measured between the study group and controls except MCV, MCHC and platelet count (shown in Table 6). The majority of subjects had moderate anaemia (85%), with mean of haemoglobin concentration of 8.6±1.1g/dl (study group) and 11.2±2.0g/dl (control group). is a progressive This is in keeping with the findings of other researchers.[60,61,62,63,69] The significant difference in the haemoglobin concentration, total red blood cell count, PCV, and MCH observed between the study and control groups can thus be explained: CKD
patients had more advanced kidney disease (stage 5); there is a decline in haemoglobin concentration, total red cell count PCV, and MCH with disease progression. This can be explained by a the reduction in the synthesis and serum levels of erythropoietin which is a major drive for erythropoiesis in the bone marrow.[69]
There was a significant difference (p=0.007) in the total white blood cell count between the study and the control population of 13.6±6.3 (×109/L) and 10.8±3.5 (×109/L) respectively. This may be attributed to the higher risk of systemic infections in the study population. In the study group 32% of them were on haemodialysis, whereas no participant in the control group was on dialysis. This observation is also corroborated by epidemiological studies which pointed that infectious such as Urinary tract infection (UTI), septicaemia and pneumonia occur most commonly in hemodialysis patients.[80,81]
There was an observable difference in the platelet count of the study and control groups: 215.5±97.7 (×109/L) and 221.2±87.8 (×109/L) respectively, although the difference was not statistically significant (p=0.798). This observation is similar to findings by other authors, they established thrombocytopaenia at the severe stage (stage 5) of CKD.[60,61,62,63,69]
Blood Group Distribution
Blood group O (54.2%) was the most prevalent blood group amongst the participants (study and control groups), however an increased risk of HLA sensitization was recorded among blood group A subjects (92%).
The prevalence of blood group O in this study; is similar to the findings by Wasan and his colleagues, they studied the relationship between progression of renal failure and ABO blood groups system; the percentage of the patients that carried O blood group was the highest (55%) followed by the A blood (25%), B blood group (12.5%) and AB blood group (9.4%).[81] There was another study which compared the frequency of ABO blood groups distribution among 184 patients with renal parenchymal diseases and 3820 apparently healthy subjects. The occurrence of kidney diseases was mainly in B and O blood groups. Patients with CKD had a 7% increase in O blood group.[83] There is however no established reason(s) for the association with the blood group and chronic kidney disease.
HLA Class I alloantibodies in CKD patients
Most of the study group subjects showed alloimmunization to HLA Class I antibodies, 88% of them had high sensitization to HLA Class I antibodies.
Only one of the subjects in the control group tested HLA antibody positive (intermediate sensitization). This patient is a 54 year old female with diabetes
mellitus and she had carried five pregnancies to term. Comparison of %PRA in the study and control groups reached statistical significance, p=0.000.
Relationship between HLA Class I Alloantibodies and Gender
This study showed higher prevalence of HLA Class I antibodies in female subjects. There was a significant difference in the mean %PRA of males (38.10±27.64%) and females (61.4+25.51%) in the study group. p=0.000. The reason for this observation in the females may be due to previous maternal/fetal blood exposure during childbirth.
Researchers at the Leiden Medical Center studied the impact of a single, non-leukocyte depleted transfusion among 21 non-sensitized male recipients and 20 female recipients sensitized through pregnancy. Respective rates of sensitization among these patients were 9.5% and 35% respectively.[89] Report shows that without prior transplantation, the most likely cause of HLA sensitization among males is blood transfusion.[89]
Relationship of HLA Class I Alloimmunization and Blood Transfusion This study showed significant increase in HLA Class I alloimmunization (%PRA) with increasing number of blood units transfused. r= 0.842, p= 0.000.
Juan and his colleagues studied the impact of pre-transplant transfusions and allosensitization on renal transplant and allograft survival.[96] They identified a
total of 7494 citations, of which 206 citations relating to 180 studies were relevant to their objectives. They reported that patients that had > 5 transfusions showed positive panel reactive antibodies, compared with patients not transfused. They also observed that allosensitization was increased in pre-transplant patients with also prior blood transfusions.[96]
Most authors have reported HLA specific antibodies induced by blood transfusion as a major clinical complications impacting transplant outcomes.[90]
Leukocyte-depleted (leuko-reduced) blood has been shown to reduce HLA allo-immunization., however, it is clear that even with leuko-reduced blood, there still exists potential for HLA sensitization, which contributes to the pathology of chronic rejection.[91] Limited data is available to show whether Erythropoietin stimulating agent (ESAs) reduce the incidence of HLA
sensitization in CKD patients. There are several early reports that indicate the use of erythropoietin reduced rate of transfusion and hence this might improve transplant outcomes.[92,93,94,95] In one of these studies, Vella et al.[95] observed a 34% decrease in the number of transfusions among haemodialysis patients.
Notably, the number of patients sensitized as a consequence of blood transfusion decreased significantly from 63% in the cohort of patients pre-erythropoietin to 28% in the group post-pre-erythropoietin and the overall incidence of sensitization decreased from 50% to 36.5%.[95]
HLA Class I Alloantibodies and Estimated Glomerular Filtration Rate This study showed an increase in the development of HLA Class I alloantibodies (%PRA) with reduction in eGFR. r=-0.330, p=0.001. Decreasing glomerular function (as seen in advanced CKD), is accompanied with worsening kidney disease and anaemia, hence these group of patients will require more blood transfusions and therefore may become more likely to develop alloimmunization to HLA Class I antibodies (increasing %PRA).
Relationship between HLA Class I alloantibodies and CKD risk factors Transfused CKD patients with diabetes mellitus have the highest %mean PRA of 75.60±15.02% as compared with 39.39±22.90% and 22.38±18.14% for subjects with hypertension and glomerulonephritis respectively.