This document discusses proteinuria, its definitions, causes, classification, and diagnostic evaluation in medical practice, emphasizing its prevalence and benign nature in many cases. It outlines mechanisms leading to proteinuria and the importance of differentiating between transient and persistent proteinuria through various tests and patient evaluations. The text also highlights specific conditions linked to proteinuria and the clinical significance of microalbuminuria as a cardiovascular risk indicator.

1. Proteinuria- H T Approach?
ow o
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
References:
1. Brenner’s & Rector’s The Kidney 7th Ed.
2. Harrison’s Internal Medicine 17th Ed.
3. Oxford Textbook Of Clinical Nephrology
4. Internet

2. Problem Statement
 Proteinuria is a common finding in at least
17% adults in general practice, in routine
dip stick screening
 Fewer than 2% of patients whose urine
dipstick is positive for protein have serious
and treatable urinary tract disorders

3. Definition
 240 years ago, Hippocrates noted the
association between “Bubbles on surface
of urine” and kidney disease
 Proteinuria is defined as protein excretion
>150mg/day.
 Most of the positive dip stick test results
are due to benign proteinuria, which has
no associated morbidity and mortality

4. Causes of Benign Proteinuria
 Dehydration
 Emotional stress
 Fever
 Heat injury
 Intense physical activity
 Most acute illnesses
 Orthostatic (postural )disorder

5. Composition Of Urinary Protein
70 mg/d 35 mg/d
15 mg/d
10 mg/d 15 mg/d
5
mg/d
Tamm Horsfall Protein Blood Group Related Antigens
Albumin Mucopolysaccarides
Hormones and Enzymes Immunoglobulins

6. Mechanism of Proteinuria
 FILTRATION OF BLOOD OCCURS IN GLOMERULUS
 GLOMERULAR FILTRATION BARRIER CONSISTS OF:
1. Capillary Endothelium
2.Glomerular Basement Membrane
3.Visceral Epithelium with foot
processes forms slit diaphragm
 GLOMERULAR FILTRATION BARRIER IS SIZE &
CHARGE DEPANDENT
 CHARGE IS ACCOUNTED BY
:- Negative charge heparan sulfate present in GBM
:- Sialoglycoprotein of epithelium & Endothelium
cell

7. Mechanism of Proteinuria
 SIZE BARRIER IS ACCOUNTED BY:
Slit diphragm made up of podocytes of
visceral epithelium.
Hence structure which is negatively charged
and large size is restricted by GFB

8. Classification Of Proteinuria
01.ACCORDING TO QUANTITY:
 MILD : < 500 mg
 MODERATE : 500 mg -2 gm
 SEVERE : > 2 gm
02.ACCORDING TO NATURE:
 SELECTIVE
 NON SELECTIVE

9. 03.ACCORDING T SIT :
O E
PATHOPHYSIOLOGIC
TYPE CAUSES
FEATURES
Increased glomerular Primary or
Glomerular capillary permeability secondary
to proteins glomerulopathy
Decreased tubular Tubular or
resorbtion of proteins interstitial disease
Tubular in glomerular filterate caused by drugs,
hypertensive
glomerulosclerosis
Increased production Monoclonal
Overflow of low molecular gammopahy,
weight proteins leukemia

10. Causes Of Proteinuria
 Primary glomerulonephropathy
Primary glomerulonephropathy
 Minimal change disease
 Idiopathic membranous glomerulonephritis
 Focal segmental glomerulonephritis
 Membranoproliferative glomerulonephritis
 IgA nephropathy
 Secondary glomerulonephropathy
 Diabetes mellitus
 Collagen vascular disorders (e.g., lupus nephritis)
 Amyloidosis
 Preeclampsia
 Infection (e.g., HIV, hepatitis B and C, poststreptococcal illness, syphilis,
malaria and endocarditis)
 Gastrointestinal and lung cancers
 Lymphoma, chronic renal transplant rejection
 Glomerulonephropathy associated with the following drugs:
 Heroin
 NSAIDs
 Gold components
 Penicillamine
 Lithium
 Heavy Metal

11. Causes Of Proteinuria
 Tubular
 Hypertensive nephrosclerosis
 Tubulointerstitial disease due to
 Uric acid nephropathy
 Acute hypersenstivity
 Interstitial nephritis
 Fanconi syndrome
 Heavy metals & Drugs
 Sickle cell disease
 Overflow
 Hemoglobinuria
 Myoglobinuria
 Multiple myeloma
 Amyloidosis

12. Selectivity of Proteinuria
 It is a relative glomerular selectivity for proteins,
although it is of little significance
 It is the ratio of clearance of larger molecule with
that of smaller i.e., IgG, IgM against that of
albumin
 >20% to that of albumin, represents nonselective
proteinuria
 <10%is highly selective
 10 %to 20% is of little discriminatory value
 This is of little importance ,except to distinguish
between minimal change disease from other
forms of nephritis or glomerular disease

13. Method Description Detection Comments
limit
(mg/l)
Remove non-protein nitrogen, digest Reference and research method
protein, measure protein nitrogen
Kjeldahl 10–20
Copper reagent, measures peptide Requires precipitation of proteins,
bonds used for 24-h measurement in
Biuret 50
some laboratories
Addition of trichloracetic or Imprecise, different readings for
sulfosalicylic acids alters colloid albumin and globulin
properties and produces turbidity to
Turbidimetric be read in densitometer. 50–100
Benzethomecin also used
Indicator changes color in presence Different proteins bind differently;
of protein (e.g. Coomassie brilliant several different dyes in use; used
Dye-binding blue) 50–100 in many laboratories for 24-h
excretion
Specific antialbumin antibody used Measures albumin excretion not
total protein. Does not detect
Nephelometric globulins
Impregnated with indicator dye Reacts poorly with globulins. Usual
Stick tests (bromocresol green) which changes 100 mg/l clinical screening test
color in the presence of protein

14. Detecting And Quantifying Proteinuria
 Dipstick analysis is used in most patients in out door setting
 False positive results
 Alkaline urine (pH>7.5)
 When dipstick is immersed too long
 With highly concentrated urine
 With gross hematuria
 In presence of penicillins, sulfonamide or tolbutamide
 With pus, semen or vaginal secretions
 False negative results
 Dilute urine (sp. gravity >1.015)
 Urinary protein are of low molecular weight
 The resuts are graded as –
 Negative ( <10 mg /dl )  2+ ( 100 mg /dl )
 Trace ( 10 to 20mg/dl )  3+ ( 300 mg/dl )
 1+ ( 30mg /dl )  4+ ( >1000mg/dl )
 The SULFOSALICYLIC ACID (SSA) turbidity test and
IMMUNOELECTROPHORESIS qualitatively screens for proteinuria
especially Bence Jones proteinuria

15. Detecting And Quantifying Proteinuria
 As urine dipstick and SSA tests are crude methods and value
depends upon amount of urine produced, they correlate poorly
with quantitative urine protein determination
 Patients with persistent proteinuria should undergo 24-hr urine
protein estimation. The urinary creatinine concentration
should be included in 24-hr measurement to determine
adequacy of specimen (normal excretion in men=16 to
26mg/kg/day and in women =12 to24 mg/kg/day as it depend
on muscle mass)
 24- hr urine should be collected by instructing the patient to
discard first morning void; specimen of all subsequent voiding
should be collected including the first morning sample on
second day

16. Detecting And Quantifying Proteinuria
Spot Urinary Protein To Creatinine Ratio (Upr/Cr)
 It is an alternative to 24-hr urine protein estimation
 Correlation between UPr/Cr ratio has been
demonstrated in various diseases like diabetes
mellitus, pre-ecclampsia, rheumatic disease
 Normal value is < 0.2 which corresponds to
proteinuria < 200 mg/24hrs
 Benefit of it is-
01.Ease of collection.
02. Lack of error from over & under collection

17. Diagnostic Evaluation
 When proteinuria is found on a dipstick analysis, the urinary sediment
should be examined microscopically for-
Fatty casts, free fat or oval fat bodies Nephrotic range proteinuria (>3.5 g /24
hours)
Leukocytes, leukocyte casts with bacteria Urinary tract infection
Leukocytes, leukocyte casts without bacteria Renal interstitial disease
Normal-shaped erythrocytes Suggestive of lower urinary tract lesion
Dysmorphic erythrocytes Suggestive of upper urinary tract lesion
Erythrocyte casts Glomerular disease
Waxy, granular or cellular casts Advanced chronic renal disease
Eosinophiluria Drug-induced acute interstitial nephritis
Hyaline casts No renal disease; present with dehydration

18. RBC Cast
Hyaline cast

19. Hyaline and granular cast
Coarse granular cast
adjacent WBCs

20. Final coarse granular cast
Oval fat body with adjacent WBC cast
hyaline cast

21. Transient Proteinuria
 If results of microscopic analysis are
inconclusive and the dipstick analysis shows
trace to 2+protein, the dipstick test should be
repeated on morning specimen at least twice
during next month
 If subsequent dipstick test are negative the
patient has transient proteinuria
 It is not associated with increased mortality or
morbidity,and specific follow-up is not required

22. Persistent Proteinuria
 When diagnosis of persistent proteinuria is established, a
detailed history and physical examination should be
performed, looking for systemic disease with renal
involvement
 A medication history is important
 A 24-hr urine protein or a UPr/Cr ratio on random urine
sample should be obtained
 An adult with proteinuria >2gm /24 hr requires
aggressive work up
 If creatinine clearance is normal and if diagnosis is clear
as diabetes or uncompensated CHF, treat underlying
medical condition with regular follow up
 If there is decreased creatinine clearance or an unclear
cause, further investigations should be done in
consultation with nephrologist

23. Orthostatic Proteinuria
 Persons younger than 30 yrs who excrete
<2gm of protein /day with normal
creatinine clearance should be tested for
orthostatic or postural proteinuria
 This benign condition occur in 3 to 5 %of
adolescent and young adults, it is
characterized by increased protein excretion
in upright position but normal excretion in
supine
 Diagnosis is made by split urine specimen
collection

24. Orthostatic Proteinuria
 The first morning void is discarded , a 16 hr daytime
specimen is obtained with patient performing
normal activities and finishing the collection by
voiding before bed time, an overnight 8 hr.
specimen is then collected
 The day time specimen typically has an increased
concentration of protein, while night time specimen
has having normal concentration
 It is a benign condition associated with normal renal
function after as long as 20 to 50 yrs of follow up
 Annual blood pressure measurement is
recommended in these patients

25. Isolated Proteinuria
 A proteinuric patient with normal renal function,
no evidence of systemic disease, normal urinary
sediments and normal blood pressure is considered
to have isolated proteinuria
 Protein excretion is usually <2 gm/day
 20%of these patients have risk for renal
insufficiency after 10years and should be followed
with blood pressure measurement, urinalysis and
creatinine clearance every 6 month
 Isolated proteinuria with excretion >2 gm /day
usually signifies glomerular disease and needs
further evaluation.

26. ALGORIT M FOR E
H VALUATING
A P INT W H P
AT IT ROT INURIA
E

27. SELECTED INVESTIGATIONS TO BE CONSIDERED IN PROTEINURIA
TEST INTERPRETATION
Antinuclear Antibody Elevated in SLE
Antistreptolysin O Titre Elevated after streptococcal GN
Complement C3 & C4 Levels low in RPGN
ESR If normal help to rule out infection or inflammation
Fasting Blood sugar Elevated in Diabetes Mellitus
Hemoglobin, Hct Low in CRF
HIV, VDRL & Hepatitis serology All are associated with glomerular proteinuria
S. Electrolytes( Na+, K+ ) Screening for any abnormalities consequent to renal
disease
Serum & Urine protein Abnormal in multiple myeloma
Electrophoresis
Serum Urate Elevated urates can lead to tubulointerstitial disease
and stones
USG KUB For structural renal disease
Chest X Ray Systemic diseases like sarcoidosis

28. Microalbuminuria
 It is defined as presence of albumin in urine above normal
range of <30 mg/day but below detectable range with
conventional dipstick methodology i.e.30-299 mg/day
 It is estimated by Radioimmunoassay.
 Recent data have established that MA is not only a predictor
of diabetic complication but also a powerful independent
risk factor of CVD
 While the contribution of MA as a prognostic indicator of
cardiovascular events in people with diabetes is clear it is
still debatable in nondiabetic population.
 Present in Diabetic nephropathy, hypertension, Cardiac
failure & Viral illnesses

29. FINAL COM E
M NT
A systematic approach to the patient
with proteinuria will allow the
clinician to efficiently distinguish
between benign and pathological
causes.

30. T ANK YOU
H