Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features.

BACKGROUND: Chronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed. Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons. RESULTS: Sixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades (p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4-94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5-18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7-1.0; p = 0.042) than cats with non-ICGN. CONCLUSIONS: MGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.

Vaccination of cattle with the N terminus of LppQ of Mycoplasma mycoides subsp. mycoides results in type III immune complex disease upon experimental infection.

Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N') of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N' formulated in Freund's adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N' in a future subunit vaccine for CBPP.

Therapeutic plasma exchange for the management of a type III hypersensitivity reaction and suspected immune-mediated vasculitis assumed to be caused by human albumin administration in a dog.

OBJECTIVE: To describe the successful treatment of a life-threatening type III hypersensitivity reaction suspected to have been related to human serum albumin (HSA) administration in a dog with therapeutic plasma exchange (TPE). CASE SUMMARY: A 3-year-old neutered male mixed breed dog was suspected to have developed immune-mediated vasculitis 2 weeks after the administration of HSA (740 mg/kg) for the management of hypoalbuminemia resulting from septic peritonitis. The dog was presented with fever, edema, hypoalbuminemia (26 g/L [2.6 g/dL]; reference interval, 30-44 g/L [3.0-4.4 g/dL]), and coagulopathy. The dog was treated with fresh frozen plasma (FFP) and glucocorticoids but remained hypoalbuminemic (18 g/L [1.8 g/dL]) and developed acute kidney injury (AKI). Over 4 days, 3 TPE treatments were performed, with a total of 2.7 plasma volumes exchanged. Replacement fluids consisted of a combination of FFP, hydroxyethyl starch 6%, and 0.9% saline solution. Following TPE treatments, serum albumin concentration increased (from 18 g/L [1.8 g/dL] to 25 g/L [2.5 g/dL]), serum creatinine concentration decreased (from 340 µmol/L [3.9 mg/dL] to 87 µmol/L [0.98 mg/dL]), and clotting times normalized (activated partial thromboplastin time decreased from 33 seconds to 14.5 seconds). There was a gradual but consistent clinical improvement of the edema and overall demeanor of the dog. No significant adverse effects were noted during the TPE treatments, and the dog was discharged after 8 days of hospitalization. Following discharge, the dog had complete clinical resolution of edema and AKI. NEW/UNIQUE INFORMATION: This is the first report describing successful use of TPE for the management of an immune-mediated reaction (type III hypersensitivity) following HSA administration.

Delayed type III hypersensitivity reaction with acute kidney injury in two dogs following administration of concentrated human albumin during treatment for hypoalbuminemia secondary to septic peritonitis.

OBJECTIVE: To describe 2 dogs with acute kidney injury secondary to type III hypersensitivity reaction to 25% human serum albumin (HSA). CASE SERIES SUMMARY: Two dogs were presented with evidence of septic peritonitis. The dogs were hospitalized following definitive surgical correction of a jejunal laceration following routine ovariohysterectomy, and removal of a jejunal foreign body. In the postoperative period, both dogs developed hypoalbuminemia and received 25% HSA. At the time of initial discharge, both dogs were doing well clinically and had normal renal parameters. Eleven and 18 days after HSA infusion, respectively, both dogs were re-presented with clinical signs of inappetence, vomiting, and lameness that progressed to urticaria, peripheral and angioedema, and petechiae, consistent with a delayed type III hypersensitivity reaction. Treatment for the type III hypersensitivity reaction to HSA included administration of diphenhydramine and glucocorticoids. Despite partial resolution of edema and joint swelling, both dogs developed progressive azotemia together with hypoalbuminemia and proteinuria. One dog developed an anuric acute kidney injury (AKI). Both dogs were humanely euthanized. Histopathology of the kidneys of both dogs was consistent with immune complex deposition and vasculitis. NEW OR UNIQUE INFORMATION: Severe type III hypersensitivity reactions have been documented in healthy dogs and clinical patients following the administration of HSA. This report describes the first documented delayed type III hypersensitivity reaction in 2 dogs with septic peritonitis that resulted in AKI, glomerulonephritis, and oligo- to anuria in clinical patients following administration of 25% HSA.

An immune-complex glomerulonephritis of Chinook salmon, Oncorhynchus tshawytscha (Walbaum).

Chinook salmon from New Zealand were shown to have a generalized membranous glomerulonephritis that was most severe in large fish. Marked thickening of the glomerular basement membrane was the most consistent lesion, with the presence of an electron-dense deposit beneath the capillary endothelium.Severely affected glomeruli also had expansion of the mesangium and loss of capillaries,synechiae of the visceral and parietal epithelium and mild fibrosis of Bowmans capsule. Chinook salmon from British Columbia, Canada with bacterial kidney disease caused by Renibacterium salmoninarum had similar histological lesions. They also had thickened glomerular basement membranes that were recognized by rabbit antiserum to rainbow trout immunoglobulin. This was true only when frozen sections of kidney were used and not formalin-fixed tissue. An attempt to experimentally produce a glomerulopathy in rainbow trout by repeated immunization with killed R. salmoninarum was not successful. Case records from the Fish Pathology Laboratory at the University of Guelph over a 10-year period revealed that a range of species were diagnosed with glomerulopathies similar to those seen in Chinook salmon. The majority of these cases were determined to have chronic inflammatory disease. This report has identified the presence of immunoglobulin within thickened basement membranes of Chinook salmon with glomerulonephritis and supports the existence of type III hypersensitivity in fish.

Adverse reactions suggestive of type III hypersensitivity in six healthy dogs given human albumin.

CASE DESCRIPTION: 6 healthy dogs given human albumin solution as part of a study were examined following development of an immediate hypersensitivity reaction (1 dog) and signs suggestive of a type III hypersensitivity reaction (all 6 dogs). CLINICAL FINDINGS: All 6 dogs were healthy prior to administration of human albumin solution. One dog developed signs of an immediate hypersensitivity reaction, characterized by vomiting and facial edema, during administration of human albumin solution. All 6 dogs developed signs of a delayed adverse reaction 5 to 13 days after administration of human albumin solution. Initial clinical signs included lethargy, lameness, edema, cutaneous lesions indicative of vasculitis, vomiting, and inappetance. TREATMENT AND OUTCOME: In the dog with signs of immediate hypersensitivity, signs resolved after administration of human albumin solution was discontinued and diphenhydramine was administered. Supportive treatment was provided after dogs developed signs of a delayed adverse reaction. Four dogs recovered, but 2 dogs died despite treatment. All 6 dogs were found to have antihuman albumin antibodies. There was no evidence of contamination of the human albumin solution. CLINICAL RELEVANCE: Findings suggest that administration of human albumin solution in healthy dogs with normal serum albumin concentrations may result in signs of a type III hypersensitivity reaction.

Idiopathic immune-mediated polysynovitis in three horses.

This paper describes the clinical, laboratory and histological findings in three horses with immune-mediated polysynovitis; they had lost weight, suffered intermittent fever, were lethargic and stiff, and had effusions in several joints. Laboratory abnormalities included anaemia, leucocytosis, hyperfibrinogenaemia and hyperglobulinaemia. The diagnosis was based on the presence of a suppurative, non-septic inflammation in at least two different joints in each of the horses and the presence of immunoglobulins in the synovial membrane of one of them. The horses were treated with a combination of dexamethasone and azathioprine, and responded well to the initial treatment. Twenty months after its last re-evaluation, the first horse was being maintained on azathioprine because similar clinical signs had recurred after the cytotoxic drug was discontinued; the second horse was finishing a tapering course of prednisolone 15 months after its first examination, and the third horse was euthanased five months after it was first examined as a result of an unrelated injury.

Change in intrarenal Ghrelin expression in immune complex-mediated glomerular disease in dogs.

Ghrelin is a peptide hormone that is mainly produced by the stomach. The kidney is a major source of local ghrelin, and maintaining body fluid balance is considered a critical role of renal ghrelin. However, there are no reports on renal ghrelin in small animal medicine. The present study investigated the intrarenal localization of and change in ghrelin expression in dogs with immune complex-mediated glomerulonephritis (ICGN). Ghrelin immunoreactivity (IR) was observed in the distal tubules of normal kidneys. Ghrelin IR was weak in ICGN kidneys, and the quantitative ghrelin IR score was significantly lower in ICGN kidneys than in normal kidneys. In cases of ICGN, plasma creatinine concentrations showed a positive correlation with the ghrelin IR score.

Characterization of age-associated kidney disease in Wistar rats.

Kidney disease was studied patho-histologically, electron microscopically and immunologically in Wistar rats ranging in age from 2 weeks to 24 months. Glomerular lesions characterized by adhesion of podocyte foot processes were first detected at 3 months of age. The kidney lesions became more pronounced with age, as manifested by an increase of mesangial matrix, basement membrane thickening, crescent formation and hyalinization of glomeruli, and tubular degeneration. Evidence for the deposition of immune complexes in the kidney was obtained by immunofluorescence and electron microscopy, as well as by immuno-electrophoretic analysis of kidney elutions. Tests with antiserum reagent against Moloney leukemia virus antigen revealed its presence in some but not all glomeruli. The presence of other viruses in Moloney leukemia virus negative glomeruli was not ruled out. Serum autoantibody against an array of rat tissues could not be detected. Therefore, it would appear that autoimmune mechanism may not be the primary underlying cause of pathogenesis of the disease. Accordingly, the disease could be referred to as chronic immune complex glomerulonephropathy with nephrotic syndrome, but sources of the antigens in the complex were mostly unknown, althougn virus could be one portion of them. The possibility that diet antigens may also be present in the complex seems unlikely because attempts to demonstrate serum antibodies against diet pellet in old rats were unsuccessful.

Immune complex-mediated glomerulopathy in Marek's disease.

Chickens infected with Marek's disease (MD) virus developed immune complex (IC)-mediated glomerulopathy. Fluorescent antibody staining technique using antichicken globulin and antichicken complement was used to demonstrate IC in the kidney glomeruli. During the initial stages of MDV infection, IC deposits were seen on the glomerular basement membrane, but subsequently the entire glomerulus was involved. Mesangial cells also had IC deposits. Chicken complement was demonstrated in the glomeruli which had IC deposits. The number of glomeruli with IC deposition was higher in tumor-bearing birds than in non-tumor-bearing birds. Histologically, kidney lesion were characterized by thickening of basement membrane and proliferation of mesangial cells. It is suggested that IC-mediated glomerulopathy might be one of the major causes of death in MD.

Some aspects of humoral and cellular immunity in naturally occuring feline infectious peritonitis.

Haematology, antibody titers and serum protein electrophoresis from 48 cats (34 effusive and 14 noneffusive forms) affected with feline infectious peritonitis (FIP) were studied and compared with those of 20 healthy cats. In the effusive form, antibody titers and protein electrophoresis in the effusions were analyzed. The distribution of the immune cells and of the virus in FIP lesions were also investigated immunohistochemically with the avidin-biotin complex (ABC) method, using antibodies against the FIP virus (FIPV), myelomonocytic (MAC387) and lymphoid (CD3, CD4 and CD8 for T-cells and IgM and IgG for B-cells) antigens. Seropositive animals (antibody titer>1:100) were present among both the FIP infected cats (73%) and the healthy cats (70%). Cats with effusive FIP had neutrophilic leukocytosis (P>0.05), lymphopenia (P<0.01) and eosinopenia (P<0.001). In both effusive and noneffusive forms decreased albumin/globulin ratio (P<0.001) with hypoalbuminemia (P<0.001), hyperglobulinemia (P<0.001) and increased alpha2- (P<0.05), beta- (P<0.05) and gamma-globulins (P<0.001) were found. Hypergammaglobulinemia was not related to the antibody titers, suggesting the presence of other proteins with gamma-motility (e.g. complement fractions). The electrophoretic pattern of the effusions was always similar to that of the corresponding serum. Antibody titers higher than those of the corresponding serum were often detected in the effusions. Immunohistochemical findings were not related to the antibody titers, but they were related to the histological aspect of the lesions. In cellular foci of FIP lesions many virus-infected macrophages and few lymphocytes, mainly CD4+, were found. Extracellular viral and myelomonocytic antigens were also detectable in the foci with intercellular necrosis. Only few FIPV-infected cells were present at the periphery of the larger necrotic foci: in these lesions MAC387+ cells were mainly neutrophils, with many MAC387 macrophages, probably due to their activated state; a small number of lymphocytes, with an increasing percentage of CD8+ cells was present. Lymphocytes were more abundant when cellular foci and FIP-infected macrophages were centered around neoformed vessels. IgM and IgG exposing B-cells were always few and scattered. In conclusion the simultaneous analysis of body fluids and of the cellular composition of the lesions showed a complex immune status, on which type III and type IV hypersensitivity could coexist.

Concurrent feline immune-complex nephritis. Tubular antigen-positive and renal amyloidosis.

We describe tubular antigen-positive immune-complex nephritis in a case of feline renal amyloidosis. Amyloid deposition was observed in mesangial area, and thickening of capillary walls was shown in the majority of the glomeruli. This case was also characterized with typical fluorescent granular depositions of cat IgG and C3 along the glomerular capillary walls as seen in human membranous glomerulonephritis. The fluorescent pattern of tubular antigen was identical with that of IgG and C3. Electron micrograph showed the thickening and irregularity of glomerular basement membranes, fusion of foot processes, and deposits of electron-dense or sometimes translucent materials, mostly in the intramembranous location. The causal sequence of the coincidental deposition of amyloid and immune complexes is discussed.

Immunology of helminth infections, with special reference to immunopathology.

Immune responses resulting in immunity to infection or disease, share the same basic humoral and cellular mechanisms. While immunity to helminth infection has evolved to mediate rapid elimination of the parasite, the strategies evolved by the parasites themselves aim to delay this rejection process and ensure the survival and distribution of their progeny. Ineffective or incomplete immunity results in persistence of parasites or their products within the host tissues, inappropriate or chronic stimulation by parasite antigens, hyper-reactivity and tissue damage or immunopathology. A long standing classification by Gell and Coombs identifies four major types of hypersensitivity responses accounting for most of the immunopathogenesis, three of which are mediated by antibody and one, delayed type hypersensitivity (DTH), by T cells. This paper aims to give a short review of these four classical hypersensitivity reactions with particular reference to infections of large animals with helminth parasites. In addition, in view of the functionally different helper T cell subsets now identified, the existing DTH response is redefined as DTH Type 1 (Th-1 mediated) and two new classes of T cell-dependent DTH responses are proposed; DTH Type II, associated with the Th-2 type cytokines IL-4 and IL-5 and eosinophilic granuloma formation, and DTH Type III, associated with IL-4 and TGF-beta and fibrosis. Finally, some implications of immunopathology on parasite control strategies are discussed.

Plasma and urine biochemical changes in cats with experimental immune complex glomerulonephritis.

Biochemical changes in plasma and urine were monitored in six cats before and during the induction of immune complex-mediated glomerulonephritis (ICGN) by daily intravenous administration of human serum albumin (HSA). The earliest indication of renal dysfunction in the cats was hypoalbuminaemia, which occurred as early as 13 weeks before cats developed clinical signs of renal disease. Proteinuria occurred 2 to 3 weeks before clinical disease, but was sensitive in predicting renal pathology in two cats that did not develop clinical signs of disease. In addition, increased activities of several urinary enzymes were detected in affected cats, with measurement of N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transferase providing the earliest and most sensitive indication of renal damage. These plasma and urine measurements correlated more closely with the renal pathology, observed at postmortem, than clinical assessment of disease. It was concluded that ICGN in the cat could be diagnosed earliest by measurement of plasma protein concentration, whilst disease progress could be effectively monitored by including assays to measure urine protein and urine enzymes.

Experimental ampicillin glomerulonephropathy.

Eighteen dogs were given repeated doses (between 4 and 19) of ampicillin (7 mg per kg intramuscularly on 3 days a week). Fifteen of the dogs developed a subclinical glomerulonephropathy characterized by mesangial hypercellularity. While only 9 of the 18 dogs showed electron-dense deposits in the mesangium, 14 dogs had glomerular deposits of IgG and 11 of these had C3 deposits also.

Immune complex-associated thrombocytopenic purpura syndrome in sexually mature Göttingen minipigs.

Eleven cases of thrombocytopenic purpura (TP) in sexually mature male or female Göttingen minipigs occurred sporadically over 3 1/2 years in a closed breeding colony protected by strict barrier conditions. Typical clinical signs of TP, including extensive subcutaneous haemorrhages, were seen in all affected animals. Haematological abnormalities included marked thrombocytopenia and anaemia. A consistent histopathological finding was the presence of membranoproliferative lesions in the renal glomeruli. Immunohistochemically, glomerular deposits were positively labelled for complement factor C1q and often also for immunoglobulins. Bone marrow findings consisting of increased numbers of immature and apoptotic megakaryocytes were compatible with a state of increased platelet consumption. Based on the combined presence of thrombocytopenia and renal immune complexes, it is suggested that the syndrome was related to a type III hypersensitivity reaction. However, further studies are needed to verify this hypothesis.

Experimental immune complex glomerulonephritis and the nephrotic syndrome in cats immunised with cationised bovine serum albumin.

Membranous nephropathy was induced in four cats by repeated intravenous injections of 120 mg cationic bovine serum albumin (BSA, pI 9.5). All four cats developed diffuse granular deposits of IgG and C3 along the glomerular capillary walls as early as five weeks which persisted until the end of the experiment at 17 weeks. Ultrastructural studies revealed many subepithelial electron dense deposits. Two cats developed severe proteinuria and the nephrotic syndrome characterised by hypoalbuminaemia and oedema. An additional four cats received repeated injections of unmodified native BSA (pI 4.5) and remained basically normal. This is the first report of membranous nephropathy and the nephrotic syndrome in an experimental animal model which, unlike other animal models, is subject to the spontaneously occurring disease.

Effects of a specific thromboxane synthetase inhibitor on development of experimental Dirofilaria immitis immune complex glomerulonephritis in the dog.

Twelve Beagle dogs were immunized with aqueous-soluble Dirofilaria immitis antigens, and subsequent to at least fivefold increases in serum antibody titer, 6 mg of homologous antigen was infused into the left renal artery. Six dogs were treated once daily starting the day of infusion with 0.75 mg/kg of 1-benzylimidazole (1-BIM) in saline. Six control dogs were given saline only. Light, immunofluorescent, and transmission electron microscopic examinations of renal tissue from control dogs, 10 days after antigen infusion, showed a mesangioproliferative glomerulonephritis in the left kidney with polymorphonuclear leukocyte (PMNL) infiltration and fibrin deposition. Immunoglobulin (Ig) G, M, C3, and Dirofilaria antigen deposits were observed in a segmental granular pattern. Mesangial, subendothelial, and intramembranous electron dense deposits were observed, and anti-Dirofilaria antibodies were demonstrated in kidney eluates from each dog. Administration of 1-BIM had no significant effect on IgG, IgM, C3, or antigen deposits, electron dense deposits, or concentration of antibody in kidney eluates. However, 1-BIM-treated dogs had less glomerular cell proliferation, periodic acid-Schiff (PAS) positive glomerular staining, PMNL infiltration, and fibrin deposition. These data suggest that thromboxane is an important mediator in the development of immune complex glomerulonephritis, and that in certain circumstances, inhibition of thromboxane synthesis may be an effective therapy for immune complex glomerulonephritis in the dog.

Analysis of renal immune-deposits in canine leishmaniasis. Preliminary results.

Previous studies carried out on 34 dogs spontaneously infected by Leishmania infantum showed the presence of kidney lesions characterized by immunologically mediated glomerular and tubular damage. Glomerular immune-deposits were studied in 13 of these dogs. Immunoglobulins were isolated from kidney tissues by acid elution; IgG fractions from eluates, obtained by ammonium sulfate precipitation, were subjected to clonotypic analysis by autoradiography after isoelectrofocusing (IEF) using 125I radiolabelled goat IgG fraction-anti Fab2 of dog IgG. Idiotypic characterization of IgG eluted from kidney tissues was performed by IEF and autoradiography using both 125I radiolabelled membrane antigens of L. infantum extracted by Triton x 100 and 125I radiolabelled dog IgG for rheumatoid or anti-idiotypic activity. The IgG deposited in the kidney tissues of examined dogs were polyclonal and a specific activity against Leishmania membrane antigens was revealed. Meanwhile an anti-IgG activity of deposited immunoglobulins was not observed.

Effects of a thromboxane synthetase inhibitor on established immune complex glomerulonephritis in dogs.

Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold increase in antibody titer, 1 mg of concanavalin A was infused into each renal artery of each dog to induce in situ immune complex glomerulonephritis. Starting 4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily with 30 mg of 3-methyl-2 (3 pyridyl)-1-indolectanoic acid (CGS 12970)/kg of body weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour urinary excretion of protein and thromboxane B2 were determined for each dog prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6, and 8 weeks after initiation of treatment. In addition, methyoxy-3H inulin clearance was determined at initiation of treatment and 4 and 8 weeks later. Renal specimens were examined histologically at the initiation of treatment and 4 and 8 weeks later. Glomerular mononuclear profiles/microns 3 were determined from at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were used to compare mean values at the various time points to the respective mean baseline value and 2-sample t tests were used to evaluate differences between treatment groups. At the start of treatment (4 weeks after renal arterial infusion of concanavalin A), histologic evaluation of renal specimens revealed glomerular epithelial crescent formation, mononuclear cell proliferation, and infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of protein and thromboxane B2 were significantly increased, but endogenous creatinine clearance values were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)