Childhood AIDS nephropathy: a 10-year experience
The objective of this study was to define the demographic, immunologic, and clinical characteristics of children with acquired immunodeficiency syndrome (AIDS) and AIDS nephropathy, and contrast this with the existing adult data. Data from 62 pediatric patients with AIDS who were treated at SUNY Health Science Center, Brooklyn, New York, between 1983 and 1993 were analyzed. Human immunodeficiency virus (HIV) infection was acquired during the neonatal period by vertical transmission (n = 60) or blood transfusion (n = 2). All children with AIDS who exhibited clinical nephropathy died (n = 16), with mean survival of 55.3 months. In contrast, 32 of 56 AIDS patients (70%) who did not manifest nephropathy were alive at the end of the study period. Patients with nephropathy were noted to have significantly lower CD4+ lymphocyte counts than those without nephropathy. These observations suggest that the predominant renal lesion in pediatric patients who acquired HIV infection during the perinatal period is focal segmental glomerulosclerosis, although a variety of other histological lesions were present. As in adults, the survival in children is dismal following the onset of clinical renal disease. In contrast to the adult population in whom multiple risk factors can potentially contribute to AIDS-associated nephropathy, occurrence of nephropathy in children with vertical HIV transmission provides convincing evidence for the pathogenetic role of HIV infection.
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.
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.
Descriptions of the participating centers and patient population in the Growth Failure in Children with Renal Diseases Study
The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.
Prevalence of anemia and correlations with mild and chronic renal insufficiency
High-dose cyclosporine therapy in recurrent nephrotic syndrome following renal transplantation [Case Report]
Strategies for optimizing growth in children with kidney transplants
Children with a well-functioning graft continue to show growth retardation even with low-dose prednisone. We have attempted to utilize the steroid-sparing effect of cyclosporine by discontinuing prednisone after graft stabilization. Since 1983, 53 children have received cyclosporine as primary immunosuppressant for renal graft maintenance. The children, aged 6 months to 18 years, received 60 transplants. One-year and four-year patient survival for cadaveric transplants was 91% and 91%, compared with 96% and 96% for living related transplants. One-year and four-year graft survivals were 82% and 65% for cadaveric transplants (n = 25), compared with 91% and 63% for living related transplants (n = 35). Of 53 patients, 23 were able to discontinue prednisone and be maintained on monodrug cyclosporine therapy, and 21 of the 53 patients had growth hormone measured using L-dopa stimulation. In patients receiving more than 5 mg of prednisone daily, growth hormone levels were lower than normal (less than 10 ng/ml). Of 15 patients who had discontinued prednisone for more than 6 months, 13 showed accelerated growth by improvement in their standard deviation scores. In 4 pubescent children with growth retardation and need for maintenance prednisone, accelerated growth occurred following growth hormone administration for 3-6 months. Based on these data we suggest that (1) discontinuation of even very small doses of prednisone may be essential for normalizing growth hormone response to L-dopa and (2) further studies are needed to exploit the growth stimulation effect of recombinant growth hormone in transplanted children.
RANDOMIZED TRIAL OF CYCLOSPORINE AND LOW-DOSE PREDNISONE (P+CS) VS CONVENTIONAL PREDNISONE (P) THERAPY IN RECENT ONSET (LESS-THAN-1 YR) NEPHROTIC SYNDROME (NS) [Meeting Abstract]
A randomized trial of cyclosporine with low-dose prednisone compared with high-dose prednisone in nephrotic syndrome
Nephrotoxicity of cyclosporine A and cyclosporine G in a rat model
Cyclosporine G (CsG) like cyclosporine A (CsA) is a cyclic endecapeptide where the alpha-amino butyric acid residue in position 2 is replaced by norvaline. We studied the effects of both drugs on renal function in a nontransplant rat model to avoid the additional variable of rejection. Age- and weight-matched pairs of male Sprague-Dawley rats were treated subcutaneously for 21 days with a daily dose of 25 mg/kg bw of either powdered CsA or CsG dissolved in 1 ml of olive oil. A control group (C) received olive oil only. Blood pressure (BP) and creatinine (Cr) were measured on days 0, 7, 14, and 21. On day 22, animals were weighed, anesthetized, and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured using c14 inulin and 3H paraAminohippuric acid, respectively. Renal plasma flow and glomerular filtration rate were unaltered in CsG-treated animals compared to controls but significantly reduced in CsA-treated animals. Histologically, vacuolization and microcalcification were seen in significantly greater frequency among the CsA-treated animals. CsG with lesser nephrotoxic potential may prove to be of use in maintenance of therapy of transplants as well as selected autoimmune disorders.