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LABORATORY INDICES IN THE DIAGNOSTICS OF KIDNEY DISEASES

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LABORATORY INDICES IN THE DIAGNOSTICS OF KIDNEY DISEASES Marushchak Maria Definition Examination of urine by chemical, physical, or microscopic means. – PowerPoint PPT presentation

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Title: LABORATORY INDICES IN THE DIAGNOSTICS OF KIDNEY DISEASES


1
LABORATORY INDICES IN THE DIAGNOSTICS OF KIDNEY
DISEASES
  • 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.

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

8
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

9
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

10
  • Blue or green 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)

11
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

12
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)

13
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

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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

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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

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

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

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Urine pH
  • Normal
  • 4.5-8.0 (usually 5.5 to 6.5)
  • Background
  • Urine pH reflects serum pH except with RTA
  • In Renal Tubular Acidosis (RTA), urine pH gt5.5
  • Urine cannot be acidified despite acid load

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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

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

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Urine Microscopic Exam
  • Sample preparation
  • Obtain fresh urine sample
  • Centrifuge 10-15 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 lt2/hpf in men and lt5/hpf in women
  • Urine Red Blood Cells
  • Normal lt3/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

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  • 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)

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  • Urine Casts
  • Cast Types
  • 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
  • Glomerulonephritis
  • Interstitial Nephritis
  • Hyaline or mucoprotein casts
  • Normal finding
  • Pyelonephritis
  • Chronic renal disease

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

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Urine Protein
  • Normal
  • Dipstick with trace protein or less
  • Technique
  • First morning void collected
  • Detection Method
  • Initial Dipstick urine protein
  • Confirmation Sulfosalicylic acid
  • Dipstick turns from yellow to green for protein
    present
  • Negative lt10 mg/dl
  • Trace 10-20 mg/dl
  • Protein 1 30 mg/dl
  • Protein 2 100 mg/dl
  • Protein 3 300 mg/dl
  • Protein 4 1000 mg/dl

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False Positive
  • Alkaline urine (Urine pH gt7.5)
  • 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

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False negative
  • Albumin is not the primary protein
  • Light chain protein (detected by Sulfosalicylic
    acid)
  • Dilute urine (Urine Specific Gravity lt1.015)
  • Urine protein concentration lt10 mg per deciliter
  • Urine pH decreased (acidic)

30
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

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  • Interpretation of 24 hour Urine Protein
  • Confirm Sample adequacy
  • Calculate expected 24 hour Urine Creatinine
    excretion
  • Inadequate sample suggested if discrepancy
  • Findings
  • Normal Proteinuria lt 4 mg/m2/hour (lt150 mg/day)
  • Abnormal Proteinuria 4-40 mg/m2/hour
  • Nephrotic Syndrome Proteinuria gt 40 mg/m2/hour

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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

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Interpretation of Urine Protein to Urine
Creatinine Ratio
  • Child under age 2 years
  • Normal Ratio lt0.5
  • Adults and children over age 2 years
  • Normal ratio lt0.2 grams protein per gram
    Creatinine
  • Correlates with 0.2 g protein/day
  • Nephrotic Ratio gt3.5 (correlates with 3.5 g
    protein)

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Interpretation of Urine Albumin to Creatinine
Ratio
  • Normal Ratio (in general lt30 mg/g is normal)
  • Men lt 0.017 (or 17 mg albumin to 1 gram
    Creatinine)
  • Women lt0.025 (or 25 mg albumin to 1 gram
    Creatinine)
  • Microalbuminuria 30-300 mg albumin/g Creatinine
  • Macroalbuminuria gt300 mg albumin/g Creatinine

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

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  • 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

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

38
Tubular Causes (Decreased tubular reabsorption)
  • Hypertensive nephrosclerosis
  • Uric Acid nephropathy
  • Acute hypersensitivity
  • Interstitial Nephritis
  • Fanconi Syndrome
  • Heavy metals
  • Sickle Cell Anemia
  • NSAIDs
  • Antibiotics

39
Overflow Causes (Increased low MW protein
production)
  • Hemoglobinuria
  • Myoglobinuria
  • Multiple Myeloma
  • Amyloidosis

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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

41
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

42
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

43
Causes positive Leukocyte esterase and negative
culture
  • Chlamydia
  • Ureaplasma urealyticum
  • Balanitis
  • Bladder Cancer
  • Nephrolithiasis
  • Tuberculosis
  • Urinary tract foreign body
  • Glomerulonephritis
  • Medications (Corticosteroid, Cytoxan)

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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

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Acute Glomerulonephritis
  • Routine blood testing
  • Serum chemistries
  • Albumin and Liver Function Tests
  • Total Cholesterol
  • If over age 40 with Proteinuria gt1 gram/24 hours
  • Serum Protein Electrophoresis (SPEP)
  • Urine Protein electrophoresis

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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)

49
ACUTE PYELONEPHRITIS
  • Labs
  • Urinalysis
  • 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

50
Acute Renal Failure
  • Urinalysis with Urine sediment examination
  • Urine Specific Gravity
  • Prerenal Failure Specific Gravity gt1.020
  • Intrarenal Failure Specific Gravity 1.010 -
    1.020
  • Vascular disease
  • Urine RBCs often present
  • Glomerulonephritis
  • Urine RBCs
  • Granular casts
  • Proteinuria

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

52
Autoimmune Testing for Glomerular Disease
  • Antinuclear Antibody (ANA)
  • Antineutrophil Cytoplasmic Antibody
  • Antiglomerular basement membrane Antibody

53
Chronic Renal Failure
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NKF Classification System
  • Stage 1 GFR gt90 ml/min despite kidney damage
  • Microalbuminuria present
  • Stage 2 Mild reduction (GFR 60-89 min/min)
  • GFR of 60 may represent 50 loss in function
  • Parathyroid Hormone starts to increase

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  • 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 15-29 ml/min)
  • Serum Triglycerides increase
  • Hyperphosphatemia
  • Metabolic Acidosis
  • Hyperkalemia
  • Stage 5 Kidney Failure (GFR lt15 ml/min)
  • Azotemia

56
Acute Interstitial Nephritis
  • Urinalysis
  • Eosinophiluria
  • Proteinuria
  • Fractional Excretion of Sodium gt1
  • Renal Function tests with renal insufficiency
  • Serum Creatinine increased
  • Blood Urea Nitrogen increased
  • Miscellaneous
  • Hyperchloremic Metabolic Acidosis

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