VARIABILITY AND INFLUENCE OF ACID-BASE BALANCE IN …

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Anna et al. World Journal of Pharmacy and Pharmaceutical Sciences Anna et al. World Journal of Pharmacy and Pharmaceutical Sciences

VARIABILITY AND INFLUENCE OF ACID-BASE BALANCE IN

PATIENTS WITH RENAL DYSFUNCTION

Minnu Anna Chacko*, Akshatha G., Anitha Vani M. and K. A. Sridhar

Department of Pharmacy Practice, East West College of Pharmacy, Bengaluru,

Karnataka- 560091.

ABSTRACT

An acid-base imbalance is the most common complication of renal

dysfunction and appears to contribute to the progression of kidney

disease, hence it is necessary to understand the acid- base physiology

and management of acid-base imbalance in renal dysfunction patients.

To study the variability and influence of acid-base balance in patients

with renal dysfunction. This was a prospective and observational study

which was performed on 102 renal dysfunction patients, by enrolling

the subjects based on the inclusion and exclusion criteria using a

statistical method. Among 102 patients included in the study, the

majority 72.42% were males and 31.62% were females, frequency of

patients suffering from CKD (64.70%) was found to be higher than

AKI (15.68%) and acute on CKD (19.60%). According to serum bicarbonates level, it was

found that 47.06% of subjects had metabolic acidosis, 39.22% had a normal range of

bicarbonates and 13.72% had metabolic alkalosis. Distribution of drugs used for the

management of acid-base imbalance in renal failure showed that loop diuretics and thiazide

diuretics were effective and dialysis was recommended for patients whose potassium levels

and serum creatinine levels were high. PPI’S were prescribed to counteract the GI side effects

of the drugs and to maintain the pH of the blood. Around 15-20% of renal dysfunction patients

suffer from some degree of acid-base imbalance (commonly metabolic acidosis) and

prevalence increases with lower GFR. Hence, we have undertaken the responsibility of clinical

pharmacist to understand and analyze the influence and variability of acid-base changes in renal

dysfunction.

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 10, Issue 2, 1500-1527 Research Article ISSN 2278 – 4357

*Corresponding Author

Minnu Anna Chacko

Department of Pharmacy

Practice, East West College

of Pharmacy, Bengaluru,

Karnataka- 560091.

Article Received on

25 Nov. 2020,

Revised on 15 Dec. 2020,

Accepted on 05 Jan. 2021

DOI: 10.20959/wjpps20212-18150


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KEYWORDS: Acid-base balance, acid-base imbalance management, patient-specific

management.

INTRODUCTION

Maintenance of normal pH in the body is very much required for normal health, the state of

equilibrium between proton donors and proton acceptors in the buffering system of blood is

known as acid-base balance.[1]

The lungs, kidney, and a complex system of buffers allow the

body to maintain acid-base homeostasis. The pH of human body ranges between 7.35 to

7.45.[2] Proper acid-base balance is required to be maintained for many biological processes to

happen, one most being the oxygenation of blood, to maintain normal physiology of body and

cellular metabolism.[3] Values of arterial pH 7.35 and lower are termed as acidemia and

values of arterial pH 7.45 and higher are termed as alkalemia. By evaluating ABG’s we can

assess a patient’s acid-base status. Arterial blood gases (ABGs) include the pH, arterial partial

pressure of oxygen and carbon dioxide (paO2 and paCO2), and the bicarbonates (HCO3-)

concentration. The serum anion gap and lactate concentration provides additional information

to classify and evaluate acid-base disorders.

Generally acid-base homeostasis is maintained by the lungs and kidneys. Acid-base disorders

are categorized according to the primary abnormality, the underlying pathological event that

disturbs the pH.

When the primary abnormality is a decrease in excretion of carbon dioxide by the lungs, the

disorder is termed as respiratory acidosis.

When the primary abnormality is excessive excretion of carbon dioxide by the lungs, the

disorder is termed as respiratory alkalosis.

When the primary abnormality is deficit of bicarbonate handled by the kidneys, the

disorder is termed as metabolic acidosis.

When the primary abnormality is excessive of bicarbonates, the disorder is termed as

metabolic alkalosis.

Laboratory assessment of acid-base status is usually performed on samples of arterial blood,

which accurately reflect acid base status in the body under most conditions.[2]

Acid base physiology

Metabolism of glucose, fats and proteins as an energy source results in the daily production of

15,000 mmol of carbon dioxide, which acts as an acid in the body and 50-100mEq of


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nonvolatile acids. This continual load of acidic substances must be buffered initially to prevent

acute acidosis and then excreted to prevent exceeding body’s buffer capacity.

The principal buffer system in body is carbonic acid/bicarbonate system. Other buffers,

including proteins, phosphates and hemoglobin also contribute to maintain normal Ph.[4]

Carbonic acid (H2CO3), a weak acid, and its conjugate base, bicarbonate (HCO3-), exist in

equilibrium with hydrogen ions (H+):

HCO3- + H

+ H2CO3

If hydrogen ions are added to the body or released as a result of a cellular metabolism, the H+

ion concentration rises and is reflected by a fall in pH. However a large portion of the hydrogen

ions combines with bicarbonates to form carbonic acid, lessening the effect on pH.

In aqueous solutions, carbonic acid reversibly desiccate to form water and carbon dioxide. This

reaction is enhanced and catalyzed by the enzyme carbonic anhydrase, which is present in the

body:

HCO3- + H

+ H2CO3 CO2 + H2O

Nearly all carbonic acid in the body is present as carbon dioxide gas. Hence, carbon dioxide

is the acid form of carbonic acid/bicarbonate buffer system.

The Henderson-Hassel Balch equation for the carbonic acid/bicarbonate buffer system

describes the mathematical relationship among pH, bicarbonate concentration and partial

pressure of carbon dioxide.

This equation demonstrates an important point: the ratio of the bicarbonate and carbon dioxide

concentrations, not the absolute values, determines pH.

𝑝𝐻 = 6.1 + log [𝐻𝐶𝑂3/0.03 × 𝑃𝑎𝐶𝑂2]

Role of kidney’s in acid- base balance: The principal role of kidneys is maintaining acid-base

homeostasis to regulate the concentration of bicarbonate in the blood. Since bicarbonate are

readily filtered in the glomerulus, the kidneys reabsorb filtered bicarbonate to avoid its

depletion. This reabsorption takes place in the proximal tubule and is catalyzed by carbonic

anhydrase. The other major role of the kidneys, is to excrete nonvolatile acids that are produced

by the body. This process occurs primarily in the distal tubule and also requires carbonic


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Anna et al. World Journal of Pharmacy and Pharmaceutical Sciences

anhydrase. The hydrogen ions that are secreted into the tubule lumen are buffered by

phosphates and ammonia, so the final urine pH is usually acidic but typically not less than

4.50.[2] Hence kidneys play a major role in regulation of acid base balance. Kidney diseases

and dysfunction leads to impaired regulatory functions, resulting in alterations of acid base

balance which can be life threatening.[5] Hence there is a need to analyze and monitor the ABG

(arterial blood gases) in high risk patients, as well as in critically ill patients in the intensive

care unit.[6]

Components of arterial blood gases:- ABG evaluation include measurements of arterial pH,

PaO2 and PaCO2. The bicarbonate concentration is calculated from the pH and PaCO2 by

using Henderson-Hassel Balch equation.

PH: - Normal range- 7.36 to 7.44

The pH is the first value to be considered when using the ABG’s to assess a patient’s acid-base

status. PH of 7.35 and lesser represents acidemia, pH values of 7.45 and higher indicates

alkalemia.

Arterial partial pressure of carbon dioxide: - Normal range – 36 to 44mmHg.

Evaluation of PaCO2 provides information about the adequacy of lung function in excreting

carbon dioxide. An elevated PaCO2 usually implies inadequate ventilation.

Arterial partial pressure of oxygen: - Normal range- 80 to 100mmHg

Evaluation of the PaO2 provides information about the level of oxygenation of arterial blood.

In state of hypoventilation PaO2 is reduced with an elevation of PaCO2

Serum bicarbonate: - Normal range- 24 to 30 mEq/l

Once the PaCO2 and pH are measured, the bicarbonate concentration is calculated and

reported with the ABG results.[2]

PH and PaCO2 move in contrapositive directions. HCO3- and PaCO2 move in together in

same direction. When the pH and paCO2 change in the equal direction, the primary issue is

metabolic; when pH and paCO2 move in contrasted direction and paCO2 is normal, then the


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primary issue will be respiratory.

Mixed Disorder–if HCO3- and PaCO2 change in contrasted direction (which they should not

normally), then it said to be a mixed disorder, pH may be normal with abnormal paCO2 or vice

versa.[6]

Other tests to assess acid-base status are:- Anion gap: - Normal range- 3 to 11 mEq/l

The anion gap is a calculated value that will be helpful in classifying and evaluating possible

causes of metabolic acidosis. Normally the number of unmeasured anions exceeds the number

of unmeasured cations. When this difference is increased to the upper limit of normal, it often

indicates an increase in negatively charged, weak acids. The presence of increased anion gap

in conjugation with metabolic acidosis provides the clinician with useful information about

possible causes of acidosis. The anion gap is calculated by using sodium to approximate the

measured cations, and chlorides and bicarbonates to approximate the measured anions.

Serum lactate: - Normal range – 0.5 to 1.5 mEq/l (venous), 0.5 to 2.0 mEq/l (arterial).

When tissues are normally oxygenated, pyruvate is converted to acetyl coenzyme A and it’s

utilized as an energy source through aerobic metabolism. In patients with insufficient tissue

perfusion or enhanced tissue metabolic rates, anaerobic metabolism dominates. Anaerobic

metabolism increases the conversion of pyruvate to lactate, increasing the lactate concentration.

If these process is severe or not reversed, lactic acidosis can occur.

For each disorder, the primary abnormality will be accompanied by a compensatory change.

For example: the primary abnormality is metabolic acidosis is fall in serum bicarbonate, and

compensatory change is a fall in PaCO2.[2]

Complications of metabolic acidosis in renal failure are- bone-mineral disorder, muscle

wasting, protein degradation, encephalopathy, progression of kidney disease.[7]

Hypokalemia

and kaliuresis are common complications of metabolic alkalosis. Metabolic alkalosis are

predisposed to cardiac arrhythmias.[8]

Acid base disorders commonly accompany diuretics

use.[9]

The mortality associated with severe metabolic alkalosis is substantial; a mortality rate

of 45% was found in patients with an arterial blood pH of 7.55 and 80% when the pH was

greater than 7.65.[10]

Metabolic acidosis is a common complication kidney disease. Based on a


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cross sectional analysis of the national health and nutrition examination survey, an estimated

40 million adults in the united states have renal dysfunction, and approximately 700,000

individuals have an estimated as 30-50% of individuals with GFR less than 30 ml/min/1.73m2

have metabolic acidosis, approximately 200,000 to 350,000 individuals with CKD stage 4

and 5 have chronic metabolic acidosis in the united states.[1] Also the cross sectional study on

35 patients conducted at two centers in western part of India, found 22 out of 35 patients

(62.85%) have the mean predialysis serum pH and HCO3 of 7.32± 0.083 and 20.37 ±4.94

mmol/L.[12] The prevalence of acidosis begins to rise when GFR falls below 40ml/min per

1.73m2 and further progress to increase as GFR decreases. Lower bicarbonates levels fastens

the kidney disease progression.[13]

Since the incidence of kidney disease is increasing day by day in India and one of the common

complication of renal dysfunction is acid base imbalance. Chronic metabolic acidosis is the

most common condition to be reported which worsens the condition of the patient by

progression of the disease, reducing quality of life and increasing mortality rate by causing

complications and even death, hence there is a need for maintaining acid base balance in renal

dysfunction patients. We can reduce patient’s exposure to acidosis and alkalosis by providing

qualitative pharmaceutical care services.

Methodology

Study site

The study was conducted in the Nephrology Department of Sagar Hospitals, Bengaluru.

Study design

This was a Prospective and Observational study performed on 102 patients to assess the

variability and influence of acid-base balance in renal dysfunction patients.

Sample size

A total of 102 patients from the department of Nephrology, Sagar hospitals were included in

the study.

Study period

The study was conducted over a period of six months from October 2019 to March 2020.

Ethical approval

Ethical committee clearance was obtained by the Institutional Ethical Committee of Sagar

Hospitals, Bengaluru.

Study criteria


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Inclusion criteria

1. Patients admitted in Nephrology department

2. Patients of all stages of kidney disease

3. Patients of either gender

Exclusion criteria

1. Pregnant and lactating women

2. Patients of age <18 years

3. Patients with renal replacement therapy

Source of data

Patients demographics, clinical findings, laboratory and therapeutic data were collected from

inpatient department and the main sources for the collection of data were:

Patients case notes

Treatment charts/ medication charts

Lab reports

Progress notes

Discharge cards

Study procedure

1. Patient enrollment

A hospital based prospective study was conducted in Nephrology inpatient department of Sagar

Hospitals. The study was conducted using the data of patients who have consented to

participate. Patients who were below 18 years, pregnant and lactating women, and patients with

renal replacement therapy were excluded for the study.

2. Method of data collection

The study was carried by collecting the necessary information from the patients admitted in

nephrology department of Sagar hospitals. Data collection form, was designed to incorporate

the details of the patients. The details include demographics, past medical history, complaints

on admission, diagnosis and treatment provided with respect to renal impairment and acid-base

balance. The patients were observed on daily basis to identify the variability in acid base

balance. The treatment given to correct the acid base imbalance was recorded for the further

evaluation.


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3. Statistical methods

Descriptive statistical analysis has been carried out in the present study. Mean and standard

deviation were used to measure the central tendencies of given data.

4. Statistical software

The statistical software namely SPSS version 25.0, was used for the analysis of data

Microsoft word and excel were used to generate tables and graphs respectively

RESULTS AND DISCUSSION

The descriptive statistical analysis was performed for the given data of 102 subjects and the

results were obtained as shown below:

Table 1: Age and Gender distribution of subjects (N=102).

Age in

years

No. of subjects

(Frequency)

Total

(Percentage)

M F

31-40 02 00 02 (1.96%)

41-50 11 06 17 (16.67%)

51-60 14 07 21 (20.59%)

61-70 20 10 30 (29.41%)

71-80 16 05 21 (20.59%)

>80 08 03 11 (10.78%)

Total 71 31 102 (100%)

Fig. 01.

As shown in table 1 & Fig 1, the age distribution of the given population showed that 2 (1.96%)

of patients belong to the age group of 31-40 years, 17 (16.67%) patients belong to the age group

of 41-50 years, 21 (20.59%) belong to the age group of 51-60 years, 30 (29.41%) belong to the

group of 61-70 years, 21 (20.59%) subjects belong to the age group of 71-80 years and 11


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(10.78%) of subjects belong the age group of >80 years. According to the data obtained, it is

observed that the majority of the patients who suffer from renal dysfunction are males. Similar

results were seen in a study conducted by Wel Chen, et al. On Epidemiology of acid-base

derangements in renal dysfunction. The study results showed that the maximum number of

cases was seen in the mean age of 59 years or an average age group of 21-74 yrs with GFR

between 20 and 70ml/min per 1.73m2 was conducted the nephro study test in France. This

unlike in the more developed countries where it affects mainly middle-aged and elderly

patients.[13]

Another study conducted by Wel Chen, et al. On the epidemiology of acid-base

derangements in renal dysfunction was studied. The highest number of patients observed in

different areas of studies were male. The study results showed that in 1038 out of patients with

having 63% were male & 31% were female & 6% were black. This study was conducted in a

prospective hospital-based; France. According to this field of study, the majority of the patients

who suffer from renal diseases are males than females.[13] In table no: 1 and fig no: 1

representation of patient distribution based on age and gender. From this study, it was found

that the largest number of patients was present in the age group of 61-70 yrs with a total of 30

patients out of which 20 were male and 10 were female. The lowest number of patients was

seen in the age group of 31-40 years with 2 patients out of which all were male.

Analysis and distribution of social history

Table 2a: Distribution of subjects based on dietary habits (N=102).

Diet No. of Subjects

(Frequency)

ePatPecreP

Veg 45 44.12%

Mixed 57 55.88%

Total 102 100%

Fig. 2a.


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Both table 2a & Fig 2a revealed that, out of 102 patients, 45 (44.12%) were vegetarians, 57

(55.88%) were having mixed dietary habits. In the similar study conducted by Golaleh Asghari,

etal. on Dietary pattern and incidence of KD among adults a population based study in west

Asian. This study results shows that 1630 participants, with high fat dietary pattern was

associated with an increase of 46% of incident for developing KD, whereas a vegetarian dietary

pattern may be protective against the occurrence of KD by 43%. And also a study from the

China health and nutrition survey shows that a traditional southern dietary pattern characterized

by high intakes of rice, pork, vegetables, and low intake of wheat leads to increased prevalence

of KD and a modern dietary patterns featured by high intakes of fruits, soy milk, egg, milk and

deep fried products decreased risk of KD.[51]

Table no. 2b: Distribution of subjects based on the habits of smoking and alcohol

consumption.

Social habit No. of subjects (Frequency) Total

(Percentage) Yes No

Smoking 06 (5.88%) 96 (94.12%) 102 (100%)

Alcohol

consumption

05 (4.91%) 97 (95.09%)

Fig. 2b.

According to the table 2b & Fig 2b, the distribution of subjects based on smoking and alcohol

consumption showed that, 6 (5.88%) subjects were smokers and 5 (4.91%) were alcoholics.

out of 102 patients, 96 (94.12%) were non-smokers and 06(5.88%) were smokers this results

shows that the prevalence of Renal dysfunction is more in patients who are not smoking even

though smoking is a risk factor of renal diseases with co morbities of DM, HTN and obesity

etc. The study revealed that only 5 (4.91%) were alcoholic out of 102 patients and remaining


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97(95.09%) were non alcoholics. Based on the study conducted by Anoop Shankar, etal. On

the association among smoking, heavy drinking, and CKD. The field of study seen that the

prevalence of renal diseases was similar in both smokers and non-smokers also alcoholic and

non-alcoholic patients. High risk in the age group of 43-86 yrs of patients is may be due to life

style changes, obesity, smoking, alcoholism (male).[52]

Analysis and distribution of subjects according to diagnosis of renal dysfunction based

on stages

Table no. 3a: Distribution of subjects according to diagnosis of renal dysfunction

Diagnosis No. of Subjects

(Frequency)

PercePtaPe

CKD 66 64.70%

AKI 16 15.68%

Acute on CKD 20 19.60%

Total 102 100%

Fig. 3a.

Table no. 3b: Distribution of subjects according to diagnosis of renal dysfunction based

on stages.

Diagnosis and Stages of

renal failure

CKD AKI

Stage – I - 3

Stage - II 3 5

Stage – III 13 8

Stage – IV 19 -

ESRD 31 -

Fluid overload 23 -

Dialysis 57 -


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Fig. 3b.

According to table 3 (3a & 3b) & Fig 3 (3a & 3b), the analysis and distribution of the number

of subjects according to a diagnosis of renal dysfunction based on stages revealed that, out of

102 subjects, 66 subjects were diagnosed with CKD, 16 subjects were diagnosed with AKI and

20 subjects were found to be in the acute condition of CKD. From table 3b, it was found that

the majority (31) of the subjects were found to be in end-stage renal failure, 23 had a fluid

overload, and were on dialysis. The total number of subjects on dialysis was found to be 57

(Dialysis was done irrespective of fluid overload based on the severity of renal dysfunction and

condition of the subject). In the current study conducted, several patients in AKI were in stage

1 (3), stage 2(5), and stage 3(8). And also in CKD stages, it shows that stage 1-5 the number

of patients was increased like 3, 13, 19, &31 respectively. Patients were under fluid overload

was 23. Similar to the study conducted by Griffin P Rodgers on kidney disease statistics for


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the United States revealed that the overall prevalence of CKD increases by years to years

largest increases occurred in people with stage3 CKD. This study shows that women had more

likely to have stages 1 to 4 than men. In AKI the medicare patients ages 66 and older with an

AKI hospitalization having the risk of prevalence.[53]

Analysis of acid-base imbalance based on laboratory data obtained Table No. 4a –

Distribution of subjects based on serum bicarbonate levels.

Sr. HCO3-(MEq/Lt) No. of subjects

(Frequency)

Percentage Mean±SD

Normal ( 22-28) 40 39.22% 22.55±6.78

Metabolic acidosis (< 22) 48 47.06%

Metabolic alkalosis (> 28) 14 13.72%

Total 102 100%

Fig. 4a.

From the above table No: 4a and fig No: 4a, the analysis, and assessment of acid-base

imbalance in subjects showed that the majority 48 of the subjects out of the 102 were found to

have metabolic acidosis with having 47.06%, 40 subjects were found to have normal

bicarbonates levels with having 39.22% and 14 subjects were found to have metabolic alkalosis

with having 13.72%. In our study, the bicarbonate levels were advised, if the patients were

under hemodialysis have been increasing the bicarbonate levels and the patient’s condition

were better. The kidney excretes acids in the urine and they regulate the concentration of HCO3

in the blood. Acid-base changes due to increases or decreases in HCO3 occur more slowly than

changes in CO2. Similarly, vashistha et.al, carried out a study by randomizing the data from

121,351 maintenance dialysis 91.4% on hemodialysis treated were increasing serum

bicarbonates levels in the patients. As most epidemiologic studies have used only the serum


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bicarbonate to define metabolic acidosis, the prevalence of other acid-base disorders has not

been well characterized.[28]

Table no. 4b: Distribution of subjects based on PaCO2 levels.

PaCO2 (mmHg) No. of subjects

(Frequency)

Percentage Mean±SD

Normal ( 32-45) 53 51.97% 38.58±10.44

Metabolic

acidosis/Respiratory

alkalosis (< 32)

22 21.57%

Metabolic

alkalosis/Respiratory

acidosis (> 45)

19 18.62%

Test not advised 08 7.84%

Total 102 100%

Fig. 4b.

From the above table 4b & Fig 4b, the analysis and assessment of acid-base imbalance based

on the arterial partial pressure of carbon dioxide in subjects with renal failure showed that the

majority (53) of the subjects out of 102 were found to have normal levels of PaCO2, 22 subjects

were found to have metabolic acidosis/respiratory alkalosis, 19 subjects were found to have

metabolic alkalosis/respiratory acidosis and 08 subjects were not advised with the test. Similar

findings were observed in a study conducted by Ishita Ghatak.et al, on analysis of arterial blood

gas report in CKD. The aim of the study shows that to explore the type and prevalence of acid-

base disorders in 31 critically ill CKD patients from tertiary care hospitals in Maharashtra,

compare with two methods like systematic method and bedside method. The systematic method


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showed a higher prevalence of metabolic acidosis having 48.39% in 15 cases and the No: of

metabolic alkalosis cases were 3 having 9.68%. In this study it revealed that the most common

acid-base disorder was both simple respiratory alkalosis and mixed metabolic acidosis with

respiratory alkalosis.[54]

Table no. 4c: Distribution of subjects based on PaO2 levels.

PaO2 (mmHg) No. of subjects

(Frequency)

Percentage Mean±SD

Normal ( 75-100) 34 33.34% 67±29.3

Hypoxia (< 75) 59 57.84%


Total 102 100%

Fig. 4c.

From the above table 4c & Fig 4c, the analysis and assessment of acid-base imbalance based

on the arterial partial pressure of oxygen in subjects with renal failure showed that the majority

(34) of the subjects out of 102 were found to have normal levels of PaO2, 59 subjects were

found to have hypoxia and breathing difficulties and 09 subjects were not advised with the test.

In the study of Qiangwei Fu. et al, on Hypoxia: indicated that the force which drives to CKD

was chronic hypoxia or renal tissue hypoxia. The evidence indicated that CKD is driven by

renal tissue hypoxia that has lead to the development of therapeutic strategies that increase

kidney oxygenation and the chronic hypoxia is the final common pathway to ESRF. The lower

oxygen concentration can cause alterations of renal dysfunction, these may affects the

maintenance of a balance of the body fluids, electrolytes, pH and blood pressure homeostatic.

Increases in blood uremia profile, toxicity markers and lipid peroxidation indicated that

hypoxia causes the renal dysfunction.[55]


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Table no. 4d: Distribution of subjects based on SaO2 levels.

SaO2 (%) No. of subjects

(Frequency)

Percentage Mean±SD

Normal (95-100%) 28 27.45% 92.76±10.26

Hypoxemia (< 90%) 29 2.84%


Total 102 100%

Fig. 4d.

From the above table 4d & Fig 4d, the analysis and assessment of acid-base imbalance based

on arterial saturation of oxygen in subjects with renal failure showed that the majority (45) of

the subjects out of 102 were not tested for oxygen saturation, 29 subjects were found to have

hypoxemia and breathing difficulties and 28 subjects were found to have normal arterial

oxygen saturation value of 95-100%. When the kidney has low level of oxygen in the blood

they can produce a protein called erythropoietin which stimulates red blood cell production

which in turn increases Hb levels in the blood. That can bind to oxygen molecules hence

increasing oxygen saturation in the blood. In this study only 29 subjects have been tested the

SaO2 levels and the majority were not tested. Hb is the protein in red blood cells to tissues

throughout the renal tissue and all over the body.


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Table no. 4e: Distribution of subjects based on blood pH levels.

Blood pH No. of subjects

(Frequency)

Percentage Mean±SD

< 7.20 (Severe academia) 08 7.84% 7.32±0.36

7.20 – 7.29 (Moderate academia) 09 8.82%

7.30 – 7.34 (Mild academia) 08 7.84%

7.35 7.45 (Normal) 63 61.76%

7.46 – 7.50 (Mild alkalemia) 11 10.78%

7.51 – 7.55 (Moderate alkalemia) 00 00

>7.55 (Severe alkalemia) 00 00


Total 102 100%

Fig. 4e.

From the above table 4e & Fig 4e, the analysis and assessment of acid-base imbalance based

on blood pH in subjects with renal failure showed that the majority (63) of the subjects out of

102 were found to have normal blood pH levels. Normal blood pH must be maintained within

a narrow range of 7.35- 7.45, to ensure the proper functioning of metabolic processes and

delivery of the right amount of the oxygen to the tissues. In this study it shows that majority 63

of the subjects out of 102 were found to have normal blood PH levels, 08 subjects were found

to have severe academia, 09 subjects were found to have moderate academia, 08 subjects were

found to have mild academia, 11 subjects were found to have mild alkalemia and 03 subjects

were not tested for pH. In these 25 subjects were found to have metabolic acidosis and 11

subjects were found to be metabolic alkalosis. Majority of 63 subjects having normal pH values

in this study. In our study we had totally 57 subjects on dialysis, after the dialysis most of the

pH values are becoming normal to the patients. Blood pH depends on the balance of Co2 and


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HCO3, a change in the amount of Co2 will not change in pH until is a change in the amount

of HCO3 that preserves the balance.

Table no. 5: Assessment of management used in acid-base imbalance in subjects with

renal failure.

Drug class Generic name Frequency of use Total

Antacid Sodium bicarbonate 09 09

Calcium Supplements Calcitriol+calcium+Zinc 01 39

Calcium Carbonate 02

Calcium carbonate+Vitamin D3 31

Calcium Gluconate 04

Vitamin D3 03

Calcitriol 01

H2 Antagonists Ranitidine 06 06

Iron Supplements Iron+Vitamin B12+Folic

acid+Vitamin C

02 11

Iron Sucrose 08

Ferric Carboxymaltose 01

K+ Binder Calcium polysterene

sulfonate

16 16

Loop Diuretics Furosemide 74 102

Torsemide 28

NS Fluid Saline 04 04

Phosphate binders Calcium acetate 03 07

Sevelamir 04

PPIs Pantoprazole 92 92

Thiazide Diuretics Metolazone 09 10

Moxonidine 01

Vitamin Supplements Vitamin K 01 07

Multivitamin 02

Vitamin B complex + Lactobacillus 01

Vitamin B complex 01

Vitamin B complex+Vitamin C 02


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Fig. 5.

From the above table No: 5 and fig No: 5, distribution of drugs used for the management of

acid-base imbalance in renal failure. In this study most frequently used drug was loop

diuretics like furosemide and torsemide were used in all the subjects to cause diuresis by

inhibiting the sodium-potassium-chloride cotransporter in the thick ascending loop of Henle.

This loop diuretics reduce the reabsorption of calcium and magnesium. There might be

chances of calcium absorptions in the renal dysfunction patients so to rectify that calcium

supplements are given. So that 39 subjects were prescribed with calcium supplements like

Calcitriol+ calcium+ zinc, calcium carbonate, calcium carbonate + vitamin D3, calcium

Gluconate, vitamin D3 and calcitriol to balance the serum concentrations of calcium. PPIs

like pantoprazole was given in 92 subjects to counteract the GI side effects of other drugs,

and help to maintain the pH of the blood. The main use of the PPIs is the distribution of No:

of drugs used in per subjects was more in this study (13-15) this drug is more useful in

elderly patients according to their health conditions. This drug suppresses the gastric acid

production to maintain the acid-base balance in the patients. 9 subjects were prescribed with

sodium bicarbonate for antacid action to normalize the blood pH. Sodium bicarbonate is a

systemic and urinary alkalinized used to increases serum or urinary HCO3 concentration and

raise pH. Thiazide diuretics like metolazone and moxonidine were given in 10 subjects to

regulate fluid balance and blood pressure. One of the main symptoms of renal patients was

edema or fluid accumulation, this drug is used to increases the amount of water and salt

expelled from the body to urine. This drug also increases calcium reabsorption at the distal

tubule. Calcium polysterene sulfonate was given as a potassium binding agent in 16 subjects.

This drug exchanges calcium for potassium in the distal colon, thus potentially limiting the

sodium retention and providing calcium supplementation. Iron supplements like Iron +


1519


vitamin B12 + folic acid + vitamin C, iron sucrose, and ferric carboxymaltose were given for

anemia to restore Hb in 11 subjects. Iron supplementations are advisable for all iron deficient

CKD patients receiving erythropoiesis stimulating agents and intravenous iron may be

preferable to oral iron. Phosphate binders like calcium acetate and sevelamir were given to

increases the calcium absorption and preserve BMD in 7 subjects. In CKD patients,

controlling serum phosphate is associated with bone pathology and to regulate together with

calcium by the parathyroid hormone. It also prevents the progression of mineral and bone

disorders in renal patients. Phosphate binders help to prevent complications of kidney disease,

but sevelamir may be preferred upon calcium binders as they tend to reduce the deaths in

patients when compared to that of calcium. 6 subjects were receiving H2 antagonists like

ranitidine and 7 subjects were receiving vitamin supplements. Vitamin supplements are used

to reduce the loss of vitamins during dialysis treatment. The waste products that build up in

your body each day can change, the manner of utilization of minerals and vitamins. In our

study, all these medications used in the patients were safe and effective.

Table no. 6: Distribution of No. of drugs used per subject in management of renal

failure.

No. of drugs

used/subject

No. of subjects

(Frequency)

Percentage Mean±SD

7 to 9 10 9.80% 13.15±2.90

10 to12 36 35.29%

13 to 15 39 38.23%

16 to 18 13 12.74%

19 to 21 04 3.92%

Total 102 100%

Fig. 6.


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From the above table No: 6 and fig 6, the distribution of No. of drugs used per subject in 102

subjects revealed that, majority (39) of subjects were prescribed with 13 to 15 drugs, 36

subjects were prescribed with 10 to 12 drugs, 13mwere prescribed with 16 to 18 drugs, 10 were

prescribed with 7 to 9 drugs and 4 subjects were prescribed with 19 to 21 drugs. On average,

most of the subjects were receiving at least 13 drugs indicating polypharmacy. In our study we

observed that majority of the patients suffer from renal dysfunction between the ages of 61-70

years. And the second least of the patients age between 51-60 & 71-80 respectively. As the

aging, polypharmacy has become an important risk factor for poor outcomes in the elderly

patients. To reduce the incidence of polypharmacy and ensure the patients safety, we conducted

medication reconciliations, eliminating duplicate medications, assessing the drug-drug

interaction and reviewing dosages are decreased associated costs. Elderly patients are at the

greater risk for ADRs because of the metabolic changes and reduce drug clearance associated

with ageing: this risk is increased with the number of drugs used.[60]

Statistical methods: Descriptive statistical analysis has been carried out in the present study.

Mean and Standard deviation were used to measure the central tendencies of given data

Microsoft Word and Excel are used to generate tables and graphs respectively.

CONCLUSION

According to the WHO study, they estimated that 1.2 million people died from kidney failure,

and additionally each year around 1.7 million people are thought to die from AKI. Overall an

estimated 5-10 million people die annually from kidney diseases. Hence, our study aimed at

observing the variability and influence of acid-base balance in patients with renal dysfunction.

Out of 102 subjects, males were found to be affected more with renal dysfunction than females

comparatively. Most of the subjects were suffering from CKD than AKI and metabolic acidosis

was found to be more common based on various laboratory analyses in patients with renal

dysfunction.

The analysis of the management of acid-base balance revealed that loop diuretics like

furosemide and torsemide were used to cause diuresis and balance the pH of the blood. Other

drugs like Thiazide diuretics, proton pump inhibitors & phosphate binders were also given to

support the acid-base balance.

Hence based on the results the study concludes that fluid and electrolyte balance with the

pharmacological management of renal dysfunction helps in balancing the acid-base variations.


1521


Therefore, focusing on treating the renal impairment will bring out the effective management

of acid-base imbalance.

List of abbreviations

ABG’s Arterial blood gases

AKI Acute Kidney Injury

CKD Chronic Kidney Disease

GFR Glomerular Filtration Rate

KD Kidney Disease

PaO2 Partial Pressure of Oxygen

PaCO2 Partial Pressure of Carbon dioxide

SaO2 Oxygen Saturation

BMD Bone Mineral Density

WHO World Health Organization

ESRD End Stage Renal Disease

PPI’s Proton Pump Inhibitors

HCO3 Serum Bicarbonates

CLcr Creatinine Clearance

ESFR End Stage Renal Function

DM Diabetes Mellitus

HTN Hypertension

Hb Hemoglobin

SaO2 Arterial Saturation of Oxygen

ACKNOWLEDGEMENT

“Putting in time is an effort” which is necessary part of achieving success. We deeply

indebted to GOD almighty and my parents, for enabling us to complete this dissertation in a

fine manner. We owe a great deal of thanks to many people who supported us with their time

and encouragement throughout this enormous dissertation. We are grateful to Rguhs for

granting us permission to do this study. We express our deepest sense of gratitude to Dr.

Sridhar K A, Principal of East West College of Pharmacy, for his sincere guidance and

support.

We express our gratitude to Mrs. Mahadevamma L, Associate professor and HOD, East West

College of Pharmacy, for her valuable suggestions and guidance, which helped us greatly in

the successful completion of our thesis work.

The present study has been undertaken and completed under the expert guidance and

encouragement of Dr. K. A. Sridhar, Guide and Principal, East West College of Pharmacy.

We extend our thanks to Dr. Anitha Vani M, for her support and guidance in the statistical


1522


analysis. We take this opportunity to thank librarian Mr. Nagesh, East West College of

Pharmacy and for extending library facilities throughout this study.

Our sincere expression of gratitude to the Dr. (Major) Mahendra Kumar (Medical Director &

Member Secretary, Institutional Ethics Committee) & Justice. B.A. Muchandi, (Chairman,

Institutional Ethics Committee), Sagar Hospitals, Bangalore.

We extend our special thanks to computer operator, printers and binders for their technical

assistance and preparation of this manuscript in time. Last but not the least, we extend our

thanks to all those who have been directly or indirectly associated with our study.

Signature of the candidate

(Minnu anna chacko) (Akshatha G.)

Date:

Place:

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