glomerular diseases dr. atapour differential diagnosis and evaluation of glomerular disease

Glomerular Diseases

Dr. Atapour

Differential diagnosis and evaluation of

glomerular disease

CLINICAL PATTERNS OF GLOMERULAR DISEASE

• Nephrotic

• Nephritic

Nephrotic pattern

• The nephrotic proteinuria that is usually above 3.5

g/day

• Lipiduria

• Edema

• Hyperlipidemia

• Some patients also have microscopic hematuria

• Red cell casts

• Asymptomatic proteinuria

• Full-blown nephrotic syndrome

The bland sediment

• Absence of immune complex deposition in

most of these disorders:

– Minimal change disease

– Focal segmental glomerulosclerosis

– Diabetic nephropathy

– Amyloidosis.

• Lack of inflammation

• The serum creatinine concentration

Acute kidney injury in the nephrotic syndrome

• Concurrent acute tubular necrosis

• Usually in minimal change disease

Nephritic pattern

• Presence of red cells

• White blood cells

• Red cell – Dysmorphic appearance – Acanthocytes

• Mixed cellular casts

• Variable degrees of proteinuria

dysmorphic RBCs muddy brown casts

tubular cell casts oval fat body

RBC cast Hyaline cast

Pathologic classification

• Light microscopy

• Focal

• Diffuse

– This terminology is most often used in lupus

nephritis

– ANCA-positive vasculitis.

Limitations of this classification

• Same pathology and multiple causes

• Nonspecific nature of the histologic patterns

MPGN

Can be a systemic immune complex disease

– To infective endocarditis

– Systemic lupus erythematosus

– Hepatitis C virus complement

Membranous nephropathy

• Systemic lupus erythematosus

• Chronic hepatitis B virus infection

• Underlying malignancy

• Drugs

Focal segmental glomerulosclerosis

• Primary condition

• Secondary change induced by intraglomerular

hypertension or healing of previous

glomerular injury.

Nephrotic syndrome without a nephritic sediment

• Mild hematuria

• No red cell casts

Depend on age

What do you think?

Less than 15 years:

–Minimal change disease

– Focal segmental glomerulosclerosis

–Mesangial proliferative glomerulonephritis

15 to 40 years :

–Minimal change disease

–Membranous nephropathy

– Focal segmental glomerulosclerosis

–Diabetic nephropathy

– Preeclampsia

–Postinfectious glomerulonephritis

Greater than 40 years:

– Focal segmental glomerulosclerosis

– Membranous nephropathy

– Diabetic nephropathy

– Minimal change disease

– IgA nephropathy

– Primary amyloidosis

– Benign nephrosclerosis

– Postinfectious glomerulonephritis

Mild glomerulonephritis

• Mild glomerulonephritis is defined as a

nephritic sediment and:

– Normal or near normal estimated GFR

– Do not have the nephrotic syndrome

Less than 15 years

– Mild postinfectious glomerulonephritis

– IgA nephropathy

– Thin basement membrane disease

– Hereditary nephritis

– Henoch-Schönlein purpura

– Mesangial proliferative glomerulonephritis

15 to 40 years

• IgA nephropathy

• Thin basement membrane disease

• Lupus nephritis, hereditary nephritis

• Mesangial proliferative glomerulonephritis

Greater than 40 years

– IgA nephropathy

Moderate to severe glomerulonephritis

• Moderate to severe glomerulonephritis is

defined as a nephritic sediment

– Reduced estimated GFR

– Nephrotic syndrome ±

Less than 15 years

–Postinfectious glomerulonephritis

–Membranoproliferative glomerulonephritis

15 to 40 years

– Postinfectious glomerulonephritis

– lupus nephritis

– RPGN (crescentic glomerulonephritis)

– IgA nephropathy

– Fibrillary glomerulonephritis

– Membranoproliferative glomerulonephritis

Greater than 40 years :

–Rapidly progressive glomerulonephritis

–Vasculitis

– IgA nephropathy

– Fibrillary glomerulonephritis

–Postinfectious glomerulonephritis

Effect of race

In black patients :

– Focal segmental glomerulosclerosis (57 percent)

– Membranous nephropathy (24 percent)

– Minimal change disease (14 percent)

– Membranoproliferative glomerulonephritis, IgA

nephropathy, and immunotactoid nephropathy

were each present in 1 to 2 percent.

In white patients:

– Membranous nephropathy (36 percent),

– Focal segmental glomerulosclerosis (23 percent)

– Minimal change disease (20 percent)

– IgA nephropathy (8 percent)

– Membranoproliferative glomerulonephritis (6%)

– Immunotactoid glomerulopathy (6 percent).

Positive family history

• Thin basement membrane nephropathy

• Hereditary nephritis (Alport syndrome)

• Focal segmental glomerulosclerosis are

examples:

LABORATORY TESTING IN PATIENTS WITH SUSPECTED GLOMERULAR DISEASE

• serum creatinine• serum albumin• complete blood count• Estimation of protein excretion in patients

with proteinuria• serologic testing for disorders that cause

glomerular disease• measurement of serum complement levels

membranous nephropathy

• The value of hepatitis B virus

• Hepatitis C virus (HCV) infection

• Congenital and secondary syphilis

• HIV infection (FSGS)

• Chronic bacterial

– Endocarditis

– Shunt nephritis

– Abscesses

• Fungal

• Parasitic infections can cause

SUMMARY AND RECOMMENDATIONS

• There are many causes of glomerular disease,

• the characteristics of the urine sediment,

• The degree of proteinuria

• Patient’s age often

• Two different urinary patterns are seen:

– Nephrotic

– Nephritic.

• The nephrotic pattern

= proteinuria > 3.5 g/day

• Lipiduria

The nephritic

• Red cells

• White blood cells

• Red cell or mixed cellular casts

• Acanthocytes

• Some patients have the concurrent presence of two

glomerular diseases,

Approaching a patient

• Urinalysis

• Estimated glomerular filtration rate

• Patient age help to identify

• Race

• Family history

• Renal biopsy

Standard laboratory testing

• Serum creatinine

• Serum albumin

• Protein excretion in patients with proteinuria

• Serologic testing for disorders that cause

glomerular disease

• Serologic tests – Lupus– Amyloidosis– Hepatitis B (HBV) – Hepatitis C (HCV) – HIV infection– ANA– Anti-dsDNA– C3– C4

• Primary amyloidosis and light chain

deposition disease

– Serum and urine immunofixation

– Serum free light chain ratio analysis

Glomerulonephritis

Nephritic urineRBCs, RBC casts

Low – mod proteinuria

Nephrotic urineNo casts, few RBCsHeavy proteinuria

•Diabetes

•Amyloid

•Membranous Nephropathy

•FSGS

•Minimal Change Disease

•Sometimes MPGN

C3, C4

Low Normal

•Postinfectious

•Lupus nephritis

•MPGN (often Hep C)

progress fast progress slow

ANCA)+( ANCA)-(

•Vasculitis

•Wegener’s

•MPA

•Churg-Strauss

•IgA nepropathy

•Anti-GBM/Goodpasture’s