Amir Tejani

Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children.

The North American Pediatric Registry reports that from 1987 to 1989 blacks and Hispanic children accounted for 23% of all renal transplants performed but 38% of those performed for focal segmental glomerulosclerosis (FSGS). From these data, we infer that blacks and Hispanics form a disproportionate number of FSGS patients who progress to end-stage renal disease (ESRD) compared with white children. To explore this hypothesis we assessed our single-center experience of FSGS comparing black and Hispanic with white children. Of 177 black and Hispanic children followed in our clinic for idiopathic nephrotic syndrome (NS) between 1974 and 1989, 57 were diagnosed as having FSGS (group I). The mean age at onset of NS of these group I patients was 7.3±4.6 years and the mean duration of follow-up was 8.25±4.3 years. During the same period, 13 of 65 white patients (group II) with idiopathic NS were found to have FSGS. Their mean age (7.8±4.8 years) and duration of follow-up (8.8±4.8 years) were similar. Therapeutic modalities in the two groups were also similar. Of group I patients, 78% (42/54) reached ESRD compared with 33% (4/12) of group II patients (P<0.01). Life table analysis showed that 50% of black and Hispanic children will reach ESRD within 3 years of FSGS. In a subset of patients, multiple regression analysis revealed that the higher the serum creatinine at the onset of NS (P<0.01,r=0.519), and the higher the serum cholesterol at the onset of NS (P<0.02,r=0.511), the more rapid the progression to ESRD. Based on our findings, a national survey to determine if FSGS is more virulent in black and Hispanic children is warranted.

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.

Predictors of Eventual End Stage Renal Disease in Children with Posterior Urethral Valves

We reviewed the long-term outcome of 25 boys born with posterior urethral valves who were followed longitudinally. Patient age at diagnosis varied from 7 months intrauterine to 7 years postnatal, and the mean duration of followup was 9 years. Of the children 40 per cent had retardation of growth by the end of the followup period and 44 per cent had end stage renal disease. Of the various factors delay in diagnosis and the association of persistent vesicoureteral reflux seem to predict eventual end stage status. In 18 of 25 children the diagnosis of posterior urethral valves was made before they were 2 years old. Only 5 of these children have reached end stage disease status. In comparison, of 7 children whose diagnosis was delayed beyond 2 years 6 have end stage disease (p less than 0.01). Similarly, 7 of 9 children with persistent reflux had end stage disease compared to 4 of 16 who did not have persistent reflux (p less than 0.01). Since end stage renal disease status was reached at widely varying intervals a prolonged followup of children with this anomaly is necessary.

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.

A Randomized Controlled Trial of Low-Dose Prednisone and Ciclosporin versus High-Dose Prednisone in Nephrotic Syndrome of Children

Twenty-eight patients with an onset of nephrotic syndrome within 1 year were randomized to receive either ciclosporin and low-dose prednisone or high-dose prednisone alone. Both groups were treated for 8 weeks. Thirteen of 14 children receiving combined therapy underwent remission versus only 8 of 14 children receiving prednisone alone (p less than 0.05). However, there was no difference between the two groups as regards the duration of remission after discontinuation of therapy. In patients receiving combined therapy, immunological studies showed that high interleukin producers had a more sustained remission. There was no evidence of ciclosporin-induced nephrotoxicity in this short-term therapeutic trial.

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.

Maintenance immunosuppression therapy and outcome of renal transplantation in North American children — a report of the North American Pediatric Renal Transplant Cooperative Study

The North American Pediatric Renal Transplant Cooperative Study collects extensive data on all transplants entered into its registry. For this study we evaluated 568 cadaver kidney and 492 live-donor recipients with graft function at 30 days post transplant. Utilizing maintenance immunosuppressive therapy at 30 days post transplant we evaluated patient and graft outcome, mortality and morbidity over the first 6 months post transplant. For cadaver kidney recipients, 36 patients were receiving prednisone and azathioprine (PA), 114 were maintained on prednisone and cyclosporine (PC) and 418 were on prednisone, cyclosporine and azathioprine (PCA). Patients receiving PA had a greater incidence of rejection prior to 30 days, a greater incidence of hospitalization for rejection and for hypertension over the next 6 months and a greater loss of allograft in the first 6 months compared with the other two groups. The only difference noted between PC and PCA was a lower serum creatinine in the PCA group at 6 months. For living-related kidney recipients, there were 78 patients maintained on PA, 97 on PC and 317 on PCA. Again patients receiving PA had a higher rate of hospitalization for rejection and a higher rate of graft loss. When patients receiving PC were compared with those receiving PCA, no differences were noted in the 6-month serum creatinine values, but a greater percentage of PCA patients were receiving antibiotics on day 30. We conclude that PA is poor therapy for both groups, PCA is ideal therapy for cadaver kidney recipients, but no beneficial effects are noted when PCA is used over PC for live-related donor kidney transplants.

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.

Do children exhibit catch-up growth post transplant: North American Pediatric Renal Transplant Cooperative Study special study.

Changes in height deficit and standard deviation score (SDS) were evaluated in 524 recipients who were growth retarded at transplantation (SDS>−2.00) and were followed for at least 2 years post transplant. At 2 years the Δ SDS was 0.32±0.04 and the Δ height deficit was 0.75±0.23. Therefore despite improvement in the SDS at 2 years post transplant, the change in height deficit was <1 cm. Change in height deficit may be a better indication of “catch-up” growth following transplantation.