Robert J. Cunningham

β-Blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial

Abstract Antihypertensive medications are used extensively in children despite a paucity of randomized, placebo-controlled trials. This study was among the first randomized, controlled pediatric antihypertensive medication trials, in which the combination drug bisoprolol fumarate/hydrochlorothiazide (B/HT) was compared with placebo. The study comprised a 2-week single-blind placebo screening period, a 6-week double-blind dose titration period, a 4-week double-blind dose maintenance period, and a 2-week double-blind dose-tapering period. One hundred and forty subjects were enrolled to achieve 94 randomized subjects treated either with B/HT (n=62) or placebo (n=32). B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure (SiSBP) (9.3 vs. 4.9 mmHg, P<0.05) and sitting diastolic blood pressure (SiDBP) (7.2 vs. 2.7 mmHg, P<0.05). The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension. The percentage of subjects with BP less than the 90th percentile at study completion was 45% for B/HT and 34% for placebo (P=NS). Although the study demonstrated that B/HT reduced BP safely compared with placebo, the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension, particularly in adolescents with mild-to-moderate BP elevation.

Post-transplant renal artery stenosis : Impact of therapy on long-term kidney function and blood pressure control

PURPOSE We assessed the long-term outcome of different treatment methods for transplant renal artery stenosis. MATERIALS AND METHODS Outcome data for 23 patients with transplant renal artery stenosis treated during a 16-year period were reviewed and analyzed. RESULTS There was a higher incidence of renal artery stenosis in cadaveric donor kidneys compared to living donor kidneys (2% versus 0.3%, p < 0.02), and in cadaveric kidneys from pediatric donors less than 5 years old compared to those from adults (13.2% versus 1.3%, p < 0.01). Six patients underwent primary medical treatment for renal artery stenosis, with a successful outcome in 4 (mean followup plus or minus standard error 57 +/- 22 months) and failure in 2. Of the patients 16 were treated with percutaneous transluminal angioplasty, including 12 who were cured or improved with respect to hypertension (followup 44.7 +/- 7.6 months). Five patients underwent surgical revascularization for renal artery stenosis with postoperative improvement of hypertension (followup 18.8 +/- 11.6 months). Overall, 21 of 23 patients (91%) were treated successfully for transplant renal artery stenosis with cure or improvement of associated hypertension. Posttreatment renal function was stable or improved in 18 patients, while renal function deteriorated due to parenchymal disease in 3. CONCLUSIONS Most patients with transplant renal artery stenosis can be treated successfully. Percutaneous transluminal angioplasty is the initial interventive treatment of choice for high grade renal artery stenosis. Surgical revascularization is indicated if percutaneous transluminal angioplasty cannot be done or is unsuccessful.

Cognitive functioning and school performance in children with renal failure

Although previous studies have documented neuropsychological deficits in children with end-stage renal disease, few have evaluated and compared the cognitive functioning and the school performance of children with renal failure. The current study evaluated the influence of chronic renal failure on cognitive functioning and school performance in children and adolescents with end-stage renal disease undergoing dialysis and after renal transplantation. Participants were given standardized IQ and achievement tests to assess cognitive functioning and ability. Academic performance was determined by evaluating grades for the semester in which the testing was performed; a grade point average (GPA) was calculated based on a 4.0-point scale. The 11 dialysis patients and 13 transplant patients were comparable in age, race, sex, and socioeconomic status. Overall IQ and subtest scores demonstrated no differences between the two groups. Performance on the Woodcock-Johnson achievement tests showed that the transplant patients did better on achievement tests of written language (P=0.04) and in school performance in English compared with dialysis patients (P<0.05). Furthermore the dialysis patients tended to be below age and grade level in all areas, whereas the transplant patients were achieving at or above these levels. There were significant differences in the age equivalent scores between the dialysis and transplant patients in the areas of mathematics and written language (P<0.05). However, when grades were evaluated there were no differences in overall GPA or in the mathematics GPA. Days absent were not different between the two groups. These data demonstrate that both groups of patients were of similar intellectual ability; the achievement of the dialysis patients was behind that of the transplant patients and this lag was not necessarily reflected in school grades. Patients with chronic renal failure should have cognitive and achievement testing on a regular basis, and areas of deficit should be addressed by the schools.

Detrimental effect of cyclosporine on initial function of cadaver renal allografts following extended preservation. Results of a randomized prospective study.

We report herein the resul6ts of a randomized prospective trial comparing maintenance cyclosporine (CsA)-p prednisone immunosuppression to a regiment of aazathioprine-prednisone-antilymphocyte globulin (ALG) in cadaver renal transplant recipients. Fifty-six patients were entered into this study with 31 assigned to the ALG group and 25 to the CsA group. These two groups were well matched for most major determinants of graft outcome and the mean renal preservation time was 37 hr in each group. The incidence of acute tubular necrosis (ATN) was high in both groups (58% ALG, 72% CsA, NS). There were five cases of primary nonfunction in the CsA group and only one in the ALG group (P=.05). Of the kidneys that functioned, the mean seum creatimine nadir (1.5 vs. 2.2 mg/dl, P=.03) were both loss in the ALG group. The actuarial one-year graft survival rate in the ALG and CsA groups is 78% and 48%, respectively (P<.05). This difference is mainly due to the large number of primary nonfunctioning grafts in the latter group, which we attribute to the effect of CsAs nephrotoxicity superimposed on renal ischemia incurred prior to transplantation. These data emphasize that, in order to realize the full benefit of csA in cadaver transplantation, renewed emphasis must be placed on minimizing ischemic renal damage.

Pregnancy after donor nephrectomy

The use of living-related kidney donors has been a routine practice in most major transplant centers in the United States for more than 20 years. Concern has arisen regarding the potential for developing hypertension and progressive renal dysfunction after renal donation. Pregnancy results in hyperf

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.

Improved results of vascular reconstruction in pediatric and young adult patients with renovascular hypertension

From 1955 to 1988, 56 patients 21 years old or younger underwent surgical treatment for renovascular hypertension at our clinic. The cause of renal artery disease was fibrous dysplasia in 53 patients, Takayasus arteritis in 2 or an arterial aneurysm in 1. Bilateral or branch renal artery disease, and extrarenal arterial disease were present in 16, 23 and 11 patients, respectively. The results of 28 patients treated from 1955 to 1977 (group 1) were compared to those of 28 patients treated from 1978 to 1988 (group 2). Hypertension was cured or improved postoperatively in 83% of the patients from group 1 and in 96% from group 2 (p = 0.07). However, this outcome was achieved through surgical revascularization in only 48% of the patients from group 1 compared to 96% from group 2 (p = 0.0002). A multivariate analysis revealed that the only significant variable related to clinical outcome was the era of treatment, which reflects the improved technical efficacy of revascularization during the last decade. Aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. It currently is possible to achieve amelioration of hypertension and preservation of renal function in most young patients with renal artery disease.

Renal Transplantation in End Stage Renal Disease Patients with Existing Urinary Diversion

From 1971 to 1984 renal transplantation was performed in 20 patients with end stage renal disease who presented with an existing form of urinary diversion. These patients were evaluated with a cystometrogram, voiding cystourethrogram and cystoscopy. In some cases bladder function was studied further by cycling through a suprapubically placed catheter. The bladder was considered unstable in 13 patients and undiversion was done at transplantation. The period of prior diversion ranged from 3 to 20 years (mean 12.7 years). There were no surgical complications postoperatively and normal bladder function returned in all patients. Currently, 8 patients have a functioning renal allograft 16 months to 9 years after transplantation (mean 4.2 years). Seven patients were considered to have a nonusable bladder owing to severe neurogenic disease or refractory contracture. In these patients transplantation was done into a pre-fashioned intestinal conduit (5) or cutaneous ureterostomy (2). Currently, 4 patients have a functioning renal allograft 16 months to 6.2 years after transplantation (mean 3.8 years). Transplantation candidates who present with an existing form of urinary diversion should be evaluated carefully, since many will have a usable bladder. Regardless of whether the bladder is usable, transplantation can be performed safely with no increased surgical or immunological risk.

Rapidly progressive glomerulonephritis in children: a report of thirteen cases and a review of the literature.

Summary: The clinical course and outcome of rapidly progressive glomerulonephritis (RPGN) of variable etiology are not well defined in children. The present investigation reports on the clinical characteristics, the course and outcome, as well as the results of treatment of 13 children with apparent postinfectious RPGN. Three of 7 patients with documented streptococcal RPGN and 3 of 6 patients with RPGN of nonstreptococcal etiology progressed to chronic renal failure. In some patients, anticoagulant and anti-platelet therapy appear to have improved survival. The severity of crescent formation, not the presumable etiology, appears to be a reliable prognosticator.Speculation: A number of disease processes can result in renal damage of sufficient severity to cause crescent formation. The induction, resolution, or progression of crescents to sclerosis may be influenced by anticoagulant therapy.

Safety and cost effectiveness of pediatric percutaneous renal biopsy

Abstract. 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.