Nephrotic Syndromes

Goodpasture’s Syndrome

Goodpasture’s syndrome is a renal-pulmonary syndrome.

·        It is a combination of acute glomerulonephritis with pulmonary pneumonitis (necrotizing lung disease).

·        It is an anti-GBM (Glomerular Basement Membrane) disease and an anti-pulmonary BM (Basement Membrane) disease.

·        It is an immune complex-mediated disease. Circulating auto-antibodies target collagen (-3 chain) within the basement membrane of kidney glomeruli and lung alveoli due to a cross-reaction between the basement membranes of the two organs. The antigen-antibody complexes can also deposit in the pulmonary intra-alveolar capillaries, causing inflammation and destruction of the lungs. 

Clinical Presentation

·        Acute glomerulonephritis with hemoptysis  ***super-important!!!***

·        Vasculitis

o        Microscopic polyarteritis (small vein vasculitis) is an example.

o        It may result in hemorrhages within alveolar spaces, resulting in hemoptysis. 

Laboratory Findings

·        Immune complexes can be found in intra-alveolar spaces.

·        CXR shows focal pulmonary consolidations, which resemble bacterial pneumonia infections (It’s misdiagnosed many times!). 

Sidenote…he showed pictures of blood and hyaline casts. These casts, as well as other cast types are excreted in the urine. They are used as a diagnostic measure to determine if the patient is suffering from renal disease (acute vs. chronic glomerulonephritis).

Focal Segmental Glomerulosclerosis 

This is the most common cause of nephrotic syndromes.

(It ousted membranous glomerulonephritis for the top spot.)
 

In children, the 3 main causes of Focal Segmental Glomerulosclerosis are:

1.       Minimal Lesion Disease

a.       Progression of lipoid nephrosis in patients resistant to corticosteroids

2.       Mesangial Hyperplasia

3.       Focal Sclerosis 

The pediatric causes of Focal Segmental Glomerulosclerosis were placed in a Venn diagram fashion, signifying that there is an overlapping clinical spectrum of diseases for Focal Segmental Glomerulosclerosis.

The two most important causes of Focal Segmental Glomerulosclerosis are:

1.       Minimal Lesion Disease (in children)

2.       IV drug (heroin) abuse (in adults) 

Focal Segmental Glomerulosclerosis is not an immunological disease, but is most likely toxic/injury-related.

Laboratory Findings

·        Contracted, granular kidneys

o        Mesangial proliferation

o        Segmental sclerosis

§         Basement membranes collapse in glomeruli, and there is an increase in matrix due to reactions of mesangial cells.

§         The entire segment is replaced by a basement membrane-like substance, resulting in a solid mass (fibrosis). The kidney is not filterable.

§         Segmental sclerosis eventually progresses to global sclerosis and tubulointerstitial fibrosis.

·        IgM/C3 entrapment

o        IgM and C3 circulate in the blood and seep into the necrotic segmental area.

·        Tubulo-reticular endothelial inclusion bodies (Myxovirus-like)

o        These are visible only in AIDS-associated Focal Segmental Glomerulosclerosis.

o        The inclusion bodies are also present in monocytes, macrophages, and other circulating cells.

o        Inclusion bodies are also present in cryoglobulinemia and SLE!!

Membranous Nephropathy 

Membranous nephropathy is a slow, progressive disease due to the regeneration of new basement membranes in between the antigen-antibody deposits. There is no cellular response in the kidney. It only affects the membrane. 

70% is due to primary, idiopathic, causes. 

30% is due to secondary causes. The list of causes are below.

·        SLE

·        Rheumatoid arthritis (Gold, Penicillamine, Mercury)

·        Chronic Hepatitis B/C infection

·        Schistosomiasis, Malaria, Syphilis

·        Neoplasia: Lymphoma, Colon Carcinoma

·        Renal Allograft
 

Laboratory Findings

·        Predominant change in basement membrane

o        It looks chewed up, irregular, and not smooth.

o        There is a diffuse basement membrane thickening, with a characteristic “spike and dome” dark stain (Trichrome silver).

§         These spikes and domes are due to antigen-antibody complexes outside the basement membrane, on the side of the urinary space.

§         ***super-important*** to remember!!!

·        Immunofluorescence

o        IgG (most common)/IgA/IgM and C3 visible in isolated

but concentrated amounts, deposited

exclusively outside the basement membrane

§         Alternative complement pathway

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