Saturday, November 10, 2012

Glomerular proteinuria – Nephrotic syndrome:

Glomerular proteinuria – Nephrotic syndrome:

Albuminuria occurs if albumin excretion is >3.0g/day and losses above this are usually due to increased glomerular permeability associated with glomerular damage. Glomerulonephritis is immunologically mediated diseases and excludes other conditions associated with glomerular damage as in diabetes mellitus or amyloidosis.

Minimal change glomerulonephritis:

This is also a type of nephrotic syndrome. During this condition there is little or no abnormality and no immunoglobulin or complement components. Proteinuria involves loss of fixed negative charge on glomerular basement membrane due to fusion of epithelial cell foot processes. This leads to selective proteinuria (mainly albumin). Here T-cell dysfunction may play a role. In this condition there is good long-term prognosis with preserved renal function as all cases respond to treatment (steroid-responsive nephrotic syndrome). It is common in children.

Membranous glomerulonephritis: 

It is the commonest cause of nephrotic syndrome in adults. The cause may be idiopathic or associated with inflammatory or neoplastic disease. There is thickening of glomerular basement membrane. There is IgG deposits seen most commonly. It may also be associated with SLE where immune complexes formed in circulation deposits in GBM. There is massive proteinuria and poorly selective and some have asymptomatic proteinuria or microscopic hematuria. Proposed hypothesis is the role of extrinsic antigen deposition in the glomerulus with subsequent IC formation, glomerular trapping of circulating IC or antibodies binding to intrinsic glomerular antigens. Currently treatment is aimed at lowering blood pressure with ACE inhibitors or angiotensin II receptor antagonists which reduces proteinuria over six months. If proteinuria persists immunosuppressive treatment is generally started e.g. cyclosporine, cyclophosphamide, etc.

Proliferative glomerulonephritis: 

Here glomeruli appear hypercellular, due, for example, to invading macrophages or mesangial cells. Different disease can elicit immunologically mediated glomerular damage, including bacterial endocarditis, Group A streptococcal infection and SLE. There is frequent IgA, IgG and C3 deposits, and complement activation. Patients have proteinuria and microscopic hematuria and the proteinuria is predominantly non selective. Anti-inflammatory therapy with cyclophosphamide is effective treatment.

Focal and segmental glomerulonephritis: 

Here hyaline material is deposited in the subendothelial spaces of affected capillary in certain area thus called focal and segmental. Patients present with mild proteinuria or recurrent hematuria. The etiology is not known but is immune mediated. Low dose corticosteroid with addition of cyclosporine is used for treatment.

Classification of glomerulonephritis according to proteinuria:

Selective proteinuria:

It is a proteinuria in which the principal protein is albumin with relative paucity of Large Molecular Weight proteins like IgG.

Non-selective proteinuria: 

It is a proteinuria in which albumin along with large molecular weight proteins are found in urine almost equally.

Under normal circumstances glomerular barrier had a sharp molecular size cut-off above which protein molecules were excluded, but in patients with glomerular disease there is an increasing tendency to allow HMW proteins to pass into the tubules. Protein selectivity is based on a comparison of the relative concentrations of proteins of differing molecular weight in plasma and urine. Two proteins used for selectivity studies are IgG (150 kDa) and transferrin (69 kDa). Their relative clearances can be calculated as:

Clearance of IgG/Clearance of transferrin = [IgG]u x [trans]p/[IgG]p x [trans]u

Where [IgG]u is urine IgG and [Trans]p is plasma transferrin concentration.

Where the selectivity index is >0.5, the proteinuria is said to be non-selective, 0.3-0.5 moderately selective and <0.2 highly selective.

Patients with minimal change nephritis has highly selective proteinuria, membraneous glomerulonephritiss and proliferative glomerulonephritis show decreased selectivity and increased of HMW proteins relative to albumin. Patients with highly selective proteinuria tend to respond well to steroid therapy in contrast to those with non-selective proteinuria. Recently, coexisting tubular damage has been identified and monitored by measuring low molecular weight proteins like α1-microglobulin or retinol binding protein (RBP) which are normally filtered by glomeruli and reabsorbed by renal tubules. Studies show progression to CRF is better predicted both by selectivity index or IgG excretion and tubular component of proteinuria (e.g. α1-microglobulin) than by total 24 h urine protein excretion.
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