ORIGINAL ARTICLE. FACTORS INFLUENCING LEVEL:OF BLOOD PRESSURE CONTROL IN CHRONIC KIDNEY DISEASE PATIENTS FROM ILORIN, NIGERIA. AM Makusidi, A Chijioke, MO Rafiu and EO Okoro Department of Medicine, University of lorin Teaching Hospital, lori. ABSTRACT Background: The impact of recent guidelines recommending more aggressive BP contro! in patients with chronic kidney disease (CKD) is not known in our environment. We evaluated trends and predictors of BP control among our CKD patients with a view to determining factors influencing control in comparison with the results from other studies. Methods: Records of 179 CKD patients (120 males, 59 females) with mean age of 49.0515.48 years and male to female ratio of 2:1 were reviewed. Information on sociodemographic data, causes of CKD, blood pressure (BP) control and antihypertensive drug use were sought, categorized and recorded. CKD was defined as GFR less than 60mi/min per 1.73m’, while target treatment goal was taken as systolic and diastolic BPS130mmbg and s80mmHg respectively. Results: Majority had isolated diastolic hypertension (53%) with few systolic hypertension (2%) while 27% had resistant hypertension and only 18% achieved target BP control. Pattern of drug use showed that 58% were compliant and the commonest drug combination (35%) was angiotensin receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACEI), calcium channel blocker (CCB) and Diuretics. The use of multiple drugs including ARB and ACEI was associated with better contro! of BP. Conclusions: Uncontrolled hypertension was unacceptably high among our CKD patients using the newer control guidelines. Ignorance, poverty, advancing age, lack of treatment and poor compliance to treatment were associated with poor BP control. We recommend aggressive management including the use of three or more drugs at increasing doses especially in those having PKD and chronic glomerulonephritis (CGN) as aetiology. We also advocate health education with emphasis on compliance with medication in order to forestall socioeconomic burden of end stage renal disease. Keywords: CKD, Blood Pressure Control, Factors, llorin, Nigeria. normotensive persons and adequate control of HTN can delay the onset of end stage renal disease and cardiovascular events’. Epidemiological studies from different countries have demonstrated the unsatisfactory control of arterial systemic hypertension". There is paucity of information on pattern of blood INTRODUCTION ‘The prevalence of chronic kidney disease (CKD) is increasing worldwide, and has become a major health burden '*, Hypertension in CKD. increases the risk of loss of renal function, early development of cardiovascular disease (CVD) and premature death’, It is commoner among Blacks and is responsible for considerable morbidity and mortality “’. The excess risk of end stage renal disease (ESRD) in Blacks is due to very high rate of renal failure from systemic hypertension™. In Nigeria, hypertension (HTN) is a major non-communicable disease which ranks second to chronic glomerulonephritis, (CGN) as a cause of CKD"". In developed countries, HTN is second -to diabetic Nephropathy as the commonest cause of CKD". The risk of developing CKD in hypertensive patients is double that of Correspondence: Dr A Chijioke, Baboko Post office, P.O. Box 13945, Hlorin, Nigeria, Phone: +2348070982101 pressure and factors influencing its control among CKD patients in our environment. The foregoing reasons prompted us to undertake this study. METHODS This is a retrospective cross sectional study of all CKD patients’ not yet requiring renal replacement therapy and seen from January 2000- December 2009 in the nephrology clinic of University of llorin Teaching Hospital, Ilorin, Nigeria. The demographic and clinical information including age, sex, and BP at the time of first clinic visit, body mass index (BMI) during subsequent visits, anti-hypertensive medication and social habits were documented. Information and inference ‘Sahel Medical Journal, Vol. 14 No. 2, April - June, 2011 (74 -84) 74Blood Pressure Control in Chronic Kidney Disease ‘AM Makusidi, et al. was obtained on factors responsible for poor control of BP by documenting the type of occupation, level of education, regular clinical attendance, prior knowledge about HTN and kidney diseases, importance of medication, ‘compliance on treatment and lack of orthodox medication. The foregoing information was used to assess ignorance, poverty and lack of appropriate treatment. CKD was defined by an estimated GFR<60mis/min. per 1.73m’ using modification of diet in renal disease (MDRD) study equation and /or presence of dipstick proteinuria for more than three months. Adequate BP control was defined as the BP less than or equal to 130/80 mmbg in the preceding 3 successive clinic visits following the published guidelines for disease specific definition of BP control”. Resistant HTN was defined as persistence of BP above 130/80mmHg, despite regular use of three anti- hypertensive drugs including a diuretic for at least one month. Systolic hypertension was taken as BP >130/<80mmHg while BP of <130/>80mmHg stood for diastolic hypertension. Blood pressure is routinely measured in our renal patients using a standard mercury sphygmomanometer after five minutes of rest and average of two readings taken. A cuff of appropriate size is usually applied to exposed right upper arm and rapidly inflated to 20mmHg above the level at which the pulse disappeared and then deflected gradually. Phases | and V of Korotkoff sound are taken as systolic and diastolic BP respectively. Patient was said to be complaint, if regular on medication and clinic attendance in at least the preceding 5 scheduled clinic visits. Patients with 60% clinic attendance were regarded to be adherent to clinic follow up. Data analysis was done using statistical soft ware SPSS version 16. Mean + standard deviation are used for continuous daia, student's t test for comparison of means while comparison of proportion was by chi-square test. Pearson's method was used to determine the correlation between blood pressure control, age of the patients and their body mass index The level of statistical significant was taken as p<0.05. RESULTS The sociodemographic characteristic of the patients is summarized in Table. A total of 179(120 males, 59 females) CKD patients with male to female ratio of 2:1 were studied. Majority were males, civil servants, non smokers and non alcoholics. The mean age, systolic and diastolic blood pressure of the patients were 49.05 + 15.48 years, 146 + 24.57 mmHg, and 88.44 + 14.62 mmHg respectively. The aetiology of CKD as summarized in Figure 1, shows the commonest cause of CKD was systemic hypertension (HTN), followed by chronic glomerulonephritis (CGN) and diabetic nephropathy (DN). Pattern of drug compliance shows that one hundred and four (58.1%) patients were compliant on antihypertensive medication. Pattern of BP control in the study population is demonstrated in Figure 2 Majority of the patients had diastolic hypertension (53%), few had systolic hypertension (2%), while 27% had resistant hypertension and only 18% achieved target BP control. The commonest drug combination used in 35.2% of the patients was angiotensin receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACEI), diuretic and calcium channel blocker (CCB). The least antihypertensive prescribed were beta blockers and hydrallazine. Table 2 shows there was no significant gender difference in blood pressure pattern among various BP groups(X? = 2.76, df = 3, p = 0.431). There was also no significant correlation between systolic BP and BMI (r = -0.097, p = 0.196) or the age of the patients (r = -0.025, p = 0.743). Diastolic BP correlated significantly with age of the patients (= 0.267, p= 0.001) but not with their BMI (r 0.067, p = 0.373). Table 3. summarizes categories of BP control with different causes of CKD. Patients with CGN had_ highest incidence of resistant hypertension (79.7%), patients with CPN had the highest incidence of systolic hypertension (50%), while patients with PKD had highest incidence of diastol hypertension. None of the patients with PKD had good BP control. (x? = 43.71, df= 15, p = 0.001). Table 4 depicts categories of BP control with level of education and occupation of the patients. Categories of BP control in different ‘occupational group showed incidence of resistant hypertension was highest in students (33%), traders (31%) and lowest among the civil servants (11%) and teachers (11%). There was however no significant difference in the BP. categories between the occupational groups. (= 9.30, df =12, p = 0.677). Also ‘Sahel Medical Journal, Vol. 14 No. 2, April- June, 2011 (74-64) 75Blood Pressure Control in Chronic Kidney Disease AM Makusidi, et al. Table 1: Sociodemographic characteristics of study population Variable Frequency (n = 178) Percentage (%) a ee Gender (n= 179)mate female Occupation (n= 179) students civil servant teacher trader Cigarette smoking (n= 179) smoker non-smoker Alcohol intake (1 = 179) alcoholic 120 67.0 59 33.0 46 25.7 62 34.6 36 20.1 35 19.5 12 67 167 93.3 23 12.8 156 87.2 Figure : Aetiology of CRF in the study population categories of BP control with level of education showed that those without formal education and primary school leavers had the highest resistant HTN, while the lowest was observed in those with tertiary education. Ignorance and poverty seems to ‘Sahel Medical Journal, Vol. 14 Ni ‘June, 2011 (74 - 84) contribute to the high rate of resistant hypertension as majority of patients in this category were traders with little or no formal education and students who can hardly affords the cost of therapy. Table V depicts BP categories among alcoholic and non 76Blood Pressure Control in Chronic Kidney Disease AM Makusidi, et al. Table 2: BP categories by Gender BP Categories Gender Male Female Total RESISTANT HT Count 88 36 124 % within gender 73.3% 62.1% 69.7% GOOD CONTROL Count 20 13 33 % within gender 16.7% 22.0% 18.0% SYSTOLIC HT Count 4 3 7 % within gender 3.3% 5.2% 3.9% DIASTOLIC HT Count 8 7 15 % within gender 6.7% 12.1% 8.4% Total Count 420 59 179 % within gender 100.0% 100.0% 100.0% Systolichypertension % Figure 2: BP categories in CRF patients 7Blood Pressure Control in Chronic Kidney AM Makusidi, et al. Table 3: _ BP categories by aetiology of CRF BP category Aetiology RESISTANT GOOD SYSTOLIC DIASTOLIC. HT CONTROL HT. HT Total CGN Count 51 5 2 6 64 % with aetiology 79.7% 7.8% 3.1% 9.4% 100.0% HTN Count 60 17 2 5 84 9% within aetiology 71.4% 20.2% 2.4% 6.0% 100.0% PKD Count 3 ° 0 2 5 % with aetiology 60.0% 0% 0% 40.0% 100.0% CPN Count 0 1 1 0 2 % with aetiology 0% 50.0% 50.0% 0% 100.0% DN Count 8 3 2 1 14 % with aelbioay 57.1% 21.4% 14.3% 7A% 100.0% OTHERS Count 3 6 ° 1 10 9% with Bewieay 30.0% 60.0% 0% 10.0% 100.0% Total Count 125 32 7 15 179 % with aetiology 69.8% 17.9% 3.9% 84% 100.0% Table 4: BP Categories with level of education and occupation RET Te SHT DHT Total No Formal 14 6 4 31 55 Education (26%) (11%) (7.0%) (56%) Primary 9 4 1 22 36 (25%) (11%) (2.8%) (61%) Secondary 5 9 4 14 28 (18%) (32%) (50%) Tertiary 9 13, 4 34 60 (15%) (22%) (7.0%) (67%) Students 15 6 2 23 46 (33%) (13%) (4.0%) (50%) Traders 11 3 21 35 (31%) (9.0%) (60%) Civil Servants 7 19 3 33 62 (11% 31%) (6.0%) (63%) Teachers 4 9 é 23 36 (11%) (25%) (64%) Key: RHT = Resistant hypertension, TC = Target control, SHT = Systolic hypertension, DHT = Diastolic hypertension ‘Sahel Medical Journal, Vol. 14 No. 2, April - June, 2011 (74 - 84) 78Blood Pressure Control in Chronic Kidney Disease AM Makusidi, ef al. Table 5:__ BP categories and alcohol consumption Alcohol intake BP category Alcoholic Non-alcoholic Total RESISTANT HT — Count 20 105 125 % within alcohol intake 87.0% 67.3% 69.8% GOOD CONTROL Count 1 31 32 % within alcohol intake 43% 19.9% 17.9% SYSTOLICHT Count 1 6 7 % within alcohol intake 4.3% 3.8% 3.9% DIASTOLIC HT ~—Count 1 14 15 % within alcohol intake 43% 9.0% 8.4% Total Count 23 156 179 % within alcohol intake 100.0% 100.0% 100.0% alcoholic CKD patients and there was no significant difference between the 2 groups. (X? .34, df= 3, p= 0.227). Table 6 demonstrates that there was no difference in BP categories between smokers and non-smokers. (X? associated with decreased risk of kidney disease progression, cardiovascular events and death*. Since cardiovascular risk is increased to a substantial level at BP of 1.49, df= 3, p=0.684). 130/80mmHg in CKD patients, this level of BP is considered hypertensive as against BP > 140/90 mmHg jin the general population™. Majority of patients with renal disease Table 6: BP categories and cigarette smoking ‘Smocking BP category ‘Smoker Non-smoker Total RESISTANT HT — Count 10 115 125 % within smocking 83.3% 68.9% 69.8% GOOD CONTROL Count 1 3t 32 % within smocking 8.3% 18.6% 17.9% SYSTOLICHT Count 0 7 7 % within smocking 0% 42% 3.9% DIASTOLIC HT Count 1 14 15 % within smocking 8.3% 8.4% 8.4% Total Count 12 167 179 % within smock 100.0% 100.0% 100.0% DISCUSSION of renal disease with acceleration of age Hypertension progression ofkidney disease and BP targets are at diagnosis and progression is associated with lower related loss of renal function occurs if effective antihypertensive agents are not instituted™. Prevention of rapid progression of CKD ‘Sahel Medical Journal, Vol. 14 No. 2, April- June, 2011 (74-84) 73Blood Pressure Control in Chronic Kidney Disease AM Makusidi, et al. to ESRD is therefore cheaper when compared with socioeconomic burden of managing ESRD especially in resource poor countries like Nigeria Systemic hypertension was the commonest cause of CKD, followed by CGN and DN in our study. This is in agreement with reports from some tropical and temperate countries which revealed that much of excess risk of ESRD in Blacks is due to high rate of renal failure from systemic hypertension”. It contrasts with the findings in earlier studies in the tropics which showed CGN as the commonest cause of CKD". The reason for the foregoing has been liked with variety of infective agents implicated in the aetiology of CGN which are present in endemic proportions in tropical environment”. These agents include: infected scabies”, plasmodium malariae”, schistose-miasis”, myco- bacterium leprae”, filarial worms”, toxoplasmosis”, viruses and streptococcal organisms”. However, with current trend of transition from communicable to non- communicable diseases, it is envisaged that the latter will equal or even exceed the former in developing ‘nations, thus culminating in double burden’”™. It is therefore not surprising that systemic hypertension has become the leading cause of CKD in the present study in contrast with earlier studies in which CGN due to infectious and communicable diseases predominate. The pattern of BP control shows that only 18% of these CKD patients achieved recommended target of 130/80mmHg while 27% had resistant hypertension with 2% and 53% having isolated systolic and diastolic hypertension respectively. Patient factors that may have impeded BP control include lack of primary care providers, non-adherence to medications and non-compliance with dietary guidelines. Risk factors found in other studies include non-adherence due to lack of understanding of the importance of BP control in preventing progression and complication of CKD, cognitive difficulties associated with CKD, intolerance of drug side effects and high cost of medication“. Elevated BP is an established risk factor for the development and progression of CKD. The control of BP to evidence based targets with appropriate anti- hypertensive agents has the potential of preventing serious consequences of CKD‘ Experimental studies have suggested thai systemic hypertension can be transmitted to glomeruli and that glomerular hypertension is injurious to the kidneys”. Hypertrophic and hyperplastic changes that follow nephron loss and increased protein ultra-filtration are important factors in progressive kidney damage™, The markedly lower BP threshold for kidney damage necessitates that blood pressure should be lowered to normotensive range in order to prevent progressive kidney damage". Our findings on pattern of BP control contrasts sharply with observation from similar studies in USA\n which 37% of the patients achieved target BP control and out of those with uncontrolled blood pressure, 59% had systolic hypertension while 7% had diastolic hypertension”. Our finding is however close to 13% target BP of <130/80mmHg observed in Norway renal unit patients and lack of optimal BP was mainly due to systolic hypertension which contrast with our ‘observation in which diastolic hypertension predominates”. The disparity in the findings may be related to relative high rate of poor compliance to anti-hypertensive medication as 42% of our study patients were not regular on drugs. Experimental surveys from different countries have also demonstrated the unsatisfactory control of arterial systemic hypertension"*”""*, Our finding of isolated diastolic hypertension in 53% of patients differs markedly from 7% reported in the United States”. Also of note, is the rarity of isolated systolic hypertension among our CKD patients in comparison with very high rate from United States”. The reason for the difference in prevalence of isolated systolic hypertension is not clear. It may be related to differences in lifestyle, choice of anti- hypertensive drug and more importantly, disparity in predominantly affected age bracket. Majority of our patients were in their third and fourth decade in contrast with fifth and sixth decade in developed countries. Earlier studies have documented the peak age range in CKD Patients to be third to fourth and seventh to eight decades in Blacks and Whites respectively" ©. This has been linked with pattem of diseases causing CKD in both populations’”*""*". The relatively young age at which patients with CKD due to CGN present in the tropics have been reported by several authors’*"*"""*. It has been ascribed to variety of infectious agents implicated in the aetiology of CGN which are present in endemic proportions”. The older age of patients with advanced CKD in developed countries may be responsible for the ————————————————— ‘Sahel Medical Journal, Vol. 14 No. 2, April-June, 2011 (74-84) 80Blood Pressure Control in Chronic Kidney Disease AM Makusidi, et al, high prevalence of systolic hypertension as recent data have documented higher prevalence of systolic hypertension among elderly CKD patients" ‘There was no significant gender difference in the proportion of patients from various categories of BP control in our study. This is in accord with report of Duru et al” in which there was no significant gender difference in blood pressure control among African-Americans with CKD. It however contrast with findings from other related studies in which females with CKD were at greater risk for uncontrolled blood pressure”**". Our observation that cigarette smoking and alcohol consumption did Not significantly influence the pattern of blood pressure control is difficult to explain as both are risk factors for cardio-vascular disease and progression of CKD. This may be related to very low prevalence of both social habits among our patients which could have blunted any association with BP control. In a special study of case mix severity, cigarette smoking increased mortality rate by 26% in ESRD patients”. In relation to aetiology, patients with CGN had the highest incidence of uncontrolled hypertension while those with CPN achieved better target blood pressure. However, incidence of diastolic and systolic hypertension was highest in patients with polycystic kidney disease (PKD) and chronic pyelonephritis respectively. The variability in the pattem of BP control may be linked with differences in pathogenic mechanism involved in the genesis of hypertension in both conditions. Occupational status did not significantly influence the pattern of BP control in this study. This is in agreement with a related study that revealed that socio-economic factors including higher level of education, insured status and high income were not associated with increased risk of uncontrolled hypertension after adjustment for demographic and clinical characteristics. It suggests that physiologic factors may have dominated socio-economic influence on BP control among CKD patients. The commonest drug combination utilized in treatment of hypertension in our study was angiotensin converting enzyme inhibitor (ACEI), calcium channel blockers (CCB), angiotensin II receptor blocker (ARB) and diuretics. ARBs and ACEls have emerged as leading drugs in the treatment of hypertension among CKD patients®. Both medications inhibit renin angiotensin system which play pivotal role in pathogenesis of hypertension in CKD, slow progression of the disease and reduce risk of death from cardio-vascular disease independent of their BP lowering effects”. A survey showed that physicians in training selected a BP target of 130/80 mmHg and 98% of them identified ACEVARB as part of the treatment plan, thus indicating that knowledge of CKD management guidelines is gaining wider recognition” We therefore Tecommend judicious use of these classes of anti-hypertensive agents in addition to diuretics among our CKD patients, being mindful of the presence of renal artery stenosis, In conclusion, uncontrolled hypertension was unacceptably high among our CKD patients using the newer control guidelines. 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