1. Iman Sarhan
Prof of Internal Medicineand Nephrology, Ain Shams University
ESNT 2012 Mars Alem

2. Protein excretion rate
Plasma protein the proximal tubule
50% 50%
The ability of
( if low mol wt the proximal
protein) tubule to
Overflow excrete ,
proteinuria metabolize and
reabsorb any
filtered proteins
GFR
Permeability Tubular proteinuria
GBM
Glomerular proteinuria
The permeability of the glomerular N urinary protein < 0.15 g per day
basement membrane (15% albumin)
Primary or secondary glomerulopathy N urinary albumin <30mg/gm
creatinine
>0.2 gm proteinuria

3. Normal Glomerular Capillary
 The normal thickness of the
basement membrane equals
about 250–300 nm.
 The spaces between foot
processes, with diameters of
20–60 nm, are called
filtration pores, by which
filtered fluid reaches the
urinary space
 Podocytes
 Endothelial cells on the luminal aspect of the basement membrane are
fenestrated (diameter 70–100 nm).
 The GBM.

4. Pathophysiologic classification
of proteinuria
1.
Functional 2. Orthostatic 3. Overflow proteinuria
transient proteinuria Multiple myeloma
Account for 50% of isolated
proteinuria
5. Glomerular lesion
CHF, Strenuous
exercise, fever 4. Tubular
proteinuria
Tubulointerstial injury

5. Differential diagnosis of glomerular
diseases
Diseases presented by either nephrotic and nephritic can be
idiopathic or secondary to other causes.

6. 1st Work up of proteinuria
Glucose.
 Urinalysis Urobilinogen.
Bilirubin.
Ketones.
 Urine sample Specific
gravity.
 Urine protein by dipsticks pH.
Nitrite.
Leukocyte
esterase.
False +ve blood.
Protein.
High urine PH>8
with gross hematuria.
in the presence of penicillin, False –ve
sulfonamides or tolbutamide. Small amount of albumin: microalbuminuria
with pus, semen or vaginal secretions. Large amount of non albumin protein
This method preferentially detects albumin and is less sensitive to
globulins or parts of globulins or (heavy or light chains or Bence
Jones proteins).
Laffeyette et al., 1996

7. Overflow proteinuria
Causes of Overflow
Multiple myeloma  In overflow proteinuria, low-
Amyloidosis molecular-weight proteins
Hemoglobinuria overwhelm the ability of the
Myoglobinuria proximal tubules to reabsorb filtered
proteins.
Diagnosis: urinary protein electrophoresis

8. Urinalysis
Urinary sediment
Negative
Bland urinary sediment
Trace to 2+ on dipstick test
Repeat urinalysis2-3
times in next month
-ve
Transient occur in CHF, Strenuous exercise, fever
proteinuria

9. Urinalysis
Urinary sediment
Negative
Bland urinary sediment
Trace to 2+ on dipstick test
+ve 3+-4+ on dipstick test
Repeat urinalysis2-3
times in next month
Quantatitive 24 h urinary protein , pr/cr ratio
-ve
24 h urinary protein
Protein /creatinine ratio.
Transient albumin/creatinine ratio
Timed urine collection

10. Quantitative test
Protein creatinine Vs Albumin creatinine
Equivalent to 24h urinary protein Equivalent to 24h urinary albumin.
Normally <150 mg/gm, Or 0.15 mg/mg. Normally <30mg/gm
>0.2 mg/mg considered proteinuria Microalbuminuria: 30-299 (false –ve test)
Macroalbuminuria:>300
Unites is important, if creatinine mmol x 0.088

11. Urinalysis
Urinary sediment
Negative
Bland urinary sediment
Trace to 2+ on dipstick test
+ve 3+-4+ on dipstick test
Repeat urinalysis2-3
times in next month
Quantatitive 24 h urinary protein , pr/cr ratio
GFR
-ve
Normal low
Transient Nephrological
<30 y >30y Symptomatic P Unknown cause consultation
Orthostatic P Isolated

12. Cause of Proteinuria (bland urinary sediment )Related
to Quantity
Daily protein cause
excretion
0.15 to 2.0 g Mild glomerulopathies
Orthostatic proteinuria (0.15-
<2gm)
Tubular proteinuria
Overflow proteinuria
2.0 to 4.0 g Usually glomerular
>4.0 g Always glomerular
Adapted with permission from McConnell KR, Bia MJ. Evaluation of proteinuria: an
approach for the internist. Resident Staff Phys 1994;40:41-8.

13. Orthostatic Proteinuria
 Young tall Must be tested
 <30 years for orthostatic
 < 2 g of protein per day proteinuria
 Normal GFR
Split urine specimens
A 16-hour daytime specimen is obtained
How to diagnose with the patient performing normal
activities and finishing the collection by
voiding just before bedtime. An eight-hour
overnight specimen is then collected.
Which is less than 50 mg per eight hours)

14. Isolated Proteinuria
 A proteinuria usually <2 g per day
 With normal renal function.
 No evidence of systemic disease that might cause renal
malfunction.
 Normal urinary sediment.
 Normal blood pressures

15. Tubular proteinuria
 Tubular proteinuria occurs when tubulointerstitial disease
prevents the proximal tubule from reabsorbing low-molecular-
weight proteins (part of the normal glomerular ultrafiltrate).
 When a patient has tubular disease, usually less than 2 g of
protein is excreted in 24 hours.
 Tubular proreinuria
 Hypertensive nephrosclerosis
 Tubulointerstitial disease due to:
 Uric acid nephropathy
 Acute hypersensitivity interstitial nephritis History of HTN
 Fanconi syndrome Drug intake
 Heavy metals Esinophilluria
 Sickle cell disease
 NSAIDs, antibiotics

16. Urinalysis
Urinary sediment
Negative
Bland urinary sediment
Trace to 2+ on dipstick test
+ve 3+-4+ on dipstick test
Repeat urinalysis2-3
times in next month
Quantatitive 24 h urinary protein , pr/cr ratio
GFR GFR
-ve
Normal low low
Normal
Transient Nephrological
<30 y >30y Symptomatic P consultation
Unkown cause
Orthostatic P Isolated

17. Urinalysis
Urinary sediment
Negative Positive
Bland urinary sediment Active urinary sediment
Trace to 2+ on dipstick test
+ve 3+-4+ on dipstick test
Repeat urinalysis2-3
times in next month
Quantatitive 24 h urinary protein , pr/cr ratio
GFR GFR
-ve
Normal low low
Normal
Transient Nephrological
<30 y >30y Symptomatic P consultation
Unkown cause
Orthostatic P Isolated

18. DD of cast
Epithelial cells casts White cell casts +
Acute tubular necrosis, pyuria Fatty cast
Red cell casts tubulointerstitial
Pyelonephritis. proteinuria
glomerulonephritis disease
Nephrotic syndrome. or vasculitis acute
pyelonephritis.
Advanced renal
failure
Granular cast Waxy cast Dysmorphic

19.  Non nephrotic rang proteinuria if the cause is unknown
 Nephrotic range proteinuria with normal GFR or low
GFR.
 Patient with active urinary sediment
Recognize the Laboratory
glomerular investigation to
syndrome Renal recognize the
biopsy underlying causes

20. Approach to patient with glomerular diseases
 Investigation to recognize the glomerular syndrome
 History taking and examination.
 Urinalysis : RBCs, RBCs cast, proteinuria.
1st  Quantitative urinary protein. Nephrotic range proteinuria (>3.5 gm/24h), subnephrotic range.
 Renal function tests: blood urea, creatinine, estimated GFR, creatinine clearance.
 Renal imaging ( to differentaite between acute and chronic and to exclude obstructive uropathy)
2nd •Renal biopsy: Investigation to recognize
histopathological diagnosis
• Investigation to recognize the underlying causes:
• ANA (antinuclear antidoy) Anti-ds DNA positive in systemic lupus erythromatosis (SLE).
• C3, C4 (complement) may be comsumed.
• ASOT (anti-streptolysin O titre) positive in post streptococcal GN.
3rd • ANCA (antineutrophilic antibody) positive in Wagner granulomatosis.
• Antiglomerular basement membrane (AGBM) positive in Goodpasuture syndrome.

21. All cases of
In non nephrotic Hematuria
nephrotic syndrome
range proteinuria
RPGN If Unexplained
<2gm only if low +proteinuria AKI
Except
Except GFR OR low
+ve Anti-GBM,
Children with INS GFR
+ve ANCA Post tx
Diabetic CAD
nephropathy
Some cases light
chain dis
Result of renal biopsy

22. Minimal change disease
FSGS MN MN

23. Pathological terms in glomerular disease
Normal Global Segmental
if the whole glomerular tuft is only a part of the glomerulus is
involved affected
Focal
Normal Diffuse some but not all the
most of the glomeruli (> glomeruli contain the
75%) contain the lesion. lesion.

24. Glomerular proteinuria
2-4 gm
>4gm
 Renal biopsy
Isolated proteinuria
MCD
FSGS
Proteinuric Syndromes Membranous nephropathy
< nephrotic range— Diabetic glomerulosclerosis
nephrotic range Amyloidosis
proteinuria without RBCs Light-chain deposition
disease
Secondary cause

25. Proteinuria + active urinary sediment
 Mesangial proliferative GN,
Membranoproliferative GN  IgA nephropathy)
 Focal and segmental GN
Fibrillary glomerulopathies  class III lupus N.
 Infective endocarditis)
Hereditary nephritis (Alport  Diffuse proliferative GN
syndrome)  post- streptococcal GN,
 Class IV lupus N
 Crescentic GN
 Anti-GBM nephritis, Pauci-immune
nephritis )
Both Nephritic and Nephrotic Hematuric
Features Syndromes
>nephrotic range+ RBCs cast <nephrotic range+ RBCs cast

26. Fibrillary glomerulonephritis.
IgA
MPGN
Ivanyi B , Degrell P Nephrol. Dial. Transplant.
2004;19:2166-2170
Nephrol Dial Transplant Vol. 19 No. 9 © ERA-EDTA 2004; all rights reserved

27. Antibody mediated glomerulopathy
Immunofleurescence
Linear glomerular Paucity of
Glomerular immune complex glomerular IF
IgG IF staining
localization with granular IF Immunoglobulin
Serology Anti-GBM
Serology : anti DNA, low staining
complement, anti HCV, anti HBV, Serology: ANCA
cryoglobulinemia, ASOT, IgA
+Lunge -Lunge
vasculitis Esinophilia
hge hge
Anti GBM No vasculitis No asthema +asthema
Good
GN ANCA GN Wegner GN Churg
Pasture S Strauss
IgA Fibillary
IgA SLE MPGN Sub-ep
No vasculitis ASOT GN
+ vasculitis Lupus I, II deposite
IgA PSGN 20 nm fibrill
HSP Nephritis MGN
nephropathy

28. Finally
 To assess the presence of proteinuria (dip stick)
 Quantitative protein.
 In mild 0.2-2gm--- we need to think in transient proteinuria,
orthostatic proteinuria, isolated proteinuria.
 In moderate proteinuria 2-4gm differ acc to
 Presence or absence of active sediment.
 GFR.
 Nephrological consultation with renal biopsy and laboratory
investigation is indicated in:
 Non nephrotic rang proteinuria if the cause is unknown
 Nephrotic range proteinuria with normal GFR or with low GFR
 Patient with active urinary sediment

29. Approach to patient with glomerular diseases
 Investigation to recognize the glomerular syndrome
1s  History taking and examination.
 Urinalysis : RBCs, RBCs cast, proteinuria.
t  Quantitative urinary protein. Nephrotic range proteinuria (>3.5 gm/24h), subnephrotic range.
 Renal function tests: blood urea, creatinine, estimated GFR, creatinine clearance.
 Renal imaging ( to differentaite between acute and chronic and to exclude obstructive uropathy)
•Investigation to recognize histopathological diagnosis
2nd
•Renal biopsy
• Investigation to recognize the underlying causes:
• ANA (antinuclear antidoy) Anti-ds DNA positive in systemic lupus erythromatosis (SLE).
• C3, C4 (complement) may be comsumed.
3r • ASOT (anti-streptolysin O titre) positive in post streptococcal GN.
d • ANCA (antineutrophilic antibody) positive in Wagner granulomatosis.
• Antiglomerular basement membrane (AGBM) positive in Goodpasuture syndrome.