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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
The Abnormal Urinalysis
What to do about Microhematuria,
Proteinuria, and Pyuria without
Overt Infection Michael Levin, D.O., F.A.C.O.I.
Chair: Division of Nephrology
Philadelphia College of Osteopathic Medicine
Metropolitan Nephrology Associates
www.metroneph.com
@MetroNephro
Disclosures
I have no relevant financial relationships or conflicts of
interest to disclose.
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Objectives
◼ Review the evaluation of an abnormal urinalysis and the
clinical considerations
◼ Discuss the etiologies in the work up of microscopic
hematuria with a bland Urological work up
◼ Evaluate the appropriate studies in Proteinuria
◼ Define whether to screen for or treat asymptomatic
bacteriuria in an elderly population
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
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Uroscopy
◼ Laboratory Medicine began 6000 years ago with Human Urine analysis
◼ Babylonia and Egyptian Physicians
“Devine Fluid”
◼ Sanskrit Medical Works from 100 BC
Describe 20 different types of urine
◼ 2nd Century documented “Sweet Urine”
‘A melting down of Flesh and Limbs into urine’
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
◼ Middle Ages (AD 500-1500)
◼ Protospatharius composed De Urinis which described the range of colors of urine and implications
◼ Created first documented laboratory techniques
Heating Urine→ Cloudy from protein precipitation
◼ Gilles de Corbeil (1165-1213) related 20 different type of urine and sediment
◼ Created Matula → glass vessel rounded at the bottom shaped like a bladder for urine inspection
Uroscopy
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
Composition of Urine
◼ What is urine?
◼ A fluid composed of:
◼ Water (95%)
◼ Nitrogen containing waste
◼ Urea
◼ Uric acid
◼ Ammonia
◼ Creatinine
◼ Electrolytes
◼ Normal urine will not have significant amounts of blood, protein or white cell
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
Urine Formation
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Microscopic
Hematuria
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Microscopic Hematuria
More than two-three red blood cells are found in
centrifuged urine per high-power field microscopy
( >2- 3 RBC/HP).
Definitions in literature 1-10 RBC/HP
Normal urine:
no red blood cell or less than three red blood cell
+ Test by Dipstick then need microscopic exam to
differentiate glomerular vs. extraglomerular or
other etiology
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
#POMA19 #ChooseKnowledge
Prevalence
◼ Very few population based studies
◼ Results vary based on age, sex, number of urines
evaluated and based on dipstick vs.. microscopy
◼ Review of 76 separate studies
◼ Prevalence: 0.18-16.1 %
◼ Some show increased with age, others show no
difference
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Transient
◼ Male Soldiers underwent yearly examination of urinary
sediment over 12 years : Population Bias→ “March
Hematuria”
◼ Cumulative Incidence 39 % microscopic on 1 exam
16 % on 2 or more exams
◼ Transient microscopic hematuria 13% postmenopausal
women
◼ Etiology: vigorous exercise, sexual intercourse, trauma or
menstrual contamination
◼ No data on transient vs. persistent in regards to underlying
disease
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
Etiology◼ Divide by
◼ Glomerular
◼ Non-glomerular
◼ Vascular
◼ Renal Interstitial
◼ Uroepithelital:
◼ upper vs. lower tract involvement
◼ Systemic
◼ Hematologic
◼ Infectious
◼ Medications
◼ Adjacent Involvement
◼ Miscellaneous
Glomerular vs. Extraglomerular
Hematuria
Extraglomerular Glomerular
Color (if macroscopic)
Clots
Proteinuria
RBC Morphology
RBC Casts
Red or Pink
May be Present
< 500 mg/day
Normal
Absent
Red, Smoky Brown, “Coca-Cola”
Absent
May be > 500mg/day
Dysmorphic ( Darkfield Microscopy)
May be Present
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Glomerular Hematuria
◼ Red Cell Casts very specific
◼ Dysmorphic Red Cell is strongly
associated with a glomerular
origin
◼ Crenated Red Cell-form in
concentrated urine
◼ Acanthocytes- most accurate
urine finding of red cells to
isolated a glomerular origin
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
◼ Glomerular- with isolated microhematuria
◼ IgA Nephropathy- (Bergers Disease)
Increased Incidence in Asians, Most Common GN
◼ Thin Basement Membrane Disease (Hereditary Nephritis)
◼ Alport’s Syndrome
◼ Mild Focal Glomerularnephritis
◼ Sickle Cell Disease
◼ Hemolytic Uremic Syndrome (HUS)
◼ Glomerular- with proteinuria◼ Diabetes Mellitus, SLE, PSGN, MPGN, RPGN, Wegners
Granulomatosis, Polyarteritis Nodosa, MPA, NSAID abuse, FSGS, HIV Nephropathy, Henoch-Schönlein Purpara
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◼ Vascular
◼Malignant Hypertension
◼Arterial Emboli or Thrombosis/Infarction
◼Arteriovenous Fistula
◼Excessive Anticoagulation
◼ Sickle Cell Disease
◼Renal Vein Thrombosis
◼Coagulation Abnormalities
◼Nutcracker Syndrome
◼ Loin Pain Hematuria
Urologic Anatomic
Abnormality
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◼ Vascular
◼Nutcracker Syndrome
◼Compression of the Left Renal Vein between the
Aorta and the Superior Mesenteric Artery at their
Bifurcation
◼Renal Venous Hypertension, Ureteral and Renal
Pelvic Varicosities→ Hematuria
◼Symptoms: Recurrent episodes of hematuria
decreases with recumbency
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
#POMA19 #ChooseKnowledge
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
Proteinuria Transient vs. Persistant
Microscopic vs. Nephrotic
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
Evaluation of Proteinuria
Standard dipstick Urine Microalbumin/Creatinine ratio
+1 Negative/Trace
Total Protein/Creatinine ratio
>200 mg/g 200 mg/g 30 mcg/mg 30 mcg/mg
Recheck at Periodic Health Exam
Diagnostic Evaluation
Treatment Consultation
Not at risk At risk
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Proteinuria
≥3.5 g/day
(protein: creatinine ratio >3-3.5)
Generalized
Edema
Hypoalbuminemia
<3g/L
◼Hyperlipidemia
◼Hypercoagulable state
◼Renal Failure
◼Hypertension#POMA19
◼Generalized Edema
-The predominant feature
-The face, particularly the
periorbital area, is swollen
in the morning& lower extremities
and genital area later in the day
-In advanced disease: the whole body
Anasarca→ shortness of breath
◼Frothy urine and urine dipstick
proteinuria value of 3+
◼Symptoms & signs for secondary cause if
present
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
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Secondary to:•DM (the leading cause of secondary nephrotic syndrome)
•SLE
•Amyloidosis ect.
•Infections: Hepatitis B and C, HIV, Syphilis
•Malignancy: Multiple myeloma , Hodgkins disease, Solid Organ
Tumor
•DrugsNSAIDs, Gold, Penicillamine ,Heavy metals etc
•Anatomic DysfunctionsReflux Nephropathy, Hypoxic Nephropathy
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
#POMA19 #ChooseKnowledge
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•24-hour urine collection→ >3.5 g/day (nephrotic-range proteinuria)
•Alternative : calculating the total protein-to-creatinine ratio (mg/mg) on
a random urine specimen.
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
10% of nephrotic syndrome cases in diabetes are due to
other renal diseases
*Presence atypical features such as
1-A rapidly progressive nephrotic syndrome
2-Unexplained progressive renal injury
3-More proteinuria than could be anticipated
4-Presence of glomerular hematuria and/or absence
of associated microvascular lesions: retinopathy
Management of patients with nephrotic syndrome. Swissmedwkly 2009
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What is Asymptomatic
Bacteriuria compared
to Sterile Pyuria ?
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Asymptomatic Bacteriuria (ASB)
• Laboratory diagnosis
• Positive urine culture
– Colony count significant (> 10⁵ cfu/mL)
• Absence of symptoms
Clinical Infectious Disease 2010;50:625-663
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
Pyuria
• Pyuria (> 10 WBC / high-power field) is evidence of
inflammation in the genitourinary tract
• Pyuria is commonly found with ASB
◼ Elderly institutionalized residents 90% (Infect Dis Clin North Am 1997;11:647-62)
◼ Short-term (< 30 days) catheters 30-75% (Arch IM 2000;160:673-82)
◼ Long-term catheters 50-100% (Am J Infect Control 1985;13:154-60)
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Treatment for ASB Not Indicated
• Premenopausal, non-pregnant women
• Diabetic women
• Older persons living in the community
• Elderly living in long term care facilities
• Persons with spinal cord injury
• Catheterized patients
CID2005;40:643-654
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Prevalence of ASB
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
No Benefit Treating ASB in the
Elderly
• Large long-term studies of ASB in pre and
postmenopausal women
– NO ADVERSE OUTCOMES in women not treated
• Randomized studies (treatment vs. no treatment) in
elderly LTC residents
– NO BENEFIT to treatment
– No decreased rate of symptoms
– No improved survivalCID2005;40:643-654
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Prospective Randomized Studies: Treatment vs. No Treatment ASB
Authors Subjects Intervention Outcome
Nicolle LE, et al.
NEJM 1983;309:1420-
5
Men, NH,
median age 80
Treated 16
Not treated 20
Duration 2 years
No difference mortality
or infectious morbidity
2 groups
Nicolle LE, et al.
Am J Med 1987;83:27-
33
Women, NH, median
age 83
Treated 26
Not treated 24
Duration 1 year
No difference
mortality/GU
morbidity. Increase
drug reactions and
AB resistance treated
group.
Abrutyn E, et al.
Ann Intern Med
1994;120:827-33
Women, ambulatory
and NH
Mean age 82
Treated 192
Not treated 166
Duration 8 years
No survival benefit
from treatment
Ouslander JG
Ann Intern Med
1995;122:749-54
Women and men
NH
Mean age 85
Treated 33
Not treated 38
Duration 4 weeks
No difference chronic
urinary incontinence
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◼ Tubulointerstitial
◼ Allergic Interstitial Nephritis
◼ Analgesic Nephropathy
◼ Renal Cystic Disease
◼ Simple, Complex Cysts
◼ Autosomal Dominant Polycystic Kidney Disease
◼ Medullary Cystic Disease
◼ Acute Pyelonephritis
◼ Sickle Cell Disease
◼ Renal Tuberculosis
◼ Renal Allograft Rejection
◼ Medullary Sponge Kidney
WBC CAST→
RENAL BIOPSY#POMA19 #ChooseKnowledge
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“The Abnormal Urinalysis – What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection”Michael L. Levin, DO
POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019
#POMA19 #ChooseKnowledge
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