Andrew J. Aronson

IgA nephropathy: morphologic predictors of progressive renal disease.

IgA nephropathy has a variable course and leads to renal failure in a substantial number of cases. In an attempt to identify prognostic indicators in this disease, we evaluated the clinical and pathologic findings of 20 unselected patients with IgA nephropathy, 13 of whom were followed for 1.5 to 5 years (mean 2.8 years). Biopsy specimens were obtained from all patients and were examined by light and electron microscopy and by immunofluorescence. The activity and severity of the lesions were graded according to a modified classification used by Meadow et al. for the nephropathy associated with Henoch-Schönlein purpura. The results reveal a correlation between the histopathologic grading in the initial biopsy and the clinical outcome: Patients with mild (grade II) or moderate (grade III) lesions had a benign course or showed evidence of active disease without deterioration of renal function, whereas all patients with grade IV or V lesions who were followed for more than one year developed end-stage renal failure. These observations suggest that histologic grading at initial renal biopsy may be a useful prognostic indicator of the clinical outcome of IgA nephropathy.

Hemolytic Uremic Syndrome Following Bone Marrow Transplantation: A Case Report and Review of the Literature

Unlike primary idiopathic childhood hemolytic uremic syndrome (HUS), certain cases of HUS are clearly secondary. This article describes a child who represents the 11th reported case of secondary HUS following bone marrow transplantation, and notably, the fourth such case without exposure to cyclosporine A. The renal biopsy was diagnostic in this case. Therefore, the pathognomonic features of the biopsy, as well as its prognostic implications are described and clarified. This patient was treated with plasma exchange, and is the second reported surviving case of secondary HUS following bone marrow transplantation.

Idiopathic membranous glomerulopathy preceding the emergence of systemic lupus erythematosus in two children

An idiopathic nephrotic syndrome associated with membranous glomerulopathy antedated the subsequent emergence of systemic lupus erythematosus in two patients (7-year-old and 14-year-old girls). At the onset of INS, there was neither clinical evidence of multisystem disease nor unequivocal serologic evidence of SLE. The only early possible indication of SLE was the presence of microtubular inclusions in glomerular endothelial cells on electron microscopy. In each instance (one year and three years after onset of INS), a second renal biopsy showed transformation of the membranous glomerular lesion to a more florid type with glomerular subendothelial dense deposits. One patient died of overwhelming pulmonary infection while she was receiving prednisone and cyclophosphamide; the other developed progressive renal failure despite steroid treatment. SLE should be considered in patients presenting with apparent idiopathic MG, in whom nephrotic syndrome persists. Intraendothelial cell microtubular inclusions may be an early clue to later emergence of SLE.

OKT3 induction in pediatric renal transplantation

Twenty cadaveric renal transplant patients (mean age 12.5±4.8 years) received 14 days (mean 13.0±2.8 days) of OKT3 (mean dose 0.16±0.09 mg/kg) along with prednisone 0.5 mg/kg per day, azathioprine 2 mg/kg per day and cyclosporine 5 mg/kg per day which was increased to obtain therapeutic levels before the discontinuation of OKT3. Actuarial patient and graft survival were 100% and 50%, respectively, at both 1 and 5 years. Four children lost their grafts within the first 48 h. One loss was technical in origin, the remaining 3 had pathological evidence of vascular thrombosis. Of the remaining 16 children, 12 (75%) experienced rejection episodes within the first 2 months post transplant (mean 27±15 days). Successful reversal of early rejection episodes was achieved in 11 of 12 patients. Clinically significant cytomegalovirus infection occurred in 4 patients and resulted in graft loss in 2 patients. Circulating OKT3 levels ranging from 1,000 to 32,000 ng/ml were seen in all patients within the first 48 h. There was a rapid and total depletion of circulating CD3-positive lymphocytes in all patients. Antiisotypic and anti-idiotypic OKT3 antibodies were assessed by enzyme-linked immunosorbent assay (ELISA), and blocking anti-idiotypic antibodies were detected by immunofluorescence inhibition assay. Positive OKT3 antibody titers were detected in 11 children by ELISA and 10 children by immunofluorescence inhibition assay. In summary, we have found that in pediatric renal transplant patients receiving OKT3 induction therap: (1) there is a high occurrence of vascular thrombosis; (2) the incidence of early acute rejection is high; (3) the time to first rejection is not as long as that reported for adults; (4) there is a substantial rate of sensitization against OKT3; (5) despite successful reversal of early acute rejection, long-term-graft survival does not appear to have been beneficially altered.

Prognostic Implications of Cutaneous Immunoglobulin Deposits In Systemic Lupus Erythematosus

The class of immunoglobulin (Ig) deposited at the dermal‐epidermal junction (DEI) of the skin in patients With systemic lupus erythematosus (SLE) has been proposed to have prognostic implications. The authors studied disease activity in 51 SLE patients with a positive lupus band. Patients with cutaneous IgM deposits had significantly more severe disease than those with only IgG or with mixed immunoglobulin deposits. While their data suggest an association between IgM depostis, severe disease and a poor prognosis, they urge caution in utilizing Ig deposits as a prognostic indicator.

185 ASYMPTOMATIC CARDIOMYOPATHY IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Twelve adolescents with SLE were studied by M-mode echocardiography. All patients had received prednisone for the duration of their illness (1 mo-7 yrs). None had symptomatic heart disease although the following were present: cardiomegaly by x-ray (4 pts), hypertension (8 pts), nonspecific ECG changes (5 pts). Pericardial effusion was present in 6 patients. Left ventricular (LV) end diastolic dimension, percent minor axis shortening and the ratio of pre-ejection period to ejection time were normal. Posterior wall thickness (p < .001), calculated LV mass (p < .05) and LV mass/volume (p < .025) were abnormal but not related (linear regression) to blood pressure. Maximum rates of continuous LV dimension change (dD/dt) were normal. However, the time from electrocardiographic Q-wave to minimum and maximum dD/dt (p < .025) and Q-wave to mitral valve opening (p < .05), corrected for heart rate, were abnormal. These data suggest that clinically unsuspected cardiomyopathy is associated with SLE and that it is not defined by the usually measured M-mode echocardiographic parameters.

1480 LYMPHOCYTE SUBPOPULATIONS IN LIPOID NEPHROSIS (LN)

Previous studies in LN have suggested an immunologic pathogenesis. We have characterized B and T cell subpopulations from peripheral blood lymphocytes(PBL) of 10 patients with LN. B lymphocytes displaying different isotypes were detected by staining with fluorescein(Fl) and Rhodamine(Rh) conjugated, affinity-purified goat anti-human μ, σ, γ, or α. T lymphocytes were evaluated using monoclonal mouse anti-human T cell reagents(OKT3 = total T, OKT4 = inducer T, OKT8 = suppressor/cytotoxic T). Plasma cells(PC) were stained after fixation with Fl or Rh goat anti-human μ, δ, γ, or α.Before therapy all patients had elevated percentages of sIgM+ B lymphocytes and IgM and IgA PC in blood. After treatment percentages of PC and B lymphocytes returned to normal. Distribution of T cell subpopulations were normal in pre- and post-treatment populations.We conclude that children with LN possess elevated numbers of B cells and PC which may indicate spontaneous activation of the humoral immune system. After treatment normal B and PC numbers are seen. Such elevations of B cells are not due to an abnormal distribution of T cell subpopulations.

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND DERMATITIS HERPETIFORMIS (OH) IN A GIRL WITH MARFAN'S SYNDROME

The concurrence of DH and SLE has previously been reported in 2 patients. Our patient is a 15 year old black girl with Marfans Syndrome who developed a bultous eruption which was clinically, histologically, and immunopathologically characteristic of DH. Sulfapyridine was given. Two months later she developed fever, pleural effusion, renal insufficiency, nephrotic syndrome, hypertension, hypocomplementemia, positive ANIF and positive LE preparation. Immunofluorescence of uninvolved skin demonstrated IgG, IgM and C3 at dermal-epidermal junction and around papillary blood vessels. Kidney biopsy showed Type III (proliferation with deposits) lupus glomerulonephritis. Prednisone treatment resulted in improvement of clinical manifestations. She subsequently expired when cystic medial necrosis of the ascending aorta resulted in cardiac tamponade. Since both DH and SLE are diseases mediated by the deposition of immune complexes, our patient clearly exhibited a rare predisposition to formation of immune complexes. The presence of two immune-mediated diseases in the same patient suggests a common underlying immune defect.

ANTICONVULSANT-INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND NEPHROTIC SYNDROME (MS)

A 3 year old boy was treated with diphenylhydantoin (DPH), ethosuximide (E), and phenobarbital for convulsions following herpes encephalitis. After 3 months of anticonvulsant treatment he developed NS (24 hour uriae protein-9.1 grams, serum albumin-0.76 gms.%, cholesterol-356 mg.%), positive ANIF (1:800), “suspiciously” positive LE preparation, positive skin biopsy (dermalepidermal IgG), and high total eosinophil count (985 - nl 50-250)., After withdrawal of DPH and E there was gradual resolution of NS and normalization of urine, serum protein, cholesterol, ANIF and eosinophilla. Renal function and serum complement levels remained normal. Corticosteroids were not given.Although anticonvulsants have been associated with SLE-like syndromes, serologic abnormalities, nephritis or NS, no previously reported patient developed SLE and NS concurrently. The urgency in discontinuing DPH and E prevented our identifying the offending drug. It is likely that this patient sustained a syndrome of drug-induced SLE with immune-mediated reversible glomerulonephritis and NS.

RENAL HISTOPATHOLGY AND CLINICAL COURSE OF 53 CHILDREN WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

53 patients with SLE have been followed for 7 months to 10 years and have undergone at least one renal biopsy (RB). Hlsto-pathologic classification of initial RB was: I normal, 9 Type I (proliferation without deposits), 5 Type II (membranous), and 38 Type III (proliferation with deposits). Each patient received prednisone. 13 received azathioprine or cyclophosphamide. Subsequent RB or post-mortem examination in 15 showed progression in 4 (I with Type I, 2 with Type II and 1 with Type III), improvement in 4 with Type III and no significant change in 7. 4 developed renal failure, 3 of whom expired, 8 died of non-renal causes and 1 is azotemic. The remainder are alive. Chronic renal failure and persistent active renal disease occurred only with Types II and III. The low incidence of renal failure (7.5%) in this large series of patients with SLE despite the preponderance of Type III suggests a better prognosis than previously reported.