Sudan University of Science and Technology

College of Graduate Studies

Evaluation of Renal Morphology for Diabetic Sudanese Patients by Using Computed Tomography ‫تقويم شكل الكلي لدي مرضي السكري السودانيين باستخدام التصوير‬ ‫باالشعه المقطعيه المحوسبة‬ A thesis Submitted for Partial Fulfillment of the requirement of Master Degree (M.Sc.) in Diagnostic Radiologic technology

By: Sara Hamadnalla Elbashir Saeed Supervisor: D. Hussain Ahmed Hussain

April 2016

‫االيه الكريمه‬ ‫أن ت َنفَد َ َك ِل َم ُ‬ ‫حر قبَ َل َ‬ ‫﴿ق ُل لَو ك َ‬ ‫ات َر ِبي َو َلو ِجئ َنا‬ ‫حر ِمداَدا ً ِل َك ِل َما ِ‬ ‫ت َر ِبي لنَ ِفد َ البَ ُ‬ ‫َان ا لبَ ُ‬ ‫بمث ِل ِه َمددَا ً ﴾ ﴿‪﴾901‬‬ ‫ِ‬ ‫االيه (‪ )901‬سورة الكهف‬

‫‪I‬‬

Abstract This study was done to evaluate renal morphology in adult diabetic Sudanese patients. The purpose is to measure thickness and CT no. for both renal cortex and medulla for each kidney, as correlated with age, gender, duration and treatment of disease. The Study was done during the period from September 2015 to April 2016 at Asia Hospital and Omdurman Military Hospital, using CT machine. A sample of 50 subjects were collected (25 control group, 25 diabetic group). The findings showed the means of (Rt. Cortex, Rt. Medulla, Rt. Cortex CT. No., Lt. Cortex, Lt. Medulla, Lt. Cortex CT. No.) were (5.3304, 7.8336), (13.6368, 17.6296), (42.0400, 32.7016), (6.0256, 7.1584), (13.8208, 16.9080), (45.5200, 34.7052), respectively for control group and diabetes group, there were statistically significant differences among the two groups p value < .05, while no statistically significant differences among the two groups in means of (Rt. Medulla CT. No and Lt. Medulla CT. No.) (25.2800, 28.4000) (25.8000, 26.6656) respectively for control and diabetic groups, p > .05. There were no statistically significant differences between the two Kidneys for diabetic group the means of (Rt and Lt. Cortex, Rt and Lt Medulla, Rt and Lt Cortex CT. No., Rt and Lt Medulla CT. No.) were (7.8336, 7.1584), (17.6296, 16.9080), (32.7016, 34.7052), (28.4000, 26.6656) respectively p >.05. There were no statistically significant differences between the two types of treatment given to the patients (insulin, tablets), the p values >.05 except in (Lt. Medulla with Sig < 0.05). No statistically significant correlation between cortex and medulla thicknesses, and corresponding CT. No.’s and the duration of disease. No statistically significant correlation between cortexes, medulla thicknesses and corresponding CT. No.’s and age in diabetes patients p >.05. No statistically significant differences between the means of (Rt. Cortex, Rt. Medulla, Rt. Cortex

II

CT. No., and Rt. Medulla CT. No, Lt. Cortex, Lt. Medulla, Lt. Cortex CT. No. and Lt. Medulla CT. No) were , (8.0088 , 7.5222), (18.1088 ,16.7778), (32.9563 , 32.2489), (28.6913 , 27.8822), (6.9412 , 7.5444), (16.9562 , 16.8222), (34.3456 , 35.3444), (26.2781 , 27.3544) respectively for male and female in diabetes p >.05. Thicknesses of cortex and medulla of both kidneys were larger than in normal (control group). This could provide a useful indicator for the diagnosis of diabetic nephropathy.

III

‫المستخلص‬ ‫اجريت هذه الدراسه بغرض تقويم تركيب الكلي لدي المرضي السودانيين المصابين بمرض السكر‪.‬عن طريق‬ ‫قياس سمك وكثافه قشره ولب الكليتين وايجاد االرتباط بين هذه المتغيرات مع العمر والنوع وفتره المرض ‪.‬‬ ‫اجريت الدراسه خالل الفتره بين سبتمبر ‪ 5102‬وابريل ‪ 5102‬في مستشفي اسيا ومستشفي السالح الطبي‬ ‫بام درمان باستخدام التصوير باالشعه المقطعيه المحوسبه‪ ,‬تم اختيار عينه من ‪ 21‬شخص) ‪ 52‬مصاب‬ ‫بالسكر‪ 52,‬مجموعه ضبط(‪ ,‬وقد اوضحت النتائج ان المتوسطات لكل من )قشره الكليه اليمين‪ ,‬لب الكليه‬ ‫اليمين‪ ,‬كثافه القشره للكليه اليمين‪ ,‬قشره الكليه الشمال‪ ,‬لب الكليه الشمال‪ ,‬وكثافه قشره الكليه الشمال( هي‬ ‫)‪,3513.03) (0235.6 ,1522.2) (35.6102 ,1511.55) (2572.06 ,2323.03) ,(3332.6 ,3315.2‬‬ ‫‪ (6125.35 ,2511.52) (7131.02‬لكل من مجموعة الضبط ومجموعة السكري علي التوالي‪ ,‬اي انه‬ ‫توجد فروق ذات دالله احصائيه بين المجموعتين فيهذه االشياء‪ ,‬بينما التوجد فروق ذات دالله احصائيه‬ ‫كبيره بين مجموعتي الضبط والسكر من ناحيه كثافه لب الكليه اليمين وكثافه لب الكليه الشمال)‬ ‫‪ (2222.52 ,3111.53) (5111.53 ,5311.52‬علي التوالي‪ ,‬كما انه التوجد فروق ذات دالله احصائيه‬ ‫بين سمك وكثافه كليتي المجموعه المصابه بمرض السكرفي كل من )قشره الكليه اليمني‪ ,‬قشره الكليه‬ ‫اليسري( )لب الكليه اليمني ‪,‬لب الكليه اليسري( )كثافه قشره الكليه اليمني‪ ,‬كثافه قشره الكليه اليسري(‬ ‫)كثافه لب الكليه اليمني‪ ,‬كثافه لب الكليه اليسري( حيث كانت المتوسطات لكل منها) ‪,3332.6‬‬ ‫‪ (2222.52 ,5111.53)(6125.35 ,6102.35)(7131,02 ,2572.06)(0235.6‬علي التوالي‪ .‬كما انه‬ ‫اليوجد فرق في تأثير العالج المستخدم علي الكليتين اال في سمك لب الكليه الشمال ‪.‬ايضا فتره المرض‬ ‫وعمر المريض ليس لها تاثير علي سمك وكثافه قشره ولب الكليتين في المجموعه المصابه بالسكري ‪ .‬كما‬ ‫اوضحت النتائج ان نوع المريض )ذكر‪/‬انثي( ليس له تاثير في كليتي مرضي السكر كما موضح في‬ ‫المتوسطات لكل من )قشره الكليه اليمين‪ ,‬لب الكليه اليمين‪ ,‬كثافه قشره الكليه اليمين‪ ,‬كثافه لب الكليه‬ ‫اليمين‪ ,‬قشره الكليه الشمال‪ ,‬لب الكليه الشمال‪ ,‬كثافه قشره الكليه الشمال‪ ,‬كثافه لب الكليه الشمال( هي)‬ ‫‪,0133.03)(2555.6 ,1133.3‬‬ ‫‪,7225.02)(7505.2,2555.6)(3355.56,2703.53)(3,7223.355537.5)(6663.02‬‬ ‫‪3555.02‬‬ ‫)‪ (3255.56 ,5630.52)(3555.32 ,3522.35‬علي التوالي‪.‬ونستنتج من هذه الدراسه ان سمك قشره‬ ‫ولب الكليتين للمجموعه المصابه بمرض السكري اكبر من سمك قشره ولب الكليتين في مجموعه الضبط‬ ‫وهذا يمكن ان يكون مؤشر جيد لتشخيص تاثير مرض السكر علي الكلي‪.‬‬

‫‪IV‬‬

Dedication

To my heart and my life my mother To dear my love my father To my sisters and my brothers To my lovely friends To soul of our father Elbashier mohammed elmobashar elmokashfy

V

Acknowledgment First of all, I Thank Allah the almighty for helping me to complete this project. I Thank D. Hussain my supervisor for his help and guidance .finally I would like to thank my friends and everybody who helped me in this project.

VI

List of contents: Topic

Page

‫االيه‬

I

Abstract English

II

Abstract Arabic

IV

Dedication

V

Acknowledgment

VI

List of content

VII

List of figures

IX

List of tables

X

Abbreviation

XI Chapter one

Introduction

2

Problem of study

3

Objective of study

3

Study significant

3

Thesis over view

3 Chapter tow

Anatomy

6

Physiology

11

Pathology

16

Previous study

20 VII

Chapter three Material and methods

23 Chapter four

Results

27 Chapter five

Discussion

37

Conclusion

40

Recommendation

41

Reference

42

Appendix

45

VIII

List of figures: Name of figure

page

Figure (2-1): Show Sagittal CT reformat of left kidney Show location of 6 the kidney. Figure (2-2): Show anterior and coronal section for renal structures.

8

Figure (2-3): Anterior relations of both kidneys.

9

Figure (2-4): show Diagram of a juxtamedullary nephron.

11

Figure (2-5) show Symptoms of diabetes.

17

Figure (4-1): show bar graphs: show differences between two groups in 28 (cortex, medulla and corresponding CT. No.’s). Figure (4-6): show bar graph: show the effect of treatment on (cortex, 30 medulla and corresponding CT. No.’s). Figure (4-7): a line graph show relation between (cortex, medulla and 31 corresponding CT. No.’s) in diabetes with respect to duration of diseases 34 Figure (4-8): show the relation between (cortex, medulla and corresponding CT. No.’s) in diabetes with age. 35 Figure (4-9) show two bar graphs: showed the effect of gender on (cortex, medulla and corresponding CT. No.’s).

IX

List of tables: Table

Page

Table (4-1): show distributions of cortex, medulla andcorresponding CT.

27

No.’s according in two groups. Table (4-2): show distributions of (cortex, medulla ancorresponding CT.

28

No.’s) for tow kidneys of diabetic group: Table (4-3): show the distributions of (cortex, medulla and corresponding 29 CT. No.’s) with respect to used treatment Table (4-4): show the distributions of (cortex, medulla and their CT. No.’s) 30 in diabetes with respect to duration of diseases. Table (4-5): show the distributions of cortex, medulla, corresponding CT. 31 No.’s in diabetes with respect to duration of diseases Table (4-6): show the distributions of (cortex, medulla and corresponding 32 CT. No.’s) in diabetes with respect to age: Table (4-7): show the distributions of (cortex, medulla and corresponding 33 CT. No.’s) in diabetes with respect to age Table (4-8): show the Correlations between (cortex, medulla and 33 corresponding CT. No.’s) and age. Table (4-9): show the distributions of (cortex, medulla and corresponding 35 CT. No.’s) with respect to gender in diabetic groups

X

Abbreviation: abbreviation Rt

Right

Lt

Left

DM

Diabetic Mellitus

HTN

Hypertension

SD

Stander Deviation

GFR

Glomerular filtration rate

ADH

Anti-diuretic hormone

XI

Chapter one

CHAPTER ONE INTRODUCTION 1-1 Prelude The kidneys are important body organs, Anatomically they are tow organs of characteristic shape (reddish brown retroperitoneal bean-shaped organs, has an anterior and posterior surface, a lateral convex border and medial border which is convex above and below, but has a central indentation, the renal hilum, through which renal vessels and ureter pass and consist of cortex and medulla, sinuses and Pelvis,) physiologically it is function to filter the blood and excrete the urine, also have other important functions (see chapter tow) . The Kidney affected by many disease which leads to changing in its function and morphology, diabetes is one of them. Diabetes is common lifelong health, it is a condition where the amount of glucose in blood is too high because the body cannot use it properly, diabetes affected most body organs like eye (blurred vision) blood vessels (atherosclerosis), With diabetes small blood vessels of the kidney injured so kidney cannot clean the blood properly, Morphologic changes in diabetic nephropathy affect all 4 renal compartments: glomeruli, tubules, interstitium, and vessels. (Kelle and Petersen 2007). Many diabetic patient developing renal disease so the function and morphology of the kidney will change. This study provided evaluation of renal morphology of diabetic Sudanese patients by using computed tomography.

2

1-2 Problem of study: The diabetes affected on many body organs. Especially the kidney and cause changes lead to renal failure. This study conducted this renal changing and effect of age, gender, treatment and duration of diabetes on kidneys. 1-3 objective of study: 1-3-1 General Objective: -To evaluate renal morphology for diabetic Sudanese patients using computed tomography. 1-3-2 Specific Objective: -To measure cortex thickness in diabetic patients. -To measure medullary thickness in diabetic patients. -To measure renal CT number in diabetic patients. -To define whether there are different between right kidney and left kidney in diabetic patients. 1-4 Study significant: To use the finding information for nephropathy diagnosis. 1-5 Thesis over view: Chapter one contain the introduction discussed prelude, problem and objective of study , Chapter tow is literature review discussed back ground (anatomy physiology pathology and previous study), Chapter three is material and methods discussed the study sample, methods, variables, data collection and data analysis, Chapter four

3

is result discussed

study results, Chapter five is discussion, conclusion

,recommendation and references.

4

Chapter tow

CHAPTER TOW (LETRETURE REVIEW) 2-1 THEORETICAL BACKGROUND 2-1-1 Anatomy of the kidney: 2-1-1-1 Location and Description: The kidneys are reddish brown retroperitoneal bean-shaped organs that lie in the paravertebral gutters against the posterior abdominal wall (Figure 1). They lie at an oblique orientation, with the upper poles more medial and posterior than the lower poles. They are located on each side of the spine between T12 and L4 and are embedded in perirenal fat. (Kelle and Petersen 2007).

1 Figure (2-1): Show Sagittal CT reformat of left kidney Show location of the kidney (Kelle and Petersen 2007). The right kidney lies slightly lower than the left kidney because of the large size of the right lobe of the liver. With contraction of the diaphragm during respiration, both kidneys move downward in a vertical direction by as much as 1 in. (2.5 cm). 6

On the medial concave border of each kidney is a vertical slit that is bounded by thick lips of renal substance and is called the hilum (Figure.2). The hilum extends into a large cavity called the renal sinus. The hilum transmits, from the front backward, the renal vein, two branches of the renal artery, the ureter, and the third branch of the renal artery .Lymph vessels and sympathetic fibers also pass through the hilum. (Richer and Snell ND). 2-1-1-2 renal structures: Renal Structure each kidney has a dark brown outer cortex and a light brown inner medulla. The renal cortex comprises the outer one third of the renal tissue and has extensions between the renal pyramids of the medulla. The cortex contains the functional subunit of the kidney, the nephron, which consists of the glomerulus and convoluted tubules and is responsible for filtration of urine (Figure.2). The renal medulla consists of segments called renal pyramids that radiate from the renal sinus to the outer surface of the kidney. The striated-appearing pyramids contain the loops of Henle and collecting tubules and function as the beginning of the collecting system. Arising from the apices of the pyramids are the cup-shaped minor calyces. Each kidney has 7 to 14 minor calyces that 100merge into 2 or 3 major calyces. Each minor calyx is indented by the apex of the renal pyramid, the renal papilla. The major calyces join to form the renal pelvis, which is the largest dilated portion of the collecting system and is continuous with the ureters. (Kelle and Petersen 2007).

7

Figure (2-2): Show Right kidney, A. anterior surface. B. Right kidney, coronal section showing the cortex, medulla, pyramids, renal papillae, and calyces. C. Section of the kidney showing the position of the nephrons and the arrangement of the blood vessels within the kidney. (Richer and Snell ND). 2-1-1-3 Renal Coverings: The kidneys have the following coverings: - Fibrous capsule: This surrounds the kidney and is closely applied to its outer surface. - Perirenal fat: This covers the fibrous capsule. - Renal fascia: This is a condensation of connective tis- sue that lies outside the perirenal fat and encloses the kidneys and suprarenal glands; it is continuous laterally with the fascia transversalis. - Pararenal fat: This lies external to the renal fascia and is often in large quantity. It forms part of the retroperitoneal fat. 2-1-1-4 Important Relations, Right Kidney:

8

- Anteriorly: The suprarenal gland, the liver, the second part of the duodenum, and the right colic flexure (Figs.3). - Posteriorly: The diaphragm; the costodiaphragmatic recess of the pleura; the 12th rib; and the psoas, quadratus lumborum, and transversus abdominis muscles. The subcostal (T12), iliohypogastric, and ilioinguinal nerves (L1) run downward and laterally. 2-1-1-4 Important Relations, Left Kidney: -Anteriorly: The suprarenal gland, the spleen, the stomach, the pancreas, the left colic flexure, and coils of jejunum (Figs. 3) - Posteriorly: The diaphragm; the costodiaphragmatic recess of the pleura; the 11th (the left kidney is higher) and 12th ribs; and the psoas, quadratus lumborum, and transversus abdominis muscles. The subcostal (T12), iliohypogastric, and ilioinguinal nerves (L1) run downward and laterally.

Figure (2-3): Anterior relations of both kidneys. Visceral peritoneum covering the kidneys has been left in position. Brown areas indicate where the kidney is in direct contact with the adjacent viscera. (Richer and Snell ND)

9

2-1-1-5 Blood Supply: 2-1-1-5-1 Arteries: The renal artery arises from the aorta at the level of the 2nd lumbar vertebra. Each renal artery usually divides into five segmental arteries that enter the hilum of the kidney. They are distributed to different segments or areas of the kidney. Lobar arteries arise from each segmental artery, one for each renal pyramid. Before entering the renal substance, each lobar artery gives off two or three inter lobar arteries .The inter lobar arteries run toward the cortex on each side of the renal pyramid. At the junction of the cortex and the medulla, inter lobar arteries give off the arcuate arteries, which arch over the bases of the pyramids (Fig.3). The arcuate arteries give off several interlobular arteries that ascend in the cortex. The afferent glomerular arterioles arise as branches of the interlobular arteries. (Richer and Snell ND). 2-1-1-5-2 Veins: The renal vein emerges from the hilum in front of the renal artery and drains into the inferior vena cava. 2-1-1-5-3 Lymph Drainage: Lymph drains to the lateral aortic lymph nodes around the origin of the renal artery. 2-1-1-5-4 Nerve Supply: The nerve supply is the renal sympathetic plexus. The afferent fibers that travel through the renal plexus enter the spinal cord in the10th, 11th, and 12th thoracic nerve.

10

2-1-2 PHYSIOLOGY: 2-1-2-1 Renal Function & Micturition: Each human kidney has approximately 1.3 million nephrons. Which is the functional unit of the kidneys, the specific structures of the nephron are shown in Figure (6), the glomerulus, which is about 200 μm in diameter, is formed by the invagination of a tuft of capillaries into the dilated, blind end of the nephron (Bowman’s capsule). (Barret et al 2010).

Figure (2-4): show Diagram of a juxtamedullary nephron. The main histologic features of the cells that make up each portion of the tubule are also shown. (Barret et al 2010). The kidneys perform the removal from the body the waste product of protein metabolism-such as urea, uric acid, creatinine, phosphate and sulphates-, regulation of body water, regulation of electrolytes and maintenance of acid-base balance by the production of urine, the urine consist mainly water, urea, uric acid, creatinine, phosphate and sulphates, sodium chloride, potassium, calcium. Normally 1-2 L of urine are product per day. (Dean and West 1987).

11

The volume depends upon the fluid intake and the amounts of fluid lost by sweeting and in the stools. Increased fluid loss due to increased sweat production or gastrointestinal losses (diarrhea, or vomiting) will result in passage of a decreased volume of concentrated urine, unless fluid intake is increased. The processes involved in the production of urine are filtration, reabsorption, and secretion. (Dean and West 1987). 2-1-2-1-1 Filtration: The blood entering the glomerulus is under high pressure and at rest up to 25% of the cardiac output flows throw the kidneys. The fluid filtered into the bowmen’s capsule is plasma minus the plasma protein and cells. The fluid filtered at the glomerulus is altered during its passage down the tubules by the removal of some of its constituent and by addition of some other. The processes involved are, respectively, reabsorption, and secretion. Thus the fluid which enters the ureter is very different in composition from that which was filtered at the glomerulus. By the processes of reabsorption and secretion of the extracellular fluid is kept constant. (Dean and West 1987). 2-1-2-1-2 Reabsorption: Some of the constituents of the fluid which is filtered as the glomerulus are reabsorbed into the blood stream this processes may be active or passive, active transport requiring energy expenditure. For example, glucose is present in glomerular filtrate but is normally absent from the urine. The glucose is completely reabsorbed from the glomerular filtrate and returned to the blood stream by the action of the cells of the proximal convoluted tubule, i.e. it’s actively reabsorbed. Urea on the other hand, passes out of the tubule back into the blood by diffusion, i.e. it’s passively reabsorbed. (Dean and West 1987). 12

Sodium chloride is actively and virtually completely reabsorbed by the renal tubule, the reabsorption in the distal tubule occurring under the control of aldosterone. Approximately 6.51 of fluid are filtered at the glomerular at each hour, but only 12L of urine are produced every 24h. Therefore nearly all the water filtered must be reabsorbed from the renal tubules. The reabsorption of water occurs at such a rate as to keep the osmotic pressure (osmolality) of the body fluid constant. The rate of reabsorption of water from the tubule is controlled by the secretion of antidiuretic hormone (ADH) from the posterior pituitary gland. The loop of Henle dips deep into the medulla of the kidney, where there a high osmotic pressure due to the active transport of sodium out of the tubule at that point. ADH increases the permeability to water of the distal tubular cells and the cells lining the collecting duct. Water therefore passes into the area of high osmatic pressure, i.e. out of the renal tubule. (Dean and West 1987). 2-1-2-1-3 Secretion: The cells of tubule remove potassium and hydrogen ions from the venous blood and secrete them into the tubules. The secretion of hydrogen ions into the tubule causes the production of an acid urine. Since metabolic processes generate a great deal of hydrogen ions, i.e. acidity, this function of the kidney is very important in in maintaining the correct PH of extracellular fluid. Tubular secretion is the method by which the kidney rids the body of drugs such as penicillin. (Dean and West 1987). 2-1-2-2 Other renal functions: 2-1-2-2-1 Regulation of Extracellular Fluid Composition & Volume: Total body osmolality is directly proportional to the total body sodium plus the total body potassium divided by the total body water. Changes in the osmolality of

13

the body fluids occur when a disproportion exists between the amount of these electrolytes and the amount of water ingested or lost from the body. -Vasopressin’s main physiologic effect is the retention of water by the kidney by increasing the water permeability of the renal collecting ducts. Water is absorbed from the urine, the urine becomes concentrated, and its volume decreases. -The amount of Na+ in the extra cellular fluids is the most important determinant of extra cellular fluids volume. -The kidneys secrete the enzyme renin and renin acts in concert with angiotensinconverting enzyme to form angiotensin II. Angiotensin II acts directly on the adrenal cortex to increase the secretion of aldosterone. Aldosterone increases the retention of sodium from the urine via action on the renal collecting duct (Gyton and Hall 2006). 2-1-2-2-2 Production of red blood corpuscles: The kidney is the main source of hormone erythropoietin, which increases the rate of red cell production. Patients with renal failure are anemic and patients with renal cell carcinoma have an increased number of red cells. (Dean and West 1987). 2-1-2-2-3 Regulation of Blood pressure: Cells in the region of glomerulus produce an enzyme renin which convert angiotensinogen in the blood to angiotensin I. A further enzyme causes the production of angiotensin II from angiotensin I. angiotensin II is powerful constrictor of blood vessels and raises blood pressure by this action. It also stimulate the production of aldosterone, the sodium retaining hormone, from the zona glomerulosa of the adrenal cortex. The secretion of renin is stimulated by a fall in

14

blood pressure within the kidney or by a fall in the plasma sodium concentration. (Dean and West 1987). 2-1-2-2-4 Calcium metabolism: The kidney is the site of formation of 1.25-dihydroxycholecalciferol, the most active form of vitamin D, the most important action of this renal metabolite is to increase calcium absorption from intestine, especially to meet the demands of growth, pregnancy and lactation. (Dean and West 1987).

15

2-1-3 Pathology: Diabetes a group of metabolic diseases in which the person has high blood glucose (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both. Patients with high blood sugar will typically experience polyuria (frequent urination), they will become increasingly thirsty (polydipsia) and hungry (polyphagia) ,weight gain, unusual weight loss, fatigue, cuts and bruises that do not heal, male sexual dysfunction, numbness and tingling in hands and feet., In 2013 it was estimated that over 382 million people throughout the world had diabetes. (Markus 2015). 2-1-3-1 there are three types of diabetes: 2-1-3-1-1 Type 1 diabetes Type 1 Diabetes the body does not produce insulin. Some people may refer to this type as insulin-dependent diabetes, juvenile diabetes, or early-onset diabetes. People usually develop type 1 diabetes before their 40th year, often in early adulthood or teenage years. Type 1 diabetes is nowhere near as common as type 2 diabetes. Approximately 10% of all diabetes cases are type 1. Patients with type 1 diabetes will need to take insulin injections for the rest of their life. They must also ensure proper blood-glucose levels by carrying out regular blood tests and following a special diet. Patients with type 1 are treated with regular insulin injections, as well as a special diet and exercise. (Markus 2015). 2-1-3-1-2 Type 2 diabetes The body does not produce enough insulin for proper function, or the cells in the body do not react to insulin (insulin resistance). Approximately 90% of all cases of diabetes worldwide are type 2. Some people may be able to control their type 2 16

diabetes symptoms by losing weight, following a healthy diet, doing plenty of exercise, and monitoring their blood glucose levels. However, type 2 diabetes is typically a progressive disease - it gradually gets worse - and the patient will probably end up have to take insulin, usually in tablet form. Patients with Type 2 diabetes are usually treated with tablets, exercise and a special diet, but sometimes insulin injections are also required. (Markus 2015). 2-1-3-1-3 Gestational diabetes This type affects females during pregnancy. Some women have very high levels of glucose in their blood, and their bodies are unable to produce enough insulin to transport all of the glucose into their cells, resulting in progressively rising levels of glucose. Diagnosis of gestational diabetes is made during pregnancy. The majority of gestational diabetes patients can control their diabetes with exercise and diet. Between 10% and 20% of them will need to take some kind of blood-glucosecontrolling medications. Undiagnosed or uncontrolled gestational diabetes can raise the risk of complications during childbirth. The baby may be bigger than he/she should be. (Markus 2015). 2-1-3-2 Diabetes symptoms:

Figure (2-5) show Symptoms of diabetes (Markus 2015). 17

2-1-3-3 Diabetic nephropathy: Diabetic nephropathy (or diabetic kidney disease) is a progressive kidney disease caused by damage to the capillaries in the kidneys' glomeruli It is characterized by nephritic syndrome and diffuse scarring of the glomeruli, It is due to longstanding diabetes mellitus, and is a prime reason for dialysis in many developed countries. It is classified as a small blood vessel complication of diabetes. (Longo et al .ND). 2-1-3-3-1 Signs and symptoms: During its early course, diabetic nephropathy often has no symptoms. Symptoms can take 5 to 10 years to appear after the kidney damage begins. These late symptoms include severe tiredness, headaches, a general feeling of illness, nausea, vomiting, lack of appetite, itchy skin, and leg swelling. (Diabetic and kidney disease 2015). 2-1-3-3-2 Causes: The cause of diabetic nephropathy is not well understood, but it is thought that high blood sugar, advanced glycation end product formation, and cytokines may be involved in the development of diabetic nephropathy. (Diabetes nephropathy 2015). 2-1-3-3-3 Mechanism: Diabetes causes a number of changes to the body's metabolism and blood circulation, which likely combine to produce excess reactive oxygen species (chemically reactive molecules containing oxygen). These changes damage the kidney's glomeruli (networks of tiny blood vessels), which leads to the hallmark feature of albumin in the urine (called albuminuria).( Zemin and mark 2011).

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As diabetic nephropathy progresses, a structure in the glomeruli known as the glomerular filtration barrier (GFB) is increasingly damaged. This barrier is composed of three layers including the fenestrated endothelium, the glomerular basement membrane, and the epithelial podocytes. The GFB is responsible for the highly selective filtration of blood entering the kidney's glomeruli and normally only allows the passage of water, small molecules, and very small proteins (albumin does not pass through the intact GFB). (Fernández et al. 2014). Diagnosis is usually based on the measurement of high levels of albumin in the urine or evidence of reduced kidney function. Albumin measurements are defined as follows: -Normal albuminuria: urinary albumin excretion