Screening for eligibility in the study of antihypertensive medication in children: experience from the Ziac Pediatric Hypertension Study.

BACKGROUND: The FDA Modernization Act has resulted in an increase in pediatric trials of antihypertensive medications. As experience is limited in children to guide the planning of these studies, we reviewed data from the Ziac Pediatric Hypertension Study to determine patterns of early study termination to help future studies. METHODS: For inclusion, subjects aged 6 to 17 years were required to have an average systolic blood pressure (SBP) or diastolic blood pressure (DBP) above the 95th percentile at the last of three visits during 2 weeks of single-blind placebo screening. Early study termination was defined as early termination for any reason. Screening termination was defined as normalization of blood pressure (BP) during the placebo screening phase. RESULTS: Early study termination rate was 27% (38 of 140 subjects). The most common reason was screening termination due to normalization of BP, accounting for 63% of all early study terminations. Among screening termination subjects who completed three screening visits, SBP was higher (P < .001) at visit 1 (129+/-8 mm Hg) than at visit 2 (123+/-7 mm Hg) or visit 3 (121+/-8 mm Hg), but did not differ between visits 2 and 3. Screening termination occurred in 15% with isolated SBP hypertension, and 21% with isolated DBP hypertension. At randomization, 83% had SBP hypertension and 53% had DBP hypertension. CONCLUSIONS: These data suggest that SBP hypertension should be part of inclusion criteria to increase enrollment and reduce the rate of screening termination, and that 1-week placebo screening is necessary and sufficient to minimize inclusion of transiently hypertensive subjects.

Tacrolimus: the good, the bad, and the ugly.

The aim of this study was to evaluate the efficacy and side-effects of tacrolimus in pediatric transplant patients previously receiving cyclosporin A (CsA). This study was a retrospective chart review strengthened by a concomitant patient interview. Eleven pediatric cardiac or renal transplant patients, who had been converted from CsA to tacrolimus from October 1995 to January 1999 at The Cleveland Clinic Foundation, were included; there were six renal and five cardiac transplant patients. Each chart was reviewed to assess transplanted organ function pre- and post-conversion. For the six renal transplant patients, creatinine levels and biopsy findings were evaluated. For the five cardiac transplant patients, cardiac catheterization and routine biopsy data were analyzed likewise. Epstein Barr virus (EBV) status was also evaluated in each patient. In addition, each parent or patient was interviewed to ascertain dates of transplant, current medications, and side-effects. The patients' ages ranged from 6 to 20 yr (mean age 14.6 yr). All patients had been converted to tacrolimus. Eight patients were converted for treatment of refractory rejection, two were converted because of CsA-associated side-effects, and one patient was converted empirically for a history of multiple previous transplant rejections. Seven out of eight patients who received tacrolimus for rejection therapy improved. One patient had complete resolution of gingival hyperplasia. Another patient who previously developed hemolytic uremic syndrome on CsA had no further evidence of hemolysis. Four patients were weaned off steroid therapy. Despite conversion, two renal transplant patients progressed to chronic rejection. Five patients exhibited no side-effects. Side-effects experienced included transient hyperglycemia in conjunction with steroid use, headaches, and tremors that subsided rapidly. Four of 11 patients developed post-transplant lymphoproliferative disease (PTLD). Fortunately, reducing the dose of tacrolimus and/or surgical resection of the mass (if present), eradicated the disease. In conclusion, conversion therapy successfully provides an alternate treatment for acute rejection. It also enabled some patients to discontinue steroid therapy, maximizing growth potential. PTLD is a severe, potentially life-threatening complication that needs to be recognized and monitored closely. In conclusion, tacrolimus has been shown to be a very effective agent for the treatment of refractory organ rejection, but must be used cautiously.

Chronic tubulo-interstitial nephropathy in children with cranioectodermal dysplasia.

We report two pairs of siblings with the syndrome cranioectodermal dysplasia who have subsequently developed chronic renal failure secondary to tubulo-interstitial nephropathy. Renal disease has not been described before in this rare syndrome but has now occurred in four of the seven reported cases. Children with cranioectodermal dysplasia appear to be at significant risk of developing chronic renal failure. This is important information for clinicians looking after such children, and their families, when considering the long-term prognosis and management.

Safety and cost effectiveness of pediatric percutaneous renal biopsy.

Because of the rising cost of health care, more patients are undergoing procedures as outpatients rather than inpatients. The purpose of this study was to compare safety and cost of outpatient versus inpatient, overnight stay, for children undergoing percutaneous renal biopsy. Charts of all such patients between January 1989 through January 1995 were reviewed for the following: age of patient, native versus allograft biopsy and preparation costs (in 1995 U.S. dollars), and complications. Of the 75 biopsies reviewed, 58 were native and 17 allograft with 35 (47%) of the biopsies being outpatient and 40 (53%) inpatient. There were four complications (11.4%) in 2 patients for the outpatient group and seven complications (17.5%) in 6 patients in the inpatient group (X2 = 0.1003, P = 0.75). The median cost for an outpatient biopsy was U.S. $1,968 while an inpatient biopsy was U.S. $3,178. We conclude that outpatient percutaneous renal biopsy in children is as safe as inpatient and more economic, with a saving of greater than U.S. $1,000 per biopsy.

Urinary tract infection in infants and children. Preventing recurrence and renal damage.

The major goal in treating urinary tract infection in children is to preserve renal parenchyma. Therefore, children with suspected pyelonephritis or anatomic abnormalities need to be examined thoroughly with the first infection. Any child with three infections should have intravenous pyelography and voiding cystourethrography, even if infections appear to be limited to the lower urinary tract. Recurrence of urinary tract infections is a major problem, and a program of follow-up urine cultures should be instituted after the first infection. Such an approach allows for early detection of anatomic abnormalities or reinfection, thus preventing loss of renal parenchyma and hence of renal function.

Focal segmental glomerulosclerosis, crescent, and rapidly progressive renal failure.

The usual clinical course of focal segmental glomerulosclerosis is marked by progressive decrease in renal functional and sclerosis on biopsy over a period of months to years. We report a variant exemplified by 2 children who developed chronic renal failure within 12 weeks of the onset of nephrotic syndrome; repeat renal biopsies demonstrated extensive extracapillary glomerular proliferation and crescent formation. Both were males, less than 5 years of age, presenting with nephrotic syndrome resistant to steroid therapy and normal renal function. Renal biopsies done after 8 weeks of therapy, demonstrated findings compatible with focal segmental glomerulosclerosis. Within 12 weeks of onset of nephrotic syndrome, both patients experienced a decrease in renal function requiring dialysis. Repeat renal biopsies revealed extensive extracapillary glomerular proliferation with crescent formation. These patients represent a variant of focal segmental glomerulosclerosis characterized by rapid progression to renal failure with extensive extracapillary glomerular proliferation and crescent formation.

Immune deposits and mesangial hypercellularity in minimal change nephrotic syndrome: clinical relevance.

Occasional patients with nephrotic syndrome and minimal histologic change demonstrate glomerular deposition of small amounts of immunoglobulin and complement. Some consider this a disease distinct from MCNS. To investigate the clinical importance of immune deposits and mesangial hypercellularity in the initial biopsy, the clinical records, follow-up data, and renal biopsies of 68 patients (ages 6 months to 16 years) with MCNS by light microscopy were reviewed. Among 68 patients followed a mean of 6.2 years, eight of 25 patients with immune deposits on initial renal biopsy were steroid nonresponsive. Only one of 43 patients without immune deposits was steroid nonresponsive (P = 0.00005). Of 44 patients with normal mesangial cellularity, 31 experienced fewer than three relapses a year, whereas of 15 patients with mesangial hypercellularity, only six experienced fewer than three relapses a year (P = 0.035). The data suggest that immune deposits and increased mesangial cellularity in children with NS and minimal light microscopic change may predict the clinical course.

IgA nephropathy in children.

Three children presented with proteinuria, microscopic hematuria, episodic gross hematuria and normal renal function. Renal histology consisted predominantly of mesangial IgA deposition. The above clinical and biopsy findings are consistent with a diagnosis of IgA nephropathy. To date, these 3 children have maintained normal renal function. The authors hypothesize that this may be due to the absence of simultaneous complement deposition within the glomerulus.

Nocardiosis in children: report of three cases and review of the literature.

The clinical illnesses observed in three adolescents with Nocardia asteroides infection are described. The organism has been classified as a bacterium and placed in the Actinomycetaceae family. Sulfonamides remain the first choice for chemotherapy but alternative drugs are available and may be essential in successful therapy. Nocardial infections in children indicate the need for evaluation for an underlying immunological deficiency. Nocardia species should be considered as possible causative agents in immunocompromised patients with infection.