CHAPTER 1 INTRODUCTION Kidney stones also known as renal calculus or nephrolith are mainly lodged in kidney. Mankind has been affected by urinary stones since centuries dating back to 4000 B.C. And it is the most common disease of the urinary tract. The prevention of kidney stone and recurrence remains to be a serious problem in human health. In 2018, chronic kidney disease (CKD) was estimated to affect approximately about 850 million people globally. Up to 10.5 million patients globally with CKD need dialysis and kidney transplant, although many patients cannot receive these lifesaving treatments because due to the high costs or lack of resources. CKD has emerged as one of more commonly and the life-threatening diseases in both developing and developed countries. All over the world, chronic kidney diseases (CKD) and common kidney stones are one of the leading causes of death and disability. CKD is kidney stone complication reported as a result also rare inherited disorders (e.g., primary hyperoxaluria, dental disease, cystinuria) by the deposition of renal crystals can lead to continuous loss of glomerular filtration rate (GFR) and end-stage renal disease (ESRD) at a young age. As the definition shows that the presence of both of these factors glomerular filtration rate (GFR) less than 60 ml/min and the albumin greater than 30 mg per gram of creatinine, along with the abnormalities of kidney structure and function which are greater than three months signifies chronic kidney diseases. End-stage renal disease, additionally, is defined as a GFR less than 14ml/min. CKD is very dangerous clinical condition because of two reasons. Firstly, renal impairment may lead to the development of end -stage renal diseases (ESRD). At this stage where dialysis and transplantation are needed. Secondly, it increases the risk for cardiovascular complications. Moreover, the early detection can prevent and decreases the progress to end -stage renal disease. Figure 1.1 shows relation of GFR with kidney diseases About 80% of kidney stones are calcium based either calcium oxalate or calcium phosphate. Many factors contribute in the formation of this types of kidney stones one of them is idiopathic hypercalciuria (IH). Idiopathic hypercalciuria is a family disorder characterized by lifelong hypercalciuria is basically, a clinical situation in which an increase amount of urinary calcium excretion is observed, in the absence of hypercalcemia and other known causes of hypercalciuria. Figure 1.2 Location of kidney stones in the urinary system For instance, sarcoidosis, Cushing syndrome and hyperthyroidism. In 19% of IH patient’s kidney stones are never form, but further increase in calcium oxalate supersaturation of urine from components of calcium would increase the risk of kidney stone formation. The biochemical changes that explained kidney stone formation, including in urine volume, urine calcium, oxalate and excretions, and animal protein and sodium ingestion were not evaluated. It is more doubtful that the new kidney stones would consist of uric acid, so that the increased excretion of calcium would not predispose uric acid stones. Additionally, the consumption of vitamin D which obtained by supplements of vitamin D is inadequate to improve the excretion of calcium in urine. The dietary oxalate may be a major factor of kidney stone development, beets, nuts, seeds and rhubarb are particularly, contain a large amounts of oxalate and they increase urinary oxalate excretion and predispose to the development of calcium oxalate stones. High amount dose of vitamin C therapy can also cause to increase oxalate generation as vitamin C (ascorbic acid) is metabolized. The reabsorption of oxalate in the colon is reduced by the formation of insoluble calcium oxalate. It is very necessary in planning therapy because restricting of dietary calcium results in less calcium being available in the intestinal lumen to bind with the oxalate. It caused to increase oxalate absorption and therefore increase the urinary oxalate excretion. Risk factors of the kidney stones formation may be hereditary and disease related, such as idiopathic hypercalciuria (IH), hyper oxalosis Dent's disease, polycystic kidney disease, hyperparathyroidism, irritable bowel disease (IBD) and renal tubular acidosis are common factors. Other risk factors may be environment or diet. Rising of global temperatures could lead to an increase in kidney stone formation. Therefore, dehydration has been linked to the formation of kidney stones, particularly in the warmer climates and the global warming will increase this effect. The relationship between the increased environmental temperature and the increased number of kidney stone events supports that the global warming has an impact on the development of kidney stones. For that reason, the prevalence of kidney stone may increase also with the costs of treating this condition. Researchers discovered that the stone formers had a 60% greater risk of developing chronic kidney diseases (CKD)and 40% risk of developing end-stage renal disease (ESRD), which is a most dangerous form of CKD. Diet may have a significant impact on the incidence of kidney stones. The diet has direct effect on the pH of urine. The urine pH is very important for the formation of some stones, the type of stone formed is depend on the diet and the nutritional habits. Fast foods increase the incidence of urinary stones. Increased animal protein, vegetable protein intake, lower potassium and other nutrients were identified as the higher risk factors of kidney stones. A less energy diet may decrease the incidence of urinary stones. Diet composition play a crucial role in urinary stone formation. There is many strong evidence that inadequate fluid intake is the main dietary risk factor for urolithiasis. While the benefit of high-level intake of fluid has been confirmed, effect of different beverages, such as tap water, mineral water, fruit juices, soft drinks and tea are debated. While other nutritional factors, including dietary protein, carbohydrates, oxalate, calcium and sodium chloride can also regulate the urinary risk profile and contribute to the risk of kidney stones formation. Assessment of the nutritional risk factors is an essential component in the specific dietary therapy of kidney stone patients. An appropriate dietary intervention can also contribute to effective prevention of recurrent stones and reduce the burden of the invasive surgical procedures for the treatment of urinary stone disease. Effective kidney stone prevention depends upon addressing cause of stone formation. Mainly, to prevent first episodes of kidney stone formation and its secondary episodes, proper management of diet and use of medications is required. And the Primary prevention of kidney stone disease via dietary intervention is low-cost public health initiative with massive societal implications. So, the nutritional management is best preventive strategy against urolithiasis. Study objectives 1. Review the basic principles for the evaluation of those patients suspected of kidney stones. 2. Describe an urgent or emergent clinical scenario associated with kidney stones. 3. Discuss medical and surgical treatment options for patients with kidney stones. CHAPTER 2 REVIEW OF LITERATURE The prevalence of kidney stones is growing globally and these changes are seen across the ages, races and sex. Kidney stone is also known as renal calculi and mor broadly as urinary stones. Kidney stones are basically solid concretions (crystal aggregations) of dissolved minerals in urine. Renal stones are of different size from a few mm to a few centimeters. Kidney stones typically leave the body by passage through the urine stream, many kidney stones are formed and passed out from body without causing any symptoms. Stones having size more than 3mm in diameter before passage they can causes obstruction in the ureter. Due to these obstructions the dilation or stretching of the upper ureter and renal pelvis as well as the spasm of the associated muscle. When stone trying to pass, it can cause severe episodic pain, commonly felt in the flank and lower abdomen. That’s why kidney stones are extremely dangerous conditions. The formation of kidney stones usually results from an imbalance between the factors that promote urinary crystallization, and those that inhibit the crystal formation and growth. The common determinants of the calcium oxalate supersaturation are oxalate and the calcium concentration, while latter associated whit the urinary pH determines calcium phosphate superstation. Urinary pH itself is the important determinant of uric acid supersaturation. The evaluation of kidney stone patient starts with detailed history focusing on occupation, dietary and lifestyle habits, previous use of medications, family predisposition, and the history of recurrent urinary tract infections and the underlying disorders that predisposes to nephrolithiasis. Incidental finding of the asymptomatic stones on a radiograph and on ultra-sound may also occur. Majority of calcium oxalate stone formers (SF) suffers from no systemic disease and they can be described as idiopathic calcium oxalate SF patients. Metabolic abnormalities are responsible for stones recurrence are currently identified in up to 90% in such patients. The changes in nutritional practice play an important role in the development of kidney stones. Large amount of starchy food consumption mainly derived from crops is a major risk factor of the kidney stones. Because intake of those crops increases the obesity. Eating a greater number of vegetables also causes kidney stones because these vegetables contain small pieces of starch in roots. These patterns should also be affected due to global warming. It is growing as a urological condition in the human health and effect almost 12 per cent of the total world population. A study survey of Pakistan (198587) shows that the incidence of kidney stone is 8.3 per 100000 for Punjab as whole and 4.2 for north and 16.4 for south (Talati,1997). The risk of kidney stones is observed very high between those people that have lower urination frequency per day cycle and also in those who eat red meat once a month or more than that of one time. Therefore, patient should be educated to consume red meat consumption. While on the other hand, they may increase the fluid and liquid consumption of particularly during the hot climates (A.R Dongre, 2017). The high molecular weight of the inhibitors of the kidney stone can also changes the process of the making of kidney stones by inhibiting the crystal interaction with the tubule’s cells, because it preventing the crystal nucleation, its growth and aggregation. The development of kidney stone is facilitated by low value of urinary pH, urine volume, oxalate volumes, calcium volumes and urinate. The hot and dry climates condition increases the rates of the fluid loss and decrease the urine PH. A diet rich with protein sometime may induces and decrease in the urinary PH and increased the excretion of the uric acid. Mostly, the formation of uric acid stone is associated with type 2 diabetes which is also caused by the excess intake of the dietary energy mainly from saturated fats and the carbohydrates. Its relation with the obesity and with the metabolic syndromes (Trinchieriet al., 2017). It is also recommended that patients should also increase their intake of the fluids by at least 2 liters per day and reduce the daily intake amount of sodium to about 2300mg and protein intake to about 0.8 to 1 gm/kg/day. The intake of calcium should not be decreased below the level of the minimum intake needed for both the age and the sex. Instead of the supplements, the calcium should not be supplied to our body via food. Such additives which we use can also increase the risk of kidney stone formation (Worcester, 2010). In more than 50% of all the kidney stones pure calcium oxalate is a major component. So, most of the stones formed in the kidney are also calcium oxalates or their mixture like calcium phosphate. When the low sensitive methods are used for the detection and analysis of kidney stones, a large number of pure calcium oxalates stones are identified, instead of the fact that may be around 20% of the total weight. (Ohman, 1992). The intake of dietary calcium is a vital protective rule against the development of kidney stone. The intake of dietary calcium is not recommended because it increased the oxalate absorption and may be induce demineralization of bones. The evidences on the intake of calcium supplementation are also still controversial. But if there is a need for calcium supplementation, the patients should be encouraged to take calcium supplements with their meal and monitor the patient timely for improvements in their stones diseases behaviors (Sorenson, 2014). There are many ways that improve the health in which the urinary oxalates can be excreted. Most effective techniques that are used to minimize the recurrence of the calcium oxalate stone diseases by reducing the amount and the concentration level of the oxalate in the urine. For patients, the simplest way for the implementation of this strategy should also have to avoid for taking oxalate rich foods. Intake of more fluids has also proven very important in the urine concentration of oxalates saturation (Holmes et al., 2016). Examine of human kidney stone under modern crystallography has shown that the stone is a mixture of both struvite and carbon-apatite. Struvite is a crystalline substance which is composed of magnesium ammonium phosphate. In some stones, struvite is found very abundant whereas in others, calcite is found more abundant. These types of stones are formed due to infection and thus referred as infection kidney stones. Kidney Stones induces from that of infection are synonymous with the struvite or carbonate apatite (Griffith, 1978). The presence of calcium and citrate in the urine are important to determinants for burette stones. Alternatively, the excretion of phosphate is not a significant determinant of brushite stones. High level of urine PH favor for brushite precipitation. Urolithiasis is among the most painful illnesses diseases that life can bring. The recent investigations worldwide have shown that the incidence of the urolithiasis has been rising for approximately half of a century. This is a multi-factorial disease that can be affected by both the chemical and physical conditions of the urinary systems. Identification of the constituents of kidney stones is very essential, because it gives information which can be helpful for physicians in finding out what is the primary cause of the kidney stones and in deciding whether the kidney stone patients should be treated surgically or therapeutically. The main purpose of treating them is the removal of the stones, the elimination of the infection and for the protection of renal function and the stopping of reoccurrence. There are many different methods for analyzing of the stones, including Energy dispersive X-ray fluorescence technique and the extracorporeal shock wave lithotripsy. Extracorporeal shock wave lithotripsy (ESWL) is also considered as a first line for the diagnosis of urolithiasis.it is very effective for the treatment of stones having size smaller than 2. 5cm.This treatment have around 85% efficiency and it takes short time and gives us a large number of treatments. This treatment proves to be more tolerable as lithotripters so that new generations do not require anesthesia and they have less complications. Ureteroscopy use is increases every day because of rise in urolithiasis. Ureteroscopy is mostly done in case of large size stone. It is also used for the treatment of bilateral stones diseases, solitary separate kidney and for bleeding of diathesis patients. Patients with high level of urolithiasis complex stones can ideally use it as an initial treatment. With the passage of time the stone in the kidney may also be more complex (Çakici, 2017). Therefore, early-stage treatment is very necessary. When stone is complex it causes more kidney pain and complications. High stage kidney stone treatments are available, but they are difficult to handle and they contain too much complications. Those foods should be avoided that are sources of kidney stones. Daily exercises and intake of enough water may prevent the people from kidney stones. Obesity is a factor that may increases risk of kidney stones. So, weight loss could undermine prevention of kidney stones if associated with a high amount of animal protein intake, laxative abuse, rapid loss of lean tissue, or poor hydration. CHAPTER 3 MATERIALS AND METHODS Data was provided by hall warden. Hall had four floors in each building, with fifteen rooms. Total five to six students were accommodating in each room and as whole 500 students were the Jinnah Hall population. Random sampling of blood was conducted according to the method and statistical inference of hogg and Tanis and a sample size of 20 were selected to collect the blood samples. They marked the volunteer students in the hall by putting note on the notice board. Information was collected for each volunteer concerning their name, age, height, body weight and home town. Blood samples were obtained for each sample in a 5ml serum separate(gold-top) tube to investigate the level of calcium oxalate in the blood samples, and the serum size of 4ml was collected. To collect blood samples the compounder services were received from the campus medical center. Blood samples were placed in a blood carrying container (VACUETTE®) taken from the campus medical center under the appropriate conditions at (4°C). For further analysis obtained samples were forwarded to the BioCare laboratory. Here are the data that was carefully collected and analyzed in Jinnah Hall to get accurate results. This data was obtained individually from different students living in different rooms at different floors of Jinnah hostel. Table Ошибка! Текст указанного стиля в документе отсутствует..1: Students' data of Jinnah Hall, PMAS-Arid Agriculture University Rawalpindi S. No. Name Age 1. Saifullah Khan 25 Blood group AB+ Body Weight 54 Home Town 2. Asadullah 28 AB- 78 Mianwali 3. Usama Ali 23 O+ 64 Kot Adu 4. Abid Ali 26 A- 60 Ali Pur 5. Saleem Shah 27 B+ 62 Bahawalpur 6. Uzair Khan 23 A+ 53 Gujranwala 7. Asad Abbas 28 AB- 77 Muzaffar Abad Faisalabad 8. Asrar Ali 29 O+ 55 Sakardu 9. Umair Khan 24 A- 57 Peshawar 10. Arslan Khan 21 B+ 63 Bahawalpur 11. Nisar Hussain 28 AB- 70 Lahore 12. Waqas Ahmad 30 A- 62 Bhakar 13. Owais Ahmad 27 AB- 63 Khan Pur 14. Yasir Khan 30 B+ 56 Rawla Kot 15. Aadeel Khan 27 B- 75 Khanewal 16. Muhammad Amran 25 A- 65 Muzaffargarh 17. Awais Qarni 24 AB+ 68 Ali pur 18. Muhammad Ali 28 AB+ 57 Sargodha 19. Affan Rafique 28 A- 60 RahimYarKhan 20. Ilyas Raza 30 O- 64 Multan CHAPTER 4 RESULTS AND DISCUSSIONS 4.1. SERUM CALCIUM OXALATE LEVEL In this scenario,20 volunteer students were engaged in blood sampling for serum calcium oxalate level investigation trial. The volunteer students had under the age of 2130. Table Ошибка! Текст указанного стиля в документе отсутствует..2: Results of Blood Sample Analysis Name Age Diagnosis 1. Saifullah Khan 25 Normal 2. Asadullah 28 Normal 3. Usama Ali 29 Abnormal 4. Abid Ali 26 Normal 5. Saleem Shah 27 Normal 6. Uzair Khan 23 Normal 7. Asad Abbas 28 Normal 8. Asrar Ali 29 Normal 9. Shahab Khan 24 Normal 10. Arslan Khan 25 Normal 11. Nisar Hussain 28 Abnormal 12. Waqas Ahmad 30 Normal 13. Owais Ahmad 27 Abnormal 14. Yasir Khan 30 Normal 15. Aadeel Khan 27 Normal S. No. 16. Muhammad Amran 25 Normal 17. Awais Qarni 24 Abnormal 18. Muhammad Ali 28 Normal 19. Affan Rafique 28 Normal 20. Ilyas Raza 30 Abnormal 80% 70% 75% 60% 50% 40% 30% 25% 20% 10% 0% Normal students Abnormal students Figure 4.1 Percentage of normal to abnormal students Abnormal 25% Normal 75% Figure Ошибка! Текст указанного стиля в документе отсутствует..2 Students percentage with normal and abnormal calcium oxalate level in serum samples Discussion The study shows that there are many causes of the kidney stone formation like dietary and nutritional imbalance. A correlation between Ca and other trace elements has been clearly shows that trace elements are relevant and process taking place during the stone formation and its growth. Calcium oxalate stones are common types of kidney stones. The calcium from the food does not increase the chance of having calcium oxalate stones. But the extra calcium that is not used by our bones and muscles goes to the kidneys and it is flushed out with urine. When this does not happen, the calcium stays in the kidneys and joins with the other waste products to form a kidney stone. In most cases, oxalate is produced as end product of vitamin C metabolism. Taking of large doses Vitamin C may increase amount of oxalate in the urine. Thus, it increasing the risk of kidney stone formations. SUMMARY Chronic kidney disease involves in a gradual loss of kidney function. Advanced chronic kidney disease can cause dangerous levels of fluid, electrolytes and the wastes to build up in our body. The most commonly known factors that rise the risk of developing stones in the kidney involve nutrition, dehydration, heredity, climate and the existence of certain types of health disorders. Treatment for chronic kidney disease focuses on slowing down the progression of kidney damage, usually by controlling the cause of diseases. Chronic kidney diseases are lethal human diseases globally due to which significant human mortalities occur every year.