De novo membranous glomerulonephropathy in renal allografts: a report of ten cases and review of the literature.

De novo posttransplantation membranous glomerulonephropathy (MGN) is the most common form of de novo glomerulopathy in renal allografts. The clinical and pathological features of ten patients with de novo MGN were studied and the related literature was reviewed to assess the clinical features, morphologic characteristics, and natural course of this disease. De novo MGN may occur in both living related and cadaveric allografts at any time after transplantation. It presents clinically either as asymptomatic proteinuria or the nephrotic syndrome, a feature of poor prognostic implication. Morphologically, de novo MGN in most instances has distinct differences from idiopathic MGN in native kidneys and is accompanied by varying features of rejection. About 50% of grafts which develop de novo MGN eventually fail. This rather poor outcome may not represent the natural history of de novo MGN per se but rather the consequences of associated chronic rejection. Evidence is presented that many of the cases of so-called de novo MGN may be a complication of transplant glomerulopathy rather than being caused by mechanisms totally independent from rejection.

Interstitial nephritis related to nonsteroidal anti-inflammatory agents and beta-lactam antibiotics: a comparative study of the interstitial infiltrates using monoclonal antibodies.

Acute interstitial nephritis (AIN) is a common pattern of renal injury induced by therapeutic agents. In order to characterize the types of mononuclear leukocytes infiltrating the kidney in drug-induced interstitial nephritis, a panel of monoclonal antibodies (Leu1, Leu3a, OKT8, OKM1, Leu14, OKT17, IL-2) was applied to cryostat sections of 13 renal biopsies (five non-steroidal anti-inflammatory agents (NSAID) (Group I); five beta-lactam antibiotics (Group II), 3 miscellaneous (Group III]. The majority of infiltrating mononuclear leukocytes were Leu1-positive T cells (71.7 +/- 18.7%), followed by monocytes (15.2 +/- 7.7%) and B cells (7.4 +/- 9.1%). Leu3a/OKT8 ratio was 0.954 +/- 0.341. Rare cells reacted with antibody to the interleukin-2 receptor (1.4 +/- 1.2%). No statistically significant differences could be found in the percentages of T lymphocytes, B lymphocytes, monocytes, activated (IL-2+) T cells or Leu3a/OKT8 (helper/suppressor) ratios in the three groups. In Group II, the following pathologic correlations were seen: Leu3a/OKT8 versus interstitial inflammation (R = -0.848), percent Leu3a versus interstitial inflammation (R = -0.818), percent OKT17 versus tubulitis (R = 0.785), percent Leu14 versus tubular atrophy (R = -0.891), and interstitial edema (R = 0.965). Our findings support a role for cellular immune mechanisms in the pathogenesis of AIN related to both NSAIDs and beta-lactam antibiotics.

Myeloma cast nephropathy: immunohistochemical and lectin studies.

Renal disease is a common cause of morbidity and mortality in patients with plasma cell dyscrasia (PCD). We have conducted a systematic study of the formalin-fixed, paraffin-embedded renal tissues from 53 patients with plasma cell dyscrasia, 24 of whom had Bence Jones cast nephropathy (with large casts, often associated with giant cells and polymorphonuclear leukocytes). A battery of 5 immunocytochemical and lectin markers for various segments of the nephron was used [Tetragonolobus lotus, Arachis hypogaea (AH), Tamm-Horsfall protein (THP), epithelial membrane antigen (EMA), and cytokeratin (AE1/AE3)]. In particular, we sought to determine the nature of the intratubular multinucleated giant cells in Bence Jones myeloma cast nephropathy with a variety of epithelial and hematopoietic cell markers. Although tubular epithelial cells stain with their respective markers (whether inflamed, thinned, detached, or adjacent to and lining casts), true intratubular giant cells in PCD were never positive for these tubular markers. In approximately one-third of the cases studied, intratubular and extratubular giant cells stained for several of the seven hematopoietic cell markers employed [i.e., alpha 1-antitrypsin (A1AT), alpha 1-antichymotrypsin (A1ACT), vimentin, and lysozyme], suggesting that giant cells are of hematopoietic origin. The majority of the casts are present in the distal nephron, although some casts were noted in more proximal sites of the nephron. Some larger casts did not stain for THP; smaller casts often showed lamination or stratification of THP staining. Finally, in one-half of the cases, Tamm Horsfall protein (THP) and other distal tubular markers (AH, EMA, AE1/AE3) were found in Bowman's space, almost always in association with interstitial deposits of THP; these markers were virtually never noted in Bowman's spaces of PCD patients without numerous large casts. This suggests that there are communications between distal and proximal nephron, most likely by intraluminal reflux but possibly also through breaks in the tubules and via the interstitium.

Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization.

The long-term course of 56 patients with systemic lupus erythematosus who had precisely defined renal histology and carefully assessed clinical status at the time of their initial renal biopsy prior to 1976 was evaluated and analyzed by life-table analysis. The average length of follow-up has now been greater than 10 years since initial biopsy. Patients with mesangial lesions (World Health Organization [WHO] classes IIA and IIB) had a more favorable renal and patient survival at five and 10 years than did patients in the other WHO classes (III, IV, and V). Individual renal histologic features of activity and chronicity when combined into an activity index and a chronicity index did not significantly predict renal survival in this population, nor did the presence of hypertension or renal dysfunction at the time of the initial renal biopsy significantly influence renal or patient survival. Patients with the nephrotic syndrome at initial biopsy had a poorer renal survival than did patients without the nephrotic syndrome. However, patients who experienced a remission of the nephrotic syndrome fared better in terms of both renal and patient survival than did those patients without a remission. By life-table analysis, patient survival was significantly better for patients in whom biopsy was performed after 1973 than for those in whom biopsy was performed prior to that time despite similar clinical features and WHO histology in each group interval. Our data suggest that improved survival for patients in recent studies may relate to better supportive care and more selective use of immunosuppressive therapy in patients with milder forms of lupus nephritis.

Renal lesions in plasma cell dyscrasias: ultrastructural observations.

The renal biopsies from 47 patients with plasma cell dyscrasias were studied by light and electronmicroscopy, and by immunohistochemical methods. This report is primarily concerned with the ultrastructural features of 24 cases of Bence Jones cast nephropathy and of ten cases of light chain deposit disease. In Bence Jones cast nephropathy, crystals derived from light chain proteins were detected in the majority of cases within the casts or in tubular cells and appeared to be related to the "hard" and "fractured" appearance of the casts as well as to the presence of foreign body type giant cells, the latter probably being of monocyte-macrophage origin. In light chain deposit disease, linear deposits of light chain proteins (eight kappa and two lambda) were present in a subendothelial position along the glomerular basement membrane and along the outer aspect of the tubular basement membranes in all cases, quite often in the mesangial matrix, but much less commonly in the interstitium and in the wall of small arteries. The light and electronmicroscopic features of both Bence Jones cast nephropathy and light chain deposit disease can be considered diagnostic for plasma cell dyscrasia. The possible pathogenetic mechanisms of these two different forms of renal involvement are discussed briefly.

Monoclonal antibody identification of infiltrating mononuclear leukocytes in lupus nephritis.

Populations of mononuclear inflammatory cells infiltrating the renal interstitium in LN were studied by means of an avidin-biotin immunoperoxidase technique applied to cryostat sections of 26 renal biopsies (3 WHO class IIb; 4 class III; 8 class IV; 4 class V; 4 class III and V; and 3 class IV and V). The majority of interstitial leukocytes were T cells (mean 65.7 +/- 14.1). The number of cells reactive with OKT8 (47.3 +/- 11.0) exceeded the number of OKT4 positive cells (32.5 +/- 11.3) in 22 of 26 biopsies. Cells reactive with antimonocyte antibodies OKM1 and OKM5 (6.7 +/- 5.9 and 7.9 +/- 5.9, respectively) and B lymphocytes (OKB2 3.9 +/- 3.5) were a minor component of the interstitial infiltrates. Monocytes were the predominant cell type among stained cells in glomerular tufts and crescents. Tissue T4/T8 ratios varied widely (range 0.31 to 1.81), and were less than 1 in 22 of 26 patients. There was no correlation between tissue T4/T8 ratios and simultaneous peripheral blood T4/T8 ratios. Using stepwise multivariate linear regression, tissue T4/T8 ratio was found to correlate highly with renal histologic activity (P less than 0.001) but was not independently predictive of any other histopathologic or clinical variable studied. Mean tissue T4/T8 ratio in LN was significantly lower than that of other glomerular and interstitial diseases studied (P less than 0.001), a finding which may reflect differences in the pathogenesis of renal injury. These findings suggest that local cellular immune mechanisms may be important in the modulation of disease activity in LN.

Tubulointerstitial disease in lupus nephritis: relationship to immune deposits, interstitial inflammation, glomerular changes, renal function, and prognosis.

The interrelationships between tubulointerstitial immune deposits (TID), interstitial inflammation, glomerular changes, renal function, and prognosis were assessed in the renal biopsies from 93 patients with lupus nephritis. The prevalence of TID was 33% by immunofluorescence and 23% by electron microscopy. Although predominantly detected along and within tubular basement membranes, extraglomerular immune deposits were also present in the wall of renal interstitial capillaries and small arteries as well as in Bowman's capsule. The prevalence of TID correlated with the activity of glomerular lesions and, to a lesser extent, with the severity of proliferative lupus nephritis (WHO classes II-IV). TID were much less common in the membranous form (WHO class V). The severity of interstitial inflammation correlated with the degree of renal insufficiency and was an accurate prognostic indicator of progressive deterioration of renal function. However, there was no correlation between prevalence of TID and prevalence and severity of interstitial inflammation, suggesting that the latter is not necessarily secondary to the presence of immune complexes and that other pathogenetic mechanisms may be involved.

Acute tubulo-interstitial nephritis from candida albicans with oliguric renal failure.

A patient developed candidemia after receiving steroids and antibiotics. Subsequently, acute oliguric renal failure occurred. Renal biopsy showed multiple cortical microabscesses. These contained encapsulated ovoid Candida, budding organisms, short hyphae, and polymorphs. Adjacent tubules showed disruption of the basement membrane, infiltration by polymorphs and necrosis. There was no evidence of pelvic-calyceal obstruction by bezoar. The acute renal failure was attributed to acute candidal tubulo-interstitial nephritis, and was successfully reversed with Amphotericin.

Thrombotic thrombocytopenic purpura syndrome in systemic lupus erythematosus: treatment with plasma infusion.

Two patients with well documented systemic lupus erythematosus developed a syndrome resembling thrombotic thrombocytopenic purpura. Both had severe thrombocytopenia, microangiopathic hemolytic anemia, seizures, and renal dysfunction. Prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen levels were normal; fibrin degradation products were minimally elevated. Histologic evaluation of renal biopsies in both patients confirmed the impression of intravascular thrombosis. Therapy with corticosteroids, other immunosuppressive drugs and splenectomy (in one case) proved unsuccessful. The infusion of fresh frozen plasma, with or without plasmapheresis, reversed the syndrome. This report indicates that patients with systemic lupus may develop a thrombotic thrombocytopenic purpura like syndrome which responds to fresh plasma infusion.

Temporal arteritis and renal disease. Case report and review of the literature.

Renal abnormalities have been described in a small percentage of patients with temporal arteritis. Transient microscopic hematuria is the most common finding. In rare instances, widespread vasculitis involving renal arteries or microscopic polyarteritis nodosa can be seen. This case report describes the association of temporal arteritis with membranous glomerulonephropathy and the nephrotic syndrome in an elderly patient, an occurrence not previously reported. Whether this association is coincidental or pathogenetically linked remains to be determined.

Tubular microfibrils in the glomeruli of membranous nephropathy.

The presence of tubular microfibrils in the mesangium and capillary walls of the renal glomeruli is a rare occurrence that has been reported by others in different glomerular disease processes. The two cases presented in this report demonstrated such microfibrils in membranous glomerulonephropathy, an association previously described in only one other case. These microfibrils differed in size and structural characteristics from collagen fibers, amyloid fibrils, and cryoglobulin microtubules.

Sequential studies of glomerular crescent formation in rats with antiglomerular basement membrane-induced glomerulonephritis and the role of coagulation factors.

Injection of presensitized rats with goat antiserum to rat glomerular basement membrane (GBM) results in a crescentic glomerulonephritis with typical linear deposition of goat IgG and host IgG and C3 along the GBM. Sequential renal biopsies from rats with this model of anti-GBM nephritis were studied by light, electron, and immunofluorescence microscopy to investigate the mechanisms of crescent formation. The localization of fibrin-related antigens (FRA) and factor VIII-related antigens (VIIIAGN) at different stages of disease was specifically studied since earlier studies of human glomerulonephritis had shown deposits of FRA without VIIIAGN in crescents and suggested that either a thrombin-independent mechanism might cause fibrin deposition or, alternatively, that glomerular fibrinolysis was relatively deficient within Bowman's space. Separation of the endothelium from the GBM or glomerular endothelial loss was the first change noted, a lesion that promotes intracapillary FRA deposition. Subsequently, intracapillary hypercellularity and GBM damage became progressively more severe. During the second and third weeks, coincident with early crescent formation, increasing amounts of FRA were noted within Bowman's space; FRA in crescents persisted throughout the study, whereas FRA within the glomerular tuft decreased over time. In early lesions, granular deposits of IgM and factor VIIIAGN were found diffusely within crescents. However, at later times, extracapillary deposits of these proteins and IgG were limited to the periphery of crescents within the markedly thickened and altered Bowman's capsule. Persistence of IgM and factor VIIIAGN at the periphery of older crescents appears to result from entrapment in areas less subject to cellular degradation and transport. Preferential clearance of FRA from the glomerular tuft suggests that fibrinolysis is less effective in Bowman's space than clearance mechanisms within glomerular capillaries.

Nephrotic syndrome associated with use of the nonsteroidal anti-inflammatory drugs. Case report and review of the literature.

Although acute interstitial nephritis associated with the use of nonsteroidal anti-inflammatory drugs has long been recognized, only recently has its association with 'minimal change' nephrotic syndrome been reported. We report here a case of this pattern of nephrotic syndrome without concurrent interstitial nephritis associated with the use of tolmetin. The clinical picture, laboratory data, course, and relevant histopathologic findings of previous cases in the literature of nephrotic syndrome related to the use of the nonsteroidal anti-inflammatory drugs are reviewed and discussed.