Potential Risk Factors of End Stage Renal Disease in Patients of

Hemodialysis

Diana Laila Ramatillah

, Syed Azhar Syed Sulaiman

, Amer Hayat Khan

, and Ihsanil Husna

1 Pharmacy Faculty, Universitas 17 Agustus 1945 Jakarta

2 School of Pharmaceutical Sciences, Universiti Sains Malaysia

3 Physician at Nephrology Ward at Cempaka Putih Islamic Hospital, Jakarta

Keywords: Potential Risk Factors, ESRD, Cardiovascular, Penang, Jakarta

Abstract: The purpose of this research is to evaluate potential risk factors and its correlation with probability of dying

and frequency of hemodialysis from the first treatment among hemodialysed patients in hemodialysis center

in Penang, Malaysia and Jakarta, Indonesia. A cohort prospective study was conducted in this research.

Universal sampling were used to select 178 and 78 patients who had been followed for 9 months in

Hemodialysis Center in Jakarta and Penang, respectively. Cox regression was used to analyze probability of

dying among these patients. In HD center Jakarta, Indonesia, 47 hemodialysed patients had cardiovascular

disease while 4 of 8 of those patients who had duration of having cardiovascular disease less than 5 years

died during study and rest of them had duration of having cardiovascular disease more than 6 years with

95% Cl 1.29-4.43, P = 0.006. In a HD center in Penang, Malaysia, 28 hemodialysed patients had

cardiovascular disease and only 4 of them died during the study and all of them had duration of having

cardiovascular disease more than 6 years with 95% Cl 0.64-6.34, P = 0.23. In this study, only duration of

having cardiovascular disease showed significant relationship with probability of dying among

hemodialysed patients in Jakarta, Indonesia.

1 INTRODUCTION

According to the World Health Organization (2005),

approximately 35 million people died due to chronic

kidney disease (Levey et al., 2007). The prevalence

of End Stage Renal Disease (ESRD) in the world

were more than 2 million people (Ortiz et al., 2014).

An adjusted 5-year survival of all patients with

ESRD (treated with dialysis or transplantation) was

41% in the USA, 48% in Europe and 60% in Japan

for patients with ESRD onset between 2004 and

2008 (Robinson et al., 2016).

Risk factor is an alarm pointing to worst

condition that may happen for CKD patients. In this

case, information about risk factors on CKD is very

important for others to avoid severity of ESRD.

People who are not aware of the risk factors, signs

and symptoms of CKD may be a victim of ESRD

patients in future.

There are four categories of risk factors of end

stage renal disease. They are susceptibility,

initiation, progression and end-stage factors.

Susceptibility factors depend on sociodemographic

variables such as age, family history and race.

Initiation factors depend on the disease such as

metabolic disorder, infection, autoimmune and drug

toxicity, while, progression factors depend on the

severity of the metabolic disorder such as the higher

blood pressure, higher proteinuria and poor

glycemic control and End-stage factors depend on

lack of attention to the progression factors such as

lower dialysis dose and high serum phosphorus

(Levey, A.S., Eckardt, K., Tsukamoto, Y., Levin, A.,

Coresh, J., Rossert, J., de Zeeuw, D., Hostetter, T.,

Lameire, N., Eknoyan et al., 2005).

2 MATERIAL AND METHODS

Research was carried out in hemodialysis (HD) ward

Jakarta, Indonesia and Pulau Pinang, Malaysia.

Universal sampling were used to select 178 and 78

patients who had been followed for 9 months in

Hemodialysis Center Jakarta and Penang,

respectively. A cohort prospective study was

conducted in this research.

Ramatillah, D., Sulaiman, S., Khan, A. and Husna, I.

Potential Risk Factors of End Stage Renal Disease in Patients of Hemodialysis.

DOI: 10.5220/0008239800840089

In Proceedings of the 1st Muhammadiyah International Conference on Health and Pharmaceutical Development (MICH-PhD 2018), pages 84-89

ISBN: 978-989-758-349-0

Before requesting for the ethical approval,

researcher had a good clinical practice certificate.

Ethical clearance were sourced from ethical medical

committee from Faculty of Medicine in Indonesia

(728/UN2.F1/ETIK/2015) and Clinical Research

Center Pulau Pinang Hospital Malaysia

((5)KKM/NIHSEC/P16-133). The approval letters

were given before starting data collection.

The collection of data also started after

determining the inclusion criteria and patients also

signed the agreement. The study included diabetic

and / hypertensive patients who undergone

hemodialysis and have aged more than 18 years old.

Patients who have cancer, HIV/AIDS, Systemic

Lupus Erythema and pregnant were excluded in this

study. All the data were transferred to the clinical

data collection form.

3 RESULTS

Table 1. shows correlation between potential risk

factors of ESRD and probability of dying in both

HD centers. Probability of dying can be measured

by these potential risk factors in this study, but only

duration of cardiovascular disease showed

significant relationship with probability of dying in

HD center Jakarta, Indonesia as shown in Table 1.

Cause of ESRD increased risk of death almost 2

times among hemodialysed patients in a HD center

in Jakarta, Indonesia and it also increased risk of

death more than 7 times among hemodialysed

patients in a HD center in Penang, Malaysia anytime

during 9 months followed up and P value for both

indicated no statistical difference as shown in Table

Duration of having cardiovascular disease

elevated risk of death more than 2 times in both HD

center in Jakarta, Indonesia and Penang, Malaysia

anytime during the 9 months followed up but only

patients of hemodialysis in Jakarta, Indonesia who

showed significant relationship.

3.1 Cause of ESRD

Cause of ESRD is one of the potential risk factors

which can influence duration of hemodialysis among

hemodialysed patients (Disease and Kidney Disease:

Improving Global Outcomes (KDIGO) Anemia

Work Group, 2012). Table 3 shows correlation

between potential risk factors of ESRD and

frequency of HD from first time on HD in both HD

center Jakarta, Indonesia and Penang, Malaysia.

Significant correlation was found among

hemodialysed patients in Penang, Malaysia. It can

be seen from median value for each group, while the

significant difference of duration of hemodialysis for

each group based on cause of ESRD was shown.

Hemodialysed patients who had hypertension had

the highest median (1062) value compared with

hemodialysed patients who had diabetic mellitus and

DM & HT in a HD center Penang, Malaysia as

shown in Table 2.

Table 1: Potential Risk Factors of ESRD and Probability of Dying Among Hypertensive/Diabetic Patients Who Undergone

Hemodialysis (Prospective Sample / 9 Months Followed up)

Potential

Risk

Factors

Exp (B)

Hazard Ratio

95% Cl For Exp (B) P * Value

Jakarta,

Indonesia

Penang,

Malaysia

Jakarta,

Indonesia

Penang,

Malaysia

Jakarta,

Indonesia

Penang,

Malaysia

Jakarta,

Indonesia

Penang,

Malaysia

Cause of

ESRD

0.49 2.02 1.64 7.53 0.75-3.58 0.66-85.58 0.22 0.10

Duration

of having

CKD

-3.24 -1.23 0.04 0.29 0.001-1.85 0.06-1.37 0.10 0.12

Duration

of having

CVD

0.87 0.70 2.39 2.01 1.29-4.43 0.64-6.34 0.006* 0.23

Duration

of having

-0.24 -0.67 0.79 0.51 0.45-1.39 0.16-1.63 0.41 0.26

Duration

of having

-0.38 0.43 0.69 1.53 0.43-1.11 0.89-2.64 0.12 0.13

Potential Risk Factors of End Stage Renal Disease in Patients of Hemodialysis

3.2 Duration of having CKD

Duration of ESRD may affect the duration of

hemodialysis among hemodialysed patients (Disease

and Kidney Disease: Improving Global Outcomes

(KDIGO) Anemia Work Group, 2012). Table 3.

shows correlation between duration of having CKD

and frequency of HD from first time on HD in both

HD centers Jakarta, Indonesia and Penang,

Malaysia.

Significant correlation between duration of

having CKD and frequency of HD from first time on

HD were found among hemodialysed patients in

both HD centers as shown in Table 3. In Indonesia,

the highest median value (1137 times) of frequency

of HD from first time on HD was shown by the third

group (≥ 11-15 years) of duration of having CKD.

However, in Malaysia, median value of 2566 times

was shown by fourth group (≥ 16-20 years) of

duration of having CKD.

Table 2. Cause of ESRD and Frequency of HD from first time on HD

N for each group of cause of

ESRD

Median for each group

(

Times of HD Fre

uenc

Frequency of HD from first

time on HD (Indonesia)

DM (33)

HT (98)

DM & HT

(

)

127

135

146

0.36

Frequency of HD from first

time on HD (Malaysia)

DM (5)

HT (43)

DM & HT (30)

238

1062

624.5

0.001*

* A Kruskal-Wallis Tests

Table 3.Duration of having CKD and Frequency of HD from first time on HD Among Diabetic/Hypertensive Patients

Who Undergone Hemodialysis

Component

Years (N) Duration of

having CKD

Median for each group

(Times of HD Frequency)

Frequency of HD from

first time on HD

(Indonesia)

≤ 5 years (153)

≥ 6-10 years (20)

≥ 11-15 years (5)

127

598

1137

< 0.001*

Frequency of HD from

first time on HD

(Malaysia)

≤ 5 years (36)

≥ 6-10 years (24)

≥ 11-15 years (9)

≥ 16-20 years (9)

291

1008

1821

2566

< 0.001*

* A Kruskal-Wallis Test

Table 4. Duration of Having Cardiovascular Disease and Frequency of HD Since First HD Among Diabetic/Hypertensive

Patients Who Undergone Hemodialysis

Component N for each group of duration of having

cardiovascular disease

Years (N)

Median for each group

(Times of HD Frequency)

Frequency of HD

Since First HD

(

Indonesia

)

≤ 5 years (41)

≥ 6 years (6)

127

280.5

0.21

Frequency of HD

Since First HD

(Malaysia)

≤ 5 years (12)

≥ 6 years (20)

659

1530

0.005*

* A Kruskal-Wallis Test

MICH-PhD 2018 - 1st Muhammadiyah International Conference on Health and Pharmaceutical Development

3.3 Duration of Having Cardiovascular

Disease

Duration of having cardiovascular disease may

influence the duration of hemodialysis among

hemodialysed patients (Ortiz et al., 2014). Table 5.

shows correlation between duration of having

cardiovascular disease and frequency of HD from

first time on HD in both HD center Jakarta,

Indonesia and Penang, Malaysia.

Significant correlation (p 0.005) between

duration of having cardiovascular disease and

frequency of HD from first time on HD was found

among hemodialysed patients in a HD center

Penang, Malaysia as shown in Table 4.

Duration of having hypertension and frequency

of HD since first HD were found significant among

hemodialysed patients in both HD centers of

Malaysia (P <0.001) and Indonesia (P <0.001) as

shown in Table 5. In Indonesia, the highest median

value of frequency (447.5 times) of HD from first

time on HD was shown by the third group (≥11-15

years) of duration of hypertensive patients.

However, in Malaysia, patients with ≥ 16-20 years

duration showed frequency of 1665 times in

hypertensive patients.

3.4 Duration of Having Diabetes

Mellitus

Duration of having diabetes Mellitus may affect the

duration of hemodialysis among hemodialysed

patients. Table 6 shows correlation between duration

of having diabetes mellitus and frequency of HD

from first time on HD in both HD center Jakarta,

Indonesia and Penang, Malaysia.

Significant correlation between duration of

having diabetes mellitus and frequency of HD since

first HD was found among hemodialysed patients in

a HD center Penang, Malaysia as shown in Table 6.

Table 5. Duration of Having Hypertension and Frequency of HD Since First HD Among Diabetic/Hypertensive Patients

Who Undergone Hemodialysis

Component N for each group

Years (N) of duration of having

ertension

Median for each group (Times of

HD Frequency)

Frequency of HD Since

First HD (Indonesia)

≤ 5 years (117)

≥ 6-10 years (34)

≥ 11-15 years (14)

≥ 16-20 years (6)

≥ 21 years (7)

125

401.5

447.5

225

197

<0.001*

Frequency of HD Since

First HD (Malaysia)

≤ 5 years (6)

≥ 6-10 years (26)

≥ 11-15 years (20)

≥ 16-20 years (13)

≥ 21

ears

(

)

208.5

636.5

966.5

1665

1542

<0.001*

*Kruskal Wallis Test

Table 6. Duration of Having Diabetes Mellitus and Frequency of HD Since First HD Among Diabetic/Hypertensive

Patients Who Undergone Hemodialysis

Component N for each group of duration of

having diabetes mellitus

Median for each group (times of

HD Frequency)

Frequency of HD Since

First HD (Indonesia)

≤ 5 years (26)

≥ 6-10 years (22)

≥ 11-15 years (17)

≥ 16-20 years (8)

≥ 21 years (9)

135

126

172

228.5

141

0.74

Frequency of HD Since

First HD (Malaysia)

≤ 5 years (5)

≥ 6-10 years (8)

≥ 11-15 years(11)

≥ 16-20 years (5)

≥ 21 years (6)

240

475

802

565

888.5

0.01*

* A Kruskal-Wallis Tests

Potential Risk Factors of End Stage Renal Disease in Patients of Hemodialysis

4 DISCUSSION

In Penang, Malaysia, all these five potential risk

factors (cause of ESRD, duration of having CKD,

duration of having cardiovascular disease, duration

of having hypertension and duration of having

diabetic mellitus) showed significant correlation

with frequency of HD from first treatment.

Meanwhile, only two potential risk factors showed

significant relationship in HD center Jakarta,

Indonesia including duration of having CKD and

duration of having hypertension.

Duration of having CKD was dependent on

frequency of hemodialysis since first treatment.

Duration of having CKD was calculated by how

many session (frequency) of hemodialysis, which

had been done by those patients. It is the same with

duration of cardiovascular, hypertensive and diabetic

among those patients. Length of duration these

diseases will be equal to frequency of hemodialysis

because those diseases can not be excluded

permanently.. Agarwal, 2005 reported that the use of

antihypertensive drugs treatment improve survival

(Agarwal, 2005).

In this finding, frequency of hemodialysis among

diabetic and / hypertensive patients influenced

duration of having CKD and duration of having

hypertension in both HD centers. Some studies

identified that increasing dialysis time and frequency

affect hypertensive condition (Fagugli et al., 2001,

2006; Culleton et al., 2007).

Many factors contributed length of hemodialysis

session, some of them are good medication and less

of complication. Chandrashekar et.al., 2014 reported

that there is no significant difference in terms of

survival among diabetics compared with non-

diabetics (Chandrashekar, Ramakrishnan and

Rangarajan, 2014). Another study revealed that the

survival of patients on hemodialysis with diabetes

mellitus was lower than those patients without

diabetes mellitus (Ghaderian et al., 2015).

In Australia, New Zealand and the United States,

Cardiovascular Disease (CVD) was reported as the

leading cause of death in dialysis patients (Annual

Data Report Minnepolis, 2006; McDonald, 2015).

Another study, Mailloux et al., 1991 identified the

causes of death in maintenance dialysis patients who

survived at least 90 days and were monitored during

a 16 year period and cardiovascular disease was one

of the causes of death among those patients

(Mailloux et al., 1991).

Cardiovascular disease is one of the

complications of end-stage renal failure (Marry

Anne and Alledredge, 2013). The statement about

correlation of CV in presence of CKD is still a

controversy (Herzog et al., 2011). In this study,

duration of cardiovascular disease influenced the

probability of dying / risk of mortality among

hemodialysed patients in a HD center Jakarta,

Indonesia.

5 CONCLUSION

Five potential risk factors of ESRD were found in

this study: cause of ESRD, duration of having CKD,

duration of having cardiovascular disease, duration

of having hypertension and duration of having

diabetes mellitus. Only duration of having

cardiovascular disease showed significant

relationship with probability of dying but only in

HD patients in Jakarta, Indonesia; whereas duration

of having cardiovascular disease elevated risk of

death more than 2 times in both HD centers in

Jakarta, Indonesia and Penang, Malaysia.

6 DISCLOSURE OF POTENTIAL

CONFLICTS OF INTEREST

AND ACKNOWLEDGEMENT

The authors declared that we have no conflict of

interest.

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Potential Risk Factors of End Stage Renal Disease in Patients of Hemodialysis