Biochemical Investigation to Determine the Factors Involved in Renal Failure Formation for Dialysis Patients

 

Marwan Talib Joudah¹, Shaker M. Saleh¹, Wisam Talib Joudah², Mohammed Talib Joudah³

¹General Directorate of Education in Anbar, Gifted Guardianship Committee, Ministry of Education in Iraq.

²General Directorate of Vocational Education in Anbar. Ministry of Education in Iraq.

³Baghdad Teaching Hospital-Medical City/Ministry of Health in Iraq.

 

ABSTRACT:

Renal failure is on the top list of kidney diseases as being frequently reported in many medical facilities around the globe. Human kidneys play an important role in excreting, reabsorbing, secreting and filtrating substances in the body. Healthy kidney must excrete the waste products of the body in urine and preserve albumin, and other useful substances in the body. The current study aims to figure out the expected factors of renal failure formation in dialysis patients. Likewise, it is designed to search for any correlation between the imbalanced levels of electrolytes and kidney deterioration. The current study was conducted in Ramadi city-Iraq with the assistance of Al-Ramadi Educational Hospital (REH). The (14^th) samples of renal failure patients were collected from dialysis unit at (REH). (2-3 mL) of blood was taken from a patient’s vein. The serum was separated from plasma with the use of a centrifuge. All samples were undergone centrifuging for (4-7 min) at (550 rpm).  Afterward, samples were subjected to biochemical examinations to determine the levels and quantities of some biochemical elements and other substances in the selected cases. It was found that some patients had been recorded with a decrease in glomerular filtration rate (GFR), high HbA1c level (˃ 6.5 mg/dL) (21.5%), anemia (˂ 12.0 mg/dL) (%100) in women and (˂ 13.5 mg/dL) in men (%100), Uremia (˃ 45mg/dL) (%100), hypercalcemia (˃10.5 mg/dL) (%7.14), hyperkalemia (˃ 5.1 mg/dL) (%92.8), and Hypernatremia (˃145 mg/dL) (%28.5). Some results obtained, imbalanced levels of the mentioned substances, are either progressed with kidney deterioration, or they are the causes of renal failure. Changes in the levels of some blood substances were observed, and positive results were obtained regarding the aim of the study. Levels or quantities of some blood substances play an important role in preserving kidneys good performance. For instance, when the level of glucose in blood raises, a severe damage to the blood vessels of the kidney takes place and results in poor kidney's performance. While, an increment in the K serum level causes a sudden cardiac death. Changing in some levels and quantities of blood substances could be a core cause of renal failure formation, however, some of them develops when kidney deteriorates.

 

 

INTRODUCTION:

Kidneys like other organs play an essential role in preserving human health including vitamin D metabolism (It produces 1, 25-hydroxycholecalciferol, and without this process, bone diseases are expected to occur), the production of erythropoietin (anemia emerges when the kidney fails to produce erythropoietin, preserving the fluid balance generally, as a filter to the minerals from blood, and filtering unwanted material as a result of food, toxic subjects, and medications. A human is basically born with a pair of kidneys that are located on both sides of the spine right above the waists. Kidneys make hormones that are utilized in the production of red blood cells, blood pressure controller, and boost bones functions¹. Kidney diseases is one of the biggest worldwide health issues that could be emerged either with born or through a certain age due to numerous factors such as associated diseases, dietary system, and medications intake. However, the most fatal ones among these diseases is renal failure. Renal failure/end-stage kidney disease is defined as the disability of kidney to perform the excretory function that results in returning the waste to the blood instead of excreting it outside the body. The kidney is failed to work when it only performs less than %15 of its normal function². Therefore, a human body will be unable to clean up the blood from the poisonous substances, dispose of the additional water in the blood, and regulating the blood pressure. In addition, it impacts the production of red blood cells that are very essential to maintain healthy body. When a kidney deteriorates, it poses the waste from blood and other toxic substance to other parts of the body which causes swelling in ankles, severe weakness, shortness of breath, nausea, and other disorders^{3, 4}. Other reason for acute renal injury (ARI) is the side effect of some medications such as anti-tuberculosis medication. It has been proven to be one of the causes of (ARI)⁵.Hypertension is also responsible for renal failure, which is formed when interaction of some environmental agents and genes take place. Arteries around the kidney may get affected, which become weak, hard, or narrow, due to hypertension. This result in a weak delivered blood to the kidney ⁶.

 

Renal failure is divided into two types, chronic and acute renal failure. Acute Renal Failure (ARF) is occurred when the glomerular filtration rate suddenly drops (hours to several days). The diagnostic of this type could be obtained by monitoring (increment) of creatinine within (48 hr.) about (0.3 mg/dL), as well as, an increment of creatinine within the last week to 1.5 times, or urine volume (about 0.5 mL/kg or less) per hour for (6 hr)⁷. Chronic Kidney disease is characterized by kidney's damage that leads to a disturbance in the glomerular filtration rate. Poisonous substances could not be properly excreted out of the body due to the kidney injury⁸.

 

The excretory function of kidney fails to work withing a few hours or days where the levels of creatinine and urea in blood elevate. In some cases, the rate of urine production decreases. Anuria or oliguria are considered the signs of renal failure ⁹. The term (ARF) has been altered to (AKI), acute kidney injury, due to that (AKI) signifies the abnormality of the level of serum creatinine until reaching a state where renal failure forms. This type of renal failure is a common problem recorded in most hospital around the globe. (ARF) incidence increases with age and about 150 cases out of million record in the UK. (Mehta RL; et al, 2007). While Chronic Renal Failure (CRF) is a continuous deterioration of kidney functions that is resulted in a significant elevation in serum creatinine for a continuous last three months, or the rate of glomerular filtration (GF) less than (60 per min / 1.73m2). (ESRD) end-stage renal disease is a stage where a patient reaches a therapy of renal transplantation. It usually comprises a gradual loss of the kidney's functions which may lead to either a kidney’s transplantation or hemodialysis^{10, 11}. Hemodialysis (HD) is a treatment that is designed for patients who suffer from end-stage renal disease. (HD) helps RF patients to filter unwanted fluid, waste, and various salt in the blood and send them out of the           body^12,13. CKDs are sometimes asymptomatic. The treatments are varied depending on the status. Early/mild kidney damage could be treated with certain medications, while end stage kidney damage is treated with either kidney transportation surgery or hemodialysis ¹⁴. Bone disorders, such as osteoporosis, is initiated early or with kidney failure diagnosis. Abnormal bone tissue is a sign of most patients with CRF¹⁵.

 

Stages of Chronic Kidney Disease:

Based on the classification presented by the National Kidney Foundation (NKF) , five stages of chronic kidney diseases are shown in table (1). These stages have been admitted by numerous clinical guidelines as an approach to deal with the (CKD)¹⁶.

 

Table (1): (CKD) Chronic kidney disease Classification

Stage	GFR (ml/min per 1.73 m2)	Kidney Condition
1	90 or more	Damage of the kidney with natural or (↑GFR)
2	60-89	Damage of the kidney with mild (↓ GFR)
3	30-59	Moderate ↓ GFR
4	15-29	Intense ↓ GFR
5	Less than 15	Renal Failure

 

Kidney’s filtration rate per day of (water, sodium, glucose, and urea) are [180 _(L), 630 _(g), 180 _(g), and 54 _(L)] respectively. While the quantity Excreted a day of the above substance are [1.8 _(L), 3.2 _(g), 0 _(g), and 30 _(g)] respectively¹⁷.

 

Aim of Study:

Aim of the study was to find out the reasons and factors that may have impacted the selected patients and ended up with renal failure. Likewise, to assess the levels of some biochemical elements in blood and corelate them to kidney's deterioration.

 

MATERIAL AND METHODS:

The current study was conducted in Ramadi city-Iraq with the assistance of Al-Ramadi Educational Hospital (REH). The (14^th) samples of renal failure patients were collected from dialysis unit at (REH). (2-3 mL) of blood was taken from a patient’s vein. The serum was separated from plasma with the use of a centrifuge. All samples were undergone centrifuging for (4-7 min) at (550 rpm).  Afterward, samples were subjected to biochemical examinations to determine the levels and quantities of some biochemical elements and other substances in the selected cases, which are explicated with their procedures as follow:

 

Urea Examination (Urease/ Glutamate Dehydrogenase):

(1 mL) of urea solution by (Biosystem) was placed into a white tube. (10 micron) of a patient’s serum was transformed to the previous urea solution. The entire mixture was mixed up for (25 sec.) and left to settle at room temperature for (12 min). After that, the value of the resulted solution was obtained using (Apple Apparatus-Japanese Made) at (600 nm) wavelength. The consumption of urea by the sample was achieved by a coupling reaction as it is shown below where nicotinamide adenine dinucleotide hydrogen (NADH) had been measured by spectrophotometry.

 

Diabetic Examination (Glucose Oxidase/Peroxidase):

(1 mL) of a sugar solution by (Biosystem) was placed into a white tube. (10 micron) of a patient’s serum was added to the previous sugar solution. The entire mixture was mixed up for (12 min) and left to settle at room temperature for (12 min). After that, the value of resulted solution was recorded by (apple apparatus-Japanese made) at (500 nm) wavelength. Glucose in the sample arises by a coupling reaction as it is explained in the following equations. Spectrophotometry was used to measure the resulted color complex of the coupling reaction.

 

Other Examinations:

While the rest of the examinations, that will be explained in the result section, were conducted using (Reflotron Plus System). The Reflotron machine was zeroed using a provided zeroing strip. After that, (32 micron) of a patient’s serum was placed on the surface of the strip, and eventually the strip was placed into the specified port of the machine. The values were obtained using the machine’s screen¹⁸.

 

RESULTS AND DISCUSSION:

In the current study, 14 renal failure patients were undergone biochemical examinations. The cases were mixed gender whose ages are ranged between (20-70 years old).

 

Biochemical examinations of the selected (RF) patients have been conducted (March-June, 2020) to figure out what factors that may have been impacted the patients' kidneys and resulted in renal failure formation based on the acquired results. The glucose level was among the conducted examination, and it was proven to be a core cause of a kidney damage. The following values depict the variations in glucose levels (HbA1c ) of renal failure patients, where HbA1c is (glycated hemoglobin).

 

Table (2): HbA1c examination values of renal failure patients

Sample NO. (RF)	HbA1c mg/dL
p1	6.2
p2	8.2
p3	4.8
p4	5.1
p5	5.9
p6	6.8
p7	9.7
p8	4.8
p9	7.4
p10	5.6
p11	4.9
p12	6.2
p13	5.8
p14	4.6

 

Normal (HbA1c) level ranges from (4.0 – 5.6 mg/dL), while from (5.7 – 6.4 mg/dL) is considered prediabetes. However, any recorded value over (6.5 mg/dL) is a case with diabetes. Based on the obtained results in table (2), it is recorded that (21.5%) of the renal failure cases with a severe elevation of the (HbA1c) level (˃ 6.5mg/dL), whereas (7.14 mg/dL) was recorded slightly higher than the normal range.  High glucose level in blood causes a severe damage to the blood vessels of the kidney, which leads to a poor performance of the kidney. As a result, the human health is affected. Due to the vessels damage, kidney losses its function of preserving albumin that possesses an essential role for maintaining the volume of extracellular fluid. Those kidney failure patients with abnormal HbAlc levels are expected to be developed with (RF) due to abnormal HbAlc levels since HbAlc examination records the level of the glucose in the blood for the past three months of the examination. The Albumin protein of the (21.5%) of the cases is anticipated to be high in urine as a result of blood vessels damage of the kidney (with an assumption as it is the reason of kidney failure of these patients). Urine Albumin examination needs to be conducted in future works as a complementary to the investigations^{19, 20}. A study was reported by Senthilkumar and Dhivya, which was found an inverse relationship between HbA1c level and GFR ²¹. 

 

Urea values of all cases were recorded and shown in table (3). A significant variation was obtained of kidney failure patients as follow:

 

Table (3): Urea examination values for renal failure patients

Renal Failure
S.NO	Creatinine mg/dL	Urea mg/dL
p1	6.0	211
p2	8.3	263
p3	8.9	287
p4	5.0	189
p5	8.2	224
p6	6.8	284
p7	8.8	191
p8	7.5	210
p9	8.8	170
p10	6.0	246
p11	5.8	192
p12	7.7	185
p13	7.7	294
p14	8.3	198

 

Uremia, high urea level in blood, urine in the blood, is a condition that is linked to kidney functions. Uremia is associated with a disturbance in the levels of hormones, electrolyte, and fluids in the body. This clinical condition is usually emerged with cases diagnosed with end-stage kidney failure or (AKI). Uremia is an indication of a kidney damage when the kidney transforms toxin, including urea and creatinine, and body’s waste to blood instead of urine¹³. The normal range of urea and creatinine in blood are ranged between (25-45 gm/dL) and (0.5-1.2 mg/dL) respectively. Urea level is always accompanied with creatinine level when it comes to examine the performance of kidney functions. Creatinine values (ranged from 5.0-8.9 mg/dL) and urea values (ranged from 170-294 mg/dL) of the selected renal failure patients in table (3) indicate a severe damage to the kidneys as a result of either diabetes, heavy metals poisonous, non-steroidal anti-inflammatory drugs, imbalanced levels of some biochemical elements in blood, and many more. The kidneys of these patients may have been impacted by the mentioned factors according to the high values of creatinine and urea. In addition, the assessment of glomerular filtration rate (GFR) relies on the creatinine and urea measurements in plasma/serum levels. A healthy kidney correlates with a normal (Glomerular Filtration Rate) GFR (~125 mL/min). When GFR declines, an elevation in the blood concentration of urea and creatinine occurs, whereas their excretion decrease²². In a healthy kidney, approximately a half of urea quantity and the whole creatinine quantity are excreted to urine.

 

Even though Hemoglobin (HGB) levels vary in women and men due to the menstrual cycle in women, however, HGB examination was essential to be conducted for all cases in order to dig deeply into the investigation. All the HGB level values were listed in table (4) for both renal failure patients.

 

Table (4): HGB examination values for renal failure patients

Sample NO. (RF)	HGB g/dL
p1	7.8
p2	11.0
p3	9.8
p4	10.2
p5	10.2
p6	10.1
p7	11.4
p8	11.4
p9	7.4
p10	10.6
p11	8.5
p12	10.0
p13	10.9
p14	10.7

 

The normal range of hemoglobin in men is (13.5 to 17.5 g/dL), while in women is (12.0 to 15.5 g/dL). Anemia (decrease hemoglobin level) is a consequence of chronic kidney disease due to a decrease in the production of erythropoietin (EPO), which stimulates the production of RBC in the bone marrow. The role of (RBC) is to carry oxygen to the organs especially brain and heart. When less (RBC) produces, less oxygen delivers to organs, which eventually leads to poor performance of these organs including kidneys. Mortality rate increases of patients with a severe anemia. Anemia is commonly progressed with kidney disease; especially renal failure, when a kidney loss (%20-50) of its functions. Deficiency of Iron in the blood is another cause of anemia. The results in table (4) show an insufficient quantity of (RBC) in renal failure patients that ranges from (7.8 – 11.4 g/dL). This suggest that fewer (EPO) was produced by the damaged kidneys, which was resulted in anemia. It was also observed that (RBC) examination of two cases were close to the normal range. This could be attributed to either, those patients were treated with iron pills to raise up the hemoglobin level, or they were injected with erythropoietin injection via intravenously through the duration of dialysis^{23, 24}. There is a significant correlation between the creatinine and Hb levels of patients with renal failure. RF patients were recorded with high levels of creatinine and a decrease in the Hb levels. The same result was also reported by Ghassan F. and co-workers ²⁵. Anemia is highly developed in diabetic patients rather than with those without diabetes. Deficiency in erythropoietin hormone production by the kidney is the major reason for the decrease in hemoglobin levels in chronic kidney patients ²⁶.

 

Imbalanced levels of some biochemical elements (Na⁺, K⁺, and Ca⁺⁺) in blood affect human health and cause numerous organs’ diseases such as cataract, renal failure, and bone diseases. The data in table (5) shows the levels of these elements in blood for renal failure patients.   

 

Table (5): Biochemical element level for renal failure patients

Sample NO. (RF)	Calcium Ca++ mg/dL	Potassium K+ mg/dL	Sodium Na+ mg/dL
p1	10.1	5.6	140
p2	9.6	4.0	148
p3	9.1	6.5	134
p4	9.7	4.0	147
p5	9.1	5.2	138
p6	10.1	5.52	141
p7	9.6	5.1	139
p8	10.1	3.8	130
p9	8.8	5.21	148
p10	10.8	5.22	148
p11	9.8	5.02	142
p12	9.5	5.22	145
p13	8.9	4.52	137
p14	9.9	4.8	139

 

Hypercalcemia, or elevated serum calcium level, is a common clinical disorder that is accompanied with numerous changes in the body, as well as, it alters the functions of some organs. Calcium (Ca⁺⁺) must be preserved at a normal range to avoid many health issues such as bone loss in elderly that associates with vitamin D deficiency. The normal range of serum (Ca⁺⁺) level is (8.5-10.5 mg/dL). The values of mineral serum calcium levels of (RF) patients were within the normal range except one case, which was in the upper of normal range (10.5 mg/dL). The association of hypercalcemia and hypocalcemia for renal failure has not been well comprehended or illustrated due to the association of high and low minerals level in blood with many diseases. However, the (RF) case is a (62 years) women with serum (Ca⁺⁺) level of (10.8 mg/dL). This slightly high serum (Ca⁺⁺) level could be due to an inadequate dialysis that left some quantity of calcium in blood, excessive intake of food containing (Ca⁺⁺), or hyperparathyroidism condition that raised up the (Ca⁺⁺) level ²⁷.

 

Many physiologic operations including preserving a regular cardiac conduction requires a normal potassium level in blood. Most chronic kidney disease (CKD) were observed with high serum potassium level compared to non-CKD, which could due to a reduction in potassium excretion, as well as, excessive intake of medications, such as diuretics, that block the kidney from receiving an enough quantity of potassium ²⁸. The normal serum potassium level is ranged from (3.5 - 5.1 mg/dL). The baseline (K⁺) result for (RF) patients, hyperkalemia (˃ 5.1 mg/dL) was overwhelmingly predominant over hypokalemia.  Sudden cardiac death could be attributed to an elevation in serum potassium level for people with renal failure. A periodic serum potassium level analysis should be conducted to CKD patients to eliminate the risk of developing sudden cardiac death ²⁹.

 

Sodium is one of the three most important electrolytes in the body that controls the fluids as they exchange between tissues and cells. When the level of (Na⁺) alters, blood pressure and acid-base balance are directly affected in the body. Vascular system and kidney are impacted when an elevation of serum sodium level occurs. The oxidative stress of the kidney elevates as sodium intake increases due to lowering the rate of breakdown interactive oxygen. The production of TGFβ1, HNO3, and a change in endothelium are resulted in glomerular and vascular fibrosis, which leads to a failure or a decrease in the kidney functions ³⁰. Hypernatremia is a disorder occurs when the serum electrolyte (Na⁺) level elevates (˃145 mg/dL). It is a reduction of the total water in the body proportionally to the sodium quantity. (%28.5) of (RF) was observed with up-normal serum sodium level. Kidney with failed functions is distinguished with a progressive development of isosthenuria and hyposthenuria, which turns eventually into a risk of hypernatremia development³¹. High serum sodium level could raise the rate of mortality of renal failure patients.

 

CONCLUSION:

Imbalanced levels and quantities of blood substances, such as electrolytes, HGB, Creatinine, urea, and uric acid, affect kidney’s performance, which leads eventually to renal failure. Some of the changes of substances quantities initiate with kidney’s deterioration, and some were recorded to be the anticipated causes of renal failure formation. High level of (HbA1c) and high levels of (Ca⁺⁺) and other substances damage the kidney, therefore, the waste and poisons return to blood instead of excreting them to urine and finally outside the body.  

 

ACKNOWLEDGEMENT:

We would like to thank all people who have been contributed differently to get our work done successfully. First and foremost, we would like to thank the Dialysis Center-Teaching Hospital in Ramadi for letting us use its facility and obtaining the samples for the study.

 

CONFLICT OF INTEREST:

There was no conflict of interest.

 

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Accepted on 27.04.2021           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(12):6275-6280.