Chronic Kidney Disease Importance of Disease ......“The Abnormal Urinalysis –What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection” Michael L. Levin, DO

“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.

#POMA19 #ChooseKnowledge

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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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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◼ 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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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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Urine Formation


Microscopic

Hematuria


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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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


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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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


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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◼ 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


◼ Vascular

◼Malignant Hypertension

◼Arterial Emboli or Thrombosis/Infarction

◼Arteriovenous Fistula

◼Excessive Anticoagulation


◼Renal Vein Thrombosis

◼Coagulation Abnormalities

◼Nutcracker Syndrome

◼ Loin Pain Hematuria

Urologic Anatomic

Abnormality


◼ 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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Proteinuria Transient vs. Persistant

Microscopic vs. Nephrotic




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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


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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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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•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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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


What is Asymptomatic

Bacteriuria compared

to Sterile Pyuria ?


Asymptomatic Bacteriuria (ASB)

• Laboratory diagnosis

• Positive urine culture

– Colony count significant (> 10⁵ cfu/mL)

• Absence of symptoms

Clinical Infectious Disease 2010;50:625-663

42#POMA19 #ChooseKnowledge

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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)


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


Prevalence of ASB


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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


Prospective Randomized Studies: Treatment vs. No Treatment ASB

Authors Subjects Intervention Outcome

Nicolle LE, et al.

NEJM 1983;309:1420-

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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-

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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


◼ Tubulointerstitial

◼ Allergic Interstitial Nephritis

◼ Analgesic Nephropathy

◼ Renal Cystic Disease

◼ Simple, Complex Cysts

◼ Autosomal Dominant Polycystic Kidney Disease

◼ Medullary Cystic Disease

◼ Acute Pyelonephritis


◼ Renal Tuberculosis

◼ Renal Allograft Rejection

◼ Medullary Sponge Kidney

WBC CAST→

RENAL BIOPSY#POMA19 #ChooseKnowledge

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Documents

Chronic Kidney Disease Importance of Disease ......“The Abnormal Urinalysis –What to do About Microhematuria, Proteinuria, Pyuria Without Overt Infection” Michael L. Levin, DO