Renal Function Tests Indication with normal valuesFunctions of kidney Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites Regulation of water electrolyte balances, body fluid osmolality Regulation of arterial pressure Regulation of acid-base balance Regulation of Erythrocyte Production Regulation of 1,25Dihydroxyvitamin D3 Production GluconeogenesisOBJECTIVES OF RFT To detect possible renal damage and assessment of its severity To diagnose renal disease To observe the progress of renal diseaseGives information about Renal blood flow Glomerular filtration Renal tubular function Urinary out flow unhindered by any obstruction4 groups of tests Urine analysis Concentration & dilution tests Blood chemistry Renal clearance tests[1] URINE ANALYSIS Under physical, chemical, Bacteriological and Microscopic examinationPHYSICAL EXAMINATIONAssess 24 hour urinery out put [volume], Appearance, Colour, Turbidity, pH, Specific gravity, osmolality etcVolume Is a measure of glomerular filtration and tubular reabsorption Normal urine volume varies from 500 2,500 ml L/24 hr typical in health Temperate climates: output of 800-2500 ml urine per day is usual. Dependent upon subjects activity, hydration status, diet and body size. Sudden changes in volume of urine can indicate problems with ability to concentrate urine Children: ca 1.5 ml/Kg of b.w./1 hour!Oliguria Urine volume less than 400 ml/24 hours or < 1 ml/kg In hypotension or hypovolaemia & intrinsic renal pathologyPolyuria urine output of > 2 litres/24 hours Disturbance in the tubular concentrating capacity or ADH failure [ diabetes insipidus] Increased osmotic load (diabetes mellitus) Excessive water intake (physiological response) Drug-induced (outdated tetracycline, lithium) Deficiency of vasopressin Associated with nocturiaAnuria < 100 mLTotal anuria is usually due to obstruction in the urinary tract.Colour appearance Normally Amber light coloured Very clear urine with high frequency of urination indicates its less likely to be a bacterial problem Deep yellow -Concentrated urine, Jaundice Red urine- Haematuria, Haemoglobinuria Myoglobinuria, Porphyria, Beet root ingestion, Drugs like rifampicin, pyridium Cloudy -Infection Milky Chyluria Pyuria Phosphaturia Dark on standing Porphyria, Alkaptonuria Turbidity-seen in Infection, Nephrotic syndrome, proteinuriaOsmolality Measures urine concentrating ability Normal 400-900 mOsm/Kg H20 Can reach Max 1200 mOsm/Kg H20 Useful for determining whether ionic imbalances exist in subject Depends on # of particles, not size or charge Largely due to ADH Prior to collection, fluid intake restricted First void submitted for evaluation Measuring using the fact of freezing point depression Increased -dehydration, DM, hyperglycemia, hypernatremia Decreased -overhydration, hyponatremia, Diabetes insipidusUrinary pH Normally acidic Normal range 4.5-8 Diagnostic significance- when it is studied serially in response to acid load in suspected renal tubular acidosis Iimportant when studying metabolism of various nutrients e.g. glucose during exerciseSpecific gravity A measure of density of urine measured with density of water With a refractometer or urinometer Gives rough estimate of osmolarity Normal -1.003 1.030 ; Average 1.018 The higher the number = the more concentrated urine A fixed specific gravity of 1.010 is characteristic of chronic renal insufficiency Iincreased -Lack of fluids, Increased ADH, Glomerular disorders Falsely high-when Glucose, dye or protein in urineDecreased -Dilute urine, Decreased ADH [diabetes insipidus ], primary tubular disordersb. CHEMICAL TESTSTo assess the permeability of glomerular membraneTo see the presence of proteinGlucose, RBCs, Hemoglobin, Ketone bodies, Nitrites, bilirubinUsing Dipstick tests -paper strips impregnated with appropriate reagents & indicator dyesModern dipsticks with multiplied zones -For Protein, hemoglobin, glucose, urobilinogen, nitrite, leukocytes, specific gravity, and pH etcTestys for Protein A 24-hour urine collection and measurement of protein is the most accurate Normally small amount of protein is excreted in the urine which may not exceed 150 mg/24 hours Screening tests Dipstix test and acid precipitation testDipstix test A paper strip impregnated with bromophenol blue dye which changes to blue in the presence of protein at a suitable pH (pH 3) As the strip has a yellow background the colour change is observed as green The intensity of green is proportional to concentration of protein in urine Disadvantages colour change is pH-dependent and a highly alkaline urine can induce it The test has to be done on fresh urine It has a low sensitivity for other proteins such as globulins and Bence-Jones protein. The lower limit of detection ranges from 50-100 mg/dl.Acid precipitation test A more sensitive but less specific test Eight drops of sulphosalicylic acid are added to 2 ml of urine A precipitate forms in the presence of protein Light chains and low-molecular-weight proteins are detected by this technique. False positive results occur with penicillin, PAS, etcMild proteinuria chronic interstitial disease, febrile illness and congestive cardiac failureSmall amount severe urinary tract infection or obvious haematuriaLarge amount (3 g/day or more) glomerular disease.Urine protein/urine creatinine ratio When 24 hours collection of urine is difficult or impractical as in children or patients with urinary fistulae, urine protein/urine creatinine ratio can be calculated in spot urine sample. Due to diurnal variation the best sample is obtained at mid morning A value of < 0.3 is considered normal, 0.3 3.0 is abnormal, and > 3 indicates massive proteinuriaMicroalbuminuria Conventional methods cannot detect urinary albumin excretion of 20 to 200 mcg/min, referred to as microalbuminuria It is a particularly useful test for detecting incipient diabetic nephropathy The urine sample is collected under standard conditions after rest of 2 hours, overnight (8 hours) or early morning. A very specific and rapid method is the radio-immunoassay technique UAE can however increase with exercise, hypertension, cardiac failure, urinary tract infection and after drinking large amounts of fluid Bence-Jones proteins -are light chains excreted by patients suffering from monoclonal gammopathies. It is not detected by dipstix and is best identified by immunoelectrophoresis of urineGlucose Using Benedicts test Dipstix are specific Normally ve Positive urine glucose- Increased blood glucose,Low renal threshold,Other tubular diseases False +ve- Ascorbic acid Renal glycosuria is not infrequent in the elderly where renal threshold for glucose is lowered below normal of 180 mg/dl or in inherited tubular defects (e.g. Fanconis syndrome)Blood Very sensitive; 2 or more cells can produce result Sometimes TOO sensitive, giving false positives Cant distinguish between blood and free Hb, so usually double-check with microscope Nitrites are positive when UTI with gram +ve bacteriaC. Bacteriological examination By proper & aseptic collections of mid stream specimen of urine The presence of any bacteria in suprapubic aspirate should be considered indicative of bacterial infection.Urine cultures should follow Bacterial counts of more than 105/ml indicate significant bacteriuria Llower counts cannot be ignored in suprapubic specimen, patients on treatment with antibiotics Immunosuppressed individuals and symptomatic infectiond. Urine Microscopy The genitalia should be cleaned with soap and water and a mid-stream specimen should be asked for. If a clean catch specimen cannot be obtained, it is better to do a suprapubic aspiration Microscopic examination should be done immediately as delay facilitates bacterial growth and disintegration of cellular components of sediments Both uncentrifuged and centrifuged samples should be examined Should check for- Red cells, pus cells, epithelial cells, crystals, urinery castsWBC cells -0-1 HPF Presence of more than 5 wbcs/hpf suggest infection, pyelonephritis, inflammation of GUT Should be complemented with urine culturesRBC cells [0-1 hpf] Large number of RBCs with renal diseases, lower urinary tract disease, exercise Dysmorphic appearance of RBCs in glomerular aetiologyEpithelial cells [0-2 HPF] :Increased in bladder inflammation, tubular injury etcCasts Cylindrical bodies formed by coagulation of Tomm-Horsfall glycoprotein within the tubules Hallmark of renal parenchymal disease The material contained within the tubular lumen at the time of cast formation gets entrapped within the cast Often seen normally after exercise Hyaline casts-non specific ;seen in normal urine Granular casts-in pyelonephritis Red cell casts in a/c glomerulonephritis WBC casts- in Proliferative GMN,Interstitial nephritis Waxy - Advanced renal failure Fatty- Nephrotic syndrome,Fabrys disease Mixed- Proliferative GMN (SLE,PAN) Bacterial Bacterial pyelonephritis Broad-Progressive renal failure with compensatory hypertrophy of nephrons Pseudocasts are composed of clumped urates, leucocytes and bacteriaCrystals Triple phosphate [coffin lid shaped]and calcium oxalate crystals [envelope shaped] may be found even in normal urine and are not significant per seOther crystals identifiable in abnormal urine are of cystine, urate, sulphonamides, etc.