Anthony Nicastri

Nephrotic syndrome associated with acquired immunodeficiency syndrome in children

We report here the cases of 15 children in whom nephrotic syndrome developed, from among 164 children (55% male, 90% black) followed in our acquired immunodeficiency syndrome clinic from 1984 through 1990. Mean age at onset of nephrotic syndrome was 4.9 +/- 2.6 years. Fourteen patients were black and one was Hispanic. Seventy-three percent of our patients with nephrotic syndrome were girls. The mean duration of clinical acquired immunodeficiency syndrome before development of nephrotic syndrome was 1.7 +/- 1.1 years. In eight patients, nephrotic syndrome appeared between 3 and 11 months after intravenous infusions of immune globulin or albumin were administered as part of a research protocol; this incidence (8/47) was higher than the incidence of nephrotic syndrome among those who did not receive intravenous infusions (7/117, p less than 0.05). Tissue for histologic examination was available for 80% of the patients, and histologic examination demonstrated mesangial hypercellularity (5 patients), focal segmental glomerulosclerosis (4 patients), minimal change disease (2 patients), and IgM nephropathy (1 patient). Deposition of one or more immunoglobulins was noted in all but one patient studied with immunofluorescence. Corresponding electron-dense deposits were seen by electron microscopy in 78% of specimens. Prednisone did not induce a remission of nephrotic syndrome in the 13 patients treated, whereas cyclosporine did so in the 3 patients to whom it was administered. Five patients were in the end stage of renal disease within 8 months. Successful maintenance peritoneal dialysis was performed in three patients, but 80% of patients have died of human immunodeficiency virus-related complications; one patient was lost to follow-up. We conclude that immune-complex deposition is consistently seen in children with human immunodeficiency virus-associated nephrotic syndrome. This nephrotic syndrome is resistant to steroid therapy, but we observed a remission of the proteinuria with cyclosporine therapy in three patients. For patients with end-stage renal disease, maintenance peritoneal dialysis may improve the quality of life.

Renal Lesions in Sickle Cell Nephropathy in Children

Sickle cell nephropathy characterized by proteinuria and predominantly glomerular lesions has not been studied as extensively as renal tubular alterations in sickle cell disease. We reviewed our experience with this entity over a 14-year period. Of 13 children with either proteinuria or the nephrotic syndrome, 8 showed focal and segmental glomerulosclerosis, and 5 had mesangial proliferation. Children with focal and segmental glomerulosclerosis were older at onset of nephropathy and presented with the nephrotic syndrome more frequently than those with mesangial proliferation (p less than 0.05). All patients with mesangial proliferation and half of the focal and segmental glomerulosclerosis patients had supranormal renal clearances at onset of nephropathy suggesting hyperfiltration. Hyperfiltration seen in animals with reduced renal mass, and in human diabetic nephropathy before reduction in nephron units leads to mesangial proliferation and sclerosis. Our study suggests that sickle cell disease produces similar lesions in patients with sickle cell nephropathy.

Long-Term Evaluation of Children with Nephrotic Syndrome and Focal Segmental Glomerular Sclerosis

We studied the long-term outcome of a group of children with the nephrotic syndrome who showed the histological lesion of focal segmental glomerular sclerosis (FSGS) during the course of their illness. Of 25 such children studied, a complete follow-up ranging from 3 to 19 years was available in 24. Two distinct groups could be identified. Patients in the first group were characterized by steroid resistance (SR) from the onset, whereas those in the second group were initially steroid sensitive (SS), and had the histological lesion of minimal change which, over time, evolved into FSGS. SR patients had a mean age of 7.7 +/- 3.7 years compared to SS patients who were 3.5 +/- 2.5 years old (p less than 0.01). There were more females (11 of 14) in the SR group than in the SS group (3 of 10; p less than 0.02). The incidence of hematuria was higher in the SR patients (9 of 14) than SS patients (2 of 10; p less than 0.05). SR patients also exhibited a greater degree of growth retardation at the end of the follow-up period (9 of 13 compared to 1 of 8 SS patients; p less than 0.02). SR patients reached end-stage renal failure earlier (2.3 +/- 1.3 years) than SS patients (10 +/- 5.8 years; p less than 0.01) after the initial biopsy. Of the 13 kidney transplanted into 9 SR patients, recurrence of FSGS was noted in two allografts. Of the 4 kidneys transplanted into 2 SS patients, recurrence was seen in 1. The overall recurrence rate of FSGS in allografts was 17.6%. Our study suggests that the two varieties of FSGS occurring in nephrotic patients may be distinct nosologic entities rather than a single disease with varied manifestations.

The paucity of minimal change disease in adolescents with primary nephrotic syndrome.

Abstract. Data are sparse regarding the histological lesions associated with the primary nephrotic syndrome in adolescents. To our knowledge there are only two published articles that have specifically addressed the histopathological lesions that typify idiopathic nephrotic syndrome in the adolescent population. We reviewed our experience from the last 14 years of children between the ages of 12 and 18 years who were referred to our center for the evaluation of the nephrotic syndrome. A total of 29 adolescents met the inclusion criteria for this review. All patients were biopsied prior to the initiation of treatment. The sex ratio consisted of 52% males and 48% females and the racial breakdown was largely African-American, with 83% black adolescents, 7% Hispanic, and 10% Caucasian patients. Minimal change nephrotic syndrome (MCNS), the predominant lesion of children at an early age, was noted in only 20% of patients. The majority of patients (55.2%) had focal segmental glomerulosclerosis (FSGS); 7% had IgM nephropathy and 3.5% had diffuse mesangial hypercellularity. Only 7% of biopsied adolescents had membranoproliferative glomerulonephritis. Our results indicate that the most common lesion in this predominantly African-American patient population is FSGS, with only a small number showing MCNS. Thus, in our experience derived from a racially mixed population, adolescents with the nephrotic syndrome are less likely to have MCNS than younger children.

Acute renal failure as the initial manifestation of systemic lupus erythematosus in children

In two patients with systemic lupus erythematosus, acute renal failure was the initial manifestation. The diagnosis was eventually established on the basis of serologic tests and characteristic renal histopathologic findings. We emphasize the need to consider systemic lupus erythematosus as a cause of acute renal failure of glomerular origin, because appropriate therapy may alter the outcome of the disease.

Hμ chain fragment and monoclonal IGA in a lymphoproliferative disorder

Abstract A patient with an indurated ulcerating lesion over the left parotid gland and left ear, and massive splehomegaly, was found to have two distinct serum immunoglobulin abnormalities. One was monoclonal immunoglobulin A (IgA) in monomeric and polymeric forms; the other was a protein fragment, immunologically related to immunoglobulin M (IgM) and devoid of light (L) chain activity. Upon Sephadex® gel filtration this fragment appeared to have a molecular weight lower than that of previously described “low molecular weight” IgM. It was concluded that of the two distinct immunoglobulin abnormalities, one was the production of an Hμ chain fragment.

Cone biopsy and pathologic findings at radical hysterectomy in stage I cervical carcinoma

OBJECTIVE To examine the association between cone biopsy and pathologic findings at radical hysterectomy in stage I cervical carcinoma. METHODS Fifty‐four patients diagnosed by cone biopsy with stage I cervical carcinoma and treated with radical hysterectomy comprised the study group. The association between the depth of invasion on conization, lymph‐vascular invasion, positive cone margins, positive endocervical curettage (ECC), and the depth of residual invasion in the radical hysterectomy specimen was examined using Pearson r and point biserial correlation. Independent predictors of the depth of residual invasion were determined by multiple regression. RESULTS The depth of residual invasion correlated significantly with the depth of invasion (r = .374) and presence of lymph‐vascular invasion (rpb = .372) in the conization specimen, post‐cone ECC status (rpb = .669), and age at diagnosis (r = .347). The same factors were jointly assessed using multiple regression (R2 = .636, P < .001). Depth of invasion on conization, lymph‐vascular invasion, and ECC status were identified as independent predictors of the depth of residual invasion. Patients with deep (5 mm or greater) stromal invasion and lymph‐vascular invasion on conization had significantly higher rates of positive parametrial margins (22% compared with zero, P = .001) and adjuvant radiation (66.7% compared with 20%, P = .004) compared with all other patients. CONCLUSION Depth of invasion, presence of lymph‐vascular invasion, and age at diagnosis were independent predictors of the depth of residual invasion in the subsequent hysterectomy specimen. These factors should be considered in treatment planning. Patients with a combination of these factors may have increased risk for deep residual invasion, positive hysterectomy margins, and adjuvant radiation.

Acute interstitial nephritis associated with ticlopidine

Ticlopidine, a platelet aggregation inhibitor, has been approved to decrease the risk of thrombotic stroke. We describe a 75-year-old white woman who developed acute renal failure 10 days after initiating ticlopidine therapy. A renal biopsy revealed interstitial infiltrates containing lymphocytes and eosinophils. To our knowledge this is the first report of ticlopidine-induced acute interstitial nephritis.

Asymptomatic Bacteriuria and the Nephrotic Syndrome in Children

Seven episodes of confirmed bacteriuria were found in 5 out of 30 children with the nephrotic syndrome over a 4-year period. Bacteriuria occurred during both remissions and exacerbations, and no relat