Abstract
Chronic kidney disease (CKD) is common in tropical Africa although there are few data on the prevalence of this disorder. Therefore we initiated a multicenter screening study to identify the prevalence and staging of CKD in 712 patients with known hypertension in four polyclinics in Accra, Ghana. We measured estimated glomerular filtration rate by the six-variable modification of diet in renal disease equation and proteinuria by the protein/creatinine ratio. All the subjects studied were Ghanaian. Of the 712 patients studied, the median age was 59 years (range 19–90 years) and 560 (78.7%) of the patients were female. The mean duration of hypertension was 4 years (range 0.1–50). The overall prevalence of CKD was 46.9% (95% CI: 43.2–50.7%); 19.1% had CKD stages 1–2 and 27.8% had CKD stages 3–5. There was no difference in age between patients with or without CKD (p = 0.12). The overall prevalence of proteinuria was 28.9% (95% CI: 25.6–32.4%); 14.7% of subjects had preexisting diabetes mellitus and their prevalence of CKD (55%; 95% CI: 42.4–62.2) did not differ from those without diabetes (46%; 95% CI: 41.9–50.0, p = 0.133). CKD is common in hypertensive patients in Ghana, with a prevalence of 46.9%. This provides justification for the inclusion of this group in CKD screening programs in Ghana.
INTRODUCTION
In studies from the United States, Europe, Asia, and Australia chronic kidney disease (CKD) affects between 5% and 15% of the adult population,Citation1–4 making this a major public health problem.Citation5 The more severe stages of CKD (3–5) are a major risk factor for cardiovascular disease as well as for more severe renal failure (CKD stages 4 and 5).Citation6 Although CKD is common in tropical Africa, there are few data on prevalence and little is known about progression in patients with this disease. Previous studies from Africa show a prevalence of CKD of 10.4%Citation7 and proteinuria of 12.4%.Citation8
Hypertension is recognized as an important cause of CKD. In one study from Ghana, of 365 outpatients with hypertension, 110 (30.2%) had serum creatinine >140 µmol/L (1.6 mg/dL), 48 had serum creatinine >400 µmol/L (>4.5 mg/dL), and 96 (25.5%) had proteinuria.Citation9 In another study from Burkina Faso, 117 out of 317 (44%) patients with hypertension who were hospitalized had chronic renal failure.Citation10 In an autopsy study, we showed that hypertension was an important cause of end-stage renal failure in Ghana, accounting for 33 out 78 (42%) cases.Citation11 This apparent high prevalence of CKD in patients with hypertension is important for two reasons. First, hypertension is common in many parts of tropical AfricaCitation12 with prevalence in adults in Ghana of over 28%.Citation13,Citation14 Second, facilities for the treatment of end-stage renal failure are not available or are unaffordable in tropical Africa. For these reasons, a study of the prevalence of CKD in patients with hypertension and the institution of measures to slow its progression is of great importance in these areas.
MATERIALS AND METHODS
This study was a prospective cross-sectional survey of hypertensive patients aged over 16 attending four polyclinics in Accra, Ghana. The subjects enrolled in this study were all being followed up for hypertension and were on treatment. After obtaining informed consent, demographic data were obtained using a questionnaire.
The blood pressure was recorded after a 5 min rest using a mercury sphygmomanometer with a standard or a large cuff.
Serum creatinine was determined using the Jaffe reaction in continuous flow on an ATAC 8000 automated chemistry analyzer. Urine creatinine concentration was measured using rate alkaline picrate methods with the ATAC 8000 automated chemistry analyzer.
The protein in the urine was precipitated with trichloroacetic acid and redissolved in alkali. The urine protein was measured colorimetrically using the Biuret reaction. The urine protein/creatinine ratio (PCR) was reported as mg/mg. Proteinuria was defined as a PCR greater than 0.3 in women and 0.2 in men.
The estimated glomerular filtration rate (eGFR) was calculated using the modification of diet in renal disease (MDRD) six-variable prediction equation Citation15 as follows: eGFR = 170*(scr) −0.999 × (age) −0.176 × (bun) −0.176 × (alb) +0.318 × 0.762 (if female) × 1.178 (if Black). Estimated GFR is reported as mL/min/1.73 m2.
The CKD stages were defined using the kidney disease outcomes quality initiative classification.Citation16
Statistical Analysis
All analyses were performed with StataCorp 2007 (Stata Statistical Software: Release 10, StataCorp LP, College Station, TX, USA). Continuous variables were summarized by their means and standard deviations or median and range and categorical variables as percentages. Differences in normally distributed continuous variables were compared using Student's t-test, in nonnormally distributed data by the Mann–Whitney U test or the Kruskal–Wallis equality-of-populations rank test, and in proportions by the χ2 test.
Institutional Ethical Clearance
This study was approved by the research and ethics committees of the Ghana Health Service and University of Ghana Medical School and undertaken in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. All patients gave written informed consent.
RESULTS
Demographic and Baseline Laboratory Data
Of the 712 participating patients, there were 152 males (21.3%) and 560 (78.7%) females as shown in . The median (range) age of the patients was 59 years (19–90) years and the median (range) body mass index (BMI) was 29.7 (12.2–67.4). The median systolic blood pressure was 150 mmHg (100–280) and the median diastolic blood pressure was 90 mmHg (60–160). The median duration of hypertension was 4 years (0.1–50.0). The median number of hypertensive drugs used was 2 (0–5), with 179 (25.1%) of the patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Other drugs taken were calcium channel blockers by 592 (83.1%), beta blockers by 255 (35.8%), and diuretics by 394 (55.3%) of the subjects.
Table 1. Demographic and clinical characteristics of participants
Using the kidney disease outcomes quality initiative staging of CKD, the overall prevalence of CKD was 46.9% (95% CI: 43.2–50.7). The percentage of subjects with an eGFR ≥ 60 mL/min/1.73 m2 with proteinuria (CKD stages 1–2) was 19.1% and with an eGFR of <60 mL/min/1.73 m2 (CKD stages 3–5) was 27.8%. The prevalence of proteinuria was 28.9% (95% CI: 25.6–32.4). There was no difference in age between patients with CKD (57; 27–89) and without CKD (59; 19–90), p = 0.12.
One hundred and five patients had diabetes mellitus (14.7%) and their data are compared with patients without diabetes in . There was no significant difference in the prevalence of CKD in patients with diabetes (52.4%; 95% CI: 42.4–62.2) as compared with patients without diabetes (46.0%; 95% CI: 41.9–50.0), p = 0.133. Cardiovascular disease, mostly cerebrovascular accidents were found in 4.9% of the patients. This did not differ between patients with diabetes or without diabetes (p = 0.392). Patients with diabetes were more likely to have a higher BMI than patients without (χ2 = 8.1; p = 0.02), and they had a higher urine PCR 0.2 (0–11.8) compared with 0.1 (0.1–17.1), p = 0.001. Patients with diabetes were more likely to be treated with angiotensin blockade 61.5% versus 19.6% (p < 0.001) and had a lower hemoglobin (p = 0.026). There was no difference in systolic or diastolic pressure between patients with diabetes and those without diabetes.
Patients with the more advanced stages of CKD were younger than patients with the earlier stages (p = 0.0001) as shown in . Patients with CKD1, 2, and 4 had higher levels of proteinuria than patients with CKD3 and 5. Although CKD occurred more frequently in older patients, the difference was not significant (χ2 for trend, p = 0.901), see . Cardiovascular events were few and did not correlate with the severity of CKD.
Table 2. Characteristics of patients by CKD stage
DISCUSSION
We screened 712 patients with known hypertension for CKD. Individuals were invited to enroll for this study, so this was not a random selection of patients with hypertension in Ghana. In keeping with this, approximately 80% of the patients studied were female. For these reasons, our findings cannot be generalized to the whole population. With these provisos, our data from Ghana show a high prevalence of CKD of 46.9% (95% CI: 43.2–50.7) in outpatients with hypertension in Accra. Of particular concern 27.1% of patients had significant CKD with a eGFR of <60 mL/min (CKD stages 3–5). Hypertension is recognized to be an important cause of chronic renal failure in outpatients as well as in inpatients in Africa.Citation9,Citation10 In a 6-year study of 3632 patients with end-stage renal disease (ESRD), based on South African Dialysis and Transplant Registry statistics, hypertension was reported to be the cause of ESRD in 4.3% of whites, 34.6% of blacks, 20.9% of mixed ethnic group, and 13.8% of Indians.Citation17
There are few data on the prevalence of CKD from Africa. Sumaili et al. reported a prevalence of proteinuria of 12.4% in a randomly selected population in the Democratic Republic of Congo.Citation8 In a “high-risk” population in the same country with diabetes, hypertension, HIV infection, or obesity, the prevalence of CKD was 36%.Citation18 In Nigeria Afolabi and colleagues reported that 10.4% of patients in a family medical practice had an eGFR <60 mL/min.Citation7
An important observation in our study was that 28.9% of the patients studied had proteinuria. The degree of proteinuria was higher in CKD1, 2, and 4 than in CKD3 and 5 and we have no good explanation for that. The causes of the proteinuria were not sought in our study but could be due to hypertensive renal damage, diabetes, or an underlying glomerulonephritis. Patients with diabetes had a significantly higher level of proteinuria than patients without diabetes. CKD was also more common in patients with coexistent diabetes at 50.5%, but this did not differ significantly from patients without diabetes at 44.7%.
Good blood pressure control and angiotensin blockade are known to be important in slowing down the progression of kidney failure.Citation19 In our study, blood pressure control was poor with a median blood pressure of 150/90. Furthermore, only 19.6% of patients without diabetes were treated with angiotensin blockade as compared with 67% of patients with diabetes. Clearly the benefits of angiotensin blockade in patients with diabetes and proteinuria were better recognized than in patients without diabetes. This is a target for ongoing education for patients and medical and nursing practitioners.
CKD is established as a major risk factor for cardiovascular disease.Citation6 In our study, prior myocardial ischemia or heart failure was found in only 0.7% of patients. This is in keeping with the relatively low rates of myocardial ischemia in Ghana.Citation20 Cerebrovascular accidents were more common and found in 4.2% of patients. There was no correlation between worsening renal function and cardiovascular disease but the numbers of events were small. This apparent low risk of cardiovascular disease in our patients with CKD is unexplained, and if confirmed in other studies from Africa, it would be of interest in view of the higher risk described in other parts of the world.Citation6 In contrast to previous studies, patients with a lower eGFR were significantly younger than patients with a higher eGFR.Citation3 They also had a higher blood pressure. Unlike in other studies, where the prevalence of CKD is higher in females than in males,Citation3 we found the prevalence to be the same.
There are several limitations to our findings. First, the serum creatinine measurement was not isotope dilution mass spectrometry traceable and this makes the eGFR calculation using the MDRD equation inaccurate. Second, CKD assessment was based on single serum creatinine and urine protein measurement. Third, we have not validated the MDRD equation in Ghana. The MDRD equation has, however, been validated in South African blacks and the four-variable MDRD equation without the ethnicity factor of 1.212 accurately reflected isotopic GFR.Citation21 If we followed this conclusion, this would increase the prevalence of CKD. With these provisos, we report a high prevalence of CKD in hypertensive patients in Ghana. Hypertension is common in Ghana and affects approximately 30% of the adult population.Citation13,Citation14 The high prevalence of CKD found in our study if confirmed is of great public health concern.
The high prevalence of hypertension-related CKD in our study merits comparison with African Americans who share a common ancestry with Ghanaians. African Americans have a 3.7 times higher age-adjusted risk of ESRD.Citation22 As compared with whites, male African Americans with hypertension are 2.1–2.2 and females 2.8–3.6 times more likely to develop end-stage renal failure.Citation23 The recently described association between nondiabetic CKD, focal segmental glomerulosclerosis, and hypertensive ESRD in African Americans and the non-muscle myosin heavy chain type II isoform A (MYH9) gene polymorphismsCitation24–26 may be of relevance to Ghanaians with CKD.
Some patients with CKD3 will eventually progress to end-stage renal failure. Follow-up of patients in our study will provide useful insight into the clinical course of CKD in Africa. In Ghana as in the rest of Africa, most people with end-stage renal failure die because of the lack of resources for treatment. Our study does, however, suggest the importance of screening for CKD in resource-poor areas as good blood pressure control and treatment with angiotensin blockade slow deterioration of renal function.Citation27,Citation28
Acknowledgment
This work was supported by a grant from the Association of Physicians of Great Britain and Ireland.
Declaration of interest:
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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