The quality of life of chronic kidney disease patients with hypertension treated with angiotensin system-related agents

The chronic kidney disease (CKD) co-exist with hypertension in approxi-mately 80 to 85 per cent of patients. The CKD stages can be de(cid:977)ined by glomerular (cid:977)iltration rate (GFR), and the deterioration of kidney function or reduction in GFR has observed in those with uncontrolled blood pressure (BP). We had conducted a prospective study to analyse the impact of the angiotensin system-related agents on the quality of life of CKD patients with hypertension. The SF-36 questionnaire, direct patients interview and medical records were the sources for retrieval of information. We observed that male patients were more prone to CKD than female. Hypertension was the primary (77.8%) aetiology behind the incidence of CKD. The angiotensin-converting enzyme inhibitors (ACEI) was responsible for very low (58%) and low (44%) health disabilities to the patients. In contrast, the angiotensin receptor blockers (ARB) even though it has a limited adverse effect, the patients complained of medium (9%) and high disabilities than the ACEIs. The discontinuation of the antihypertensive drugs by the CKD patients was almost negligible (3.4%). The study concludes that a balanced diet and reasonable blood pressure control is essential to prevent the progression of CKD and to improve the quality of life.


INTRODUCTION
The Kidney Disease Improving Global Outcomes (KDIGO) has de ined chronic kidney disease (CKD) as abnormalities of kidney structure or function presented for greater than three months with implications for health (Kidney International Supple-ments, 2013). Hypertension and CKD are interrelated and represent global public health challenges. The progression of kidney impairment may be due to changes in the demographics of the population, differences in disease burden among age groups and under-recognition of earlier stages of CKD and risk factors for CKD may partially explain this growth (National Kidney Foundation, 2002). We had conducted an epidemiological study on hypertension with CKD in our locality.

Methodology
The prospective observational study was conducted at the nephrology department of KIMS Al Shifa hospital, tertiary care referral hospital from October 2018 to August 2019. The ethical committee approval and informed consent were obtained.
The chronic kidney disease outpatients with hypertension were enrolled, and they were followed up for three consecutive consultations. The study focused on angiotensin system-related agents; those are the angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Patients with acute kidney injury, unconscious or those with serum creatinine greater than 3.5mg/dl are excluded from the study. The SF -36 questionnaire assessed the patients' quality of life. Direct patient interview, discussion with a physician, medical record database and prescription were the source for retrieval of patient demographics details, aetiology, stage and duration of CKD as well as blood pressure, glomerular iltration rate.
The data collected was spread into an excel sheet which was then imported into Statistical Package Of Social Science (SPSS) software version 23. The Chisquare was applied to relationships among the different variables and the repeatability among clinical parameters, respectively.

RESULTS AND DISCUSSION
Total of 495 patients was enrolled in the study as per the study speci ication. CKD was prominent among the age group above 60 years (Park et al., 2011). In our study, we observed a similar observation and the least below to the age of 50 years, as per Table 1. However, the pattern had extended down to adults, and this could be due to several factors such as over usage of medicines especially NSAIDs (Baker and Perazella, 2020), inherited disease (Hildebrandt, 2010) and lifestyle changes (Shankar et al., 2006). The people in the United States and Norway had a large density of CKD patients below the age of 65 years (Hallan et al., 2006). The early detection of kidney deterioration may be due to fetal nephrotoxicity of drugs administered by pregnant ladies. The practice of polypharmacy might be a reason for the early age diagnosis of CKD among their offspring (Bernstein et al., 1998).
Man (60.4%) had more prevalence of CKD with hypertension than female (Ojji et al., 2009). When Figure 2: The association between stages of CKD concerning the age of the patient we analysed the chronic kidney disease patient's stage, 46.9% had stage 3 CKD followed by stage 4 (36.8%) and only one person in stage 5 (End-Stage Renal Disease). The study conducted in Karnataka also had a high prevalence of CKD stage 3 patients, then followed by stage 4 (Duan et al., 2019). Only a few patients (16.1%) were identi ied to be in stage 1(4.8%) and stage 2 (11.3%), as shown in Table 2. From our study, 66 and 69 patients belong to the age group between 60 to 70 had stage 3 and stage 4 CKD, respectively.

Figure 3: The association between the CKD stage with the gender of the patient
Even though the total patients in stage 2 were small, most patients belonged to 60 to 70 years age group, which was followed by those with age between 50-60 years. Only in stage 1 and stage 5, we observed the patients with age less than 50 years. From Figure 2, the relationship between age and stages of chronic kidney disease was analysed with the chi-square test. There was a statistical difference in the occurrence of various stages of the disease according to age (P<0.05). Hence, we reject the null hypothesis; there is signi icance between the age and the stages of chronic kidney disease.
Only 13 female CKD patients were observed to be more in stage 1 than the male. However, while the stage progressed, the contribution of the male was superior. This association was evaluated with the chi-square test, and the inference showed to have no signi icant difference among male and female for dif-  52.32% of patients had lean body weight between 55 to 65kg, and those below 55 kg were the least. The Cockcroft-Gault equation, the tool widely used to calculate the creatinine clearance (one of a parameter to analyze the kidney function). Accordingly states that, an increase in lean body weight without a proportional increase in serum creati-nine will tend to have a favourable impact on the patient (Walker and Whittlesea, 2015). Hence, a healthy diet would improve the patients well being as well as prevent the progress of CKD (Rysz et al., 2017).
The quality of life (QOL) of 93.9% patient under treatment had low or very low disabilities, as shown in Table 3. The age, gender, stage of CKD and presence of other co-morbidities can affect the quality of  (Lekpa et al., 2017).
Majority of CKD patients of stage 1,2,3,5 had very low disabilities as observed from Figure 4. However, stage 4 had less health satisfaction compared to other stages. Chi-square test analysis rejected the null hypothesis, and it was found that there was a signi icant difference in Quality of Life (QOL) among various stages of CKD (P>0.05).
Hypertension is a risk factor for the onset and progression of CKD, a reduction in the glomerular iltration rate (GFR), occurs at a variable rate, rang-ing from less than 1 to more than 12 mL/min per 1.73 m 2 per year (Levey et al., 2011). The primary cause of progressive kidney damage is found to be due to hypertension which accounts to have a 77.8% distribution among the total chronic kidney disease patient on angiotensin related drugs, as shown in Table 2. This put light that elevated BP is one among the predominant cause of kidney damage than diabetes mellitus (Walker and Whittlesea, 2015).

Figure 4: The association between the CKD stage with the patient's Quality of Life
Increased awareness and treatment of hyperten-sion among CKD patients had improved blood pressure control. Each of the antihypertensive agents is roughly equally effective in lowering the blood pressure, producing an excellent antihypertensive response in 30 to 50 per cent of patients. Joint National Committee (JNC) 8 recommends initiating a renin-angiotensin-aldosterone system (RAAS) inhibitor, thiazide diuretic or a calcium channel blocker for normalising the blood pressure in CKD patients. Among them, ACE inhibitors or ARBs was most frequently administered drug (39%) as monotherapy followed by calcium channel blockers, diuretics and beta-blocker (Ridao et al., 2001).
The angiotensin receptor blockers opted by the nephrologist in our study was losartan (37.6%), telmisartan (18.2%) and olmesartan (0.4%). The prescription pattern of the physician also had more ramipril (39.2%) than enalapril (0.4%), as observed in Table 3. In a meta-analysis on 22 studies, Wang et al. indicated that olmesartan provided greater reduction in both diastolic and systolic blood pressure than losartan and systolic blood pressure compared to valsartan (Wang et al., 2012). In the HOPE and EUROPA trails, ramipril had a better outcome than placebo.

Figure 5: The association between the Quality of Life of the patient with the ACE Inhibitors and Angiotensin Receptor Blockers
We obtained a greater strength (23.2%) among the group who had been diagnosed with the disease more than ive years, followed by those with a duration between 1 and 2 years and least was observed in the group with a duration between 1 to 6 months, shown in Table 2. Majority of the CKD population had the long-standing disease (greater than ive years), this can be attributed to the suppression of known "causes" of progression by targeting high blood pressure (BP) as well as the impact of reninangiotensin system (RAS) related drugs (Brenner et al., 2001).
In particular, an elevation of 20 mm Hg accounts for many increased mortality (Forouzanfar et al., 2013). There are two major components to slow the rate of progression of CKD: treatment of the underlying dis-ease, if possible; and treatment of secondary factors that are predictive of progression, such as elevated blood pressure (Coresh et al., 2001 (Tozawa et al., 2003). We had patients with poor blood pressure control which could be attributed to the advancement of CKD irrespective of gender.
The discontinuation rate was found to low (3.4%), and among them, ramipril (1.8%) was the main culprit, shown in Table 3. ARBs have demonstrated excellent safety pro iles alone and in combination with other antihypertensive therapies during the past 20 years. The tolerability pro iles of ARBs are similar to placebo and superior to ACE inhibitors.
The risk of discontinuation for an adverse event was reduced by 29% with ARB treatment, by 10% with diuretics, and by 2% with calcium-channel blockers. In contrast, it was increased by 18% with ACE-inhibitors and by 13% with beta-blockers (Barreras and Gurk-Turner, 2003). The health status of patients on ACEIs was better than ARBs, observed in Figure 5. The null hypothesis was accepted using chi-square analysis, and it was observed that there is no signi icant statistical difference (P>0.05) among the administration of angiotensin related drugs on patients Quality of Life (QOL).

CONCLUSIONS
Proper diet and blood pressure control had more signi icant impact on the progression of CKD. Hence the administration of a safer drug, ACEI was found to in luence the quality of life of the patients. Even though ARBs claim to have a lesser side effect, patients had much better health outcomes with ACEI.

Con lict of Interest
The authors declare that they have no con lict of interest for this study.

Funding Support
The authors declare that they have no funding support for this study.