Search

Publication of the Fourth Report on high blood pressure (BP) in children and adolescents by the National High BP Education Program (NHBPEP) in 2004 has been followed by a remarkable increase in interest in pediatric hypertension. New data have emerged on the epidemiology of hypertension in the young, the influence of the childhood obesity epidemic on BP, how ambulatory BP monitoring (ABPM) can be used in evaluating elevated BP and the extent of hypertensive target-organ damage in the pediatric age group. Exciting new information on drug treatment of pediatric hypertension has been produced by industry-sponsored clinical trials of antihypertensive medications spurred by the FDA Modernization Act (FDAMA) and successor legislation. Despite these trends, recognition of elevated BP in children and adolescents by primary care providers remains problematic. This article will highlight these and other aspects of pediatric hypertension, hopefully providing a snapshot of where we are in early 2008, and pointing out areas where further work is needed in order to reduce the future burden of adult cardiovascular disease.

We report the spontaneous development of recurrent chyloperitoneum as a complication of peritoneal dialysis in a toddler. An 18-month-old boy with end-stage renal disease (ESRD) on continuous cycling peritoneal dialysis developed spontaneous chyloperitoneum. He was treated conservatively, with a low-fat diet supplemented with medium-chain triglycerides. The chyloperitoneum resolved within 2 days of his being on the low-fat diet, but it recurred after re-institution of regular feeds on four occasions. After 3 months, the chyle leak finally resolved after an extended period of low-fat feeds. Chyloperitoneum is a rare complication of peritoneal dialysis that can be confused with signs of peritonitis, and it is important to differentiate between the two so that appropriate management can be undertaken. This paper discusses the possible causes, management and complications of recurrent chyloperitoneum.

In children who are on chronic peritoneal dialysis, peritonitis is the primary complication compromising technique survival, and the optimal therapy of peritonitis remains uncertain. An Internet-based International Pediatric Peritonitis Registry was established in 47 pediatric centers from 14 countries to evaluate the efficacy and safety of largely opinion-based peritonitis treatment guidelines in which empiric antibiotic therapy was stratified by disease severity. Among a total of 491 episodes of nonfungal peritonitis entered into the registry, Gram-positive organisms were cultured in 44%, Gram-negative organisms were cultured in 25%, and cultures remained negative in 31% of the episodes. In vitro evaluation revealed 69% sensitivity of Gram-positive organisms to a first-generation cephalosporin and 80% sensitivity of Gram-negative organisms to a third-generation cephalosporin. Neither the risk factors assumed by the guidelines nor the choice of empiric therapy was predictive of either the early treatment response or the final functional outcome of the peritonitis episodes. Overall, 89% of cases achieved full functional recovery, a portion after relapsing peritonitis (9%). These data serve as the basis for new evidence-based guidelines. Modification of empiric therapy to include aminoglycosides should be considered.

The hemolytic-uremic syndrome (HUS) typically presents in toddlers or older children after an episode of bloody diarrhea caused by Escherichia coli 0157:H7. However, numerous ’’atypical’’ presentations have been described, including familial cases. Here we describe what we believe to be the first report of familial HUS in a premature infant during the neonatal period.

Objective To determine whether casual blood pressure (BP) or ambulatory BP monitoring (ABPM) measurements obtained at the initial visit of a child with confirmed hypertension (HTN) might predict left ventricular hypertrophy (LVH), possibly obviating the need for echocardiography. Study design We conducted a cross-sectional study of 184 children aged 3 to 20 years who were referred for initial evaluation of elevated BP at 3 tertiary care centers. Casual BP and various ambulatory BP variables were analyzed to determine their association with LVH, defined after echocardiography by cardiologist diagnosis or a left ventricular mass index equal to or greater than the sex-specific 95th percentile. Results A total of 41% of children who had echocardiograms had LVH. Children with LVH were significantly more likely to be non-white and have a higher body mass index z-score. There was no difference in casual systolic or diastolic BP index in children with hypertension who had LVH and children with hypertension without LVH. Children with systolic or diastolic BP loads ≥50% were no more likely to have LVH than children with loads Conclusion LVH is common in children with newly diagnosed HTN. The initial examination of these children should include echocardiography, because neither the severity of casual BP elevation nor the presence of abnormal ambulatory BP results at initial diagnosis are predictive of LVH.

Given the variable response of steroid-resistant nephrotic syndrome (SRNS) to treatment with cyclosporin (CsA), it may be inappropriate to expose all SR patients to additional immunosuppression. How to determine from which patients to withhold CsA is unclear. We tested the hypothesis that in patients with primary focal segmental glomerulosclerosis (FSGS), steroid resistance predicts CsA resistance. We studied 16 children with steroid-dependent (SD) or steroid-resistant (SR) histologically confirmed primary FSGS treated with CsA with no prior exposure to other immunosuppressive medications. All had received at least 4 weeks of daily prednisone, followed by addition of CsA aiming at trough levels of 200 ng/ml. Of the 16 patients, nine (56%) were SR, of whom seven (78%) were CsA resistant and two (22%) were CsA responsive. Seven patients (44%) were SD; all of them (100%) were CsA responsive (P = 0.003, Fisher’s exact test). SR patients had faster deterioration of glomerular filtration rate (GFR) over a median follow-up of 21 months (P = 0.06). These data demonstrate that in primary FSGS, steroid resistance may predict CsA resistance. Genetic testing for known mutations associated with resistance to immunosuppression may be advisable before treatment of SR-FSGS patients with cyclosporin. Prospective studies should be conducted to explore this hypothesis.

Improving and maintaining quality patient care through the development and implementation of clinical protocols is an important facet in our health care system. Identifying the need for clinical protocols, developing and maintaining the protocols, and defining the specific role of pediatric nephrology nurses in this process is presented herein. To illustrate the process we have included two examples of current clinical protocols utilized by our division.

Hypertension occurs commonly in children with chronic kidney disease (CKD) and undoubtedly contributes to the progression of disease. This review summarizes the role of hypertension in the progression of CKD in children and highlights the central role played by the renin-angiotensin system in this relentless process. Strategies for reno-protection are discussed, and treatment recommendations are made for control of hypertension in this patient population.

BP elevation in adolescence may be the first clue to underlying renal or other organ-system pathology, or it may be simply a warning sign of future cardiovascular risk. Careful measurement of BP and thorough evaluation of adolescents with sustained BP elevation should make possible the identification of those who require treatment. Usually a combination of pharmacologic and nonpharmacologic measures will result in satisfactory control of hypertension while permitting a normal quality of life.

The USPSTF methods are appropriately evidencebased and consist of a systematic search of pertinent literature and careful analysis of the available studies, but their primary question is essentially unanswerable. The Task Force attempted to find direct evidence that screening for essential HTN in children leads to decreased CV morbidity in adults. While direct evidence of correlation to “adverse health outcomes” can often be found for many screenable adult diseases where morbidity and mortality are relatively common, pediatric hypertension is likely a condition where direct evidence linking childhood BP to adult outcomes will never be available. Searching for direct evidence is therefore not an appropriate method of ascertaining future risk or benefit since children rarely develop severe CV outcomes. Any study attempting to directly answer the USPSTF question would necessarily have to follow both screened and unscreened children for many decades to determine the direct impact of early HTN detection. The report is also premature given the early state of evidence in pediatric hypertension. It was only 36 years ago that the first consensus report on BP in children was

Primary hypertension is well known to occur in children, but the characteristics of such children are changing due to the influence of the obesity epidemic. In view of this, we conducted a cross-sectional study of 70 children [age 13.3+/-4 years (mean +/- SD)] with primary hypertension referred to a specialized pediatric hypertension clinic. Secondary hypertension had been excluded after a standardized diagnostic evaluation. Isolated systolic hypertension was present in 62.9% of subjects. Family history of hypertension was present in 86.2%, and 52.9% were obese (BMIor =95th percentile). BMI was weakly correlated with systolic BP (r =0.28,P =0.10) and was significantly correlated with total cholesterol (r =0.36,P =0.005) and triglycerides (r =0.42,P =0.01). Mean plasma renin activity (PRA) was 3.1+/-2.7 ng/ml/h. PRA was correlated with diastolic but not systolic BP. Patients with high PRA had higher diastolic BP and lower BMI compared to those with low PRA. Left ventricular hypertrophy was present in 24%. Mean 24-h systolic BP load by ambulatory BP monitoring was 52+/-24%; mean 24-h diastolic BP load was 18+/-16%; BP loads were greater in patients with high PRA. These data suggest that primary hypertension in children is characterized by systolic BP elevation, positive family history and obesity. Hyperlipidemia accompanies primary hypertension in obese children, and left ventricular hypertrophy is common. Patients with high PRA have more severe BP elevation. Future studies should focus on further defining the pathophysiology of primary hypertension in children, including the roles of renin and insulin resistance, so that improved methods of prevention and treatment can be developed.

To examine the long-term efficacy and safety of amlodipine in hypertensive children, data on prolonged use (or = 6 months) of amlodipine in 33 children were reviewed. All children received amlodipine as sole therapy for their hypertension. Causes of hypertension included solid organ transplant (n=19), renal disease (n=7) primary hypertension (n=6), and drug-induced hypertension (n=1). Mean patient age at the start of amlodipine treatment was 9.8+/-4.8 years (range 1.3-16.9); there were 19 boys and 14 girls. Mean duration of amlodipine treatment was 20.4+/-11.5 months (range 6-48). Analysis of blood pressure and dosing data revealed that blood pressure reduction was sustained throughout the period of amlodipine treatment, while amlodipine dose remained stable (mean effective daily dose 0.17+/-0.12 mg/kg). No patient required discontinuation of amlodipine because of adverse effects. This small study suggests that prolonged amlodipine treatment is well tolerated in hypertensive children and provides sustained blood pressure control. Further studies are necessary to determine what effects if any long-term calcium channel blocker treatment has on the growth and development of children with hypertension.

Industry-sponsored pediatric clinical trials of antihypertensive medications have greatly increased in number since passage of the Food and Drug Modernization Act of 1997. This development should ultimately benefit the treatment of hypertensive children by increasing the amount of scientific knowledge regarding the efficacy and safety of antihypertensive agents in children. However, the designs of many of these trials raise ethical questions related to the inclusion of placebo controls, a practice that has largely been abandoned in trials of antihypertensives in adults because of the well-known adverse consequences of untreated hypertension. This is an especially important issue in pediatric hypertension, as many hypertensive children have either secondary forms of hypertension or hypertension-induced target organ damage, potentially increasing the risk of harm during exposure to placebo. Against this background, and with a strong emphasis on protection of this vulnerable patient population, a strict set of conditions for use of placebos in pediatric antihypertensive trials is proposed.

Introduction of the anti-CD-25 mAb basiliximab into renal transplant protocols has reduced the incidence of acute rejection. However, its side-effect profile is still unfolding. We report three adolescents who developed severe non-cardiogenic PE within 2 days of renal transplantation.Pretransplant cardiorespiratory evaluation was normal in all cases. Transplant immunosuppression consisted of basiliximab induction, corticosteroids, and tacrolimus. Patients received standard fluid management during and after the transplant surgery.Patients 1 and 2 were 17- and 21-yr-old females. Pretransplant Hct values were 35 and 25% respectively. Each received 5-L normal saline during surgery. EBL was 200 and 500 mL in patients 1 and 2, respectively. There was immediate post-operative diuresis. Both developed non-cardiogenic PE by POD no. 2. BIPAP and PRVC were administered respectively. In both cases PE resolved within 1 wk. Patient 3 was a 19-yr-old male with pretransplant Hct of 43% who received a cadaveric renal transplant after 23.5-h cold-ischemia; 3.5 L normal saline was given during surgery. EBL was 100 mL. Non-cardiogenic PE ensued on POD no. 2 warranting assisted ventilation. The patient died following a sudden cardiopulmonary arrest on POD no. 3.Potential mechanisms for the development of PE include cytokine release from basiliximab with increased capillary permeability, volume overload and ischemic-reperfusion injury. Improved awareness of this potential complication, prudent fluid management, and efforts to minimize graft-ischemia are recommended to prevent further cases.

Cyclosporin (Cs-A) is an effective treatment for difficult cases of nephrotic syndrome (NS), but its use can be complicated by renal toxicity and a high incidence of relapses after withdrawal. We reviewed the charts of 10 Cs-A-dependent patients and 4 patients with steroid-dependent nephrotic syndrome (SDNS) not previously treated with Cs-A therapy. All patients had persistent NS, even after prior treatment with oral cyclophosphamide. Of 10 patients treated with Cs-A, 4 had surveillance renal biopsies consistent with Cs-A toxicity, and 8 of 10 had interstitial fibrosis prior to mycophenolate mofetil (MMF). Patients were treated with MMF, at 1,200 mg/m(2) per day, in an attempt to allow weaning of Cs-A and/or steroid therapy, and reduce the frequency of relapses. Overall, a significant decrease in frequency of relapses was noted after initiation of MMF therapy. In addition, 5 patients were weaned off Cs-A by 1-2 years of follow-up. One patient was weaned off Cs-A and MMF, and remained in complete remission. However, the subgroup of patients with frequently relapsing SDNS not treated with Cs-A appeared to have a reduction in the number of relapses while on MMF that did not reach statistical significance. Two patients with intractable steroid-resistant NS continued to relapse repeatedly on MMF and Cs-A therapy. We conclude that in this small, single-center, uncontrolled experience, MMF therapy in patients with Cs-A-dependent NS appears to be effective in reducing Cs-A exposure. In addition, MMF appears to significantly decrease the frequency of relapses in this patient population. Further controlled studies are warranted to better define the potential efficacy and side effects of long-term MMF therapy in this setting.

IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing30 kg, and twice that dose for those30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127+/-50 vs. 112+/-31 ml/min/1.73 m(2), respectively ( P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24+/-0.38 vs. 0.61+/-1.37 ( P0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy.

A 17-year-old patient with sickle cell-beta thalassemia undergoing treatment with home iron chelation therapy inadvertently received ten times the recommended dose of intravenous deferoxamine. Acute renal failure (ARF) developed within hours. Immediate treatment with high-efficiency hemodialysis resulted in the prompt return of renal function after only one hemodialysis session. No long-term nephrotoxic effects of the deferoxamine overdose developed after more than 1 year of follow-up. Children with sickle cell disease who are on intravenous deferoxamine and their parents should be cautioned about the possibility of ARF with overdose due to malfunction of the pump and/or inadequate monitoring during treatment. ARF, should it occur in such children, appears to respond well to treatment with high-efficiency hemodialysis.

[Regarding the homemade sodium solutions][1] that we provided in the appendix to our article ([1][2]), use of these solutions began at our institution over 10 y ago after a pharmacy error resulted in an adverse event in a young child. It is estimated that medication errors occur in 6 of 100 orders

Many children with hypertension, particularly those with new-onset hypertension related to glomerulonephritis, organ transplantation, or other forms of secondary hypertension, require treatment with a short-acting antihypertensive in order to quickly achieve blood pressure (BP) control. We administered isradipine, a short-acting, second-generation calcium antagonist, to 72 such children. Retrospective data collection was undertaken to determine the effects of isradipine treatment. The mean age of children treated with isradipine was 74+/-55 months (mean+/-SD). Nearly all of these children had secondary hypertension and were initially treated as hospital inpatients for newly diagnosed hypertension. Mean isradipine dose was 0.36+/-0.17 mg/kg per day, with no significant variation in dose according to patient age. Isradipine was administered three times per day in most instances, but 21% of the time it was administered four times per day. An extemporaneous isradipine suspension was used in 62% of treatment courses. BP control was achieved with isradipine alone in 38 children; the remainder received isradipine in combination with additional antihypertensives. Comparison of pre-treatment BP with BP obtained 8+/-9 days later demonstrated a significant BP reduction with isradipine treatment, with a mean reduction of 14+/-13 mmHg for systolic BP and 13+/-15 mmHg for diastolic BP. There was no effect of isradipine treatment on heart rate. Adverse effects occurred in 9.5% of treatment courses, and included headache, flushing, dizziness, and tachycardia. We conclude that isradipine successfully lowers BP in hypertensive children with secondary forms of hypertension. Use of isradipine suspension allows infants and young children to be treated as readily as older children.

To examine the associations between abnormal birth history (birth weight2500 g, gestational age36 weeks, or small for gestational age), blood pressure (BP), and renal function among 332 participants (97 with abnormal and 235 with normal birth history) in the Chronic Kidney Disease in Children Study, a cohort of children with chronic kidney disease (CKD).Casual and 24-hour ambulatory BP were obtained. Glomerular filtration rate (GFR) was determined by iohexol disappearance. Confounders (birth and maternal characteristics, socioeconomic status) were used to generate predicted probabilities of abnormal birth history for propensity score matching. Weighted linear and logistic regression models with adjustment for quintiles of propensity scores and CKD diagnosis were used to assess the impact of birth history on BP and GFR.Age at enrollment, percent with glomerular disease, and baseline GFR were similar between the groups. Those with abnormal birth history were more likely to be female, of Black race or Hispanic ethnicity, to have low household income, or part of a multiple birth. Unadjusted BP measurements, baseline GFR, and change in GFR did not differ significantly between the groups; no differences were seen after adjusting for confounders by propensity score matching.Abnormal birth history does not appear to have exerted a significant influence on BP or GFR in this cohort of children with CKD. The absence of an observed association is likely secondary to the dominant effects of underlying CKD and its treatment.

Growth in children with chronic renal failure caused by polyuric, salt-wasting diseases may be hampered if ongoing sodium and water losses are not corrected. Twenty-four children were treated with polyuric chronic renal insufficiency (CRI; creatinine clearance

Acute renal failure in children requiring dialysis can be managed with a variety of modalities, including peritoneal dialysis, intermittent hemodialysis, and continuous hemofiltration or hemodiafiltration. The choice of dialysis modality to be used in managing a specific patient is influenced by several factors, including the goals of dialysis, the unique advantages and disadvantages of each modality, and institutional resources. This review will examine these aspects of acute renal failure management, with the goal of providing practical guidance regarding modality selection to the physician involved in the management of pediatric acute renal failure.

Of the several causes of nondiarrheal hemolytic uremic syndrome (HUS), infection with Streptococcus pneumoniae is infrequent, but important, because of its unique pathogenesis. A comprehensive literature review found 37 well-documented cases of S pneumoniae-associated HUS (SP-HUS), only 2 of which progressed to end-stage renal disease (ESRD). We report the third such child, and the first to receive a renal transplant following SP-HUS. Her course illustrates several unique characteristics of SP-HUS common to previous patients reported in the literature, including a greater duration of oligoanuria compared with cases not progressing to ESRD, the significant adverse effect of unwashed blood products, and a possible influence of female gender on outcome. Clinicians caring for children with SP-HUS should be aware of these differences and modify therapy appropriately to avoid known risk factors for poor outcome, specifically the use of unwashed blood products.

The calcium channel blockers (CCBs) are a diverse group of antihypertensive medications with variable pharmacokinetics and clinical effects. Although CCBs have been widely applied to the treatment of hypertensive children, data regarding the pharmacokinetics, efficacy and safety of these agents in children are extremely limited. In this review we briefly summarize the mechanism of action of CCBs and then summarize pertinent pharmacokinetic information on each of the CCBs commonly used in children, including amlodipine, diltiazem, felodipine, isradipine, intravenous nicardipine, nifedipine and verapamil. Clinically important drug interactions and adverse effects are discussed, as well as the potential role of CCBs in renal protection. Available pediatric efficacy and safety data are summarized, and recommendations made regarding the rational use of CCBs in the management of pediatric hypertension.

The optimal blood pressure target for the protection of kidney function in children with chronic kidney disease is controversial. The ESCAPE trial has now shown, however, that lowering the blood pressure target to below the 50th percentile slows pediatric chronic kidney disease progression.

Advances in technology and experience accumulated over the past 2 decades have resulted in the ability to successfully provide chronic peritoneal dialysis (PD) to children of all ages and sizes. However, many important clinical issues remain, including uncertainty regarding the "optimal" dialysis dose for children, the treatment of growth retardation associated with renal insufficiency, prevention of peritonitis, and the challenge of caring for newborn infants with end-stage renal disease (ESRD). This article summarizes current knowledge in each of these 4 areas, highlighting not only the advances of the past quarter-century, but also the questions that persist as we initiate the new millennium. The outcome of children receiving PD will be markedly improved only when ongoing and future research efforts reveal the optimal solutions to these important issues.

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.

Ambulatory blood pressure monitoring (ABPM) is widely utilized for the evaluation and management of hypertension in adults but has not been routinely used in the care of hypertensive children.To examine the potential impact that the routine use of ABPM might have on the evaluation and management of hypertension in children, we reviewed our early experience with this technique, comparing management decisions based on ABPM with those based on casual blood pressure readings.Twenty children (4-17 years old) underwent ABPM for either the initial evaluation of suspected hypertension or the ongoing management of known hypertension. ABPM studies were considered abnormal if over 40% of both systolic and/or diastolic blood pressure readings were above the 95th percentile for the child's age and gender.Of 13 children studied for suspected hypertension, nine had abnormal ABPM studies and were treated, but four had normal results and were therefore not treated. Of seven children with known hypertension studied by ABPM to assess their blood pressure control further, three had normal results and no management changes were made, but four had abnormal studies, prompting a change in therapy or further diagnostic testing. Overall, eight out of 20 ABPM studies led to the initiation of further diagnostic evaluation or a change in planned or ongoing therapy.We conclude that ABPM has the potential to become an important tool in the evaluation and management of childhood hypertension, and suggest that more widespread use of this technique in children is appropriate.

Traditionally, most cases of hypertension in children and adolescents have been attributed to secondary causes, with renal and cardiac disorders being the most common, at least in preadolescent children. However, most hypertensive adolescents have no identifiable underlying cause for their hypertension, perhaps with the exception of obese adolescents, in whom the hypertension is likely attributable to the same renal, central, and hormonal mechanisms present in hypertensive obese adults. 1 But what causes hypertension in youth with no underlying renal or other systemic disease and who are not obese? The answer to this question would likely provide significant insight into the pathophysiology of “essential” hypertension in adults as well. In this issue of Hypertension, Pludowski et al2 present intriguing data supporting the hypothesis that hypertension in the young is a disorder of maturation. Using dual x-ray absorptiometry to assess bone age, they demonstrate that hypertensive children and adolescents manifest advanced skeletal maturation compared with matched, normotensive control subjects. Advanced bone age was an independent predictor of blood pressure (BP) status in children with normal BP, prehypertension, and stages 1 and 2 hypertension. Significantly, the investigators matched not only for sex and age, but also for body mass index, thereby avoiding the confounding effects of obesity, which is known to be associated with accelerated skeletal growth in children.3 These data reinvigorate a line of investigation from several decades ago, when the phenomenon of pediatric hypertension was first being recognized, and mechanisms of hypertension in the young were first being examined. As summarized by Ingelfinger, 4 early investigators interested in childhood primary hypertension focused on multiple possible underlying factors, including altered hemodynamic regulation, abnormalities of the renin-angiotensin system, and other hormonal perturbations that had already been demonstrated in adults with hypertension. At the same time, epidemiologists interested in childhood hypertension were recognizing that normative values for childhood BP based on age only might result in misclassification of BP because of differences in maturation among children of comparable ages.5 It was, therefore, suggested that height as an index of maturation should be considered when classifying a child’s or an adolescent’s BP as normal or elevated, an approach that was adopted by the Working Group on High Blood Pressure in Children and Adolescents in 1996 and that remains a cornerstone of current consensus recommendations for evaluating childhood BP. At approximately the same time, investigators associated with the Philadelphia Blood Pressure Project analyzed data including bone age on a sample of children (all black) followed longitudinally into adolescence and found those children who had the highest levels of BP at 7 years of age achieved adult levels of BP earlier than those who had the lowest levels of BP at age 7 and had advanced bone age in adolescence compared with those with the lowest levels of BP at 7 years of age. 6 In other words, advanced skeletal maturation in children with high BP was demonstrated to be associated with higher BP in early adolescence. Although drawn from different data, these findings reinforced the conclusions drawn by epidemiologists5 that growth and maturational status should be considered when assessing BP in the young. It was Lever and Harrap 7 who eventually summarized multiple lines of evidence, including the bone age data from the Philadelphia Blood Pressure Project, to advance the hypothesis that, in childhood, the development of primary hypertension is likely tied to other growth-promoting processes and suggested 3 possible endocrinologic mechanisms

Neoral was instituted in pediatric renal transplant patients with the hypothesis it would have more predictable kinetics than Sandimmun. However, significant questions have arisen concerning potential toxicity and dosing interval related to its rapid absorption with subsequent high initial peak. This is compounded by the fact that children appear to metabolize cyclosporine at a greater rate than adults. This combination of a rapid peak and rapid absorption may then result in lower trough levels at 12 h. We compared the trough cyclosporine levels of nine children who received Neoral with nine who received Sandimmun at the time of initial transplantation. More frequent dosing (every 8 h) was required in the Neoral population compared with the Sandimmun population for the 1st month in order to obtain comparable trough levels. Beyond the initial 4-6 weeks, trough levels were similar for Neoral and Sandimmun. Whereas 1-month creatinine levels and blood pressures were similar, the number of blood pressure medications was significantly higher in the Neoral group. At 5.5 +/- 1.1 months' followup, a single patient in the current Neoral group and in the retrospective Sandimmun group each experienced a single OKT3 allograft-treated rejection. We suggest that the area under the curve is different in Neoral than Sandimmun, and the initial dosing frequency may need to be adjusted accordingly.

Purpose Kumasi, Ghana has an extraordinarily high number of cases of severe malaria. A community project was designed to supplement the current Ghanaian public health projects aimed at teaching people how to avoid malaria infection and how to handle a suspected case of malaria. Methods The first task was to educate teenage girls on the dangers of malaria. The second task was to educate current Ghana Red Cross Youth Educators on the topic of malaria prevention and first aid so that they can do talks on malaria. The third and final task was to develop a culturally appropriate reference guide on the topic of malaria. Results Twenty youth educators were trained to give talks on malaria. Ninety teenage girls were supplied with the same information, and a guide to giving such talks was written and submitted to the Ghana Red Cross Society for possible nationwide use. Conclusions Malaria education in Ghana is an ongoing and overwhelming struggle that frustrates many health professionals. Malaria itself is an omnipresent and overwhelming disease that destroys lives. A large hurdle in malaria education is finding a way to teach people who struggle with illiteracy and poor education how they can fight something they do not understand. Teaching youth educators about malaria is one step towards making complicated microbiology accessible to people who do not even know how to read. Providing those youth educators with a reference guide that puts scientific information into terms that they can understand is another step.

P-176 Key Words: Ambulatory Blood Pressure, Type 2 Diabetes Mellitus, Microalbuminuria