Renal function test


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Renal function test

  2. 2. KIDNEY FUNCTION A plumbers view Input Arterial Filter Processor Output Output Venous Urine
  3. 3. RELATIONSHIP OF NEPHRON AREAS TO RENALFUNCTION TESTS PAH Osmolarity Clearance tests Ammonia Titratable acidity Free water clearance Osmolarity
  4. 4. EVAULUATION OF RENAL FUNCTION Various aspects of renal function are -GFR(Glomerular Filtration Rate) -RPF(Renal Plasma Flow) -Reabsorption & Excretion of various substances like Na+, K+, Ca+2, inorganic phosphate, glucose, urea, a.a, H2O & osmoles. In clinical practice -determination of Creatinine Clearance is a measure of GFR -water deprivation & vasopressin administration tests to determine urinary concentrating ability, & -bicarbonate & ammonium chloride loading test to examine urinary acidification are usually sufficient for diagnostic evaluation & measurement of kidney function. 5
  5. 5. CONT… The results of these tests are important in assessing the excretory function of the kidneys. For example, grading of chronic renal insufficiency and dosage of drugs that are excreted primarily via urine are based on GFR (or creatinine clearance). 6
  6. 6. GLOMERULAR FILTRATION TESTS Standard Test – Clearance Test Substance analyzed must not be reabsorbed or secreted by the tubules Other factors to consider: - stability of subst. in 24 hr. urine collection period, consistency of the plasma level, substance availability to the body, availability of the tests for analysis of the substance
  7. 7. PRINCIPLE OF CLEARANCE Some substances when filtered enter the tubules are not reabsorbed and so 100% excreted= GFR (inulin= gold standard for GFR, creatinine (but this one partially reabsorbed, particularly in uremia, then clearance <GFR Some substances are filtered, enter tubules, and more of the substance is secreted enters the tubules by excretion. Clearance>GFR Some substances are filtered, enter tubules, but are completely reabsorbed, so they did not reach the final urine (e.g. cystatin C)
  8. 8. TEST SUBSTANCES FOR GLOMERULARFILTRATION TESTS1. Urea2. Creatinine3. Inulin4. Beta 2 microglobulin5. Microglobulin6. Cystatin C7. Radioisotopes
  9. 9. UREA  Used historically as marker of GFR  Freely filtered but both re-absorbed and excreted into the urine  Re-absorption into blood increased with volume depletion; therefore GFR underestimated  Diet, drugs, disease all significantly effect Urea production
  10. 10. CYSTATIN C CYSTATIN C : It is a LMW nonglycosylated protein produced at a constant rate by all nucleated cells in the body, freely filtered by the glomeruli, not secreted, but totally reabsorbed by the renal tubules. Little or no cystatin is excreted in urine. Normal adults have circulating level of approx. 1mg/l. This is better indicator of renal function as compared to creatinine in early stages of GFR impairment as it is independent of age, gender, body composition & muscle mass. Cystatin C can be estimated in blood by enzyme immunoassays or immuno-turbidometry. Both techniques are currently kit based & expensive. 11
  11. 11. SERUM CREATININE & CREATININE CLEARANCE Creatinine is derived from the metabolism of creatine & phosphocreatine, the bulk of which is in muscle. Since creatinine is chiefly excreted by glomerular filtration serum creatinine levels reflects changes in GFR. Currently, routine lab. measurements of GFR use creatinine as a test substance Serum creatinine values are low when the muscle mass is decreased, as in malnutrition. Billirubin interferes with creatinine measurements. 12
  12. 12. DISADVANTAGES – USE OF CREATININE1. Some creatinine is secreted by the tubules, secretion increases as bld. levels increase2. Chromogens react in the chemical analysis3. Medications inhibit secretion – gentamycin, cephalosporins, cimetidine – false low serum levels.4. Bacteria breaks down urinary creatinine (room temp. for extended periods)
  13. 13. DISADVANTAGES – USE OF CREATININE5. Diet heavy in meat eaten during 24 hr. urine collection affect results, if plasma drawn before collection.6. In muscle wasting diseases, not reliable indicator
  14. 14. FORMULA FOR URINE VOLUME amount of urine V = time of collectionEx. Urine vol. for a 2-hour specimen (120 min) measuring 240 ml. 240 ml./120 min. = 2 ml/min.
  15. 15. GLOMERULAR FUNCTION TEST The concept of clearance is based upon the fact that the rate of removal of a substance from the plasma must equal its simultaneous rate of excretion in urine. Thus if the urinary excretion rate & plasma concentration of a substance are known, we can calculate the volume of plasma from which that substance would have been completely removed. The standard formula for clearance is : C = U x V PC = clearence/min(ml/min)U = urinary concenteration(mg/dl)P = plasma concenteration(mg/dl)V = urine volume/min(ml/min) 16
  16. 16. SAMPLE PROBLEM FOR GFR C=UxV PUrine creatinine = 120 mg/dlPlasma creatinine = 1.0 mg/dl1440 ml urine from 24 hr collection (1440 min)Urine volume: ___1440 ml____ = 1 ml/min. 1440 min.
  17. 17. C=UxV PC = 120 mg/dl (U) X 1 ml/min (V) 1 ml/min. = 120 ml/min.
  18. 18. GFR ADJUSTMENTSAverage person = 1.73 m2 body surfaceApprox. amt. of plasma filtrate produced per min = 120 ml.Variations in size and muscle mass – adjust clearance for body size: formula is: C = UV x 1.73 P A- With A being the actual body size in sq. m. of surface
  19. 19. CALCULATION OF ACTUAL BODY SIZELog A=(0.425 X log wt.)+(0.725 X log Ht.) – 2.144 where height is in meters and weight is in kilogramsOr BSA (m2) = (W0.425 x H0.725) x 0.007184 where BSA is body surface area
  20. 20. CLINICAL SIGNIFICANCE OF GFR GFR is determined not just by the number of functioning nephrons but the functional capacities of these nephrons. Does not detect early renal disease1. determines extent of nephron damage in known cases of renal disease.2. monitor effectiveness of treatment3. determine feasibility of giving medications
  21. 21. CALCULATED GLOMERULAR FILTRATION ESTIMATES What is the currently recommended method to estimate GFR? The National Kidney Disease Education Program (NKDEP) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Kidney Foundation (NKF), and American Society of Nephrology (ASN) recommend estimating GFR from serum creatinine. Two commonly used equations are the Modification of Diet in Renal Disease (MDRD) Study equation and Cockcroft Gault equation. Both equations use serum creatinine in combination with age, sex, weight, or race to estimate GFR and therefore improve upon several of the limitations with the use of serum creatinine alone. Epidemiology Collaboration (CKD-EPI) equation is a new equation based on serum creatinine.
  22. 22.  What is the Cockcroft-Gault formula? The Cockcroft-Gault formula was developed in1973 using data from 249 men with creatinine clearance (CCr) from approximately 30 to130 mL/m2. It is not adjusted for body surface area.CCr={((140-age) x weight)/(72 SCr)} x 0.85 if female where CCr is expressed in milliliters per minute, age in years, weight in kilograms, and serum creatinine (SCr) in milligrams per deciliter
  23. 23.  What is the MDRD Study equation? (modification of diet in renal disease) The 4-variable MDRD Study equation was developed in 1999 using data from 1628 patients with CKD with GFR from approximately 5 to 90 milliliters per minute per 1.73 m2. It estimates GFR adjusted for body surface area4 and is more accurate than measured creatinine clearance from 24-hour urine collections or estimated by the Cockcroft-Gault formula. The equation is: GFR = 186 x (SCr)-1.154 x (age)-0.203 x (0.742 if female) x (1.210 if African American) The equation was re-expressed in 2005 for use with a standardized serum creatinine assay, which yields 5% lower values for serum creatinine concentration: GFR = 175 x (Standardized SCr)-1.154 x (age)-0.203 x (0.742 if female) x (1.210 if African American) GFR is expressed in mL/min/1.73 m2, SCr is serum creatinine expressed in mg/dL, and age is expressed in years.
  24. 24. RADIOISOTOPES SINGLE INJECTION TECHNIQUE : in clinical practice, radionuclides are often used to estimate total GFR or to measure difference in clearance bet. one kidney compared to other in the same patient. The technique is based on use of a single injection, plasma disappearance curves to estimate the true GFR. Briefly, the radionuclide dye is injected & the signal from radiolabelled form is used to obtain measurement. The most commonly used Radionuclides for GFR are -DTPA (Diethyl triamine Penta-acetic acid) -EDTA (ethylene diamine tetra acetic acid) & -Iothalamate Iohexol, a non ionic non radioactive LMW radiocontrast agent, as an alternative to inulin, measured easily by HPLC(high performance liquid chromatography) 25
  25. 25. CONT… Renal Clearance of INULIN is the Gold Standard for determination of GFR. 51Cr-EDTA clearance closely resembles Inulin clearance & it is the radionuclide of choice for GFR estimation in Europe. However, 99m Tc-DPTA is often the preferred agent, because 99m Tc-DPTA is inexpensive, easily available & renal imaging can be simultaneously performed. GFR can be estimated based upon either plasma clearance or upon the tracer uptake by the kidneys. When a substance is freely filtered & not protein bound,& is not reabsorbed, secreted or metabolised by the kidney, then its clearance is similar to GFR. 26
  26. 26. TUBULAR REABSORPTION TESTS Loss of tubular reabsorption is the first function affected in renal disease. Concentration Tests = determine the ability of tubules to reabsorb essential salt & water Ultrafiltrate – specific gravity 1.010 Fishberg test – 24 hr. water deprivation Mosenthat Test – compare vol. & specific gravity of day and night urine samples to evaluate concentrating ability Specific gravity of 1.025 after 16 hr H2O deprivation, urine osmolality of 800 mOsm
  27. 27. OSMOLARITY Specific gravity = number and density of the particles present in a soln. (urea, Na, Cl) Osmolarity = number of particles present Osmole = 1 gm. molec. wt. of subst. / number of particles into which it dissociates ex. Glucose – 180 MW = 180 g per osmole NaCl – 58.5 MW = 29.25 g per osmoleOsmolarity of a soln. measured by colliagative property of the soln.
  28. 28.  Solute dissolved in solvent causes change in the colligative properties 1. lower freezing point 2. higher boiling point 3. increased osmotic pressure 4. lower vapor pressureWater is the solvent in both urine & plasma = comparison to pure water.Clinical lab. instruments measure freezing point depression and vapor pressure depression.
  29. 29. FREEZING POINT OSMOMETERS1. Measured amt. of sample cooled to 27 C2. Sample vibrated to produce crystallization.3. Heat of fusion due to crystallization raises temp of sample to freezing point.4. Temp. sensitive probe measures temp increase which corresponds to freezing point5. Info. converted to milliosmoles (comparison to a known subst.)
  30. 30. VAPOR PRESSURE OSMOMETERS1. Measurement performed is the dew point.2. Samples absorbed on filter paper discs & placed in a sealed chamber w/ temp-sensitive thermocoupler.3. Sample vaporizes & temp. is lowered4. H20 condenses in chamber & on the thermocoupler.5. Heat of condensation produced raises temp. of thermocoupler to dew point temp.6. Info. converted to milliosmoles (comparison to a known subst.)
  31. 31. FALSE ELEVATED OSMARALITY READINGS DUE:1. Lipemic serum = displacement of serum water by insoluble lipids – erroneous results2. Lactic acid formation occurs if serum samples are not separated or refrigerated within 20 min. = falsely elevated values with both methods3. Volatile substances (become part of solvent phase) = freezing point osmometers are elevated.
  32. 32. CLINICAL USES OF OSMOLARITY1. Evaluation of renal concentrating ability2. Monitoring course of renal disease3. Monitoring fluid and electrolyte theraphy4. Diff. Dx of hypernatremia and hyponatremia5. Evaluating secretion and renal response of ADH.Ratio urine to serum osmolarity 1:1
  33. 33.  Response to Vasopressin : subsequently,to confirm the lack of renal concentrating ability & distinguish Nephrogenic Diabetes Insipidus (NDI) from Central Diabetes Insipidus (CDI), a vasopressin test is performed. Failure to achieve a ratio of 3:1 ff. injection of ADH = inability of renal tubules to respond Concentration after ADH injection, inability to produce adequate ADH
  34. 34. FREE WATER CLEARANCE (CH2O) Use of water deprivation and timed urine specimen (negative value=less amt. excreted =dehydration) Osmolar clearance Formula Cosm = Uosm X V PosmEx. Uosm of 600 mOsm, V of 2 ml/min, Posm – 300 mOsm.CH2O = V- Cosm
  35. 35. TUBULAR SECRETION AND RBF TESTS PAH (para-amino-hippuric acid = secreted by prox. tubule Before PSP (phenolsulfonphthalein) was used but standardization difficult due to interference from medications, elevated waste products, odtain very accurately timed urine specimens PAH test done in specialized renal labs. PAH is nontoxic and loosely bound to plasma proteins thus PAH completely removed as bld. passes thru peritubular capillaries.
  36. 36. RENAL BLOOD FLOW Renal blood flow measurements are performed using the clearance of PAH(para aminohippuric acid) >90% PAH is extracted from the plasma during the 1st pass through the kidneys. Therefore, renal clearance of PAH is commonly used as an estimate of renal plasma flow (RPF). Plasma clearance following single injection of 131I- hippuran or 99mTc-mercaptoacetyltriglycine(MAG- 3)is an alternative method. (radioisotopes) Other methods-Color Doppler US,Contrast Enhanced US & MRI. 37
  37. 37. STANDARD CLEARANCE FORMULA CPAH (ml/min) = U(mg/dl PAH) X V(ml/min urine P(mg/dl PAH)
  38. 38. TITRATABLE ACIDITY & URINARY AMMONIA Distal convoluted tubule secrete H ions and ammonium ions. Excretion of 70mEq/day of acid in the form of 1. titratable acid (H+) 2. hydrogen phosphate ions (H2PO4) 3. ammonium ions (NH4+)Diurnal variation of alkaline tides (after arising & postprandially 2pm & 8 pm – lowest at night
  39. 39. TESTS OF URINARY ACIDIFICATION Renal acidification mechanism are usually examined in patients with suspected renal tubular acidosis. RTA inability to produce an acid urine in metabolic acidosis Urine pH : The pH of a fresh specimen of urine is tested with pH meter. A concentrated, fasting, morning sample of urine is acidic. A pH of <5.5 virtually excludes distal renal tubular acidosis. Urine Anion Gap : Urine anion gap is the difference between concentration of principal urinary cations (Na + k) & anion (Cl) This difference is expected to estimate the unmeasured anions & cation, which normally include ammonium & bicarbonate. Since the latter is mostly reabsorbed ,urine anion gap is chiefly measure of ammonium excretion. 40
  40. 40. CONT… In presence of systemic metabolic acidosis, ammonium excretion is expected to be stimulated while the bicarbonate excretion is minimal, hence, the urine anion gap should be –ve due to obligatory chloride excretion with ammonium. In patients with renal tubular acidosis the gap remains +ve due to impaired ammonium production. Sodium Bicarbonate Loading Test : The Bicarbonate threshold is the plasma bicarbonate level at which bicarbonate appears in urine. -The bicarbonate threshold is determined by infusion of bicarbonate & increasing the plasma bicarbonate in a stepwise manner to elevate the serum bicarbonate level to 23-26mEq/l. 41
  41. 41. CONT… Other tests for urine acidification are -Urine PCO2 -Ammonium Chloride Loading testTests can be ran simultaneously on either fresh or toluene preserved urine specimens collected at 2 hr. intervals from patients who have been primed with oral ammonium chloride. 42
  42. 42. CONT… 43