Association of High Normal Body Weight in Youths With Risk of Hypertension.

Importance: Ample evidence links obesity to hypertension in youths. However, the association of high normal body mass index (BMI) with obesity and the interaction with different weight trajectories are not well understood. Objective: To examine the hypertension risk associated with high normal BMI for age and different weight trajectories in youths. Design, Setting, and Participants: This retrospective cohort study assessed 801 019 youths aged 3 to 17 years in an integrated health care system in Southern California from January 1, 2008, to February 28, 2015, with a maximum follow-up of 5 years from January 1, 2008, to February 28, 2020. Data analysis was performed from 2018 to 2022. Exposures: Youths were compared by first available (baseline) sex-specific BMI for age and change in the distance to the median BMI for age during the 5-year follow-up. Main Outcomes and Measures: Cox proportional hazards regression models with age as a time scale to assess hypertension risk (based on 2017 Blood Pressure Guidelines by the American Academy of Pediatrics from 3 consecutive independent visits), adjusted for sex, race and ethnicity, socioeconomic status, baseline year, and birth year. Results: A total of 801 019 youths (mean [SD] age, 9.4 [4.6] years; 409 167 [51.1%] female]; 59 399 [7.4%] Asian and Pacific Islanders, 65 712 [8.2%] Black, and 427 492 [53.4%] Hispanic) were studied. Compared with youths with a baseline BMI for age in the 40th to 59th percentiles, the adjusted hazard ratio (aHR) for hypertension within a maximum of 5 years was 1.26 (95% CI, 1.20-1.33) for youths between the 60th and 84th percentiles if they maintained their BMI for age. With every 1-unit annual increase in the distance to the median BMI for age, the aHR increased by 1.04 (95% CI, 1.04-1.05). The aHR was 4.94 (95% CI, 4.72-5.18) in youths with a baseline BMI for age in the 97th percentile or higher who maintained their body weight. Weight gain increased the risk associated with baseline BMI for age in the 97th percentile or higher with an aHR of 1.04 (95% CI, 1.04-1.05) per 1-unit annual increase in the distance to the median BMI for age. The risk associated with weight change was higher in youths living with low to high normal weight and overweight than in youths living with severe obesity. Conclusions and Relevance: In this cohort study of youths, high normal body weight above the 60th percentile of BMI for age was associated with increased risk of hypertension. Weight gain was associated with further increases in hypertension risk. Further research is needed to evaluate the wide range of body weight considered normal in youths and the health risks associated with high normal weight.

Failure to confirm high blood pressures in pediatric care-quantifying the risks of misclassification.

Pediatric practice guidelines call for repeating an elevated office blood pressure (BP) at the same visit, but there are few data available to support this recommendation. We compared the visit results in children aged 3 to 17 years with a BP reading ≥95th percentile (n = 186 732) based on the initial BP and the mean of two BP readings, using electronic medical records from 2012-2015. Failure to repeat an initial BP reading ≥95th percentile would lead to a false "hypertensive" visit result in 54.1% of children who would require follow-up visits. After an initial visit result indicating hypertension, hypertension stage I or stage II was sustained in 2.3% and 11.3% of youth during their next visits, respectively. In conclusion, only approximately half of the pediatric patients would be correctly classified based on their initial BP. The recommendation to repeat high BP during the same visit needs to be emphasized because it saves unnecessary follow-up visits.

The prevalence of primary pediatric prehypertension and hypertension in a real-world managed care system.

To assess the burden associated with hypertension, reliable estimates for the prevalence of pediatric hypertension are vital. For this cross-sectional study of 237,248 youths aged 6 to 17 years without indication of secondary hypertension, blood pressure (BP) was classified according to age, sex, and height using standards from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents as prehypertension with at least 1 BP ≥90th percentile and as hypertension with 3 BPs ≥95th percentile. The prevalence of prehypertension and hypertension were 31.4% and 2.1%, respectively. An additional 21.4% had either 1 (16.6%) or 2 (4.8%) BPs ≥95th percentile. Based on this large population-based study using routinely measured BP from clinical care, a remarkable proportion of youth (6.9%) has hypertension or nearly meets the definition of hypertension with 2 documented BPs in the hypertensive range.

Trabecular bone volume and osteoprotegerin expression in uremic rats given high calcium.

Calcium (Ca)-containing phosphate binders have been recommended for the treatment of hyperphosphatemia in children with chronic kidney disease. To study the effects of high Ca levels on trabecular bone volume (BV) and osteoprotegerin (OPG) expression in uremic young rats, a model of marked overcorrection of secondary hyperparathyroidism was created by providing a diet of high Ca to 5/6 nephrectomized young rats (Nx-Ca) for 4 weeks. The results of chondrocyte proliferation and apoptosis, osteoclastic activity, OPG expression and BV were compared among intact rats given the control diet, intact rats given a high Ca diet and 5/6 nephrectomized rats given the control diet (Nx-Control) and the high Ca diet (Nx-Ca). Ionized Ca levels were higher and parathyroid hormone levels were lower in Nx-Ca rats than in the other groups. Final weight, final length and final tibial length of Nx-Ca rats were significantly less than those of the other groups, although the length gain did not differ among the groups. The hypertrophic zone width was markedly enlarged in Nx-Ca rats. Chondrocyte proliferation rates did not differ among the groups, whereas osteoclastic activity was decreased in Nx-Ca rats compared with the Nx-Control animals. The OPG expression and BV were increased in Nx-Ca rats compared with the Nx-Control rats. Increased BV should improve bone strength, whereas disturbance of osteoclastogenesis interferes with bone remodeling. Bone quality has yet to be determined in high Ca-fed uremic young rats.

Sevelamer hydrochloride: an effective phosphate binder in dialyzed children.

This pilot study was designed to evaluate the efficacy and acceptability of sevelamer hydrochloride as a phosphate binder in pediatric patients treated with dialysis. A 6-month open-label trial of sevelamer hydrochloride (Renagel) was initiated in 17 patients, aged 11.8+/-3.7 years, undergoing hemodialysis ( n=3) or peritoneal dialysis ( n=14). Following a 2-week washout period of the phosphate binders, serum phosphorus increased from 5.2+/-1.3 mg/dl to 7.5+/-2.2 mg/dl ( P<0.0002). After initiation of therapy with sevelamer hydrochloride, serum phosphorus levels decreased to 6.2+/-1.2 mg/dl ( P<0.01) during the first 8 weeks and final values were 6.3+/-1.5 mg/dl. Serum calcium concentration decreased during the washout period from 9.4+/-0.9 mg/dl to 8.9+/-1.5 mg/dl ( P<0.01); values remained unchanged thereafter. The serum calcium-phosphorus ion product decreased during the first 8 weeks and values did not change subsequently. Serum bicarbonate, parathyroid hormone, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride levels did not change. The initial prescribed dose of sevelamer hydrochloride was 121+/-50 mg/kg (4.5+/-5 g/day) and the final prescribed dose was 163+/-46 mg/kg (6.7+/-2.4 g/day). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug.

Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis.

BACKGROUND: Accurate measurements of the concentration of parathyroid hormone (PTH) in serum or plasma are essential for the proper assessment of renal osteodystrophy. The first-generation immunometric PTH assay (1st PTH-IMA) not only detects the intact hormone, but also additional PTH fragments truncated at the amino N-terminally truncated PTH-derived fragments [ntPTH(1-84)]. A second-generation immunometric PTH assay (2nd PTH-IMA) recognizes only PTH(1-84) and possibly PTH fragments that are truncated at the carboxyl-terminus but not PTH(7-84). Whether estimates of the ratio between PTH(1-84) and ntPTH(1-84) fragments are a better predictor of bone turnover remains controversial. METHODS: Thirty-three patients aged 12.8 +/- 4.4 years treated with continuous cycling peritoneal dialysis (CCPD) for 13 +/- 9 months underwent iliac crest bone biopsy. PTH levels were measured by two newly developed first-generation and second-generation PTH-IMA. The ntPTH(1-84) fragments were calculated by subtracting PTH values determined using the 2nd PTH-IMA from values obtained using 1st PTH-IMA that detects both PTH(1-84) and relatively large ntPTH(1-84). RESULTS: Determinations of PTH levels by both assays were highly correlated (r = 0.89, P < 0.001). The relationships between first-generation and second-generation PTH-IMA and bone formation were similar (r = 0.67, P < 0.0001 and r = 0.64, P < 0.0001, respectively). When patients were grouped according to the presence or absence of secondary hyperparathyroidism, the ratio PTH(1-84) to ntPTH(1-84) did not differ between groups. CONCLUSION: PTH concentrations determined by either the first- or the second-generation PTH-IMA were found to be better predictors of bone formation than the PTH(1-84) to ntPTH(1-84) fragments ratio.

Bone density measurements in pediatric patients with renal osteodystrophy.

Peripheral quantitative computed tomography (pQCT) can selectively measure the densities of cortical and trabecular bone, but there is limited information about its use in patients with renal osteodystrophy. Thus pQCT (Norland XCT-2000, Stratec, Pforzheim, Germany) was performed at the ultradistal radius in 21 patients aged 16+/-3.6 (SD) years on continuous cycling peritoneal dialysis. Trabecular bone density (TBD) was higher in patients, 206+/-16 mg/cm(3), than in controls, 182.7+/-24.8 mg/cm(3) ( P<0.0001), whereas cortical bone density (CBD) was lower in patients, 946.5+/-147.5 mg/cm(3), than in controls, 1,153+/-25.4 mg/cm(3) ( P<0.001). TBD was inversely correlated with age ( r=-0.59, P=0.05), height ( r=-0.59, P<0.01), and weight ( r=-0.51, P<0.05). In contrast, CBD was positively correlated with age ( r=0.53, P<0.05), height ( r=0.56, P<0.05), and weight ( r=0.53, P<0.05). CBD was inversely related to serum alkaline phosphatase ( r=-0.71, P<0.001) and parathyroid hormone levels ( r=-0.50, P<0.05). In patients with adynamic bone, TBD was less, 192+/-9 mg/cm(3), than in those with high-turnover lesions, 215+/-13 mg/cm(3), P<0.001. CBD, however, was lower in patients with high-turnover lesions, 900+/-151 mg/cm(3), than in those with low turnover, 1,022+/-111 mg/cm(3), P<0.05. Compared with controls, in patients with high-turnover lesions, CBD was lower ( P<0.0001) and TBD higher ( P<0.0001). These findings suggest that pQCT may be an additional tool in the assessment of renal osteodystrophy.

Cell biology of renal osteodystrophy.

Renal osteodystrophy, a well-recognized complication of chronic renal failure, encompasses a spectrum of skeletal disorders ranging from high-turnover lesions of secondary hyperparathyroidism, the most common histologic lesion in pediatric patients with end-stage renal disease, to low-turnover lesions of adynamic renal osteodystrophy, which has become a common skeletal lesion in adults with chronic renal failure. Several advances have been made in the understanding of the pathogenesis of secondary hyperparathyroidism, particularly the critical roles of calcium, phosphorus, and vitamin D in promoting excess parathyroid hormone (PTH) synthesis and secretion, and parathyroid gland hyperplasia in renal failure. These insights will guide the development of more effective strategies for the prevention and management of renal bone disease.

Growth hormone and the skeleton in pediatric renal allograft recipients.

Recombinant human growth hormone has been utilized to augment linear growth in pediatric renal allograft recipients. The skeletal changes that accompany growth hormone therapy have not been described in children. Thus, 23 stable prepubertal pediatric kidney recipients, aged 10 +/- 3 years, with a mean transplant time of 3.4 +/- 2.5 years and histological findings of normal bone formation and adynamic bone on bone biopsies were prospectively randomized into two groups. These comprised a treated group that received 12 months of growth hormone and a control group that did not receive any treatment. Anthropometric measurements and blood for serum calcium, phosphorus, parathyroid hormone (PTH), osteocalcin, and insulin-like growth factor-I (IGF-I) were obtained every 3 months. Measurements of bone mass by dual-energy X-ray absorptiometry were performed at the beginning and end of the study period. All patients underwent an initial and final bone biopsy procedure after double tetracycline labeling. Annual growth velocity increased and standard deviation scores for height improved in the treated group. Serum IGF-I levels increased in the treated group and the increase was evident in patients with normal bone formation who received growth hormone but not in patients with adynamic bone. Serum calcium, phosphorus, osteocalcin, and PTH levels did not differ between the treated and control groups. Bone mass did not change in the treated group, but declined after 12 months in the control group. Bone formation rates did not increase with growth hormone treatment. Thus, growth hormone therapy improves linear growth and maintains bone mass, but does not favorably affect bone formation rates in stable pediatric renal allograft recipients.