الفهرس 
AIM of the WorkOnly 14 pages are availabe for public view
 |  | from | 202 |  |  |
| | | from | 202 | | |
Abstract
The kidneys are affected by many forms of systemic vasculitis, which cause a wide variety of sometimes confusing clinical manifestations (Jennette JC and Falk RJ 2005).
Classically, the vasculitic syndromes have been categorized by the predominant sizes of the blood vessels and types of vessels most commonly affected. The presence or absence of antineutrophil cytoplasmic antibodies (ANCA) is a more recent addition to proposed classification criteria (Liu et al., 2008).
The clinical features are extremely varied and dicated by the category of vasculitis, the type of vessel involved the organ system distribution of vascular injury, and the stage of disease. Irrespective of the type of vasculitis, most patients have accompanying constitutional features of inflammatory disease, such as fever, arthralgias, myalgias, and weight loss. These probably are caused by increased circulating levels of proinflammatory cytokines (Jennette and Falk, 1994).
The clinical manifestations commonly include renal insufficiency (that may be severe enough to initially require dialysis) and hypertension, which is primarily mediated by ischemia-induced activation of the renin-angiotensin system. Although an angiotensin converting enzyme inhibitor is likely to be an effective antihypertensive agent in this setting, there is a risk of worsening renal function due to removal of the angiotensin II effect on autoregulation and maintenance of the glomerular filtration rate (Stockigt et al., 1979).
The urinalysis typically reveals active urine sediment similar to that found in acute glomerulonephritis: red cells, red cell and other cellular and granular casts, and proteinuria (that is usually not in the nephrotic range) all may be seen. These findings are primarily due to glomerular inflammation and necrosis that may be induced either by direct immune-mediated injury of the glomerular capillaries or by ischemia resulting from narrowing of the lumen of affected arteries and arterioles. One exception may occur in patients with classic polyarteritis nodosa in which the muscular arteries are involved. If this process leads only to incomplete narrowing, then there may only be glomerular ischemia (not necrosis) and the urinalysis may be relatively normal (Balow, 1985).
Progressive elevation in the plasma creatinine concentration with bland urine sediment may also be seen after effective immunosuppressive therapy has been instituted. In this setting, healing of the vascular injury leads sequentially to scarring, further narrowing of the vascular lumens, decreased glomerular perfusion, and a decline in renal function. Similar ischemic changes may be seen in other affected organs (Hellmann, 2007).
This diagnostic confusion arose in part because the incidence of hematuria and hypertension, and the average serum creatinine concentration were somewhat similar among the three groups. One useful distinguishing clinical feature was the degree of proteinuria, with an average of 2.8 g/day for those with pauci-immune crescentic glomerulonephritis or acute interstitial nephritis versus 14 g/day for patients with acute renal failure and nephrotic syndrome (most of whom had ATN with minimal change disease). In addition, the discovery of a red cell cast on careful urinalysis, when found, is diagnostic of glomerulonephritis or vasculitis (Nachman et al, 2001).
Histologic examination from renal tissue may be clearly diagnostic if inflammation and necrosis is seen in affected arteries and arterioles, including the glomerular capillaries. Involvement of medium-sized arteries is characteristic of classic polyarteritis nodosa. In comparison, the smaller vessels (venules, capillaries, arterioles) are typically involved in microscopic polyarteritis nodosa and Wegener’s granulomatosis (Jennette and Falk, 1994).
However, only a small number of vessels are usually obtained by percutaneous biopsy and it is common to see no affected vessels on this limited specimen. In this setting, the major finding is a focal (involving some but not all glomeruli), necrotizing glomerulonephritis, often with prominent crescent formation. Although this finding on light microscopy may be seen in other disorders, these conditions are typically associated with characteristic immunofluorescence and electron microscopic findings, such as IgA deposition in IgA nephropathy or Henoch-Schönlein purpura (which, in the kidney is histologically identical to IgA nephropathy); linear deposition of IgG in anti-GBM antibody disease. In comparison, few or no immune deposits (pauci-immune glomerulonephritis) can be found in the glomeruli in the necrotizing glomerulonephritis associated with vasculitis (Black, 1987).
Fortunately, available treatments are helpful, particularly in the acute phase. However, during maintenance therapy with corticosteroids and immunosuppressive agents, the adverse effects of drugs and superimposed infections may assume increasing importance. Mortality data suggest that while early deaths in vasculitis are due to the active disease, late deaths may be due to the complications of therapy (Langford, 1997).
Patients with systemic vasculitic involvement usually require at least glucocorticoid therapy. As an example, glucocorticoid therapy usually leads to remission in giant cell arteritis. In most patients, the dose can be reduced and eventually discontinued, but some require chronic therapy with low dose prednisone (Booth et al., 2004).
By comparison, patients with rapidly progressive vasculitic diseases, such as Wegener granulomatosis or polyarteritis nodosa, are likely to require combination therapy consisting of a cytotoxic drug (usually cyclophosphamide) and steroids. Both oral or pulse cyclophosphamide have been utilized based upon physician experience and disease severity; after one or two months of combined therapy, the steroid dose may be reduced; therapy is usually continued for 6 to 12 months to diminish the risk of relapse. Azathioprine and Methotrexate have been used in less severe forms of vasculitis and as maintenance therapy after remission has been induced by cyclophosphamide (Langford et al., 1998).