Prof. e. sarhan.work up of_proteinuric_patients

Iman SarhanProf of Internal Medicineand Nephrology, Ain Shams University

ESNT 2012 Mars Alem

Protein excretion rate

( if low mol wt

protein)

Overflow

proteinuria

GFR

The permeability of the glomerular

basement membrane

Primary or secondary glomerulopathy

The ability of

the proximal

tubule to

excrete ,

metabolize and

reabsorb any

filtered proteins

N urinary protein < 0.15 g per day

(15% albumin)

N urinary albumin <30mg/gm

creatinine

>0.2 gm proteinuria

Tubular proteinuria

Glomerular proteinuria

50% 50%Plasma protein the proximal tubule

Permeability

GBM

Normal Glomerular Capillary

Podocytes

Endothelial cells on the luminal aspect of the basement membrane are

fenestrated (diameter 70–100 nm).

The GBM.

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

1.

Functional

transient

CHF, Strenuous

exercise, fever

2. Orthostatic

proteinuria

Account for 50% of isolated

proteinuria5. Glomerular lesion

3. Overflow proteinuria

Pathophysiologic classification

of proteinuria

4. Tubular

proteinuria

Tubulointerstial injury

Multiple myeloma

Differential diagnosis of glomerular

diseases

Diseases presented by either nephrotic and nephritic can be

idiopathic or secondary to other causes.

1st Work up of proteinuria

Urinalysis

Urine sample

Urine protein by dipsticks

False +veHigh urine PH>8

with gross hematuria.

in the presence of penicillin,

sulfonamides or tolbutamide.

with pus, semen or vaginal secretions.

False –veSmall amount of albumin: microalbuminuria

Large amount of non albumin protein

Glucose. Urobilinogen. Bilirubin.Ketones. Specific gravity.pH.Nitrite.Leukocyte esterase.blood. 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

Overflow proteinuria

In overflow proteinuria, low-molecular-weight proteins overwhelm the ability of the proximal tubules to reabsorb filtered proteins.

Causes of Overflow

Multiple myeloma

Amyloidosis

Hemoglobinuria

Myoglobinuria

Diagnosis: urinary protein electrophoresis

UrinalysisUrinary sediment

Negative

Bland urinary sediment

Trace to 2+ on dipstick test

Repeat urinalysis2-3

times in next month

-ve

Transient

proteinuria

occur in CHF, Strenuous exercise, fever


Negative




times in next month

-ve

Transient

+ve 3+-4+ on dipstick test

Quantatitive 24 h urinary protein , pr/cr ratio

24 h urinary protein

Protein /creatinine ratio.

albumin/creatinine ratio

Timed urine collection

Protein creatinineVs Albumin creatinine

Equivalent to 24h urinary protein

Normally <150 mg/gm, Or 0.15 mg/mg.

>0.2 mg/mg considered proteinuria

Equivalent to 24h urinary albumin.

Normally <30mg/gm

Microalbuminuria: 30-299 (false –ve test)

Macroalbuminuria:>300

Quantitative test

Unites is important, if creatinine mmol x 0.088


Negative




times in next month

-ve

Transient



Nephrological

consultation

GFR

Normal low

<30 y

Orthostatic P >30y

Isolated

P

Symptomatic P Unknown cause

Cause of Proteinuria (bland urinary sediment )Relatedto Quantity

Adapted with permission from McConnell KR, Bia MJ. Evaluation of proteinuria: an approach for the internist. Resident Staff Phys 1994;40:41-8.

Daily protein

excretion

cause

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

Orthostatic Proteinuria

Young tall

<30 years

< 2 g of protein per day

Normal GFR

Must be tested

for orthostatic

proteinuria

How to diagnose

Split urine specimens

A 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.

Which is less than 50 mg per eight hours)

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

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 Fanconi syndrome Heavy metals Sickle cell disease NSAIDs, antibiotics

History of HTN

Drug intake

Esinophilluria


Negative




times in next month

-ve

Transient



Nephrological

consultation

GFR

Normal low

<30 y

Orthostatic P >30y

Isolated

P

GFR

Symptomatic P Unkown cause

Normal low


Negative

Bland urinary sediment Positive

Active urinary sediment



times in next month

-ve

Transient



Nephrological

consultation

GFR

Normal low

<30 y

Orthostatic P >30y

Isolated

P

GFR

Symptomatic P Unkown cause

Normal low

DD of cast

Epithelial cells casts

Acute tubular necrosis,

Pyelonephritis.

Nephrotic syndrome.

Red cell casts

glomerulonephritisor vasculitis

White cell casts +

pyuriatubulointerstitial

disease

acute pyelonephritis.

Fatty cast

proteinuria

Granular cast Waxy cast DysmorphicRBCs

Advanced renal

failure

Non nephrotic rang proteinuria if the cause is unknown

Nephrotic range proteinuria with normal GFR or low GFR.

Patient with active urinary sediment

Laboratory

investigation to

recognize the

underlying causes

Recognize the

glomerular

syndrome Renal

biopsy

Approach to patient with glomerular diseases

Investigation to recognize the glomerular syndrome History taking and examination.

Urinalysis : RBCs, RBCs cast, proteinuria.

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)

1st

•Renal biopsy: Investigation to recognize

histopathological diagnosis2nd

• 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.

• ANCA (antineutrophilic antibody) positive in Wagner granulomatosis.

• Antiglomerular basement membrane (AGBM) positive in Goodpasuture syndrome.

3rd

Result of renal biopsy

All cases of

nephrotic syndrome

Except

Children with INS

Diabetic

nephropathy

Some cases light

chain dis

In non nephrotic

range proteinuria

<2gm only if low

GFR

RPGNHematuria

If

+proteinuria

OR low

GFR

Unexplained

AKIExcept

+ve Anti-GBM,

+ve ANCA Post tx

CAD

Minimal change disease

FSGS MN MN

Pathological terms in glomerular disease

Normal Global

if the whole glomerular tuft is

involved

Segmental

only a part of the glomerulus is

affected

Normal Diffuse

most of the glomeruli (>

75%) contain the lesion.

Focal

some but not all the

glomeruli contain the

lesion.

Glomerular proteinuria2-4 gm>4gm

Renal biopsy

Proteinuric Syndromes

< nephrotic range—

nephrotic range

proteinuria without RBCs

Isolated proteinuria

MCD

FSGS

Membranous nephropathy

Diabetic glomerulosclerosis

Amyloidosis

Light-chain deposition

disease

Secondary cause

Proteinuria + active urinary sediment

Mesangial proliferative GN,

IgA nephropathy)

Focal and segmental GN

class III lupus N.

Infective endocarditis)

Diffuse proliferative GN

post- streptococcal GN,

Class IV lupus N

Crescentic GN

Anti-GBM nephritis, Pauci-immune

nephritis)

Hematuric

Syndromes<nephrotic range+ RBCs cast

Both Nephritic and Nephrotic

Features

>nephrotic range+ RBCs cast

Membranoproliferative GN

Fibrillary glomerulopathies

Hereditary nephritis (Alport

syndrome)

Antibody mediated glomerulopathy

Immunofleurescence

Linear glomerular

IgG IF staining

Serology Anti-GBM

Glomerular immune complex

localization with granular IF

Serology : anti DNA, low

complement, anti HCV, anti HBV,

cryoglobulinemia, ASOT, IgA

Paucity of

glomerular IF

Immunoglobulin

staining

Serology: ANCA

+Lunge

hge

Good

Pasture S

-Lunge

hge

Anti GBM

GN

IgA

No vasculitis

IgA

nephropathy

IgA

+ vasculitis

HSP

SLE

Lupus

Nephritis

ASOT

PSGN

MPGN

I, II

Sub-ep

deposite

MGN

Fibillary

GN

20 nm fibrill

No vasculitis

ANCA GN

vasculitis

No asthema

Wegner GN

Esinophilia

+asthema

Churg

Strauss

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

Approach to patient with glomerular diseases

Investigation to recognize the glomerular syndrome History taking and examination.

Urinalysis : RBCs, RBCs cast, proteinuria.

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)

1s

t

•Investigation to recognize histopathological diagnosis

•Renal biopsy2nd

• 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.

• ANCA (antineutrophilic antibody) positive in Wagner granulomatosis.

• Antiglomerular basement membrane (AGBM) positive in Goodpasuture syndrome.

3r

d

Prof. e. sarhan.work up of_proteinuric_patients

Technology

Transcript of Prof. e. sarhan.work up of_proteinuric_patients