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| Membranous glomerulonephritis |
Membranous glomerulonephritis is an antibody mediated disease in which the immune complexes localize to the subepithelial aspect of the capillary loop. That is, between the outer aspect of the basement membrane and the podocyte (epithelial cell)
The immune complexes develop in situ or, less likely, by the deposition of circulating immune complexes. The antibody may bind to an intrinsic glomerular antigen or to an exogenous antigen planted on the capillary wall.
Approximately 25 to 30% of cases are secondary. Common associations include:
1. Systemic lupus erythematosus and other connective tissue disorders
2. Drugs (gold, penicillamine, non-steroidal anti-inflammatory agents)
3. Hepatitis B, syphilis, quartan malaria, leprosy, schistosomiasis
4. Carcinoma, melanoma, leukemia, non-Hodgkin's lymphomas.
Membranous glomerulonephritis is more common in adults and most patients are older than 30 years at diagnosis. Membranous glomerulonephritis accounts for 35-50% of cases of adult nephrotic syndrome. Most patients present with heavy proteinuria, most commonly in the nephrotic range, that is insidious in onset. A few patients have accompanying microscopic hematuria.
Clinical Course
The course of untreated idiopathic membranous glomerulonephritis is variable. Of patients presenting with the nephrotic syndrome and a normal serum creatinine:
· 30% will have a spontaneous complete remission and a stable GFR for up to 20 years.
· 25% will have a spontaneous partial remission with a stable GFR (Glomerular Filteration Rate)
· 20-25% experience persistent nephtrotic syndrome with stable or very slowly progressive loss of GFR.
Twenty to 25% of patients progress to end-stage renal failure over a 20 to 30 year follow-up. Patients in whom a causitive agent is identified, usually respond to treatment of the underlying disorder, or withdrawl of the offending agent.
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 IgA nephropathy |
IgA nephropathy, first descibed in 1968, is the most common form of primary glomerulonephritis in the world. It is an antibody-mediated glomerular disease in which the immune deposits localize to the mesangium. It is not certain whether the deposits form in situ or from circulating immune complexes.
Patients with IgA nephropathy usually present with one of three syndromes:
· Macroscopic hematuria concurrent with an upper respiratory infection; so-called synpharyngitic hematuria.
· Asymptomatic microscopic hematuria and variable proteinuria.
· Henoch-Schonlein purpura is the systemic form of the disease process causing IgA nephropathy, and occurs more frequently in children than adults. Patients with Henoch-Schonlein purpura manifest skin, joint and intestinal involvement.
A less common presentation is with the nephrotic syndrome. These patients may have advanced disease or normal renal function. In the latter case, the light microscopic features are of minimal change disease but with intense mesangial staining for IgA.
Clinical Course
Renal function progressively worsens in approximately 40% of patients, about half of whom reach end-stage renal failure after 20 years of clinically apparent disease. Nearly 30% of patients exhibit a benign course with chronic microscopic hematuria, a normal serum creatinine and proteinuria usually less than 1 gram/day. Hypertension is not uncommon and malignant hypertension develops in about 5% of patients.
Secondary deposits of IgA may occur in chronic liver disease, dermatitis herpetiformis, psoriasis, ankylosing spondylitis, celiac disease, inflammatory bowel disease, carcinoma, IgA monoclonal gammopathy, HIV infection and mycosis fungoides.
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| Membranoproliferative glomerulonephritis |
Membranoproliferative, or mesangiocapillary, glomerulonephritis (MPGN) is a chronic progressive
glomerulonephritis that occurs in older children and adults.
Circulating immune complexes have been identified in 50% of patients and activation of the complement system with hypocomplementemia, is a hallmark of MPGN.
Idiopathic MPGN has several distinct histopathologic and immunopathologic features and three variants have been described.
 Type I MPGN characterized by mesangial and subendothelial immune deposits.
Type II MPGN (dense deposit disease) characterized by interrupted linear deposits in the lamina densa of the basement membrane.
Type III MPGN, an uncommon variant, characterized by features of both type I MPGN and membranous GN, or by disurption of the glomerular basement membrane with accumulation of new basement membrane material arranged in layers.
Clinical Course
Patients with MPGN may present with the nephrotic syndrome, an abnormal urinary sediment with non-nephrotic proteinuria or with acute nephritis. The diagnosis is suspected when serum complement levels are depressed.
Type I MPGN :
is the most frequent primary MPGN
is also often associated with systemic disease, infection and neoplasms.
Membranoproliferative glomerulonephritis secondary to cyroglobulinemia is strongly associated with Hepatitis C virus infection.
The nephrotic syndrome is the most common presenting illness.
Type I MPGN is a slowly progressive disease; in 30-40% of patients the disease remains stable despite persistent nephrotic range proteinuria. Median survival, free of renal failure in both children and adults ranges from 9 to 12 years.
In type II MPGN :
Acute nephritis or recurrent macroscopic hematuria are the most common presentations.
Most patients with type II MPGN are younger than 20 years of age, have more persistent C3 depression and more commonly present with nephritis.
Approximately 20% of patients remain stable for many years and median survival, free of renal failure ranges from 5 to 10 years.
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| Post-infectious glomerulonephritis |
Infectious agents are the most common inciting antigens associated with immune complex mediated glomerulonephritis. Post-streptococcal glomerulonephritis is the most common form of glomerulonephritis in children and occurs following a skin or pharyngeal infection with Group A beta-hemolytic streptococci.
Post-infectious glomerulonephritis has also been associated with other bacterial, viral, parasitic, rickettsial and fungal infections.
The precise nature of the antigens involved in the formation of the nephritogenic immune complexes is unknown. Streptococcal antigenic substances have been inconsistently detected in glomeruli and circulating immune complexes have been detected in some patients. Since streptococcal antigens do not always cause disease, other mechanisms may be involved, including alterations in IgG or glomerular components making them immunogenic. Antigens derived from infectious agents may bind to glomerular structures and induce development of in situ immune complexes.
Clinical Course
Post-streptococcal glomerulonephritis is primarily a disease of children, 6 to 7 years of age. The onset is usually abrupt, with a latent period of 7 to 21 days beteen infection and the development of nephritis. During epidemics, the clinical attack rate is 10-12%, but subclinical disease occurs four times more frequently than overt idsease. Asymptomatic contacts may have hematuria.
Common initial clinical manifestations of post-streptococcal glomerulonephritis are:
· Hematuria (micro or macroscopic)
· Edema
· Hypertension
· Oliguria
The acute clinical episode of post-streptococcal glomerulonephritis is usually self-limited and complement levels return to normal within 6 weeks. In most patients hematuria disappears by 6 months but proteinuria may persist for two years in a third of patients.
Early antimicrobial therapy in affected individuals and family members may prevent the spread of streptococcal infections. Treatment of established infection does not prevent the development of post-streptococcal glomerulonephritis, but may lessen its severity.
The prognosis for complete recovery is excellent in children, even in patients with the nephrotic syndrome or crescentic disease at presentation.
The prognosis in adults is less favorable, especially when accompanied by initial severe impairment in renal function, persistent proteinuria and the nephrotic syndrome. The development of crescents is more common in adults.
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| Anti-glomerular basement membrane disease |
Goodpasture's syndrome is a clinical constellation of glomerulonephritis and pulmonary hemorrhage, mediated by an anti-glomerular basement membrane antibody which also reacts with the basement membrane of pulmonary capillaries. Up to one-third of patients with rapidly progressive glomerulonephritis and anti-GBM antibodies, do not have detectable evidence of pulmonary involvement (anti-glomerular basement membrane disease).
Since the antibody response is directed toward a normal antigen present in the GBM, Goodpasture's syndrome and anti-GBM disease are classic examples of autoimmune disorders.
Clinical Course
Goodpasture's syndrome may occur at any time, but peaks in the spring and summer months are common. It frequently begins with a flu-like illness with evidence of pulmonary compromise. Progressive dyspnea, hemoptysis and occasionally ventilatory failure occur. Urinalysis reveals hematuria with red blood cell casts and variable proteinuria.
Patients with Goodpasture's syndrome require immediate institution of plasma exchange and immunosuppressive therapy.
Prompt institution of therapy usually results in significant improvement in renal function. Patients with an initial serum creatinine less than 7 mg/dl and fewer than 50% crescents have a greater liklihood of responding favorably to therapy.
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| Minimal Change disease |
Minimal change disease is the most common cause of the nephrotic syndrome in childhood. In a prospective study of untreated children with the nephrotic syndrome, minimal change disease was found in 76.6%.
In contrast, minimal change disease accounts for only 10% to 30% of adult cases of nephrotic syndrome. In both children and adults these percentages vary in different parts of the world. The clinical onset of nephrotic syndrome may be associated with an upper respiratory infection or with routine prophylactic immunizations. Other genetic and environmental factors may also be important.
Clinical Course
Most patients with minimal change disease develop mild periorbital edema as the initial complaint.
The proteinuria in minimal change disease is said to be "selective", that is composed primarily of albumin. Microscopic hematuria is rare with reported frequencies of 13 to 36%, and hypertension is also unusual in minimal change disease.
Most patients (90%) respond to an 8 week course of steroids. Cytotoxic agents may be used in steroid resistant cases (~10%). Renal failure from minimal change disease is rare, but relapses are common.
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| Focal Segmental Glomerulosclerosis |
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