This document provides information on proteinuria (abnormal amounts of protein in the urine) including its history, physiology, detection, quantification, causes, and diagnostic evaluation. It details the normal mechanisms by which the kidneys filter and reabsorb albumin and other proteins from the blood. Common causes of proteinuria include benign causes like exercise as well as pathological glomerular, tubular, and overflow proteinuria due to various kidney diseases and disorders. The diagnostic approach involves urinalysis, urine protein creatinine ratio, and ruling out transient causes through repeated testing.

1. Proteinuria in Adults: A
Diagnostic Approach
Dr.I.A.P.B.Illeperuma
15/07/2015

2. Bit of history…..
Hippocrates (400 B.C.) described bubbles on the surface of the urine as
indicating kidney disease and a long illness.

3. Physiology
 Although the glomerular filtration coefficient of albumin is small, the daily
filtered load can be as much as 8 g.
 To prevent such massive losses of albumin, quantitative reabsorption along
the proximal tubules is accomplished by “receptor”-mediated endocytosis
 Because of its size, albumin cannot leave the tubular lumen on the
paracellular route across the tight junctions.
 Furthermore, albumin is not cleaved in the tubular lumen and therefore does
not cross the apical membrane of the proximal tubular cell in the form of free
amino acids
 Thus the only mechanism able to mediate albumin reabsorption is
endocytosis.

4. Proteinuria
 The presence of abnormal quantities of protein in the urine, which may
indicate damage to the kidneys.
 Normal urinary protein excretion - < 150mg/ 24 hours
 Of that
40% - Tamm – Horsfall proteins secreted by thick ascending limb of the loop
of Henle
40% - Low molecular weight immunoglobulins (IgA), Urokinase, Peptide
hormones
20% - Albumin
 Normal albumin excretion - < 30mg/ 24 hours

5. Proteinuria
 Microalbuminuria – Albumin excretion 30 – 300mg/ 24 hours
 Macroalbuminuria – Albumin excretion 300 – 3500mg/ 24 hours
 Nephrotic range proteinuria – Albumin excretion > 3500mg / 24h

6. Isaac Sarrabat 1600; Physician
examining a urine flask. (US National
Library of Medicine)

7. Detecting and Quantifying Proteinuria
1.Urine dipstick test
Negative - Less than 10 mg per dL
Trace - 10 to 20 mg per dL
1+ - 30 mg per dL
2+ - 100 mg per dL
3+ - 300 mg per dL
4+ - 1,000 mg per dL

8. Detecting and Quantifying Proteinuria
2. Sulfosalicylic acid (SSA) turbidity test
 The advantage of this easily performed test is its greater sensitivity for
proteins such as Bence Jones
 An equal amount of 3 percent SSA is added to that specimen of urine
 The acidification causes precipitation of protein in the sample (seen as
increasing turbidity), which is subjectively graded as trace,1+, 2+, 3+ or 4+

9. Detecting and Quantifying Proteinuria
3. Heat and Acetic Acid Test
 If turbidity develops add 1-2 drops of glacial acetic acid
 If turbidity is due to phosphate or carbonate precipitation, it will disappear
with acetic acid
Negative : No cloudiness
Trace: Barely visible cloudiness.
1+ : Definite cloud without granular flocculation
2+ : Heavy and granular cloud without granular flocculation
3+ : Densed cloud with marked flocculation.
4+ : Thick curdy precipitation and coagulation

10. Detecting and Quantifying Proteinuria
4. 24 hour urine protein excretion
5. Urine protein creatinine ratio
 Determined in a random urine specimen while the person carries on normal
activity
 Recent evidence indicates that the UPr/Cr ratio is more accurate than the 24-
hour urine protein measurement.
 Fortunately, the ratio is about the same numerically as the number of grams
of protein excreted in urine per day. Thus, a ratio of less than 0.2 is
equivalent to 0.2 g of protein per day

11. Causes of proteinuria
 Benign
1. Fever
2. Strenuous exercise
3. Acute illness
4. Emotional stress
5. Orthostatic proteinuria
Due to increased renal blood flow

12. Causes of proteinuria
 False positives in dipstick testing
1. Concentrated urine
2. Alkaline urine (pH > 7)
3. Gross hematuria
4. Mucous
5. Semen
6. White cells

13. Pathological proteinuria
 Glomerular – Due to increased capillary permeability of glomerulus
Glomerulonephritides – Primary or secondary
 Tubular – Due to decreased tubular reabsorption of filtered proteins
Tubulo-interstitial diseases
 Overflow – Due to increased production of low molecular weight proteins
Monoclonal gammopathies, Leukaemias, Lymphomas

14. Pathological proteinuria
 Glomerular
Primary Minimal change disease
Idiopathic membranous GN
FSGS
Membranoproliferative GN
IgA nephropathy
Secondary Diabetes
Connective tissue disorders – Lupus nephritis
Infection – Post streptococcal, Hep B
Malignancy – Lymphoma, Lung cancer

15. Pathological proteinuria
 Tubular
Hypertensive nephrosclerosis
Uric acid nephropathy
Heavy metals
Sickle cell disease
NSAIDS
Hypersensitive interstitial nephritis
 Overflow
Haemoglobinuria/Myoglobinuria
Myeloma
Amyloidosis

16. Diagnostic Evaluation of Proteinuria
1. When proteinuria is found on a dipstick urinalysis, the urinary sediment
should be examined microscopically
MICROSCOPIC FINDING PATHOLOGIC PROCESS
Fatty casts, free fat or oval fat bodies Nephrotic range proteinuria (> 3.5 g
per 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* Suggestive of drug-induced acute
interstitial nephritis
Hyaline casts No renal disease; present with
dehydration and with diuretic therapy
* A Wright’s stain of the urine specimen is necessary to detect eosinophiluria

17. Diagnostic Evaluation of Proteinuria
2. If urinary sediments are positive, investigate accordingly.
3. Findings suggestive of infection on microscopic urinalysis mandate antibiotic
treatment and then repeated dipstick testing
4. If the results of microscopic urinalysis are inconclusive and the dipstick
urinalysis shows trace to 2+ protein, the dipstick test should be repeated on a
morning specimen at least twice during the next month
5. If a subsequent dipstick test result is negative, the patient has transient
proteinuria, which is not associated with increased morbidity and
mortality, a specific follow-up is not indicated.

18. Diagnostic Evaluation of Proteinuria

19. ORTHOSTATIC PROTEINURIA
 This benign condition occurs in about 3 to 5 percent of adolescents and young
adults which is characterized by increased protein excretion in the upright
position but normal protein excretion when the patient is supine.
 To diagnose orthostatic proteinuria, split urine specimens are obtained for
comparison.
 The first morning void is discarded and 16-hour daytime specimen is obtained
with the patient performing normal activities and finishing the collection by
voiding just before bedtime
 An eight-hour overnight specimen is then collected.
 The daytime specimen typically has an increased concentration of protein,
with the nighttime specimen having a normal concentration.

20. ISOLATED PROTEINURIA
 A proteinuric patient with normal renal function, no evidence of systemic
disease that might cause renal malfunction, normal urinary sediment and
normal blood pressures is considered to have isolated proteinuria.
 Protein excretion is usually less than 2 g per day
 These patients have a 20 percent risk for renal insufficiency after 10 years
and should be observed with blood pressure measurement, urinalysis and a
creatinine clearance every six months

21. References
 American family physician online - Proteinuria in Adults: A Diagnostic
Approach
http://www.aafp.org/afp/2000/0915/p1333.html
 Medscape online - Proteinuria: Background, Pathophysiology, Etiology
http://emedicine.medscape.com/article/238158-overview
 Harrisons Principles of Internal Medicine,18th Edition

22. Thank you
for your
attention