Kidney Function: Diagnostic Tools & Tests PDF

Diagnostic tools for renal diseases  Anatomy of the kidney The kidneys are bean-shaped organs Location: near the middle of the back, just below the rib cage in the abdominal cavity, in the retroperitoneum.  The right kidney being slightly lower than the...

Diagnostic tools for renal diseases  Anatomy of the kidney The kidneys are bean-shaped organs Location: near the middle of the back, just below the rib cage in the abdominal cavity, in the retroperitoneum.  The right kidney being slightly lower than the left, and left kidney being located slightly more medial than the right. The left kidney is typically slightly larger than the right.  Function of kidney Filtration Secretion Re-absorption The kidney generates 180 liters of filtrate a day, while reabsorbing a large percentage, allowing for only the generation of approximately Structure of Nephron 2 liters of urine.  Function of kidney 1. Excretion of wastes: Waste products produced by metabolism. These include the nitrogenous wastes: urea, from protein catabolism, uric acid, from nucleic acid metabolism. 2. Acid-base homeostasis: Two organ systems, the kidneys and lungs, maintain acid-base homeostasis, which is the maintenance of pH around a relatively stable value. The kidneys contribute to acid-base homeostasis by regulating bicarbonate (HCO3-) concentration.  3. Osmolality regulation: Any significant rise or drop in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. A rise in osmolality causes the gland to secrete antidiuretic hormone (ADH), resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels.  ADH binds to principal cells in the collecting duct that translocate aquaporins to the membrane allowing water to leave the normally impermeable membrane and be reabsorbed into the body, thus increasing the plasma volume of the body.  4. Blood pressure regulation: Long-term regulation of blood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of the extracellular fluid compartment, the size of which depends on the plasma sodium concentration. Although the kidney cannot directly sense blood pressure, changes in the delivery of sodium and chloride to the distal part of the nephron alter the kidney's secretion of the enzyme renin.  When the extracellular fluid compartment is expanded and blood pressure is high, the delivery of these ions is increased and renin secretion is decreased. Similarly, when the extracellular fluid compartment is contracted and blood pressure is low, sodium and chloride delivery is decreased and renin secretion is increased in response. Renin is the first in a series of important chemical messengers that comprise the renin-angiotensin system. Changes in renin ultimately alter the output of this system, principally the hormones angiotensin II and aldosterone.  Renin Angiotensin II Aldosterone NaCl reabsorption Extracellular fluid compartment Blood pressure and vesa versa.  5. Hormone secretion: The kidneys secrete a variety of hormones: 1-Erythropoietin It stimulates erythropoiesis (production of red blood cells) in the bone marrow. 2-Calcitriol, the activated form of vitamin D, promotes intestinal absorption of calcium. 3-Part of the renin-angiotensin- aldosterone system, renin is an enzyme involved in the regulation of aldosterone levels.  Causes of Chronic renal diseases Type 1 and type 2 diabetes mellitus cause a condition called diabetic nephropathy, which is the leading cause of kidney disease. High blood pressure (hypertension), if not controlled, can damage the kidneys over time. Glomerulonephritis is the inflammation and damage of the filtration system of the kidneys, which can cause kidney failure. Polycystic kidney disease is an example of a hereditary cause of chronic kidney disease in which both kidneys have multiple cysts.  Atherosclerosis: clogging and hardening of the arteries leading to the kidneys causes a condition called ischemic nephropathy, which is another cause of progressive kidney damage. Obstruction of the flow of urine by stones, an enlarged prostate, strictures (narrowings), or cancers may also cause kidney disease. Use of analgesics such as acetaminophen (Tylenol) and ibuprofen (Motrin, Advil) regularly over long durations of time can cause analgesic nephropathy, another cause of kidney disease. Certain other medications can also damage the kidneys.  Chronic kidney Stage Description GFR* mL/min/ disease : 1.73m² usually permanent 1 Slight kidney damage with normal or More loss of kidney increased filtration than 90 function over time. 2 Mild decrease in 60-89 This happens kidney function gradually, usually months to years. 3 Moderate decrease in 30-59 kidney function Chronic kidney disease is divided 4 Severe decrease in 15-29 into five stages of kidney function increasing severity 5 Kidney faiure Less than 15 (or dialysis)  Unlike chronic kidney disease, acute kidney failure develops rapidly, over days or weeks: Acute kidney failure usually develops in response to a disorder that directly affects the kidney, its blood supply, or urine flow from it. Acute kidney failure is often reversible, with complete recovery of kidney function. Some patients are left with residual damage and can have a progressive decline in kidney function in the future. Others may develop irreversible kidney failure after an acute injury and remain dialysis- dependent  Diagnosis of renal diseases 1-History Acute or chronic symptoms (many patients in the early stages of CKD usually do not feel sick at all). Past medical history: previous infections or concurrent diseases (DM, liver diseases, ….etc) especially in pregnant women. Family history of renal disease Social history: Drug and toxin exposure: acetaminophen and ibuprofen. 2-Physical examination Several signs and symptoms may suggest complications of chronic kidney disease: – Need to urinate frequently, especially at night (nocturia). – Swelling of the legs and puffiness around the eyes (fluid retention). – High blood pressure. – Fatigue and weakness (from anemia or accumulation of waste products in the body). – Loss of appetite, nausea and vomiting. – Itching, easy bruising, and pale skin (from anemia). – Shortness of breath from fluid accumulation in the lungs. – Headaches, numbness in the feet or hands (peripheral neuropathy), disturbed sleep, altered mental status (encephalopathy from the accumulation of waste products or uremic poisons), and restless legs syndrome. – Chest pain due to pericarditis (inflammation around the heart). – Bone pain and fractures.  What is Renal Function Test? Renal function tests are use to detect the presence of renal diseases and assess their progress. Chronic kidney disease usually causes no symptoms in its early stages.  TESTS INVOLVED IN RFT: 1. Urea 2. Ammonia 3. Para Thyroid Hormone 4. Calcium 5. Uric acid 6. Potassium 7. Creatinine clearance 8. Glomerular filtration rate  A-Urine tests Urinalysis: Analysis of the urine affords enormous insight into the function of the kidneys. Twenty-four hour urine tests: This test requires collection of urine for 24 consecutive hours. The urine may be analyzed for protein and waste products (urea nitrogen, and creatinine). The presence of protein in the urine indicates kidney damage. The amount of creatinine and urea excreted in the urine can be used to calculate the level of kidney function and the glomerular filtration rate (GFR).  What is the GFR? The GFR is equal to the sum of the filtration rates in all of the functioning nephrons. GFR is not routinely measured in clinical settings. An estimation of GFR (eGFR), using serum creatinine level, gives a rough measure of the number of functioning nephrons. Slide 11 of 53  The rate at which plasma is filtered by the kindney glomeruli. An important measurement in the evaluation of kidney function GFR = 120 ml plasma/min or, 180 L/day Plasma volume (70-kg young adult man)= about 3L, the Kidneys filter the plasma some 60 time in a day.  Factors affecting GFR 1. Change in renal blood flow 2. Glomerular capillary hydrostatic pressure 3. Change in capsular hydrostatic pressure 4. Oncotic pressure 5. Glomerular capillary permeability 6. Effective filtration surface area 7. Size, shape & electrical change of the macromolecules  Major Hormones that Influence GFR & RBF Vasoconstrictors Sympathetic nerves Angitensin II Endothelin Vasodilators Prostaglandin (PGE2, PGI2) Nitric Oxide Bradykinin  Urine Albumin is a Marker for Kidney Damage An abnormal urine albumin level is a marker for glomerular disease, including diabetes. Urine albumin is a marker for cardiovascular disease and is a hypothesized marker of generalized endothelial dysfunction. Slide 21 of 53 May be associated with increased mortality.  Damaged Kidneys Allow More Albumin to Cross the Filtration Barrier into the Urine Increased glomerular permeability allows albumin and other proteins to cross the glomerulus into the urine. Higher levels of protein which exceed the tubule’s capacity to reabsorb that protein may exacerbate kidney damage through injury to the tubules. The term albuminuria describes all levels of urine albumin. The modifiers micro and macro are going out of use. The term microalbuminuria has been used to denote  30 mg/g – 300 mg/g Slide 22 of The term macroalbuminuria has been used to denote 53  > 300 mg/g  Diagnosing Kidney Disease II. Kidney damage Slide 20 of 53  Interventions for Reducing Urine Albumin Control blood pressure Reduce sodium intake Achieve good control of diabetes early; may help prevent albuminuria Reduce weight, if obese Reduce protein intake, if excessive Achieve tobacco cessation Slide 29 of 53 Clearance of ‘X’, CX = GFR when the substance ‘X’ meets the following criteria, i. freely filterable at the glomerulus ii. not reabsorbed by tubules iii. not secreted by tubules iv. not synthesised by tubules v. not broken-down by tubules Creatinine clearance test: Clearance is a theoretical concept defined as the volume of plasma from which a measured amount of substance can be completely eliminated, or cleared, into the urine per unit time. It can be used to estimate glomerular function. This test evaluates how efficiently the kidneys clear a substance called creatinine from the blood. Creatinine, a waste product of muscle energy metabolism, is produced at a constant rate that is proportional to the individual's muscle mass. Because the body does not recycle it, all creatinine filtered by the kidneys in a given amount of time is excreted in the urine, making creatinine clearance a very specific measurement of kidney function. The test is performed on a timed urine specimen—a cumulative sample collected over a two to 24-hour period. Determination of the blood creatinine level is also required to calculate the urine clearance. Creatinine clearance test: Creatinine clearance is calculated as follows: where ClCR is the creatinine clearance in milliliters per minute, CU is the concentration of creatinine in the urine, V is the volume of urine (in milliliters per minute of urine formed over the collection period), and C CR is the serum creatinine concentration. Creatinine clearance test: Suppose the serum creatinine concentration is 1 mg/dL, and 1440 mL of urine was collected in 24 hrs (1440 mins) for a urine volume of 1 mL/min. The urine contains 100 mg/dL of creatinine. Creatinine clearance is calculated as: d  Interpretation High creatinine level causes: Acute and Chronic kidney disease Ureter obstruction Dehydration Glomerulonephritis  inulin clearance, procedure by which the filtering capacity of the glomeruli (the main filtering structures of the kidney) is determined by measuring the rate at which inulin, the test substance, is cleared from blood plasma. Inulin is the most accurate substance to measure because it is a small, inert polysaccharide molecule that readily passes through the glomeruli into the urine without being reabsorbed by the renal tubules. The steps involved in this measurement, however, are quite involved; consequently, inulin is seldom used in clinical testing, although it is used in research. Creatinine clearance (q.v.) is the more common procedure used to assess renal function. The average rate at which substances are filtered out of the plasma (the glomerular filtration rate) is about 75–115 ml per minute for women and 85–125 ml per minute for men. The rate decreases with age. It is markedly reduced in such conditions as acute glomerulonephritis  Urine osmolality test: Urine osmolality is a measurement of the number of dissolved particles in urine. Kidneys that are functioning normally will excrete more water into the urine as fluid intake is increased, diluting the urine. If fluid intake is decreased, the kidneys excrete less water and the urine becomes more concentrated.  The test may be done on a urine sample collected first thing in the morning, on multiple timed samples, or on a cumulative sample collected over a 24-hour period. The patient will typically be prescribed a high-protein diet for several days before the test and be asked to drink no fluids the night before the test.  Urea clearance test:  BUN reflects only the nitrogen content of urea (MW 28) and urea measurement reflects the whole of the molecule (MW 60), urea is approximately twice (60/28 = 2.14) that of BUN. Urea clearance test is less than the GFR and it is influenced by the protein content of the diet.  Approximately 40% of filtered urea is normally reabsorbed by tubules  The sensitivity of urea clearance is much less than the creatinine clearance because plasma concentration of urea is affected by number of factors.  Like, Dietary protein fluid intake infection surgery, etc.  Maximum value of urea clearance: 75 ml/min.  Urea clearance is defined as the volume(ml) of plasma that would be completely cleared of urea per minute.  It is calculated by the formula: Cm= U*V/P Cm= Maximum Urea clearance. U = Urea concentration in urine (mg/dl). V = Urine excreted per minute in ml. P = Urea concentration in plasma. If the output of urine is more than 2ml per minute. This is referred to as maximum urea clearance. Standard Urea Clearance:  the urea clearance drastically changes when the volume of urine is less than 2ml/min.  This is known as standard urea clearance(C) is around 54ml/min. Diagnostic importance:  A Urea clearance value below 75% of the normal is serious. Since it is an indicator of renal damage.  Blood urea level is found to increase only when the clearance falls below 50% normal.  Normal level of blood urea:20-40 mg/dl.  B-Blood tests  Blood urea nitrogen test (BUN): Urea is a by-product of protein metabolism, is formed in the liver, this waste product is then filtered from the blood and excreted in the urine by the kidneys. High BUN levels can indicate kidney dysfunction, but because BUN is also affected by protein intake and liver function, the test is usually done together with a blood creatinine, a more specific indicator of kidney function. Normal values for BUN range from 8 mg/dL to 18 mg/dL (3.0 to 6.5 mmol/L). a. Decreased BUN levels occur with significant liver disease. b. Increased BUN levels may indicate renal disease. However, factors other than glomerular function (e.g., protein intake, reduced renal blood flow, blood in the gastrointestinal tract) readily affect BUN levels, sometimes making interpretation of results difficult. Causes for increased blood urea: Pre-renal condition: -Dehydration: Severe vomiting, intestinal obstruction, diarrhea, diabetic coma, severe burns, fever and severe infections. Renal diseases: 1.Acute glomerulonephritis 2.Nephrosis 3.Malignant hypertension 4.Chronic pyelonephritis  Decreased blood urea: Urea concentration in serum may be low in late pregnancy, in starvation, in diet grossly deficient in protein and in hepatic failure.  Azotemia describes excessive retention of nitrogenous waste products (BUN and creatinine) in the blood. The clinical syndrome resulting from decreased renal function and azotemia is called uremia. a. Renal azotemia results from renal disease, such as glomerulonephritis and chronic pyelonephritis. b. Prerenal azotemia results from such conditions as severe dehydration, hemorrhagic shock, and excessive protein intake. c. Postrenal azotemia results from such conditions as ureteral or urethral stones or tumors and prostatic obstructions.