Wednesday, October 19, 2011

Nephrotic syndrome

Nephrotic syndrome is a podocyte disorder and is discussed in this review.

Points of interest---

The podocyte provides structural support for the glomerular capillary tuft and is important in the secretion of the collagen network of the GBM:

Failure to secrete this network results in a range of hereditary nephropathies, the type IV collagenopathies.
Type IV collagenopathies include Alport syndrome, nail patella syndrome, and thin basement membrane disease; all can be considered podocyte disorders.

The pathophysiology of podocyte injury explains why patients do not generally have active urinary sediment, in contrast to the glomerulonephritides:

Subepithelial immune complexes (as in MN) or podocyte injury usually do not lead to leukocyte recruitment and inflammation, but rather disrupt the GFB.
Typically, urine sediment is devoid of leukocytes and erythrocytes.
Disruption of GFB leads to proteinuria.
In contrast, injury to mesangial or endothelial cells, which are in direct contact with blood (containing leukocytes, complement, and inflammatory proteins), typically leads to inflammatory kidney disease (nephritis) with active urine sediment.

All patients with nephrotic syndrome are at risk for renal vein thrombosis, but especially those with membranous nephropathy. RVT may be asymptomatic, present with pain, or as a sudden decline in renal function.

Minimal change disease (MCD)

Inflammatory mediators---> podocyte injury---> foot process effacement.

10%-15% of nephrotic syndrome (NS) in adults, 90% in kids.

Secondary causes of MCD: drugs, neoplasia, others.

Focal segmental glomerulosclerosis (FSGS)

Pathogenesis complex and varied, but involves podocyte injury and podocytopenia.

Most common cause of NS in adults overall.

Can progress to ESRD.

Can be idiopathic but many secondary causes.

Collapsing glomerulopathy

Controversial whether a type of FSGS or a distinct entity.

Disease association: HIV.

Membranous nephropathy (MN)

Subepithelial immune complex deposition.

Primary or secondary. Many secondary causes.

Primary: antibodies enter subepithelial space and bind to podocyte antigen.

Secondary: a) circulating immune complex dissociates then reforms in subepithelial space or b) antigen lodged in subepithelial space and subsequent immune response. Specific antigen (tumor antigen, infectious particle, etc.) depends on underlying disease.

Long list of secondary causes (drugs, infections, neoplasia, rheumatic diseases).

Most common cause of NS in elderly, caucasians.

Urine: no “active sediment” but microhematuria common.

Miscellaneous disorders

Collagenopathies, etc., see above.

Via Nephron Power.

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