Kidney Function Test PDF - Clinical Tests Oct 2024

Clinical Tests for Evaluation of Kidney (Renal) Function Prof. Abdullah Gibriel  Kidney 1-The kidneys are bean shaped organs that are located in retroperitonial cavity near the vertebral column. Normal individuals have two kidneys and each one contains millions of n...

Clinical Tests for Evaluation of Kidney (Renal) Function Prof. Abdullah Gibriel  Kidney 1-The kidneys are bean shaped organs that are located in retroperitonial cavity near the vertebral column. Normal individuals have two kidneys and each one contains millions of nephrons that represent the basic structural and functional unit of the kidney. 2- Each nephron consists of glomerulus, Bowman’s capsule, proximal and distal convoluted tubule, loop of Henle and a collective tube. 3- Nephron is connected to artery, vein and blood caplillaries. 4- At least one kidney must function properly. 1- Glomerulus 3 Bowman’s capsule 5- The main function of kidney 4 Proximal convoluted tubule is to remove waste and excess 6 Distal convoluted tubule 7Loop of Henle fluid from blood. 8- Collective tube 9 Blood capillaries 10 Vein 11 Artery  Many of the kidney's functions are accomplished by relatively simple mechanisms of filtration, reabsorption, and excretion. 1- Filtration is the process by which water and small molecular weight molecules (present in the blood) pass through the tiny pores of Glomerulus and Bowman’s capsule to be excreted in urine while preventing RBCs and WBCs and large proteins from being filtered. This is driven by the net pressure resulting from the hydrostatic pressure of blood which opposes the osmotic pressure (In normal individuals the hydrostatic pressure is larger). ❑ Glomerular filtration rate (GFR): Is the rate at which kidney filters blood plasma. It is a good way for assessing kidney functions. 2- Reabsorption is the process by which important molecules such as glucose, amino acids, urea, and electrolytes (Na+, HCO3-) in the filtrate that are needed by the body will be retained again to blood.  3) Secretion It is the process by which some molecules such as protons, potassium and toxic substances such as urea, poisons and drugs are moved from blood into renal tubules to be excreted in urine. This usually occurs in exchange with sodium ions that are on the contrary reabsorbed from tubules into blood stream. 4- Excretion: The molecules that are not reabsorbed are then excreted in the collective tube to be excreted through the ureter forming the urine. Approximately 1200 ml of blood flow through the kidneys each minute (about 1/4 of the total blood volume) but only 1.5-2L of urine is collected due to reabsorption. NB: If urine excretion is ˂ 0.5 L/day, this is called oligouria (mainly in acute renal failure) while urine excretion of ˃ 3 L/day is termed polyuria (mainly in chronic renal failure). NB: Urine output= Glomerular filtration- tubular reabsorption Factors affecting Glomerular Filtration: A- Filtration coefficient: 1 Number of pores: affects the surface area of filtration 2 Pore size: affects permeability of the Glomerulus filtrating membrane B- Net filtration pressure 1- Hydrostatic pressure (Driving force) 2- Osmotic pressure (Opposing force) Number of nephrons declines with age, to about 50% at age 60; this causes the Glomerular filtration rate (GFR) to drop to 50% of value.  Kidney Functions: The kidney plays an important role in maintaining the homeostasis condition of the whole body either independently or in conjunction with other systems especially the endocrine system by; 1- Getting rid of waste and toxic materials such as urea, creatinine and toxins. 2- Conserving water and extracellular fluid volume with the help of anti diuretic hormone (ADH) (Vasopressin). 3- Maintaining electrolyte and mineral concentration with the help of Aldosterone. 4- Regulating blood pressure with the secretion of Renin (which Stimulate angiotension II) and aldosterone which stimulate Na reabsorption. 5- Preserving acid-base balance. 6- Generation of the active form of vitaimin D (calcitrol). 7- Production of Erythropoietin which regulated RBC’s production. Disturbances in urine formation may be due to : a) Pre-renal factors: factors affecting blood pressure, volume or flow. b)Renal factors: factors affecting the kidneys themselves which may affect the Glomerular filtration rate, different tubular activities or the renal blood vessels. c)Post-renal factors: factors obstructing the flow of urine such as renal calculi, carcinomas or tumors which may compress the ureters, urethra or bladder opening, or enlarged prostate gland that partially occludes the urethra. Chemical tests alone cannot differentiate between the 3 previous causes of renal dysfunction. Physical examination of the patient & other tests such as X-ray or ultrasonography may lead to the knowledge of the problem. When to assess Renal function???  Classification of renal function tests: Tests based on Glomerular filtration Tests based on tubular function (GF) 1- Urine concentration test 1-Serum urea conc. 2- Urine dilution test 2-Serum creatinine conc. 3- Vasopressin test 3- Urea clearance test 4- Urine acidification test 4- Creatinine clearance test 5- Dye excretion test 5- Inulin clearance test 6- Para-amino hippuric acid clearance 6- Cystatin C test. 7- Micropuncturing 7- Single radiolabeled injection test 8- Microcryoscopic test 8- Serum Uric acid conc. 9- Microelectrode test 10- Plasma electrolyte determination ▪ Tests based on Glomerular filtration 1- Urea: Ingested Protein Digetion Amino acids Absorption in Excess amino acids blood Excretion via the kidneys Urea In the liver Urea cycle NH3 + Keto acids Urea in humans NB: Protein & amino acids catabolism gives Uric acid in birds NH3 in fish It is derived from the metabolism of dietary protein & endogenous tissue protein (Dependent on protein intake as well). ❑Urea is filtered through glomerulus and then partially reabsorbed passively in the renal tubules, so its clearance does not accurataely measure GFR. ▪ Tests based on Glomerular filtration 1- Determination of serum urea Determination of serum urea concentration by Urease method: Principle: The formed NH3 reacts with phenol in the presence of hypochlorite to form indophenol which in alkali gives a blue colored compound. ▪ Tests based on Glomerular filtration 1- Determination of serum urea Determination of serum urea concentration by Urease method: Principle: Nitroprusside acts as a catalyst to increase: 1) The reaction rate. 2) The intensity of the color & its reproducibility ▪ Tests based on Glomerular filtration 1- Determination of serum urea Determination of serum urea concentration by Urease method: Interpretation: Conversion factors of mg urea/dl to mmol/l & vice versa mmol/l x 6.02 = mg/dl mg/dl x 0.166 = mmol/l Normal range: 14 – 50 mg/dl, the range is wide because serum urea depends on protein diet (  Protein diet   serum urea & vice versa ) It is higher in men than women, there is a slow rise with age. Urea concentration can decrease in normal persons & patients with kidney disease on a low protein diet   a decrease in serum urea may occur without a real improvement in the condition. ▪ Tests based on Glomerular filtration 1- Determination of serum urea Determination of serum urea concentration by Urease method: 1) Serum urea decreases in: Physiologically: * Serum urea decreases in pregnant women due to hemodilution (15 – 20 mg/dl). * It could also decrease due to low protein intake (occasionally starvation/malnutrition or malabsorption) Pathologically: 1) Serum urea decreases below 10 mg/dl in severe liver diseases (NO SYTHESIS). It could also decrease in case of impairment of Vasopressin secretion (increased level) leading to water retention (more dilution of urea concentration)  Pathologically: 2) Serum urea increases in: (a) Pre-renal diseases: i.– Severe & prolonged vomiting, dehydration or diarrhea where the body fluid & plasma volume decrease leading to lower blood pressure with a decreased cardiac output leading to decreased renal blood flow which decreases glomerular filtration resulting in urea retention. ii.–Increased protein catabolism as in fever, trauma, surgery & diabetic coma. (b) Renal diseases (see last slide number 47) for various renal disease types): i – Acute glomerulonephritis: > 300 mg/dl. ii– Malignant hypertension, chronic pyelonephritis & mercurial poisoning: 420 – 720 mg/dl. Iii- Drug induced nephrotoxicity; Such as Aminoglycosides and NSAIDS (c) Post-renal diseases: Prostate enlargement, urinary stones or urinary tumour  obstruction of urine flow with urine retention  decrease effective filtration pressure at the glomeruli. ▪ Tests based on Glomerular filtration 2- Creatinine: ❑It is not a component of diet but formed in the body at a constant rate which depends on the mass of the muscle. ❑ Creatinine is formed primarily in liver with minor contribution from kidney and then is cyclized in muscle The excretion rate of creatinine is constant, but may fall slowly if muscle wasting occurs. ❑Unlike urea, Creatinine once filtered from the Glomerulus is not reabsorbed nor secreted again from the tubules so it reflects filtration more efficiently. The endogenous creatinine clearance is used as a measure of Glomerular filtration rate (GFR). S. Creatinine conc. is a better indicator for kidney function than s.urea concn. Why???: 1)The excretion rate of creatinine is relatively constant per day & not influenced by protein in diet, protein catabolism or other external factors. 2) Urea (but not creatinine) is partially reabsorbed in the renal tubules after filtration. ▪ Tests based on Glomerular filtration 2- Determination of serum Creatinine (Test for Glomerular Filtration Rate “GFR”) Creatinine is formed primarily in liver with minor contribution from kidney and then is cyclized in muscle. It is stored in muscle in the form of is creatinine which is the anhydride form of creatine. NB: ATP which is the source of energy can not be stored in muscles as it is but is stored in the form of creatine phosphate (phosphocreatine) at rest. ▪ Tests based on Glomerular filtration 2- Determination of serum Creatinine (Test for Glomerular Filtration Rate “GFR”) Principle: In alkaline Creatinine + Picric acid medium Orange complex measured at 500 nm Protein in the sample is precipitated by tungestic acid (sodium tungestate + H2SO4) so as not to interfere with the reading. ▪ Tests based on Glomerular filtration 2- Determination of serum Creatinine (Test for Glomerular Filtration Rate “GFR”) Interpretation: Conversion factors of mg creatinine/dl to mol/l & vice versa are: 1) mol/l x 0.0113 = mg/dl. 2) mg/dl x 88.4 = mol/l. Normal range = 0.8 – 1.5 mg/dl The daily production & excretion of creatinine is constant & is proportional to body muscle mass.  It is higher in men than women. The normal daily excretion of creatinine in urine ranges from 1 – 2 gm. ▪ Tests based on Glomerular filtration 2- Determination of serum Creatinine (Test for Glomerular Filtration Rate “GFR”) Interpretation: Pathological causes for serum creatinine increase are similar to those of serum urea with the addition of the followings; a) Increased rate of formation as in gigantism & acromegaly. b) Decreased renal excretion as in renal failure. In late renal failure serum creatinine may reach 20 mg/dl or even exceed 30 mg/dl. Please note the followings; 1 S. Creatinine level is inversely proportional to glomerular filtration rate. 2 Increased s. creatinine levels definitely indicate impaired renal function 3 Normal s.creatinine levels do not exclude renal impairment as it is notusually elevated until the GFR reaches 50-70%. ▪ Tests based on Glomerular filtration ▪ Tests based on Glomerular filtration 3-5 : Clearance rate (Urea/creatinine or inulin): It is the volume of plasma (in ml) which is cleared of the substance each minute, in order to account for the rate of excretion of the substance. C = UV/P Where U → concn. of the substance in Urine. P → concn. of the substance in Plasma V → rate of urine flow in ml/min If U & P are in the same units → C has the dimensions of ml/min. This calculation of clearance is independent of the mode of excretion of a substance by the kidney. ▪ Tests based on Glomerular filtration 3- Endogenous creatinine clearance test It is the most sensitive method of assessing renal function (especially in moderate to late stages of renal impairment). “ It is the determination of the amount of plasma that must be flowed through the kidney glomeruli per minute with complete removal of its contents of creatinine.” Procedure: Urine is collected for 24 hours while blood samples are taken during the day. Clearance is given by: C=UV / P Where U = concn. of creatinine in Urine in mg/dl. P = concn. of creatinine in serum in mg/dl. V= Rate of urine flow (production) in ml/min (calculated by dividing urine volume in ml by time in minutes). ▪ Tests based on Glomerular filtration 3- Endogenous creatinine clearance test Normal level: 100  20 ml/min The decrease in clearance indicates a decrease in the GFR (Direct proportion; unlike s.creatinine levels) due to: a)acute or chronic damage of the glomeruli (due to diseases or drugs= see last slide for kidney diseases), or b) reduced blood flow to the glomeruli (pre-renal factors). c) Post renal factors NB: Inulin (a polysaccharide which is not found in the body and is not metabolized) is injected (IV) into the body to be used for measuring GFR. This substance gives the most accurate results (even more accurate than creatinine). But this test is not commonly performed in the clinical labs.  Estimated GFR (eGFR) Modification of Diet in Renal Disease (MDRD)  eGFR interpretation Stage Renal staus description GFR value 1 Normal 90-120 2 Mild renal failure 60-90 3 Moderate renal failure 30-60 4 Severe renal failure 15-30 5 Complete renal failure (treated