Kidney Function Tests Diploma PDF

# Renal Function Tests (RFT) ## Anatomy - The kidneys are bean shaped organs located in the abdominal cavity. - They are responsible for filtering blood and producing urine. - Each kidney consists of millions of nephrons, which are the functional units of the kidney. ## Function The main funct...

# Renal Function Tests (RFT) ## Anatomy - The kidneys are bean shaped organs located in the abdominal cavity. - They are responsible for filtering blood and producing urine. - Each kidney consists of millions of nephrons, which are the functional units of the kidney. ## Function The main functions of the kidney are: - **Maintenance of homeostasis:** The kidneys regulate water, electrolytes, and acid-base balance in the body. - **Excretion of metabolic waste products:** The kidneys eliminate waste products from the body, including urea, creatinine, creatine, uric acid, sulfate, and phosphate. - **Retention of substances vital to body:** The kidneys reabsorb and retain several substances of biochemical importance in the body, such as glucose and amino acids. - **Hormonal functions:** The kidneys produce hormones, including: - **Erythropoietin:** A peptide hormone that stimulates hemoglobin synthesis and the formation of erythrocytes. - **1,25-Dihydroxycholecalciferol (calcitriol):** The active form of vitamin D, which is produced in the kidney and regulates calcium absorption from the gut. - **Renin**: A proteolytic enzyme liberated by the kidney that stimulates the formation of angiotensin II, which in turn, leads to aldosterone production. Angiotensin II and aldosterone are the hormones involved in the regulation of electrolyte balance. ## Urine Formation - **Nephron:** The nephron is the functional unit of the kidney. - **The nephron consists of:** A Bowman's capsule with blood capillaries, proximal convoluted tubule (PCT), loop of Henle, distal convoluted tubule (DCT), and collecting tubule. ### Blood Supply - The blood supply to the kidneys is relatively large. - About 1200 ml of blood (650 ml plasma) passes through the kidneys every minute. - About 120-125 ml is filtered per minute by the kidneys, which is referred to as the glomerular filtration rate (GFR). ### Urine Formation Process - **Glomerular filtration:** This is a passive process that results in the formation of ultrafiltrate of blood. All the (unbound) constituents of plasma with a molecular weight < 70,000, are passed into the filtrate. The glomerular filtrate is almost similar in composition to plasma - **Tubular reabsorption:** The renal tubules (PCT, DCT, and collecting tubules) retain water and most of the soluble constituents of the glomerular filtrate by reabsorption. This may occur either by passive or active processes. ## Renal Threshold Substances - Some substances in the blood have excretion that depends on concentration. - These substances are referred to as renal threshold substances. - At normal concentrations in the blood, they are completely reabsorbed by the kidneys. - **Renal threshold:** Defined as the concentration of a substance in blood (or plasma) beyond which it is excreted into urine. - **Glucose:** 180 mg/dl - **Ketone bodies:** 3 mg/dl - **Calcium:** 10 mg/dl - **Bicarbonate:** 30 mEq/l - **Tubular maximum (Tm):** The maximum capacity of the kidneys to absorb a particular substance. - **Glucose:** 350 mg/min ## Kidney Function Tests Kidney function tests may be divided into four groups: 1. **Glomerular function tests:** - Includes clearance tests (inulin, creatinine, and urea) 2. **Tubular function tests:** - **Urine concentration or dilution tests** - **Urine acidification tests** 3. **Analysis of blood/serum:** - **Estimation of blood urea, serum creatinine, protein, and electrolyte.** These are useful for assessing renal function. 4. **Urine Examination:** - Includes the following: - **Volume** - **pH** - **Specific gravity** - **Osmolality** - **Presence of abnormal constituents (proteins, blood, ketone bodies, glucose, etc.)** ## Clearance tests - **Clearance:** Defined as the volume of plasma that would be completely cleared of a substance per minute. - In other words, clearance refers to the milliliters of plasma that contains the amount of a substance excreted by the kidney per minute. - **Formula:** $C=\frac{U\times V}{P}$ - **U:** Concentration of the substance in urine. - **V:** Volume of urine in ml excreted per minute. - **P:** Concentration of the substance in plasma. ### Glomerular Filtration Rate (GFR) - The maximum rate at which plasma can be cleared of any substance is equal to the GFR. - This can be calculated by measuring the clearance of a plasma compound that is freely filtered by the glomerulus and is neither absorbed nor secreted by the tubule. - **Inulin:** A plant carbohydrate composed of fructose units, is used to measure GFR. Inulin is intravenously administered for this test. ### Creatinine Clearance Tests - **Creatinine:** An excretory product derived from creatine phosphate. - Creatinine excretion is constant and not influenced by body metabolism or dietary factors. - Creatinine is filtered by the glomeruli and only marginally secreted by the tubules. - **Creatinine Clearance:** Defined as the volume (ml) of plasma that would be completely cleared of creatinine per minute. - **Procedure:** The traditional method involves estimating creatinine content in a 24-hour urine collection and the plasma concentration in this period. - **Modified Procedure:** The procedure can be modified to collect urine for 1 hour after giving water. The volume of urine is recorded and creatinine content in plasma and urine is estimated. - **Formula:** $C=\frac{U\times V}{P}$ - **U:** Urine concentration of creatinine. - **V:** Urine output in ml/min (24-hour urine volume divided by 24 x 60). - **P:** Concentration of creatinine. - **Normal range:** 120-145 ml/min. - **Values are slightly lower in women.** ### Serum Creatinine Normal Range - **Adult male:** 0.7-1.4 mg/dl - **Adult female:** 0.6-1.3 mg/dl - **Children:** 0.5-1.2 mg/dl #### Diagnostic Importance of Creatinine Clearance - A decrease in creatinine clearance (<75% normal) serves as a sensitive indicator of a decreased GFR, due to renal damage. - This test is used in the early detection of impairment in kidney function. ### Creatinine Coefficient - Defined as urinary creatinine expressed in mg/kg body weight. - Normal range:** 20–28 mg/kg for males and 15–21 mg/kg for females. - An elevated value may indicate muscular dystrophy. ### Urea Clearance Tests - **Urea** is the end product of protein metabolism. - After being filtered by the glomeruli, urea is partially reabsorbed by the renal tubules. - **Urea Clearance:** Less sensitive than creatinine clearance. It is influenced by protein content in the diet. - **Defined as:** The volume (ml) of plasma that would be completely cleared of urea per minute. - **Formula:** $Cm=\frac{U\times V}{P}$ - **Cm:** Maximum urea clearance. - **U:** Urea concentration in urine (mg/dl). - **V:** Urine excreted per minute in ml. - **P:** Urea concentration in plasma. #### Maximum Urea Clearance - If urine output is more than 2 ml per minute, this is referred to as the maximum urea clearance. - **Normal value:** 75 ml/min #### Standard Urea Clearance - **Defined as:** The urea clearance drastically changes when the volume of urine is less than 2 ml/min. - **Normal value:** 54 ml/min. - **Formula:** $Cs=\frac{U\times \sqrt{V}}{P}$ #### Diagnostic Importance of Urea Clearance - A urea clearance value below 75% of the normal is serious, since it is an indicator of renal damage. - Blood urea levels increase only when the clearance falls below 50% normal. - **Normal blood urea levels:** 20–40 mg/dl ### Causes for Increased Blood Urea - **Pre-renal conditions:** - **Dehydration:** Severe vomiting, intestinal obstruction, diarrhea, diabetic coma, severe burns, fever, and infections. - **Renal diseases:** - **Acute glomerulonephritis** - **Nephrosis** - **Malignant hypertension** - **Chronic pyelonephritis** - **Post-renal causes:** - **Stones in the urinary tract** - **Enlarged prostate** - **Tumors of the bladder** - **Medications** - **ACE inhibitors** - **Acetaminophen** - **Aminoglycosides** - **Diuretics** ### Decreased Blood Urea - Urea concentration in serum may be low in cases such as: - Late pregnancy - Starvation - Diets deficient in protein - Hepatic failure ### Azotemia - **Defined as:** Increase in the blood levels of NPN (creatinine, urea, and uric acid). - **Hallmark of:** Kidney failure. ### Uremic Syndrome - **Defined as:** The terminal manifestation of renal failure. - **Caused by:** A group of toxins. - **Characteristics:** - Increased urea leads to carbamoylation of proteins. - Increased uric acid causes uremic pericarditis. - Excess polyols cause peripheral neuropathy. - ß-2 microglobulin causes renal amyloidosis. ## Urine Concentration Tests - **Purpose:** To assess renal tubular function. - **Procedure:** A simple test that involves the accurate measurement of specific gravity, which depends on the concentration of solutes in urine. - **Normal value:** A specific gravity of 1.020 in the early morning urine sample. ## Osmolality and Specific Gravity - **Osmolality:** Variable in urine. - In normal individuals, it ranges from 500–1,200 milliosmoles/kg. - **Plasma osmolality:** Around 300 milliosmoles/kg. - **Normal ratio of osmolality between urine and plasma:** 2–4. - It is found that urine (without any protein or high molecular weight substance) with an osmolality of 800 mosm/kg has a specific gravity of 1.020. Therefore, measuring urine osmolality helps to assess tubular function. ## Analysis of Blood (or Serum) - **Estimation of:** Serum creatinine and blood urea are useful. - **Sensitivity:** These tests are less sensitive than the clearance tests. - **Serum creatinine:** A better indicator than urea. ## Urine Examination - The volume of urine excreted, its pH, specific gravity, osmolality, and the concentration of abnormal constituents (such as proteins, ketone bodies, glucose, and blood) may help to have some preliminary knowledge of kidney function. ## Proteinuria ### Glomerular proteinuria - **Characteristic:** The glomeruli of the kidney are not permeable to substances with molecular weights greater than 69,000; plasma proteins are absent in normal urine. - **Caused by:** When glomeruli are damaged or diseased they become permeable and plasma proteins may appear in urine. - **Albumin:** The smaller molecules pass through damaged glomeruli more readily. - **Albuminuria:** Always pathological. - **Nophrosis:** Large quantities of albumin are lost in urine - **Acute nephritis, strenuous exercise, pregnancy:** Small quantities are seen. ### Micro-albuminuria - **Defined as:** The presence of a small quantity of albumin (30–300 mg/day) in urine. - **Also known as:** Minimal albuminuria or paucialbuminuria. - **Not indicated for:** Patients with overt proteinuria. - **Recommended sample:** Early morning midstream sample. - **Early indication of:** Nephropathy in patients with diabetes mellitus and hypertension. - **Recommended screening:** All diabetics and hypertensives should be screened for microalbuminuria. - **An early indicator of:** The onset of nephropathy. - **Frequency of testing:** At least once a year. ### Overflow proteinuria - **Characterized by:** When small molecular weight proteins are increased in blood, they overflow into urine. - **Example:** Hemoglobin, with a molecular weight of 67,000, can pass through normal glomeruli. If it exists in free form (as in hemolytic conditions), hemoglobin can appear in urine (hemoglobinuria). ### Tubular proteinuria - Occurs when: Functional nephrons are reduced, GFR is decreased, and remaining nephrons are overworking. - **Mechanism:** Impaired tubular reabsorption. - **Proteins:** Low molecular weight proteins appear in urine. - **Examples:** Retinol binding protein (RBP), α-1 microglobulin. ### Nephron Loss Proteinuria - **Characterized by:** A decrease in the number of functioning nephrons in CKD. - The compensatory rise in glomerular filtration by other nephrons increases the filtered load of proteins. - Even if there are no glomerular permeability changes, tubular proteinuria is seen. ### Urogenic proteinuria - **Caused by:** Inflammation of the lower urinary tract, when proteins are secreted into the tract. - **Trigger:** Accumulation of proteins in tubular lumen can trigger an inflammatory reaction. ## References - Textbook of Biochemistry – DM Vasudevan - Textbook of Biochemistry – U Satyanarayana - Textbook of Biochemistry – MN Chatterjea ## Thank you.