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.

3. 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

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 • 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 • PhenolphthaleinLaxatives • Phenothiazines • Porphyria • Rifampin • Pyridium • Bilirubinuria • Phenytoin • Pyridium • 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 • 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 >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 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 <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 ProteusUrinary Tract Infection • Uric Acid crystals (diamond shape) • Cystine crystals (hexagonal shape)

19. 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 • Granular casts • Severe renal disease • Waxy casts • Severe renal disease • Fatty casts • Nephrotic Syndrome Hypothyroidism

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

23. 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: <10 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

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 SyndromeProteinuria > 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: < 0.017 (or 17 mg albumin to 1 gram Creatinine) • Women: <0.025 (or 25 mg albumin to 1 gram Creatinine) • Microalbuminuria: 30-300 mg albumin/g Creatinine • Macroalbuminuria: >300 mg albumin/g Creatinine

31. 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 • NeutrophilGranulocytes 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)

45. 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

46. Acute Renal Failure • Urinalysis with Urine sediment examination • Urine Specific Gravity • Prerenal Failure: Specific Gravity >1.020 • Intrarenal Failure: Specific Gravity 1.010 - 1.020 • 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 • Eosinophils • 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 60-89 min/min) • GFR of 60 may represent 50% loss in function • Parathyroid Hormone starts to increase