Design of Phosphate Binder Used as Chronic Kidney Disease Therapy

at General Hospital Dr. Iskak Tulungagung

Aghnia Fuadatul Inayah

, Khoridatur Rohmah

, Didik Hasmono

Lilik Yusetyani

and Binti Muzayyanah

Department of Pharmacy, Faculty of Health Sciences, University of Muhammadiyah Malang, Jalan Bendungan Sutami

188 A Malang 65145, East Java, Indonesia.

Faculty of Pharmacy, University of Airlangga, Jalan Mulyorejo Surabaya 60115, East Java, Indonesia.

General Hospital Dr. Iskak Tulungagung, l. Dr. Wahidin Sudiro Husodo Tulungagung 66223, Indonesia.

Keywords: Phosphate binder, Chronic kidney disease, Calcium acetate, Calcium carbonate

Abstract: Chronic Kidney Disease (CKD) can be defined as impaired kidney function that occurs for > 3 months or

more. This was indicated by a decrease in Glomerular Filtration Rate (GFR) (<60 ml/minute/ 1.73m

). CKD

stage 3 has frequent hyperphosphatemia, a complication of the disease. The effects of hyperphosphatemia are

the bone mineral connection and tissue calcification process. Phosphate binder was one of the therapeutic

options that can be used for hyperphosphatemia. This study aims to determine the design therapy of phosphate

binders used by CKD patients at hospitalization services of General Hospital Dr. Iskak Tulungagung.

Observational research and retrospective. The presentation data has used descriptive of the medical record

patients CKD hospitalized in the period Juli to December 2017. Phosphate binder has been used as a single

therapy without combination, 130 patients (77%) used calcium carbonate, while 11 patients (7%) used

calcium acetate, and of 27 patients (16%) had received switching therapy. The hyperphosphatemia therapy

regimen used more calcium carbonate orally (3x500mg) in 121 patients (62%) than calcium acetate orally

(1x169mg) in 16 patients (8%).

1 INTRODUCTION

Chronic kidney disease (CKD) can be defined as

abnormalities in the structure or function kidney that

occurred for three months or more (joseph T. DiPiro,

Barbara G. Wells, 2015). Patients with GFR values >

60ml/min can't be said to suffer from CKD unless

accompanied by a matter which shows the damage in

the kidneys like disorders in urine composition,

kidney structure, genetic diseases, and disorders that

are detected by histological examination (Leung and

Taal, 2007). The prevalence of CKD in Asia based on

epidemiology in 2011, Indonesia ranks 10th out of 12

countries in Asia. CKD prevalence was higher in

Central Sulawesi. The etiology of CKD that has

occurred hypertension 44%, diabetic nephropathy

22%, and primary glomerulopathy / GNC 8%

(Indonesian renal Registry, 2012).

The development of clinical manifestations in

CKD patients one of which is impaired mineral

homeostasis and bone nutrition (hyperphosphatemia

and hypocalcemia) (Munoz et al., 2014)(goleman,

daniel; boyatzis, Richard; Mckee, 2019).

Hyperphosphatemia causes complications including

osteomalacia, fibrous cystic osteitis, and soft tissue

calcification. This condition requires non-

pharmacological therapy such as phosphorus diet,

hemodialysis, and parathyroidectomy.

Pharmacological therapies used are phosphate binder,

vitamin D and calcimimetics. Effective therapy to

overcome hyperphosphatemia has reduced phosphate

absorption in the GI tract using phosphate binders

(joseph T. DiPiro, Barbara G. Wells, 2015). If serum

phosphorus levels can't be controlled by limiting food

intake, the phosphate binder group can be used to

bind phosphate to the digestive tract. The use of

phosphate binders must be with a meal to bind the

phosphate that is in food.

2 METHODS

This research was conducted in an observational

descriptive manner and retrospective retrieval of data.

This descriptive observational study aims not to treat

Inayah, A., Rohmah, K., Hasmono, D., Yusetyani, L. and Muzayyanah, B.

Design of Phosphate Binder Used as Chronic Kidney Disease Therapy at General Hospital Dr. Iskak Tulungagung.

DOI: 10.5220/0009127101970200

In Proceedings of the 2nd Health Science International Conference (HSIC 2019), pages 197-200

ISBN: 978-989-758-462-6

197

the sample. Data were collected retrospectively

because used patient's medical records (PMR) in the

July-September 2017 period at General Hospital Dr.

Iskak Tulungagung. Based on Patient's Medical

Record (PMR) data for the period July-September

2017 obtained 218. The population that received

inclusion criteria was 168 samples and 50 samples

were excluded.

3 RESULTS AND DISCUSSION

The study showed 78 male patients (46%) and 90

female patients (54%). History of the disease based

on this study included diabetes 53 patients (38%),

hypertension 76 patients (55%), heart disease 5

patients (4%), and stroke 4 patients (3%). Disease

complications in this study included anemia (39%),

hypertension (17%), hyperkalemia (13%), diabetes

mellitus (9%), dyspepsia (5%), pneumonia (4%),

sepsis (3%), uremic syndrome (3%), CVA (2%),

metabolic acidosis (2%), acute myocardial infarction

(1%), decompensation Cordis (1%) and acute lung

oedema (1%).

The study showed 78 male patients (46%) and 90

female patients (54%). The results of a study

conducted by Yu et al., 2015 the women with diabetes

had a higher risk of CKD than the men, which can't

be explained by biological risk factors, depression or

diabetes self-care (Yu, Katon and Young, 2015).

Goldberg & Krause, 2016 showed the male has more

potential to increase disease progression, but the

prevalence CKD in women more often as a result of

postmenopausal disease and diabetes (Goldberg and

Krause, 2016). In this study, the highest percentage of

patients with CKD were aged 51-60 years, namely 67

patients (40%). In a study by Delima, et al., 2017 the

highest percentage was at age 52-60 years (28.2%)

(Indrayanti et al., 2019). Aging has been a natural

biological process and the kidney has decreased

function (Berlin, 2013).

History of the disease based on this study included

diabetes 53 patients (38%), hypertension 76 patients

(55%), heart disease 5 patients (4%), and stroke 4

patients (3%). As IRR data, 2015 etiology of CKD

patients undergoing hemodialysis 44% have been

caused by hypertension, and 22% caused by diabetes

mellitus (Indonesian renal Registry, 2012).

Table 1 a profile of the use of phosphate binders.

All patients received single therapy from phosphate

binder, none of the patients received combination

therapy.

Table 1: Profile of used of Phosphate binder therapy.

Profile of Therapy

Patients *

Single

195

100

Combination

Total

195

100

* Each patient can get more than one phosphate binder

therapy design

Table 2 shows the type of phosphate binder used

in patients while being hospitalized. There was a

switch/change in the use of phosphate binder both in

changing the dose, frequency, or type of phosphate

binder.

Table 2: Type of Phosphate binder used in CKD patients.

Phosphate binder

Patients *

Calcium carbonate

130

Calcium acetate

Switch

Total

168

100

* Each patient can get two type phosphate binder therapy

The dosage regimen for the use of phosphate binders

can be seen in Table 3.

Table 3: Profile of the use of a single therapeutic Phosphate

binder in CKD patients.

Regimentation dosis

Patients *

CaCO3 (1x500mg) PO

CaCO3 (2x500mg) PO

CaCO3 (3x500mg) PO

121

Subtotal

173

Ca-Asetat (1x169mg) PO

Ca-Asetat (2x169mg) PO

Ca-Asetat (3x169mg) PO

Subtotal

Total

195

100

* Each patient can get more than one phosphate binder

therapy with difference regiment

Table 4 switch designs the use of phosphate

binders. This study has been dominated by

hypertension and diabetes mellitus. Disease

complications in this study included anemia (39%),

hypertension (17%), hyperkalemia (13%), diabetes

mellitus (9%), dyspepsia (5%), pneumonia (4%),

sepsis (3%), uremic syndrome (3%), CVA (2%),

metabolic acidosis (2%), acute myocardial infarction

(1%), decompensation Cordis (1%) and acute lung

oedema (1%). Data from this study came as the

results of a study by Wetmore, et al., 2016, comorbid

conditions in CKD patients that often occur, namely

anemia, and hypertension (Cozzolino et al., 2018).

HSIC 2019 - The Health Science International Conference

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Table 4: Design of Substitution of Phosphate Binders in CKD Patients.

Phosphate Binder

Patients

Design 1

Design 2

CaCO3 (1x500mg) PO



CaCO3 (3x500mg) PO

CaCO3 (1x500mg) PO



CaCO3 (2x500mg) PO



CaCO3 (3x500mg) PO

CaCO3 (2x500mg) PO



CaCO3 (1x500mg) PO

CaCO3 (3x500mg) PO



CaCO3 (2x500mg) PO

CaCO3 (3x500mg) PO



CaCO3 (1x500mg) PO



Ca-Asetat (1x169mg) PO

CaCO3 (3x500mg) PO



Ca-Asetat (1x169mg) PO

CaCO3 (3x500mg) PO



Ca-Asetat (3x169mg) PO

Ca-Asetat (1x169mg) PO



CaCO3 (3x500mg) PO

Ca-Asetat (2x169mg) PO



CaCO3 (3x500mg) PO

Ca-Asetat (1x169mg) PO



CaCO3 (2x500mg) PO

Total

100

All patients received single therapy from

phosphate binder, none of the patients received

combination therapy. Table 2 a type of phosphate

binder used. There are two types of phosphate binders

used, namely calcium carbonate and calcium acetate.

Research by Wang, et al., 2015 explains that calcium-

based phosphate binders can increase serum calcium,

there was no significant difference in calcium

concentration between therapy using calcium

carbonate and calcium acetate (Wang et al., 2015).

Based on research by Mai, et al., 1989 in the in vivo

test.

This research showed the effectiveness of

calcium-based phosphate binder in phosphate

binding, the dose of calcium acetate and calcium

carbonate which was equivalent to 50 mEq of calcium

showed that calcium acetate was twice as much in

phosphate binding (Mai et al., 1989). Calcium acetate

is more effective in binding phosphate because

calcium acetate has more rapid solubility than acidic

or basic conditions. Unlike calcium carbonate, it must

be acidic to dissolve, and phosphate binding takes

longer. Calcium carbonate has a fairly slow solubility

compared to calcium acetate, so when consumed it

need to chew, while calcium acetate doesn't. Based on

the explanation, calcium acetate was more beneficial

as a phosphate binder than calcium acetate.

Calcium carbonate (CaCO3) in acidic pH in the

stomach would be broken down to form Ca

and

HCO3

or to form Ca(HCO

)

, both of these forms can

be absorbed in the body (Engineering, 2006). When

using calcium carbonate with food, the free calcium

ions would bind to the phosphate ion to form a

complex that cannot be absorbed. HCO

ions can be

absorbed in the body so that they reduced metabolic

acidosis. Study by Akatsuka, et al., 2008

administration of calcium carbonate in metabolic

acidosis can increase HCO3

from 17.7 ± 0.5 mmol /

L to 20.6 ± 0.7 mmol / L (Akatsuka, Mochizuki and

Koike, 2008). Calcium-based phosphate binders such

as calcium carbonate and calcium acetate were

alkaline so that they have an effect on the correction

of metabolic acidosis (Chávez Valencia et al., 2018).

Table 2 shows the type of phosphate binder used

in patients while being hospitalized. There was a

switch/change in the use of phosphate binder both in

changing the dose, frequency, or type of phosphate

binder. The dosage regimen for the use of phosphate

binders can be seen in Table 3. The dosage and type

of phosphate binder that is often used is calcium

carbonate (3x500mg) by mouth. Phosphate binders

are most effective when taken with food (Setiani

Agus, Effendi and Abdillah, 2014). It aims to bind the

phosphate contained in food so that most of its use

with a frequency of 3x1 with meals. The difference in

the frequency of the used of phosphate binders in

General Hospital Dr. Iskak based on the condition of

the patient, especially the patient's food intake and

laboratory data.

Table 4 switch designs the use of phosphate

binders. The design changes in the type, daily dose,

or frequency in the use of phosphate binders. The

substitution of the phosphate binder is the same as the

difference in the frequency of the used of phosphate

binder. This change was also due to the patient's food

intake and the patient's calcium laboratory data. Side

effects of calcium-based phosphate binder are

hypercalcemia, besides this in a state of

hyperphosphatemia, CKD patients usually

experience hypocalcemia due to reduced calcium

absorption from food.

The maximum length of the phosphate binder has

been used 1-3 days as many as 91 patients (54)%. The

results from the duration use of phosphate binder in

CKD patients only refer to the length of use during

hospitalization, whereas to maintain phosphate

Design of Phosphate Binder Used as Chronic Kidney Disease Therapy at General Hospital Dr. Iskak Tulungagung

199

homeostasis this therapy not only used during

hospitalization but also used as outpatient care. Goal

therapy was to help reduce the amount of phosphate

absorbed from food. Therefore the duration of use of

phosphate binders doesn't indicate the actual duration

of therapy. Duration hospitalization was 40% of

patients treated for ≤ 4 days, 87% treated 5-10 days,

9% treated for 11-15 days and 4% treated for> 15

days. The length of patient care depends on the

development of the patient's condition. Patients were

discharged from the hospital with 166 patients (99%)

and 2 patients (1%) forcibly discharged. None of the

patients recovered fully due to hemodialysis.

4 CONCLUSIONS

Only one phosphate binder was used, 130 patients

(77%) used calcium carbonate, 11 patients (7%) used

calcium acetate, and 27 patients (16%) had a switch.

Regimentation of the highest dose of calcium

carbonate (3x500mg) PO in 121 patients (62%),

while calcium acetate was the most (1x169mg) PO in

16 patients (8%).

ACKNOWLEDGEMENTS

The authors thanks to our agency for providing the

best facilities.

REFERENCES

Akatsuka, T., Mochizuki, T. and Koike, T. (2008)

‘Buffering effects of calcium carbonate as clarified by

sevelamer hydrochloride monotherapy’, Therapeutic

Apheresis and Dialysis, 12(3), pp. 216–225. doi:

10.1111/j.1744-9987.2008.00577.x.

Berlin, F. (2013) ‘Analytik organischer

Spurenbestandteile’, 82(3), pp. 270–277. doi:

10.1038/ki.2012.65.The.

Chávez Valencia, V. et al. (2018) ‘Prevalence of

malnutrition-inflammation complex syndrome and its

correlation with thyroid hormones in chronic

haemodialysis patients’, Nefrologia. Sociedad

Española de Nefrología, 38(1), pp. 57–63. doi:

10.1016/j.nefroe.2017.11.019.

Cozzolino, M. et al. (2018) ‘Clinical Management of

Chronic Kidney Disease Patients in Italy: Results from

the IRIDE Study’, Nephron, 140(1), pp. 39–47. doi:

10.1159/000490769.

Engineering, B. (2006) ‘Thermodynamic Modeling of

Activity Coefficient and Prediction of Solubility: Part

2. Semipredictive or Semiempirical Models’, Online,

95(4), pp. 798–809. doi: 10.1002/jps.

Goldberg, I. and Krause, I. (2016) ‘the Role of Gender in

Chronic Kidney Disease’, Citation: EMJ, 1(2), pp. 58–

64.

goleman, daniel; boyatzis, Richard; Mckee, A. (2019)

済無

No Title No Title, Journal of Chemical Information and

Modeling. doi: 10.1017/CBO9781107415324.004.

Indonesian renal Registry (2012) ‘5 th Report Of

Indonesian Renal Registry 2012’, Program Indonesia

Renal Registry, pp. 12–13.

Indrayanti, S. et al. (2019) ‘Risk Factors for Chronic

Kidney Disease : A Case- Control Study in a District

Hospital in Indonesia’, 11(7), pp. 2549–2554.

joseph T. DiPiro, Barbara G. Wells, T. L. S. (2015)

Pharmacoterapy Handbook, Laser Focus World.

Leung, J. C. and Taal, M. W. (2007) Oxford Handbook of

Nephrology and Hypertension, Nature Clinical

Practice Nephrology. doi: 10.1038/ncpneph0439.

Mai, M. L. et al. (1989) ‘Calcium acetate, an effective

phosphorus binder in patients with renal failure’,

Kidney International. Elsevier Masson SAS, 36(4), pp.

690–695. doi: 10.1038/ki.1989.247.

Munoz, R. et al. (2014) Handbook of pediatric

cardiovascular drugs: Second edition, Handbook of

Pediatric Cardiovascular Drugs: Second Edition. doi:

10.1007/978-1-4471-2464-1.

Setiani Agus, L., Effendi, I. and Abdillah, S. (2014)

‘Influence of the use of phosphate binders on serum

levels of calcium phosphate in patients with chronic

kidney disease undergoing hemodialysis: A

retrospective and prospective study’, Saudi

Pharmaceutical Journal. King Saud University, 22(4),

pp. 333–337. doi: 10.1016/j.jsps.2013.08.004.

Wang, Y. et al. (2015) ‘Calcium acetate or calcium

carbonate for hyperphosphatemia of hemodialysis

patients: A meta-analysis’, PLoS ONE, 10(3), pp. 1–11.

doi: 10.1371/journal.pone.0121376.

Yu, M. K., Katon, W. and Young, B. A. (2015)

‘Associations between sex and incident chronic kidney

disease in a prospective diabetic cohort’, Nephrology,

20(7), pp. 451–458. doi: 10.1111/nep.12468.

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