#Clinical Chemistry RENAL FUNCTION TESTS - Lecture Dr. Kakul Husain # The Kidney Kidneys are bean-shaped organs, each about the size of fist, located near the middle of the back, just below the ribs cage. Produces urine Transports urine towards bladder Temporarily store urine Conducts urine to exterior Kidneys work as filters for the waste products and extra water from the blood and produce urine as a result. Urine flows to Bladder through Ureters; Bladder stores the urine which will pass through the Urethra in the process of urination. 15 P a g e
# Functions of the Kidney Urine Formation 4 Processes: Glomerular Filtration Ultrafiltration of plasma in the glomerulus producing cells- and protein - free filtrate which passes to the Bowman s capsule. Tubular Reabsorption Reabsorption of important molecules back to the blood (water, a.a. glucose and ions). Tubular Secretion Secretion of waste and toxic substances into the tubules. Urine Excretion 16 P a g e
Excretion of harmful/toxic substances: Non-nitrogenous substances *Bilirubin *Metabolites *Drugs/Toxins Non-protein nitrogenous NPN substances *Urea *Creatinine *Uric Acid Production of Hormone: - Erythropoietin (EPO) Secreted in response to low blood oxygen content. It acts on bone marrow, stimulating the production of RBCs. - Renin Regulates blood pressure and fluid and electrolyte balance via the Renin-Angiotensin-Aldosterone System (RAAS). Homeostasis: - Acid/Base Balance - Electrolytes Balance Notice >> Glomerular filtration, tubular reabsorption, and tubular secretion permit rapid removal of toxic substances and entire plasma filtration about 60 times/day. Each of these processes is regulated according to the body needs. e.g. when there is excess sodium in the body, the rate at which sodium is filtered increases and a smaller fraction of the filtered sodium is reabsorbed, resulting in increased urinary excretion of sodium. 3 17 P a g e
# Why Testing Renal Function..?? Laboratory evaluation may be the only way of detection because patients with kidney disease have few signs and symptoms early in disease course. For early detection to allow corrective therapy especially to high risk people. To follow up renal disease progression. To assess appropriate dosing for different medications. # Signs and Symptoms of Kidney Disorders Early Symptoms Weight loss Nausea, vomiting General ill feeling Fatigue Headache Frequent hiccups Generalized itching (pruri tus) Late Symptoms Increased or decreased urine output Need to urinate at night Easy bruising or bleeding Decreased alertness Muscle cramps Decreased sensation in the hands an d/or feet. 18 P a g e
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# Types of Renal Disorders Acute Renal Failure (ARF) Occurs quickly and suddenly as a result of kidney injures. It results from pre-, renal, or post-renal causes. May lead to permanent loss of kidney function. Can be reversed if kidneys are not seriously damaged. Physiologic impact includes: Retention of water (edema), electrolytes (hypertension), and metabolic bi-products (neurotoxicity). In severe cases, complete anuria occurs. Death may occur in 8 to 14 days. Pre-renal causes: Reduced perfusion due to: Blood loss (hemorrhage) Cardiac failure Peripheral vasodilation resulting in hypotension (e.g. anesthesia) Renal artery Obstruction Stenosis, embolism, or thrombosis. Renal causes: Acute Glomerulonephritis due to: Infections (e.g. post-streptococcal infection) Autoimmune disorders (e.g.systemic lupus erythematosus SLE) Acute Tubular Necrosis due to: Renal Ischemia ( O 2 ). Hemolysis (Hb degradations interfere tubules Toxins or Medications (e.g. carbon tetrachloride CCl 4, insecticides, etc.) 20 P a g e
Post-renal causes: Obstruction of renal flow due to: Renal Calculi. Benign or malignant masses (e.g. BPH, bladder and prostate cancer) Normal kidney function can be restored if the basic cause is corrected. Chronic obstruction of the urinary tract, lasting for several days or weeks, can lead to irreversible kidney damage. Chronic Renal Disease (CRD) Occurs gradually and slowly as a result of a long-term disease, such as high blood pressure or diabetes which slowly damages the kidneys and reduces their function over time. May remain asymptomatic for years. Patients with CRD are susceptible to heart attacks and strokes due to electrolyte imbalance. Most kidney disorders are included under this category. Common causes and predisposing factors: *Diabetes *Increased Blood Pressure*Poisons *Certain drugs *Recurrent urinary tract infection UTI Physiologic Impact Anaemia ( EPO hormone) Metabolic acidosis (Accumulation of acids) Active form of Vit. D Ca intestinal absorption 2 ry HPT Osteomalacia End-Stage Renal Disease (ESRD) If CRD cannot be controlled, total or nearly total permanent loss of kidney function will occur. Dialysis or transplantation is necessary at this stage 21 P a g e
# Classes of Renal Function Tests Glomerular Function Serum Urea, Creatinine and Uric acid Clearance Tests Proteinuria Hematuria Tubular Function Specific Gravity Urine Analysis Physical, Chemical and Microscopic Examination of urine. # Biochemical Tests of Renal Function Blood Urea Nitrogen (BUN) 7.0-20 mg/dl Urea is produced in the liver as a result of protein metabolism. It is transported in the blood to the kidneys, where it is excreted. Since urea is cleared from the blood stream by the kidneys, measurement of the level of urea nitrogen in the blood is an appropriate test of renal function, specifically that of glomerular function. High Blood Urea Nitrogen (BUN) Renal impairment - Glomerulonephtitis - Obstructive uropathy 22 P a g e
High protein diet Catabolic states: (Protein catabolism e.g. fever, severe infections, etc.) Dehydration: (increased tubular reabsorption of urea) Drugs: Steroids, Diuretics, etc. Low Blood Urea Nitrogen (BUN) Diet inadequate in protein Liver failure Malnutrition Serum Uric Acid 3.6 8.5 mg/dl 2.3 6.6 mg/dl Uric acid is produced by the breakdown of purines, chemicals that are the building blocks for DNA and RNA. Excess serum uric acid can become deposited in joints and soft tissues, causing gout, an inflammatory response to the deposition of the urate crystals. High Serum Uric Acid Conditions of rapid turnover of cells due to cell damage (e.g. Malignant conditions Leukemias) Gout Glomerulonephritis Chronic renal disease 23 P a g e
Serum Creatinine 0.8 1.4 mg/dl 0.6 1.2 mg/dl Chidren 0.2 1.0 mg/dl Creatinine is the waste product of creatine phosphate, a compound found in the skeletal muscle tissue. It is excreted entirely by the kidneys. The creatinine level is affected primarily by renal dysfunction and is thus very useful in evaluating renal function. Liver Muscle Kidney excretion High Serum Creatinine Increased levels of creatinine indicate a slowing of the glomerular filtration rate which indicates to a renal disorder. Decreased Serum Creatinine Muscle Atrophy 24 P a g e
Clinical A Chemistry lthough BUN and Creatinine are routine tests of kidney function, their values start to abnormally increase only when more than 60% of kidney function is impaired..!! Thus, if kidney disease is suspected but standard blood tests (BUN and Creatinine) are normal, more specific tests of kidney function should be performed to assess the Glomerular filtration rate (GFR). # Estimation of Glomerular Filtration Rate GFR GFR is the volume (ml) of fluid filtered from the glomeruli into Bowman's capsule per unit time (min). Avg Normal Value: 100 ml/min in average-sized (70kg). GFR is directly proportional to number of intact nephrons. GFR can be estimated by Clearance Tests. Clearance Tests Clearance means the blood volume (ml) from which a marker substances is totally cleared in unit time (minute) ml/min GFR = Clearance of a Substance = (USubs/SSubs) x Urine flow rate (Urine Vol. (ml)/24 h USubs = Conc. of the marker substance in Urine mg/dl SSubs = Conc. of the marker substance in Plasma mg/dl *Marker substance used to measure GFR may be Exogenous (e.g. Inulin) or Endogenous (e.g. Creatinine) 25 P a g e
Ideal Marker for GFR Measurement: Constant rate of production (endogenous) or of delivery (i.v.) (exogenous). Freely filtered in the glomerulus i.e. no protein binding. Metabolically inactive No tubular reabsorption No tubular secretion Can be estimated in the Lab Inulin Clearance Inulin is a fructose polysaccharide that gives very accurate estimations of GFR since it meets all the criteria mentioned above. A loading dose of inulin can be administered iv, followed by a sustaining infusion (usually for 3 hr) Inulin concentration in urine and plasma is determined and hence GFR can be calculated. Inulin clearance is infrequently used in clinical lab. Creatinine Clearance 95 135 ml/min 85 125 ml/min Children Lower values than adults Creatinine clearance test is a more sensitive indicator of kidney function than serum creatinine and BUN alone. Creatinine clearance normally decreases with aging due to a decline in the glomerular filtration rate (Above age 30 y, normal range decreases 6.5 ml/min every 1decade). 26 P a g e
Creatinine clearance test consists of 2 components: I. 24 -hour urine sample to: Determine Urinary creatinine (mg/dl) Determine Urine flow rate (Urine volume/1440 min) II. Blood sample to: Determine Seum creatinine (mg/dl) Creatinine Clearance (ml/min) = G Ucreat / Screat x Urine flow rate (Vol. /1440 min) lomerular filtration membrane retains blood cells and large molecules. Thus, the presence of RBCs and/or protein in the urine strongly suggest a kidney disorder** Hematuria It is the presence of Red blood cells (RBCs) in urine detected by microscopic examination of urine. Proteinuria (Albuminuria) It is the presence of protein (albumin) in urine. It can be detected by several ways that differs in their accuracy: - Dipsticks (qualitative) - Microalbuminuria (MA) (Normal: < 30 mg/l) - Albumin/Creatinine ratio (UACR) U Albumin mg/dl/u creat g/dl (mg/g creatinine) In contrast to the other detection methods, UACR is unaffected by urine dilution and concentration and can be detected in random urine sample. 27 P a g e
Urine Analysis The urinalysis is a routine screening test which is usually done as a part of a physical examination, during preoperative testing, and upon hospital admission. It is used in the diagnosis of infections of the kidneys and urinary tract and also in the diagnosis of diseases unrelated to the urinary system. It involves 3 examinations: Physical Exam. Chemical Exam. Microscopic Exam. Physical Exam. Appearance (Normal: Clear A) Cloudy (turbid) B: bacteria and/or pyuria UTI-urinary tract infection Smoky C: red blood cells Hematuria Crystalluria/renal calculi A B C 28 P a g e
Color (Normal: Light to amber yellow) *Pale yellow (Polyuria) *Deep yellow (Oliguria) *Greenish yellow (Bacterial infection or drugs) Chemical Exam. Urine Dipstick Glucose Bilirubin Ketones Specific Gravity Blood ph Protein Urobilinogen Nitrite Leukocyte Esterase 29 P a g e
Specific Gravity Normal: 1.010 1.025 The specific gravity is a measure of the concentration of the urine compared to the concentration of water, which is 1.000. The value of this test is an indication of the kidney tubules ability to concentrate and excrete urine. Sp.Gr (Diluted urine) Causes include: High fluid intake, Diuretics, ADH deficiency (diabetes insipidus), and Chronic pyelonephritis. Sp.Gr (Concentrated urine) Causes include: Fluid loss, DM, ADH and acute glomerulonephritis. ph Normal: Acidic Alkaline UTI and Chronic renal failure. Protein Normal: Nil (i.e. not found) Proteinuria renal dysfunction (e.g. glomerulonephritis) Detection of proteinuria (albuminuria) was previously mentioned page 12 Microscopic Exam. Red blood cells (Hematuria) Urinary tract injury Leukocytes (Pyuria) Urinary tract infection Crystals (Crystaluria) Renal stone The accumulation of certain substances in the urine leads to the formation of crystals resulting in the formation of renal stones. For example, numerous calcium oxalate crystals, resulting from hypercalcemia, may form calcium oxalate stones. Casts Chronic renal disease Casts are collections of gel-like protein material which result from the agglutination of cells and cellular debris. They take the shape of the renal tubules. 15 30 P a g e
Urine Pus Cells - Pyuria Urine RBCs - Hematuria Urine Crystals Crystalluria Urinary crystals. (A) Calcium oxalate crystals; (B) uric acid crystals; (C) triple phosphate crystals with amorphous phosphates; (D) cystine crystals. 31 P a g e
Urine Casts Red blood cell cast White blood cell cast Urinary casts. (A) Hyaline cast (B) Erythrocyte cast (C) Leukocyte cast (D) Granular cast kakulhusain @gmail.com 32 P a g e