INTRODUCTION:

Chronic kidney disease (CKD) is defined according to international instructions as a weakness in the function of the kidneys, which appears through a decrease in the glomerular filtration rate (GFR),less than 60ml/min per 1.73m2 within three months, as a chronic kidney disease .any impairment in the kidneys extraction of body wastes as a result of the loss of the function of the renal glomeruli in the glomerular filtration or the decrease in their number, CKD is associated with increasing age, hypertension, diabetes, cardiovascular diseases and lack of physical exercise^1,2,3. CKD is a risk factor for end –stage renal failure and cardiovascular⁴ and other risk factors for developing the disease are, smoking, obesity, family history of the disease, advanced age, and frequent use of medications that affect the kidneys, Azotemia, cationic electrolytes are retained in systemic circulation^5,6

FGF23 was discovered for the first time in the (2000)year, the first known discovery of phosphatonin for its effect on the metabolism of phosphate in body⁷, it is polypeptide with a molecular weight of (32 kilo Daltons), and it contains a polypeptide composed of (24)amino acid in the amino portion of the protein⁸ the carboxylic terminus is formed from (72)amino acid⁹, it is secreted by the osteoblasts and osteocytes in response to an increase in extracellular phosphate or an increase in vitamin D3, FGF23 is binds to receptors (FGFR1c) at the nitrogenous end and to the co-receptor (α-Klotho) at the carbon end, and is more stable by binding to its receptors, the activity of the receptor depends on its association with heparin sulphate as a catalyst^10,11. The human gene of FGF23 is located on the chromosome 12 and it is a member of the subfamily (FGF19)^12,13. The fibroblast growth factor family (FGF)has divided into seven subcategories based on genetic or genotypic similarity that include FGF1, 2 –FGF4, 5, 6 – FGF3, 7, 10, 22 – FGF8, 17,18- FGF9, 16, 20 –FGF11, 12, 13,14) and FGF15, 19, 21, 23)¹⁴. A relationship FGF23 with kidney disease is evident through a binding to receptors FGFR1c and with co-receptor (α-klotho) in proximal renal tubules, FGF23 prevents sodium –phosphate transporters (Npt2a, Npt2c) from crossing the kidney wall for the purpose of reabsorption of phosphate and then extracting it through the urinary system. FGF23 also inhibits the gene expression of α1-hydroxylase enzyme that is responsible for vitamin D formation, so it reduces the absorption of phosphate in the intestine while in the distal renal tubules, FGF23 is sends signals to inside the cells of the kidney tissues to increase the re absorption of calcium and sodium through the renal tubules, so a decrease FGF23 is increases phosphate, tumors, calcification.^10,15,16

Aim of researched:

Since there were a little previous studies In Iraq about the relation FGF23with metabolism of phosphate in the body , especially in patients with chronic kidney disease, so it was proposed to study its mechanism of action in patients and its relationship with the measured biochemical parameters.

MATERIALS AND METHODS:

Experimental:

(60) blood samples were collected from chronic kidney patients, (30)samples for both sexes (females and males), their ages between (15-55)year and over, also (30) blood samples were collected from healthy people, (15)samples for both (females and males) from Ibn-Sina Teaching Hospital. After the blood serum was isolated from the samples, it was used to estimate the following some biochemical parameters.

FGF23-was estimated by using SHANGHAI YEHUA Biological Technology Co., Ltd kit(China)by enzyme linked immunoassay ELISA technique¹⁷.

Phosphate –was determined by using BIOLABO kit(Farance)¹⁸.

Vitamin D- was determined by using BIOMERIEUX kit(Farance)¹⁹.

Urea- was determined by using enzymatic and chromogenic method (Urease-Modified Barthelod Reaction)²⁰.

Creatinine- was determined by using BIOLABO kit (Farance)²¹.

Calcium-was determined by using BIOLABO kit (Farance)²².

Chloride-was determined by using AGAppE DIAGNOSTICS (Switzerland)²³.

Potassium-was determined by using Biosam kit (Dubai-UAE)²⁴.

Albumin-was determined by using BIOLABO kit (Farance)²⁵.

Alkaline phosphatase enzyme- was determined by using BIOLABO kit (Farance)^26,²⁷.

Transaminase enzyme GOT and GPT-were determined by using BIOLABO kit (Farance)^27,28.

Data analysis:

The obtained data were analysed using T-test used for comparing between two parameters, Standard statistical methods were used to found the mean and standard deviation, also Linear regression analysis [pearson correlation coefficient (r) was performed to identify the relation between different clinical parameters²⁹.

RESULTS AND DISCUSSION:

Concentration of FGF23 in chronic kidney disease patients compared with control group:

The result showed that the normal concentration of FGF23 was ( 273.88±188.5pg/ml)in control group and the result also elucidated that chronic kidney patients have a significant increase in FGF23 concentration to (324.06±291.1pg/ml) compared with control group as in fig.1 below, the reason for the increase FGF23 concentration might be due to FGF23 is a bone –derived phosphaturic hormone, that acts on the kidney via FGF receptor (FGFR)1/Klotho –mediated down regulation and mineralization of sodium –phosphate cotranspoters Nap2a and Nap2c decreasing phosphate reabsorption and finally serum phosphate levels, also FGF23 suppresses renal synthesis of 1,25 di hydroxy vitamin D that leads to reduced dietary phosphate absorption in the intestine and lowering serum phosphate concentration by increase in its excretion in the urine, as a feedback on the lack of phosphate in the blood, FGF23 inhibits the parathyroid hormone and wokes on the formation of vitamin D, which stimulates the absorption of phosphate in the intestines and increases it in the blood^30,31.

Figure 1. FGF23 concentration in chronic kidney patients and control group

Some clinical parameter concentration in chronic kidney patients compared with control group:

The results in table (1) showed a significant increase in concentration phosphate this conclusion is consistent with what was stated by both^30,31. the results also showed a significant increase in (urea, creatinine, potassium) and a non significant increase in chloride concentration in patients compared with control group, this increase might be due to the decrease in the glomerular filtration rate (GFR) in patients chronic kidney, also kidney disturbance is a common for patients with heart failure and potassium plays role in myocardial contraction^23,33,34. the reduction of creatinine average in the renal failure patients, as they ages and that is because the reduction of their muscles³⁵ also the result had been showed a significant increase in ALP enzyme at patients compared with control group, these results were in consistent with^36,37 while the result shown a significant decrease in (vitamin D, Calcium) because in CKD serum 1,25di (OH) vitamin D level are decreased due to the effect of FGF23 decreasing to conversion of 25 vitamin D to 1,25 vitamin D by inhibiting the 1-α hydroxylase enzyme, thus patients with CKD are at risk for low calcium absorption due to decreased levels of 1,25 vitamin D and low active calcium transport³⁸, table (1) also shows that there is a significant decrease in the albumin concentration, the reason is due to overload excretion albumin by kidneys ³⁹, Finally, the results showed that there was a significant decrease in the effectiveness of each of GOT and GPT enzymes, as a result of lipid metabolism disturbances⁴⁰.

Table 1. Some clinical parameters concentration in chronic kidney patient and control

Clinical Parameters	Control Group	Patients
Phosphate gm/dl	2.73 + 0.69	** 4.736 + 1.69
Vit. D ng/dl	30.39 + 5.07	** 21.74 + 11.7
Calcium mg/dl	2.129 + 0.36	** 1.19 + 0.26
Urea mg/dl	38.36 + 8.3	** 128.8 + 29.4
Creatinine mmd/ L	81.56 + 22.51	** 658.7 + 104.7
Chloride meq/ L	97.2 + 9.3	100.42 + 11.49
Potassium meq/ L	4.24 + 0.7	** 5.099 + 1.51
Albumin mg/dl	4.22 + 0.7	** 3.54 + 0.5
ALP Iu/L	53.79 + 13.6	** 150.74 + 100.16
GOT Iu/L	14.5 + 4.47	** 10.58 + 4.39
GPT Iu/L	17.23 + 5.45	** 13.91 + 6.94

Significant difference at **p<0.01

Correlation between FGF23 Concentration and some clinical parameters in Chronic kidney diseases (CKD)patient comparing to control group:

The result in table (2) showed that FGF23had a negative significant correlation with phosphate and vitamin D, while a positive significant correlation with calcium in chronic kidney patients, this results is in agreement with the research findings⁴¹when FGF23 level increases to maintain a normal phosphate concentration by increasing phosphate excretion and inhibiting the synthesis of vitamin D .also the result in table (2) showed that FGF23 had a negative significant correlation with albumin, this result is in agreement with research⁴²,there are correlation between FGF23 and serum albumin was a significant and had a negative inverse correlation, while FGF23 had a non-significant correlation with the rest of the biochemical parameters.

Table (2) : Correlation between FGF23 concentration and some clinical parameters in chronic kidney patient comparing to control group

Clinical Parameters	Control Group r-value	Patients r-value
Phosphate gm/dl	- 0.129	- 0.298 *
Vit. D ng/dl	- 0.029	- 0.227 *
Calcium mg/dl	0.288	0.381 **
Urea mg/dl	0.194	- 0.008
Creatinine mmole/ L	0.033	0.108
Chloride meq/ L	0.148	- 0.024
Potassium meq/ L	0.053	0.121
Albumin mg/dl	- 0.009	- 0.383 **
ALP IU/L	- 0.165	- 0.212
GOT IU/L	0.128	0.015
GPT IU/L	0.162	- 0.107

* Correlation is significant at the 0.05 level

** Correlation is significant at the 0.01 level

ACKNOWLEDGMENTS:

I would like to extend my thanks and report to the University of Mosul for providing me with all the necessary facilities to complete this research.

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Received on 19.03.2022 Modified on 10.04.2022

Research J. Pharm. and Tech 2023; 16(1):115-118.

DOI: 10.52711/0974-360X.2023.00021