Mesangiolysis: an update.

Mesangiolysis occurs in many renal diseases, both human and experimental. At least three types of mesangiolysis may be recognized, which differ in their mode of origin and in morphologic features. The first type is severe mesangiolysis with formation of glomerular cysts and subsequent cellular proliferation resembling glomerulonephritis. In the second type, mesangiolysis is associated with extensive widening of the subendothelial space and is thought to follow endothelial injury. The third type is mesangiolysis with lamellated mesangial nodules which is believed to result from relatively mild but persistent or recurrent localized mesangial, and perhaps also endothelial damage, with lysis of mesangial anchor points.

Renal biopsy: why and when.

The purpose of this paper is to emphasize the importance of information obtained by renal biopsy in the diagnosis, prognosis, and therapy of patients with renal disease. Because controversy persists regarding the value of renal biopsy as an aid in determining prognosis and in choosing appropriate therapy, there has been some reluctance to use it early after the onset of obvious signs, symptoms, and laboratory findings indicative of renal disease with or without involvement of other organs. Although all such patients may not benefit from the information provided by a proper biopsy, we will illustrate some of the characteristic histologic details found in specific circumstances in our experience where the biopsy has been particularly helpful in reaching a diagnosis, in assessing prognosis, and in choosing therapy.

Renal disease in Marfan syndrome.

We encountered 4 individuals with Marfan syndrome who presented with microhematuria and proteinuria. In 2 of them, a renal biopsy was performed. The predominant glomerular change by light microscopy was a focal segmental increase in mesangial matrix with early sclerotic lesions. Ultrastructurally, there was variable subendothelial widening containing haphazardly arranged microfibrils, 10-13 nm in diameter. Changes in small arteries present in the biopsies were mild in case 1 and more striking in case 2 which consisted of elastolysis and fragmentation and focal disruption of internal elastic lamina, and focal degenerative changes in the media. In light of observations on the abnormalities of microfibrillar protein (fibrillin) in the microfibrillar-fiber system and the presence of abnormal type IV collagen in the connective tissues in Marfan syndrome, the glomerular basement membrane alterations may be related to these defects and lead to microhematuria and proteinuria.

Formes frustes of Churg-Strauss syndrome.

We report 4 cases of Churg-Strauss syndrome (CSS) that occurred in patients being treated with corticosteroids for a diagnosis of asthma. One patient had asthma, eosinophilia, and eosinophilic lymphadenopathy that regressed with higher doses of corticosteroids. The second patient had both eosinophilic tissue infiltration and symptoms suggestive of vasculitis, while the remaining two patients had overt vasculitis; in all three, vasculitis developed after tapering or discontinuation of corticosteroid therapy. Two patients died of their disease. We have labelled these cases as formes frustes CSS. Our observations suggest that some cases of CSS may be partially or totally suppressed by corticosteroid therapy for asthma for very long periods and that asthmatic subjects maintained on low-dose corticosteroid therapy or asthmatic subjects whose corticosteroid doses are being tapered should be carefully monitored for the development of CSS signs and symptoms.

Protracted superficial Wegener's granulomatosis.

We describe a patient with protracted superficial Wegener's granulomatosis. On the basis of nasal mucosa and conjunctival biopsy specimens, a diagnosis of sarcoidosis was originally made. However, later biopsy specimens and the clinical condition indicated a rare variant of Wegener's granulomatosis, one with a protracted course of granulomatous ulcers localized to the skin and mucosa.

Nomenclature of systemic vasculitides. Proposal of an international consensus conference.

The following are some of the conclusions and proposals made at the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis. 1. Although not a prerequisite component of the definitions, patient age is recognized as a useful discriminator between Takayasu arteritis and giant cell (temporal) arteritis. 2. The name "polyarteritis nodosa," or alternatively, the name "classic polyarteritis nodosa," is restricted to disease in which there is arteritis in medium-sized and small arteries without involvement of smaller vessels. Therefore, patients with vasculitis affecting arterioles, venules, or capillaries, including glomerular capillaries (i.e., with glomerulonephritis), are excluded from this diagnostic category. 3. The name "Wegener's granulomatosis" is restricted to patients with granulomatous inflammation. Patients with exclusively nongranulomatous small vessel vasculitis involving the upper or lower respiratory tract (e.g., alveolar capillaritis) fall into the category of microscopic polyangiitis (microscopic polyarteritis). 4. The term "hypersensitivity vasculitis" is not used. Most patients who would have been given this diagnosis fall into the category of microscopic polyangiitis (microscopic polyarteritis) or cutaneous leukocytoclastic angiitis. 5. The name "microscopic polyangiitis," or alternatively, "microscopic polyarteritis," connotes pauci-immune (i.e., few or no immune deposits) necrotizing vasculitis affecting small vessels, with or without involvement of medium-sized arteries. Cryoglobulinemic vasculitis, Henoch-Schönlein purpura, and other forms of immune complex-mediated small vessel vasculitis must be ruled out to make this diagnosis. 6. The name "cutaneous leukocytoclastic angiitis" is restricted to vasculitis in the skin without involvement of vessels in any other organ. 7. Mucocutaneous lymph node syndrome must be present to make a diagnosis of Kawasaki disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic necrotizing vasculitis.

Systemic necrotizing vasculitis may be idiopathic or associated with a variety of diseases of known etiology. A typical example is polyarteritis nodosa, which is characterized by fibrinoid necrosis and severe inflammation leading to destruction of the wall, narrowing of the lumen, and interference with blood circulation. In addition to the idiopathic form, histologically similar lesions are seen in hepatitis B, rheumatoid arthritis, Kawasaki mucocutaneous lymph node syndrome, and other diseases. Microscopic polyangitis involves mainly small vessels-venules more often than arterioles-but occasionally also small arteries. Its characteristic feature is leukocytoclasia of neutrophilic leukocytes, but fibrinoid necrosis also occurs. Churg-Strauss syndrome consists of granulomas in patients with a background of severe allergy, such as asthma, allergic rhinitis, or occasionally drug sensitization.

Fibrillary glomerulonephritis without immunoglobulin deposits in the kidney.

Three patients are presented, who by electron microscopy, showed prominent fibrillary deposits in the glomeruli, and in two, also around the tubules. By immunohistology these two cases had no immunoglobulins in either glomeruli or around the tubules. In the third case, which probably represents a slightly different form of the disease, minor deposits of IgM were found in the glomeruli, while fibrillary deposits were extensive and widespread. It is suggested that precursors of fibrillary deposits may not be the same in all cases.

Vasculitis in childhood.

Systemic vasculitic syndromes are rare in childhood. Vasculitis is the predominant feature of a large number of different clinical entities that are linked by the presence of inflammatory changes in the blood vessels. The nature of these diseases and their relationship to each other remain unclear. The clinical presentation associated with the size of the affected vessels and epidemiological data are very helpful for the diagnosis of those diseases. Recent advances are beginning to shed some light on the etiology and pathogenetic mechanisms involved in the various vasculitides. There is good evidence to support roles for circulating immune complexes, cell-mediated immunity, anti-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies in the pathogenesis. Renal involvement in vasculitis in children is commonly seen in Henoch-Schönlein purpura, microscopic polyarteritis, Wegener's granulomatosis, Churg-Strauss syndrome and polyarteritis nodosa. However, kidney disease can also be part of the clinical picture of Kawasaki disease and Takayasu arteritis. Recently, with the institution of early and aggressive immunosuppressive treatment of severe cases, significant improvement in the long-term survival of patients has been achieved. This review article addresses the pathological and clinical features (particularly renal involvement), therapeutic intervention and prognosis of the above-mentioned diseases.

Renal failure due to tubular obstruction by large protein casts in patients with massive proteinuria.

We describe two patients with nephrotic syndrome whose histologic findings on renal biopsy and at autopsy are characterized by numerous large protein casts in dilated cortical tubules, as well as podocyte swelling with effacement of foot processes in the glomeruli. Both patients progressed rapidly to renal failure. The casts and the protein precipitate in the Bowman's capsule were found to be composed of varying proportions of albumin and globulin but contained no Tamm-Horsfall protein. This suggests a glomerular rather than tubular origin of proteins. Light and electron microscopic examination of tubules revealed changes mainly due to compression by the casts. We propose that tubular obstruction due to the large casts was the main cause of renal failure.

Nomenclature of vasculitic syndromes: a historical perspective.

Since the original description of periarteritis nodosa (PAN) in 1866, the number of recognized forms of so-called idiopathic vasculitis has risen to about a dozen. Their relation to each other and their nature remain unclear, although the recent discovery of antineutrophil cytoplasmic autoantibodies (ANCA) promises a clue to the origin of at least some of them, particularly Wegener's granulomatosis (WG) and perhaps also Churg-Strauss syndrome (CSS). On the other hand, PAN appears to be a nonspecific syndrome of various etiologies.

Mesangiocapillary glomerulonephritis in Down's syndrome.

The clinical and pathologic features of progressive renal disease in 4 patients with Down's syndrome are described. All patients were male, between 20 and 30 years of age at the time of clinical presentation. Three out of 4 had proteinuria, and 2 had hematuria. Serologic tests for hepatitis B virus infection and antinuclear antibodies performed in 2 patients were negative. Examination of renal tissue from biopsy and/or from autopsy revealed mesangiocapillary glomerulonephritis (MCGN), type 1. While an increased incidence of congenital heart disease and acute leukemias has been documented in Down's syndrome, an association with MCGN has not been reported previously to our knowledge. This probably represents a form of idiopathic MCGN and may be related to the long survival of these individuals.

Correlation of glomerular basement membrane alterations with clinical data in progressive hereditary nephritis (Alport's syndrome).

Electron microscopic examination of glomerular basement membrane (GBM) was performed in 19 patients whose morphological changes as well as clinical features indicated the diagnosis of progressive hereditary nephritis (Alport's syndrome). The percentage of characteristically thickened and split and of thin GBM portions was determined in all the cases. The clinical course was more severe in males, which corresponded to higher rate of GBM alterations. In males, 58% of GBM was thickened and split and 24% was thin, while in females, the reverse was true, 28% was split and 48% of GBM was thin. There was a positive correlation of the split lesions and age in males, but not in females. The degree of splitting was directly proportional to the grade of proteinuria, while GBM thinning did not significantly correlate with proteinuria.

Morphometric analysis of glomerular basement membranes (GBM) in thin basement membrane disease (TBMD).

We measured the thickness of glomerular basement membrane in 46 patients with thin basement membrane disease (TBMD), (age range 15-50 years, almost equal M:F ratio), and compared with that in a control group of 5 patients (age range 5-38 years) with normal glomerular morphology. The measurements of glomerular basement membrane taken from electron micrographs (magnification x 12,500) were analyzed using an interactive image analysis system assembled around an INTEL 10 microcomputer, with a high resolution touch sensitive screen as the interactive peripheral. Calculation was done by printing on an electron micrograph a grating replica (21,600 lines/cm), with the same magnification as the electron micrographs of the glomeruli and calibrating the arithmetic (AM) and harmonic (HM) mean for each case. Comparing the results of TBMD cases (AM 129-202 nm; HM 128-213 nm) with those of the control group consisting of 5 cases of "minimal change nephrotic syndrome" (AM 287-317 nm; HM 300-333 nm) it was found that GBM in TBMD is remarkably thin. The thinning was caused mainly by the decreased width of the lamina densa (TBMD group: 71.4-147.0 nm; HM 72.4-154.4 nm in comparison with the control group: AM 174.4-235.5 nm; HM 184.2-249.6 nm). This finding allows us to differentiate thin basement membrane disease from other glomerulopathies presenting primarily with isolated or recurrent hematuria.