An Observational Study on Management of Refractory Hypertension in patients with Chronic Kidney Disease Stage-V on maintenance Haemodialysis

 

Nazma1, Syeda Zuleqaunnisa Begum2, Mohammed Fareedullah3, Shaik Abdul Kareem4,

Anjum Fatima4, Asfia Firdous4, Sulaiman Abdul Majeed4

1Professor, Department of Nephrology, Owaisi Hospital and Research Centre.

2Assistant Professor, Department of Pharmacy Practice, Deccan School of Pharmacy.

3Associate Professor, Department of Pharmacy Practice, Deccan School of Pharmacy.

4Pharm. D Student, Deccan School of Pharmacy.

*Corresponding Author E-mail: najju.2k3@gmail.com, syedazuleqaunnisa@gmail.com

 

ABSTRACT:

Refractory hypertension (RfHTN) presents a challenge in managing patients with chronic kidney disease (CKD) and undergoing maintenance haemodialysis (MHD). Hypertension exacerbates kidney function loss and adversely impacts CKD patients' quality of life. In order to enhance the quality of life for patients with stage-V chronic kidney disease (CKD) receiving maintenance hemodialysis, the study set out to detect, define, and treat refractory hypertension (RfHTN). A six-month prospective observational study was carried out at a tertiary care hospital's outpatient dialysis unit. Patients with CKD on MHD and uncontrolled blood pressure (BP) despite ≥5 antihypertensive medications were enrolled. BP monitoring pre- and post-dialysis was performed thrice weekly. The effect of antihypertensive agents was evaluated using symptom frequency, target BP, medication adherence (MMAS-8 Score), kidney disease quality of life (KDQOL-36 score), and adverse effects monitoring. 50 participants were enrolled, with a higher percentage of male patients (60%). Significant differences in systolic BP and pulse rate were observed pre and post-dialysis. In our research, approximately 48% of the participants fell within the adult age range (25 to 65 years), while only 2% were classified as elderly, aged (65 years and above). In the BMI distribution, a significant portion of patients showed diverse weight categories: 18% were underweight, 64% fell within the normal weight range, 16% were overweight, and 2% were classified as obese.A notable variation in hemoglobin levels across all patients was reported, which might contribute to poor kidney function and challenges in managing blood pressure among them. A significant contrast was noted in the MMAS-8 score between the initial evaluation and the subsequent follow-up assessments. a significant variance was noted in the MMAS-8 score between the initial and follow-up evaluations. Medication adherence was found to correlate with improved BP control. Higher KDQOL-36 scores indicated better health-related quality of life. In managing hypertension in MHD patients, angiotensin II receptor blockers (ARBs) proved effective, alongside dietary salt restrictions and appropriate diuretic therapy. Hypertensive MHD patients face increased cardiovascular and renal risks, emphasizing the importance of maintaining normal BP.

 

KEYWORDS: Refractory Hypertension, Chronic Kidney Disease, Maintenance Haemodialysis, Blood Pressure.

 

 

INTRODUCTION: 

Chronic kidney disease (CKD) individuals frequently haveelevated blood pressure. The frequency ranges from 60% to 90%, contingent on the underlying etiology and the stage of chronic kidney disease. Among the causes of hypertension in chronic kidney disease (CKD) include endothelial dysfunction, sympathetic hyperactivity, volume overload, salt retention, and modifications to the hormonal systems that regulate blood pressure (BP).1 Abnormalities of renal structure or function that have been present for longer than three months and have an effect on health are referred to as chronic kidney disease (CKD) in the 2012 KDIGO clinical practice recommendations.2 Uncontrolled blood pressure (BP) despite the use of five or more antihypertensive drugs at their highest effective dosages from various classes is referred to as refractory hypertension.3

 

Refractory hypertension is currently defined as the inability to control blood pressure despite the use of at least five antihypertensive medications from various classes, including a long-acting thiamine-like diuretic such as chlorthalidone and spironolactone.4 Only about 5% of people with uncontrolled resistant hypertension have the unusual condition of refractory hypertension.5 Renal function decreases are often associated with rises in blood pressure (BP), and prolonged elevations in BP accelerate the process of renal function loss.6 There are still numerous unresolved issues and worries regarding the management of hypertension, mostly because there aren't enough high-quality clinical trials, making it difficult to treat hypertension in dialysis patients.7 The most significant contributors to hypertension are excess sodium and volume. They are frequently seen in patients who do not comply with dietary salt and water restrictions. Increased pre-dialysis SBP and cardiovascular mortality have been linked to increased salt intake.8

 

Therefore, it is evident from guidelines like those provided by JSDT and Kidney Disease/Improving Global Outcomes (KDIGO) how important it is to limit salt.9,10 These guidelines suggest limiting daily salt consumption to 5-7g. Weight gain during interdialysis should not surpass 0.8kg/day, and the body's weight can be utilized to track increases in fluid volume.1

 

METHODOLOGY:

Study design and subjects:

A prospective observational study conducted for six months at the outpatient dialysis unit department of nephrology of Owaisi Hospital, Hyderabad.The Deccan College of Medical Sciences' institutional review board (IRB) accepted this study under IRB project No. 2023/39/003.Written informed consent was obtained from all study participants. All subjects aged more than 25 years with Refractory hypertension, chronic kidney disease stage-V on maintenance haemodialysis were allowed to participate in this study. Patients who were not willing to participate were excluded from this study.

 

Treatment and data collection:

Data relevant to the study was obtained from the patients, case sheets, laboratory investigation reports, and patients medical records. The collected data were documented in a designed case report form.

 

Statistical analysis:                                                                                     

For continuous data, the mean and standard deviation (SD) were given, whereas percentages and numbers were provided for qualitative variables. Software known as the Statistical Package for the Social Sciences (SPSS) version 26.0 was used to analyze the study data. Descriptive statistics were performed to analyse demographic profile, co morbidities, complaints, BMI, Medications, duration of CKD and hypertension. For categorical variables in the comparative analysis, the chi-square test was applied, whereas the dependent t-test was utilized for continuous variables. The 5% level was used to identify the differences between groups that were of statistical significance (P-value <0.05) since the CI is 95%.

 

RESULTS:

Age and gender:

According to the inclusion criteria, 50 participants in total were enrolled in the study; 40 percent of them were female and 60 percent of them were male. In total, 48% of people are adults (those between the ages of 25 and 64), and 2% are seniors (those over 65). For age-based data, the mean and standard deviation are 49.78 and 11.22, respectively (i.e., Mean± SD is 49.78± 11.22).

 

 

Fig.1 Gender distribution          

        

 

Fig.2 Age distribution

Body Mass Index and Clinical Presentation:

In the distribution of Body Mass Index (BMI), a notable proportion of patients exhibited varying weight categories: 18% were classified as underweight, 64% fell within the normal weight range, 16% were categorized as overweight, and 2% were identified as obese. Frequently reported symptoms among these individuals encompassed sensations of weakness, dryness in the mouth, breathing difficulties, coughing, numbness, and muscle soreness.

 

 

Fig.3 Body mass index of subjects.                          

 

 

Fig.4 complaints of subjects.

 

Co morbidities:

Most common co morbidities include: diabetes mellitus, Hypothyroidism and Anaemia.

 

 

Fig.5Comorbidities present in subjects.

Anti-Hypertensive Drugs:

Patients on 5 antihypertensive agents were higher than those on 6 antihypertensive agents

 

 

Fig.6 Number of hypertensives subject are prescribed.

 

Fig.7 Different hypertensive drugs prescribed

 

Duration of CKD and HTN:

38% of patients had CKD for 4-6 years and 22% of patients had HTN for 13-15 years and 10-12 years.

 

 

Fig. 8 Duration the subjects are diagnosed with different comorbidities.

 

Blood pressure and Pulse rate:

Table 1: Distribution based on blood pressure and pulse rate

Parameter

Review

Minimum

Maximum

Mean± SD

P value

Systolic Blood Pressure

Pre-dialysis

109

163

140.6±12.03

 

0.52

Post dialysis

115

155

132.3±8.42

Diastolic Blood Pressure

Pre-dialysis

79

98

85.40±4.46

0.1221

Post dialysis

79

91

84.05±2.78

Pulse Rate

Pre-dialysis

55

51

77.12±11.14

0.0408*

Post dialysis

100

98

80.14±9.13

 

·       The pre-dialysis systolic blood pressure was found to be high based on the preceding table. The results of the Dependent t-test indicate that the p-value exceeds 0.05. As a result, there was no discernible change in the systolic blood pressure before and after dialysis.  Also, there was nodiscernible change in the diastolic blood pressure before and after dialysis.

·       The pre-dialysis pulse rate was found to be higher based on the table. As indicated by the Dependent t-test, the p-value is less than 0.05. As a result, there was a noticeable variation in the pulse rate before and after dialysis.

          

Fig.9 Systolic blood pressure                              Fig.10Diastolic blood pressure                          Fig.11 Pulse rate

Laboratory Investigations:

Table2: laboratory investigations

Parameter

Review

Minimum

Maximum

Mean ± SD

P value

 

Serum sodium

Baseline

137

149

141.31±2.82

 

0.277

Follow up

137

146

139.9±2.28

Serum potassium

Baseline

3.60

4.60

4.09±0.29

 

0.963

Follow up

3.80

4.40

4.09±0.17

 

Serum chloride

Baseline

100

105

101.7±1.49

 

0.4559

Follow up

98

106

101.4±2.44

Urea

Baseline

51

110

81.30±17.93

 

0.8497

Follow up

55

105

80.88±15.25

 

Uric acid

Baseline

4

6.70

4.85±0.51

 

0.5362

Follow up

4

6.80

4.80±0.59

Haemoglobin

Baseline

6.50

11

9.32±0.99

 

0.040*

Follow up

7

10.90

9.47±0.79

Creatinine

Baseline

5.10

10.20

6.57±1.32

 

0.868

Follow up

4.90

10.90

6.03±1.65

 

The baseline hemoglobin was at its maximum, as observed in the preceding table. As indicated by dependent t-test, the p-value is less than 0.05. Therefore, a substantial variation in hemoglobin between the baseline and follow-up was observed.Throughout the investigation, there were no appreciable changes in the other lab values. Consequently, a statistically notable disparity was observed between the initial and subsequent measurements of laboratory parameters.

 

Comparison of Morisky Medication Adherence Scale-8 score:

 

Table3: Comparison of MMAS-8 score

Adherence

Review

P value

Baseline

Follow up

High (8)

05

17

 

0.004*

Medium (6-7)

43

33

Low (<6)

02

0

 

 

 

 

 

From the above table the baseline and follow up medium adherence was maximum. The Wilcoxon signed ranks analysis test shows that the p-value is below 0.05. Therefore, a notable difference was observed in the MMAS-8 score between the baseline and follow-up assessments.

 

Kidney Disease Quality of Life-36 Score:

Table. 4 Comparison of kidney disease quality of life- 36 score

Parameter

Review

Minimum

Maximum

Mean ± SD

P value

KDQOL

Baseline

39

88

70.07±6.94

 

0.0439*

Follow up

50

89

74.80±7.40

 

The follow-up score exceeded the baseline, as can be seen in the comparison of KDQOL score tables above.The p-value is below 0.05, according to the dependent t-test.Consequently, a substantial discrepancy was identified between the initial and subsequent KDQOL scores.

 

Fig.13 Scoring of KDQOL score

 

DISCUSSION:

·       Total of 50 patients of Refractory hypertension with CKD stage-V on maintenance haemodialysis were implicated in the study, according to inclusion criteria.

·       Patients were diagnosed as refractory hypertensive based on number of antihypertensive agents (≥ 5 agents) and Blood pressure >140/90mmHg. 4 According to NKF-KDOQI guidelines, pre-dialysis and post-dialysis blood pressure goals should be less than 140/90mmHg respectively. In our investigation, we observed a notable disparity in systolic blood pressure before and after dialysis.

·       In a study, patients with RfHTN hypertension were predominantly female(by Dudenbostel et al). 11In our study out of 50 patients, the percentage of male patients is higher (60%) and that of female patients is 40%.

·       Previous studies clearly demonstrate that an increase in sympathetic nervous system activity is associated with the development and maintenance of arterial hypertension, i.e. there is a gradual rise in sympathetic nerve activities parallel to severity of high blood pressure. Increased heart rate has been demonstrated, which is also a reliable sign of SNA and cardiological risk. 11In our research, we found a meaningful variation in the pulse rate of patients, indicating a reduced likelihood of heightened sympathetic activity and cardiovascular risk.

·       According to NKF-KDOQI guidelines, the recommended antihypertensive agents (ARB/ACEi + CCB+ BB/other sympathetic inhibitors + diuretics + MRA/vasodilators) were administered to the patients 11,15. A total of 92% patients were on 5 antihypertensive agents and 8% were on 6 antihypertensive agents (adding a vasodilator such as minoxidil and nitro-glycerine).

·       The patients of age between 25-79 years are included in the study in comparison to the literature where there are more number of elderly patients.12 In our study the adults (age between 25-65) constitute of about 48% and that of elderly (age more than 65) is 2%.

·       An essential aspect of dialysis treatment is determining the target weight. If the target weight is set too low, it can cause hypotension and accelerate the decline of kidney function. Conversely, setting the weight too high can lead to hypervolemia (Kidney International, 2020).13 In our study there are 18% underweight, 16% overweight and 2% obese patients requires weight management.

·       In comparison with the literature, the most common clinical presentations are weakness, dry mouth, numbness, muscle soreness, chest pain and shortness of breath. 13And there is higher percentage of patients with DM (48%), hypothyroidism (12%), CAD (8%) and Anaemia (10%) which can be a risk factor for decreasing patient quality of life and poor BP control (according to NKF-KDOQI).

·       Based on a similar study, the prevailing comorbidity among chronic kidney disease (CKD) patients is hypertension (33%), followed by anaemia (29%), diabetes (24%), and additional conditions like lipid disorders, cardiovascular system (CVS) disorders, and mineral bone abnormalities (14%).14

·       Literature review showed that, antihypertensive medications were administered the most often (30.1%). Then came the administration of phosphate binders (13.1%), and hematopoietic agents (23.6%). Hormone medicines received the fewest prescriptions (1.1%).15

·       Concomitant therapy includes: Iron sucrose, erythropoietin, vitamin D3, calcitriol, aspirin, atorvastatin, iron supplements, thyroxine sodium, sodium bicarbonate.

·       A significant difference inhaemoglobin is seen in all patients which could have lead to patients poor kidney function and blood pressure management 15.

·       In comparison with the literature ,adherence was considered inadequate if patients score less than 2 points. In our study, number of patients being low adherent-0, medium adherent-33 respectively showing a significant difference in the score marking a criterion for blood pressure control. 16

·       According to NKF (National Kidney Foundation) guidelines the higher score in kdqol-36 indicates better health related QOL; there was significant difference in the score (patients scored >50)17,18.

 

CONCLUSION:

In management of hypertension in patients on dialysis, ARBs act effectively in addition to dietary salt restrictions and appropriate diuretic therapy. The goal to achieve the desired levels of BP is gained through individualised patient characteristics. Hypertensive patients on dialysis have higher cardiovascular and renal complications compared to patients not on dialysis, so maintenance of normal range BP value in such patients have profound long-term outcomes. ARB’s is mainstay drug in this group of patients. Various other parameters like maintenance of body weight, high medication adherence and proper balanced diet should be taken into consideration.

 

ACKNOWLEDGEMENT:

We would like to thank our guides, and colleagues for their unwavering assistance during project conducting.

 

CONFLICTS OF INTEREST:

The authors declare no conflicts of interest.

 

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Received on 24.04.2024      Revised on 19.08.2024

Accepted on 26.10.2024      Published on 27.03.2025

Available online from March 27, 2025

Research J. Pharmacy and Technology. 2025;18(3):1290-1295.

DOI: 10.52711/0974-360X.2025.00187

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