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Presentation on theme: "LABORATORY INDICES IN THE DIAGNOSTICS OF KIDNEY DISEASES"— Presentation transcript:

Marushchak Maria

2 Definition Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically.

3 Collection Method Multiple reagent test strip Urine Microscopic Exam
First morning sample Midstream, clean catch collection Minimum volume of 3 ml (1 ml for children) Analyze within 1-2 hours or refrigerate

4 General Tests Urine Appearance (Urine Color) Urine Odor
Urine Specific Gravity Urine pH Urine Microscopic Exam Urine cells (RBCs, WBCs, epithelial cells) Urine bacteria Urine Casts Urine Crystals

5 Urine Appearance (Urine Color)
Cloudy urine causes Urine with high phosphate, oxalate, lipids, Urine WBCs High purine food intake (increased Uric Acid) Brown urine causes Bile pigment Myoglobinuria Fava beans Medications (Levodopa, Flagyl, Nitrofurantoin) Black urine causes Melanin Methemoglobinuria Cascara or senna Methydopa

6 Blue or green urine Orange to yellow urine
Urinary Tract Infection due to Pseudomonas Bilverdin Medications Amitriptyline, Triamterene Intravenous mendications (Cimetidine, Phenergan) Dyes Methylene blue Indigo carmine or indigo blue Orange to yellow urine Increased urine concentration Bile pigments Phenothiazines Pyridium Carrots Tetracycline Rhubarb (red in alkaline urine) Senna (red in alkaline urine)

7 RED URINE CAUSES Red Urine Microscopic Hematuria
Urinary tract source Urethra or bladder Prostate Ureter or kidney Non-Urinary tract source Vagina Anus or rectum Pseudohematuria (non-Hematuria related red urine) Myoglobinuria Hemoglobinuria Phenolphthalein Laxatives Phenothiazines Porphyria Rifampin Pyridium Bilirubinuria Phenytoin Red diaper syndrome Foods (Beets, Blackberries, Rhubarb)

8 Causes of Asymptomatic Gross Hematuria by Incidence
Acute Cystitis (23%) Bladder Cancer (17%) Benign Prostatic Hyperplasia (12%) Nephrolithiasis (10%) Benign essential Hematuria (10%) Prostatitis (9%) Renal cancer (6%) Pyelonephritis (4%) Prostate Cancer (3%) Urethral stricture (2%)

9 Medical Causes of abnormal urine odor
Sweet or fruity odor Diabetic Ketoacidosis Maple syrup urine disease (infants, rare) Ammonia odor Bladder retention Urine at room temperature for prolonged period Fecal odor Bladder-Intestinal fistula Pungent odor Urinary Tract Infection Strong odor Concentrated urine Musty odor Phenylketonuria Sulfur odor Cystine decomposition

10 Food and medication causes of abnormal urine odor
Asparagus Vitamin B6 Supplementation Inborn Errors of Metabolism causing urine odor Phenylketonuria Maple syrup urine disease (infants, rare) Glutaric acidemia Isovaleric acidemia Hawkinsinuria Hypermethioninemia Multiple carboxylase deficiency Oasthouse urine disease Trimethylaminuria Tyrosinemia

11 Specific Gravity: 1.005-1.030 Increased Dehydration Fever Vomiting
Diarrhea Diabetes Mellitus and other causes of Glycosuria Congestive Heart Failure Syndrome Inappropriate ADH Secretion (SIADH) Adrenal Insufficiency X-Ray contrast

12 Decreased Diabetes Insipidus Excessive hydration Glomerulonephritis
Pyelonephritis Diuretics Adrenal Insufficiency Aldosteronism Renal insufficiency

13 Falsely decreased specific gravity
Alkaline urine Falsely increased specific gravity Intravenous dextran or radiopague dye Proteinuria

14 Urine pH Normal Background 4.5-8.0 (usually 5.5 to 6.5)
Urine pH reflects serum pH except with RTA In Renal Tubular Acidosis (RTA), urine pH >5.5 Urine cannot be acidified despite acid load

15 Increased (Alkalotic urine)
Stale ammoniacal sample (Very high pH) Void testing if old sample Bacteriuria Reflects urea splitting organisms Associated with magnesium-ammonium phosphate crystals Vegetarian diet High citrate diet Renal Failure Drugs Antibiotics Bicarbonate Acetazolamide

16 Decreased (Acidic urine)
Acidosis Diabetes Mellitus Starvation Diarrhea Uric Acid Calculi Acidic fruits (Cranberry) Drugs Ammonium chloride

17 Urine Microscopic Exam
Sample preparation Obtain fresh urine sample Centrifuge ml at 1500 to 3000 rpm for 5 minutes Decant supernatant and resuspend remainder of urine Place 1 drop of urine on slide and apply cover slip Examination Urine Cells Urine White Blood Cells Normal <2/hpf in men and <5/hpf in women Urine Red Blood Cells Normal <3/hpf Dysmorphic RBCs suggest glomerular disease Epithelial cells Transitional epithelial cells are normally present Squamous epithelial cells suggest contamination Renal tubule epithelial cells suggest renal disease Bacteria Five bacteria per hpf represents 100,000 CFU/ml Diagnostic for Urinary Tract Infection Men: Any bacteria Women: 5 or more bacteria per hpf

18 Urine Crystals Types Calcium oxalate crystals (square envelope shape)
Triple phosphate crystals (coffin lid shape) Associated with increased Urine pH (alkaline) Associated with Proteus Urinary Tract Infection Uric Acid crystals (diamond shape) Cystine crystals (hexagonal shape)

19 Urine Casts Cast Types Hypothyroidism
Epithelial cell casts of renal tubule Acute Tubular Necrosis Interstitial Nephritis Eclampsia Heavy metal poisoning Rejected transplant Red Blood Cell casts Glomerulonephritis May be normal in collision sport athletes White Blood Cell casts Pyelonephritis Hyaline or mucoprotein casts Normal finding Chronic renal disease Granular casts Severe renal disease Waxy casts Fatty casts Nephrotic Syndrome Hypothyroidism

20 Kidney and Urinary Tract Disease Tests
Urine Protein Urine Blood Gross Hematuria Microscopic Hematuria



23 Urine Protein Normal Technique Dipstick with trace protein or less
First morning void collected Detection Method Initial: Dipstick urine protein Confirmation: Sulfosalicylic acid Dipstick turns from yellow to green for protein present Negative: <10 mg/dl Trace: mg/dl Protein 1+: 30 mg/dl Protein 2+: 100 mg/dl Protein 3+: 300 mg/dl Protein 4+: 1000 mg/dl

24 False Positive Alkaline urine (Urine pH >7.5)
Increased Urine Specific Gravity (concentrated) Specimen contaminated by chlorhexidine detergent Dipstick immersed too long in urine Medications Penicillin Sulfonamide Tolbutamide Phenazopyridine Body fluid contamination Gross Hematuria present Pus Semen Vaginal secretions

25 False negative Albumin is not the primary protein
Light chain protein (detected by Sulfosalicylic acid) Dilute urine (Urine Specific Gravity <1.015) Urine protein concentration <10 mg per deciliter Urine pH decreased (acidic)

26 24 Hour Urine Protein Technique
Start collection after first morning void (e.g. 7 am) Collect urine over 24 hours until the next morning Include first morning void in collection

27 Interpretation of 24 hour Urine Protein
Confirm Sample adequacy Calculate expected 24 hour Urine Creatinine excretion Inadequate sample suggested if discrepancy Findings Normal Proteinuria < 4 mg/m2/hour (<150 mg/day) Abnormal Proteinuria 4-40 mg/m2/hour Nephrotic Syndrome Proteinuria > 40 mg/m2/hour

28 Urine Protein to Creatinine Ratio
Indication Monitor persistant Proteinuria Efficacy More accurate than 24 Hour Urine Protein collection Most accurate if first morning void is used Technique: Random urine collection Urine Creatinine in mg Urine Protein in mg Calculate Urine Protein mg to Urine Creatinine mg Ratio

29 Interpretation of Urine Protein to Urine Creatinine Ratio
Child under age 2 years Normal Ratio <0.5 Adults and children over age 2 years Normal ratio <0.2 grams protein per gram Creatinine Correlates with 0.2 g protein/day Nephrotic Ratio >3.5 (correlates with 3.5 g protein)

30 Interpretation of Urine Albumin to Creatinine Ratio
Normal Ratio (in general <30 mg/g is normal) Men: < (or 17 mg albumin to 1 gram Creatinine) Women: <0.025 (or 25 mg albumin to 1 gram Creatinine) Microalbuminuria: mg albumin/g Creatinine Macroalbuminuria: >300 mg albumin/g Creatinine

31 Glomerular Causes (Increased glomerulus permeability)
Proteinuria in Adults Causes Glomerular Causes (Increased glomerulus permeability) Primary Glomerulonephropathy Minimal Change Disease IgA Nephropathy Idiopathic membranous Glomerulonephritis Focal segmental Glomerulonephritis Membranoproliferative Glomerulonephritis

32 Secondary Glomerulonephropathy
Diabetes Mellitus (Diabetic Nephropathy) Systemic Lupus Erythematosus (Lupus Nephritis) Amyloidosis Preeclampsia (Pregnancy Induced Hypertension) Infection HIV Infection Hepatitis B Hepatitis C Poststreptococcal Glomerulonephritis Syphilis Malaria Endocarditis Lung Cancer Gastrointestinal Cancer Lymphoma Renal transplant rejection

33 Drug-induced Glomerulonephropathy
Heroin NSAIDs Gold Penicillamine Lithium Heavy metals

34 Tubular Causes (Decreased tubular reabsorption)
Hypertensive nephrosclerosis Uric Acid nephropathy Acute hypersensitivity Interstitial Nephritis Fanconi Syndrome Heavy metals Sickle Cell Anemia NSAIDs Antibiotics

35 Overflow Causes (Increased low MW protein production)
Hemoglobinuria Myoglobinuria Multiple Myeloma Amyloidosis

36 Microscopic Urinalysis findings of renal disease
Urine fats (Nephrotic Syndrome) Urine WBCs without bacteruria (Renal Interstitial) Dysmorphic erythrocytes (Glomerular disease) Cellular or granular casts (chronic renal disease) Urine Eosinophils

37 Urine Leukocyte Esterase
Mechanism Neutrophil Granulocytes contain esterases Positive test suggests pyuria Dipstick requires 5 minutes to change color Normal Negative Abnormal: Positive Urinary Tract Infection Vaginal contaminant

38 Causes of false negative Leukocyte esterase on Urinalysis
Inadequate time allowed for dipstick reading Increased Urine Specific Gravity Urine Glucose present (Glycosuria) Urine Ketones present (Ketonuria) Proteinuria Keflex Nitrofurantoin Tetracycline Gentamicin Vitamin C

39 Causes positive Leukocyte esterase and negative culture
Chlamydia Ureaplasma urealyticum Balanitis Bladder Cancer Nephrolithiasis Tuberculosis Urinary tract foreign body Glomerulonephritis Medications (Corticosteroid, Cytoxan)



42 Acute Glomerulonephritis
Labs: Initial (characterize condition) Urine sediment examination Proteinuria Glomerular Hematuria Pigmented or Red Blood Cell casts Dysmorphic Red Blood Cells Twenty-four hour urine collection 24 Hour Urine Protein Creatine Clearance Renal insufficiency

43 Acute Glomerulonephritis
Routine blood testing Serum chemistries Albumin and Liver Function Tests Total Cholesterol If over age 40 with Proteinuria >1 gram/24 hours Serum Protein Electrophoresis (SPEP) Urine Protein electrophoresis

44 Acute Glomerulonephritis
Labs: Next (Screen for etiology) Serum Complement (C3, C4, CH50) Antinuclear Antibody (ANA) Rheumatoid Factor (RF) Erythrocyte Sedimentation Rate (ESR) Anti-Glomerular Basement Membrane Antibody titer Hepatitis serology (HBsAg, xHBc IgM, HCV) Anti-Neutrophilic cytoplasmic Antibody (ANCA) Anti-streptolysin O titer (ASO Titer) Human Immunodeficiency Virus (HIV)

Leukocyte esterase or nitrite positive Hematuria may be present Microscopic examination may show WBC casts Urine Culture (positive in 90% of pyelonephritis) Diagnosis requires at least 10,000 CFU/mm3 Consider lower threshold in men and in pregnancy Blood Culture indications (not indicated in most cases) Immunocompromised patient Unclear diagnosis Hematogenous source suspected

46 Acute Renal Failure Urinalysis with Urine sediment examination
Urine Specific Gravity Prerenal Failure: Specific Gravity >1.020 Intrarenal Failure: Specific Gravity Vascular disease Urine RBCs often present Glomerulonephritis Urine RBCs Granular casts Proteinuria

47 Acute Renal Failure Interstitial Nephritis
Pyuria Eosinophils White Blood Cell and Eosinophil casts Drug hypersensitivity nephritis Tubular Necrosis Pigmented granular casts Tubular epithelial cells Granular casts Prerenal Failure Hyaline Casts

48 Autoimmune Testing for Glomerular Disease
Antinuclear Antibody (ANA) Antineutrophil Cytoplasmic Antibody Antiglomerular basement membrane Antibody

49 Chronic Renal Failure

50 NKF Classification System
Stage 1: GFR >90 ml/min despite kidney damage Microalbuminuria present Stage 2: Mild reduction (GFR min/min) GFR of 60 may represent 50% loss in function Parathyroid Hormone starts to increase

51 Stage 3: Moderate reduction (GFR 30-59 ml/min)
Calcium absorption decreases Malnutrition onset Anemia secondary to Erythropoietin deficiency Left Ventricular Hypertrophy Stage 4: Severe reduction (GFR ml/min) Serum Triglycerides increase Hyperphosphatemia Metabolic Acidosis Hyperkalemia Stage 5: Kidney Failure (GFR <15 ml/min) Azotemia

52 Acute Interstitial Nephritis
Urinalysis Eosinophiluria Proteinuria Fractional Excretion of Sodium >1% Renal Function tests with renal insufficiency Serum Creatinine increased Blood Urea Nitrogen increased Miscellaneous Hyperchloremic Metabolic Acidosis




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