Purpose: The efficacy and safety of the new immunosuppressant agent, FK506 (tacrolimus), was assessed in pediatric renal transplant recipients over a mean 12-month follow-up period. Methods: Twenty pediatric renal transplant recipients received oral FK506 therapy (0.3 mg/kg/d) in combination with azathioprine (1 to 2 mg/kg/d) and lowdose prednisone as primary therapy (n = 11) or were converted from cyclosporine-based therapy (n = 9) for complications including cyclosporine toxicity (n = 2), acute refractory rejection (n = 4), and chronic rejection (n = 3). Patients were then followed-up prospectively to evaluate effectiveness of therapy and complications. Results: In the primary treatment group, 45% of patients had one or more rejection episodes. Two required OKT3 therapy (18%) for persistent rejection, with one (9%) graft loss at 3 months. All other episodes were treated effectively with FK506 dose adjustment and steroid pulses. Patient and graft survival was 100% and 91%, respectively, at 12 months mean follow-up. In the FK506 conversion group, two teenage girls with intractable acne and hirsutism were converted with complete resolution and no change in renal function. Four patients were converted for acute rejection: two who did not respond to steroid pulse and two who did not respond to both steroids and OKT3. All four grafts were salvaged (mean follow-up, 12 months; mean Creatinine [Cr], 1.1). Three patients were converted for biopsy-proven chronic rejection at 3, 10, and 12 years after transplant (mean Cr, 2.4) with two of three of patients stable with functioning grafts at 1 year after conversion. Complications of FK506 therapy included temporary insulin-dependent diabetes mellitus (10%), neurological complications (25%), renal toxicity (15%), and hypertension (85%). There were no cases of gastrointestinal toxicity, hepatic dysfunction, lymphoproliferative disorders, or life threatening viral infection. All symptoms of toxicity responded to dose adjustment. No patient required conversion from FK506 to other agents. Conclusion: This early experience indicates that FK506 in combination with low-dose steroids and azathioprine appears to provide safe and effective immunosuppression in the pediatric age group as a primary agent and may salvage grafts in patients with refractory steroid and OKT3 resistant rejection. Graft and patient survival is comparable to that seen with conventional cyclosporine-based immunosuppression.
We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer ≥1.0 μg/ml IgG at 1 month was highly predictive of retaining a protective antibody level ≥0.15 μg/ml at 1 year. (J PEDIATR 1996;128:99-101)
Although immunization with influenza vaccine is recommended for children with chronic renal disease and after organ transplantation, the antibody response in these children has not been well described. We studied the response to the 1993-1994 trivalent influenza vaccine in children, aged 1-21 years, with chronic renal failure (n = 15), end-stage renal disease requiring dialysis (n = 10), and post renal transplantation (n = 17). Each group's antibody response was compared with that of a control group (n = 7). No significant differences were found in seroconversion rates, percentage of patients achieving protective hemagglutination-inhibition titers post vaccination or change in geometric mean titers from pre to post vaccination between study groups and controls. These results suggest that pediatric patients with renal disease will respond and therefore will benefit from currently recommended influenza immunization.
Neisseria sicca, previously classified as a "nonpathogenic" organism, has now been recognized as a cause of many infections, including endocarditis and meningitis. However, it has not been reported as a cause of peritonitis. We present a case of documented N. sicca peritonitis immediately following an episode of Staphylococcus aureus peritonitis in a pediatric chronic peritoneal dialysis (CPD) patient. N. sicca should be considered as a possible pathogen in CPD-associated peritonitis.
Pediatric end-stage renal disease patients, maintained on chronic peritoneal dialysis (CPD), may have a variety of immunological abnormalities, including hypogammaglobulinemia and poor responses to vaccines. We measured antibody levels to Hemophilus influenzae type b (Hib) in 24 CPD patients. Eight children received primary Hib immunization while undergoing CPD. Of these, 1 of 8 (12%) lacked protective levels of antibody. In another child, who had an initial protective response, antibody levels were undetectable 12 months after immunization. Sixteen of the patients had not been immunized with Hib vaccine because they were more than 5 years old when the vaccine was licensed. In this group, 5 of 16 (31%) lacked protective levels of anti-Hib antibody. Of those available for follow-up, 3 responded normally to Hib vaccine. It is not sufficient to provide childhood immunizations to CPD patients with the assumption that those immunizations will lead to long-lived immunity. Antibody levels should be measured within a month of immunization and at regular intervals thereafter to document immunity.
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Humoral immunity was evaluated in seven children undergoing continuous ambulatory peritoneal dialysis (CAPD). Five children (71%) had serum immunoglobulin levels which were more than 2 SD below the mean for age. One mechanism contributing to hypogammaglobulinemia was loss via the peritoneal membrane. Daily losses of IgG into peritoneal dialysis effluents represented 7%–29% of normal daily IgG synthesis, and losses increased with duration of CAPD therapy. Despite the observed hypogammaglobulinemia, all children had protective antibody responses to immunization.
AbstractA sterotaxic atlas of the hypothalamus of the 1‐, 7‐, and 14‐day‐old rat is presented. Ancillary techniques for anesthetizing these young animals, mounting the neonates in the instrument, and special histological considerations are discussed.