CLINICAL
INVESTIGATION OF
URINE. CHANGES IN THE
URINE IN PATHOLOGICAL
PROCESSES OF INTERNAL
ORGANS
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.
Method
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Multiple reagent test strip
Urine Microscopic Exam
Collection
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First morning sample
Midstream, clean catch
collection
Minimum volume of 3 ml (1
ml for children)
Analyze within 1-2 hours or
refrigerate
General Tests
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Urine Appearance (Urine Color)
Urine Odor
Urine Specific Gravity
Urine pH
Urine Microscopic Exam
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Urine cells (RBCs, WBCs, epithelial cells)
Urine bacteria
Urine Casts
Urine Crystals
Urine Appearance (Urine Color)
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Cloudy urine causes
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Brown urine causes
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Urine with high phosphate, oxalate, lipids, Urine WBCs
High purine food intake (increased Uric Acid)
Bile pigment
Myoglobinuria
Fava beans
Medications (Levodopa, Flagyl, Nitrofurantoin)
Black urine causes
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Melanin
Methemoglobinuria
Cascara or senna
Methydopa
Blue or green urine
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Urinary Tract Infection due to Pseudomonas
Bilverdin
Medications
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Amitriptyline, Triamterene
Intravenous mendications (Cimetidine, Phenergan)
Dyes
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Methylene blue
Indigo carmine or indigo blue
Orange to yellow urine
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Increased urine concentration
Bile pigments
Phenothiazines
Pyridium
Carrots
Tetracycline
Rhubarb (red in alkaline urine)
Senna (red in alkaline urine)
RED URINE CAUSES
Red Urine
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Microscopic Hematuria
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Urinary tract source
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Non-Urinary tract source
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Urethra or bladder
Prostate
Ureter or kidney
Vagina
Anus or rectum
Pseudohematuria (non-Hematuria related red urine)
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Myoglobinuria
Hemoglobinuria
Phenolphthalein Laxatives
Phenothiazines
Porphyria
Rifampin
Pyridium
Bilirubinuria
Phenytoin
Pyridium
Red diaper syndrome
Foods (Beets, Blackberries, Rhubarb)
Causes of Asymptomatic Gross
Hematuria by Incidence
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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%)
Medical Causes of abnormal urine
odor
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Sweet or fruity odor
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Ammonia odor
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Concentrated urine
Musty odor
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Urinary Tract Infection
Strong odor
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Bladder-Intestinal fistula
Pungent odor
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Bladder retention
Urine at room temperature for prolonged period
Fecal odor
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Diabetic Ketoacidosis
Maple syrup urine disease (infants, rare)
Phenylketonuria
Sulfur odor
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Cystine decomposition
Food and medication causes of abnormal urine
odor
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Asparagus
Vitamin B6 Supplementation
Inborn Errors of Metabolism causing urine odor
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Phenylketonuria
Maple syrup urine disease (infants, rare)
Glutaric acidemia
Isovaleric acidemia
Hawkinsinuria
Hypermethioninemia
Multiple carboxylase deficiency
Oasthouse urine disease
Trimethylaminuria
Tyrosinemia
Specific Gravity: 1.005-1.030
Increased
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Dehydration
Fever
Vomiting
Diarrhea
Diabetes Mellitus and other causes of Glycosuria
Congestive Heart Failure
Syndrome Inappropriate ADH Secretion (SIADH)
Adrenal Insufficiency
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X-Ray contrast
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Decreased
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Diabetes Insipidus
Excessive hydration
Glomerulonephritis
Pyelonephritis
Diuretics
Adrenal Insufficiency
Aldosteronism
Renal insufficiency
Urine pH
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Normal
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4.5-8.0 (usually 5.5 to 6.5)
Background
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Urine pH reflects serum pH except with RTA
In Renal Tubular Acidosis (RTA), urine pH >5.5
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Urine cannot be acidified despite acid load
Decreased (Acidic urine)
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Acidosis
Diabetes Mellitus
Starvation
Diarrhea
Uric Acid Calculi
Acidic fruits (Cranberry)
Drugs
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Ammonium chloride
Urine Microscopic Exam
Sample preparation
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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
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Urine Cells
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Urine White Blood Cells
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Urine Red Blood Cells
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Normal <3/hpf
Dysmorphic RBCs suggest glomerular disease
Epithelial cells
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Normal <2/hpf in men and <5/hpf in women
Transitional epithelial cells are normally present
Squamous epithelial cells suggest contamination
Renal tubule epithelial cells suggest renal disease
Bacteria
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Five bacteria per hpf represents 100,000 CFU/ml
Diagnostic for Urinary Tract Infection
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Men: Any bacteria
Women: 5 or more bacteria per hpf
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Urine Crystals
Types
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Calcium oxalate crystals (square envelope shape)
Triple phosphate crystals (coffin lid shape)
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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
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Epithelial cell casts of renal tubule
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Red Blood Cell casts
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Severe renal disease
Waxy casts
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Normal finding
Pyelonephritis
Chronic renal disease
Granular casts
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Pyelonephritis
Glomerulonephritis
Interstitial Nephritis
Hyaline or mucoprotein casts
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Glomerulonephritis
May be normal in collision sport athletes
White Blood Cell casts
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Acute Tubular Necrosis
Interstitial Nephritis
Eclampsia
Heavy metal poisoning
Rejected transplant
Severe renal disease
Fatty casts
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Nephrotic Syndrome
Hypothyroidism
Kidney and Urinary Tract
Disease Tests
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Urine Protein
Urine Blood
 Gross Hematuria
 Microscopic Hematuria
Urine Protein
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Normal
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Dipstick with trace protein or less
Technique
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First morning void collected
Detection Method
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Initial: Dipstick urine protein
Confirmation: Sulfosalicylic acid
Dipstick turns from yellow to green for protein present
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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
False Positive
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Alkaline urine (Urine pH >7.5)
Increased Urine Specific Gravity (concentrated)
Specimen contaminated by chlorhexidine detergent
Dipstick immersed too long in urine
Medications
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Penicillin
Sulfonamide
Tolbutamide
Phenazopyridine
Body fluid contamination
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Gross Hematuria present
Pus
Semen
Vaginal secretions
Urine Protein to Creatinine Ratio
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Indication
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Efficacy
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Monitor persistant Proteinuria
More accurate than 24 Hour Urine Protein
collection
Most accurate if first morning void is used
Technique: Random urine collection
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Urine Creatinine in mg
Urine Protein in mg
Calculate Urine Protein mg to Urine Creatinine mg
Ratio
Interpretation of Urine Protein to
Urine Creatinine Ratio
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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)
Interpretation of Urine Albumin to
Creatinine Ratio
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Normal Ratio (in general <30 mg/g is normal)
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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
Proteinuria in Adults
Causes
Glomerular Causes (Increased glomerulus
permeability)
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Primary Glomerulonephropathy
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Minimal Change Disease
IgA Nephropathy
Idiopathic membranous Glomerulonephritis
Focal segmental Glomerulonephritis
Membranoproliferative Glomerulonephritis
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Secondary Glomerulonephropathy
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Diabetes Mellitus (Diabetic Nephropathy)
Systemic Lupus Erythematosus (Lupus Nephritis)
Amyloidosis
Preeclampsia (Pregnancy Induced Hypertension)
Infection
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HIV Infection
Hepatitis B
Hepatitis C
Poststreptococcal Glomerulonephritis
Syphilis
Malaria
Endocarditis
Lung Cancer
Gastrointestinal Cancer
Lymphoma
Renal transplant rejection
Microscopic Urinalysis findings of
renal disease
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Urine fats (Nephrotic Syndrome)
Urine WBCs without bacteruria (Renal
Interstitial)
Dysmorphic erythrocytes (Glomerular
disease)
Cellular or granular casts (chronic renal
disease)
Urine Eosinophils
Urine Leukocyte Esterase
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Mechanism
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Neutrophil Granulocytes contain esterases
Positive test suggests pyuria
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Normal
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Dipstick requires 5 minutes to change color
Negative
Abnormal: Positive
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Urinary Tract Infection
Vaginal contaminant
Causes of false negative Leukocyte
esterase on Urinalysis
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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
Causes positive Leukocyte esterase and
negative culture
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Chlamydia
Ureaplasma urealyticum
Balanitis
Bladder Cancer
Nephrolithiasis
Tuberculosis
Urinary tract foreign body
Glomerulonephritis
Medications (Corticosteroid, Cytoxan)
Acute Glomerulonephritis
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Labs: Initial (characterize condition)
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Urine sediment examination
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Proteinuria
Glomerular Hematuria
 Pigmented or Red Blood Cell casts
 Dysmorphic Red Blood Cells
Twenty-four hour urine collection
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24 Hour Urine Protein
Creatine Clearance
 Renal insufficiency
Acute Glomerulonephritis
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Routine blood testing
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Serum chemistries
Albumin and Liver Function Tests
Total Cholesterol
If over age 40 with Proteinuria >1 gram/24 hours
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Serum Protein Electrophoresis (SPEP)
Urine Protein electrophoresis
Acute Glomerulonephritis
Labs: Next (Screen for etiology)
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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)
ACUTE PYELONEPHRITIS
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Labs
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Urinalysis
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Urine Culture (positive in 90% of pyelonephritis)
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Leukocyte esterase or nitrite positive
Hematuria may be present
Microscopic examination may show WBC casts
Diagnosis requires at least 10,000 CFU/mm3
Consider lower threshold in men and in pregnancy
Blood Culture indications (not indicated in most cases)
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Immunocompromised patient
Unclear diagnosis
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Hematogenous source suspected
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Acute Renal Failure
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Urinalysis with Urine sediment examination
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Urine Specific Gravity
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Vascular disease
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Prerenal Failure: Specific Gravity >1.020
Intrarenal Failure: Specific Gravity 1.010 - 1.020
Urine RBCs often present
Glomerulonephritis
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Urine RBCs
Granular casts
Proteinuria
Acute Renal Failure
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Interstitial Nephritis
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Drug hypersensitivity nephritis
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Eosinophils
Tubular Necrosis
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Pyuria
Eosinophils
White Blood Cell and Eosinophil casts
Pigmented granular casts
Tubular epithelial cells
Granular casts
Prerenal Failure
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Hyaline Casts
Autoimmune Testing for Glomerular
Disease
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Antinuclear Antibody (ANA)
Antineutrophil Cytoplasmic Antibody
Antiglomerular basement membrane
Antibody
Chronic Renal Failure
Stage 1: GFR >90 ml/min despite kidney damage
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Microalbuminuria present
Stage 2: Mild reduction (GFR 60-89 min/min)
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GFR of 60 may represent 50% loss in function
Parathyroid Hormone starts to increase
NKF Classification System
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Stage 3: Moderate reduction (GFR 30-59
ml/min)
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Stage 4: Severe reduction (GFR 15-29 ml/min)
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Calcium absorption decreases
Malnutrition onset
Anemia secondary to Erythropoietin deficiency
Left Ventricular Hypertrophy
Serum Triglycerides increase
Hyperphosphatemia
Metabolic Acidosis
Hyperkalemia
Stage 5: Kidney Failure (GFR <15 ml/min)
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Azotemia
Acute Interstitial Nephritis
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Urinalysis
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Renal Function tests with renal insufficiency
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Eosinophiluria
Proteinuria
Fractional Excretion of Sodium >1%
Serum Creatinine increased
Blood Urea Nitrogen increased
Miscellaneous
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Hyperchloremic Metabolic Acidosis