Cynthia S. Bell

Left Ventricular Hypertrophy in Hypertensive Adolescents Analysis of Risk by 2004 National High Blood Pressure Education Program Working Group Staging Criteria

The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recently recommended staging hypertension (HTN) in children and adolescents based on blood pressure severity. The use of blood pressure staging and its corresponding therapeutic approach was examined in this pooled analysis assessing the risk for end-organ damage, specifically left ventricular hypertrophy among hypertensive adolescents stratified by working group criteria. Newly diagnosed hypertensive adolescents and normotensive control subjects similar in age, race/ethnicity, gender, and body mass index completed casual and 24-hour ambulatory blood pressure measurements, M-mode echocardiography, and fasting serum laboratories. Hypertensive subjects had higher insulin and cholesterol but similar glucose levels as compared with control subjects. Among subjects with stage 1 HTN by casual blood pressure, 34% had white-coat HTN as opposed to 15% of stage 2 hypertensive subjects. Of the subjects with normal casual measurements, 20% had HTN by ambulatory monitoring. Subjects with stage 2 HTN by casual measurement alone (odds ratio: 4.13; 95% CI: 1.04 to 16.48) and after 24-hour ambulatory confirmation (odds ratio: 7.23; 95% CI: 1.28 to 40.68) had increased odds for left ventricular hypertrophy. In addition, the risk for left ventricular hypertrophy was similar for subjects with masked and confirmed stage 1 HTN, whereas subjects with white-coat HTN had a risk comparable to normotensive subjects. Thus, recommendations that adolescents with stage 2 HTN by casual measurements alone receive medication initially along with therapeutic lifestyle counseling are reasonable, though ambulatory blood pressure monitoring remains a valuable tool for evaluating children with stage 2 HTN, because >10% have white-coat HTN.

Sevelamer Versus Calcium Carbonate in Incident Hemodialysis Patients: Results of an Open-Label 24-Month Randomized Clinical Trial

BACKGROUND Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis remains to be elucidated. STUDY DESIGN Open-label randomized controlled trial with parallel groups. SETTINGS & PARTICIPANTS 466 incident hemodialysis patients recruited from 18 centers in Italy. INTERVENTION Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate) for 24 months. OUTCOMES All individuals were followed up until completion of 36 months of follow-up or censoring. CV death due to cardiac arrhythmias was regarded as the primary end point. MEASUREMENTS Blind event adjudication. RESULTS At baseline, patients allocated to sevelamer had higher serum phosphorus (mean, 5.6 ± 1.7 [SD] vs 4.8 ± 1.4 mg/dL) and C-reactive protein levels (mean, 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL) and lower coronary artery calcification scores (median, 19 [IQR, 0-30] vs 30 [IQR, 7-180]). At study completion, serum phosphate levels were lower in the sevelamer arm (median dosages, 4,800 and 2,000 mg/d for sevelamer and calcium carbonate, respectively). After a mean follow-up of 28 ± 10 months, 128 deaths were recorded (29 and 88 due to cardiac arrhythmias and all-cause CV death). Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate (HR, 0.06; 95% CI, 0.01-0.25; P < 0.001). Similar results were noted for all-cause CV mortality and all-cause mortality, but not for non-CV mortality. Adjustments for potential confounders did not affect results. LIMITATIONS Open-label design, higher baseline coronary artery calcification burden in calcium carbonate-treated patients, different mineral metabolism control in sevelamer-treated patients, overall lower than expected mortality. CONCLUSIONS These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients. However, the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load.

Effect of IV Contrast Medium on Renal Function in Oncologic Patients Undergoing CT in ICU

OBJECTIVE The purpose of our study was to assess the effect of IV contrast medium administered at CT on serum creatinine in an oncologic ICU population and to determine which of the variables before CT are most associated with renal function after administration of contrast material. MATERIALS AND METHODS We retrospectively reviewed 3,848 patient admissions to an oncology ICU. The following matched comparisons were undertaken: contrast-enhanced CT versus unenhanced CT and CT (with or without contrast medium) versus no CT. Matching criteria included age, sex, baseline serum creatinine, and severity of illness (modified sequential organ failure assessment [mSOFA] score). No patients with creatinine > 2.0 mg/dL received contrast material. Groups were compared using a rank sum test. Factors influencing creatinine after administration of contrast material were evaluated by multiple regression analysis. Parallel analyses using estimated glomerular filtration rate (eGFR) also were performed. RESULTS No significant difference was found in absolute change in creatinine between matched contrast-enhanced CT and unenhanced CT groups (n = 81), with mean (95% CI) creatinine rises after CT of 0.25 (0.04-0.46) and 0.11 (0.04-0.18) mg/dL, respectively. Similarly, for matched CT versus non-CT groups (n = 152), mean creatinine rises were 0.15 (0.05-0.25) and 0.12 (0.08-0.16) mg/dL, respectively. Parallel analyses using eGFR yielded similar results. Creatinine after administration of contrast material was associated with sex and mSOFA (p = 0.04 and 0.02, respectively) but not baseline creatinine. eGFR after administration of contrast material was associated with baseline eGFR (p < 0.0001). CONCLUSION Administration of IV contrast medium in oncologic ICU patients with relatively normal creatinine is associated with an increase in creatinine but not beyond that of simply undergoing CT or of a matched non-CT group in ICU. The eGFR, which includes sex in its derivation, may be a better predictor of contrast-enhanced renal function than creatinine.

Allograft Failure in Kidney Transplant Recipients With Membranoproliferative Glomerulonephritis

BACKGROUND Membranoproliferative glomerulonephritis types I (MPGN-I) and II (MPGN-II) are rare diseases that in limited case series have been reported to recur frequently in kidney transplants and have a negative impact on allograft survival. STUDY DESIGN Retrospective database review. SETTING & PARTICIPANTS 189,211 primary kidney transplants in the United Network for Organ Sharing (UNOS) database from September 1987 to May 2007. PREDICTOR OR FACTOR MPGN-I (811 patients; 0.4%), MPGN-II (179 patients; 0.1%), other GN (58,129 patients; 30.7%), and all other diagnoses (130,092 patients; 68.7%). OUTCOMES Death-censored and non-death-censored allograft survival. RESULTS Compared with controls, patients with MPGN-I and MPGN-II were significantly younger at the time of transplant, with a median age of 36 and 27 years compared with 44 years in the GN group and 46 years in all other disease groups, respectively (all P < 0.001). Mortality in patients with MPGN-I (8.8%) was significantly lower compared with the GN (11.3%; P = 0.02) and other disease (16.6%; P < 0.001) populations and lower in those with MPGN-II (9.5%) compared with the other disease (16.6%; P = 0.01) population. Graft failure rates were significantly higher in the MPGN-I (44.5%) cohort, but not in the MPGN-II (45.3%) cohort compared with the GN (38.0%) population (P < 0.001 and P = 0.05, respectively); neither MPGN cohort differed from the other disease (43.0%) population (P = 0.4 and P = 0.5). Overall, 10-year death-censored graft survival was similar for MPGN-I (56.2%) and MPGN-II (57.5%); both were significantly worse than for GN (65.2%; P < 0.001 and P = 0.003, respectively), and only MPGN-I was significantly worse than the other disease (60.0%) population (P = 0.004). Of allograft failures with a reported cause, disease recurrence was the primary cause in 36 (14.5%) MPGN-I and 18 (29.5%) MPGN-II transplant recipients and was significantly higher compared with 879 (6.6%) GN and 1,319 (4.4%) all-other-disease recurrence failures (P < 0.001). LIMITATIONS Limited pretransplant clinical and biopsy data. CONCLUSIONS A diagnosis of MPGN-I or MPGN-II has a significant negative impact on overall primary allograft survival compared with other forms of glomerulonephritis, whereas only MPGN-I has a significant, but modest, negative effect compared with other causes of end-stage renal disease.

Long-term Outcome of Renal Transplantation Patients with Henoch-Schönlein Purpura

BACKGROUND AND OBJECTIVES Although Henoch-Schönlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival. RESULTS Compared with the remainder of the database, the HSP population was younger (25 years versus 46 years), and had a higher proportion of women (47% versus 40%), live donors (50% versus 35%), and Caucasians (77% versus 60%). Controlling for age, gender, donor source, ethnicity, and year of transplantation, death-censored graft survival for patients with HSP was 80.0% at 5 years and 58.8% at 10 years compared with 79.0% at 5 years and 55.4% at 10 years in the non-HSP population. Among patients with reported causes of graft loss, failure from recurrent disease occurred in 13.6% of patients with HSP, compared with 6.6% in the non-HSP population. When analyzing allograft survival in recipients with HSP compared with those with IgA nephropathy, there was no difference in 10-year allograft survival (58.4% and 59.3%, respectively). CONCLUSIONS These data indicate that although there is an increased risk of graft failure attributable to recurrent disease in patients with HSP, a diagnosis of HSP has little effect on overall renal allograft survival.

Screening Children for High Blood Pressure: Where the US Preventive Services Task Force Went Wrong

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

Contrast-associated acute kidney injury in the critically ill: systematic review and Bayesian meta-analysis

Purpose Critically ill patients, among whom acute kidney injury is common, are often considered particularly vulnerable to iodinated contrast medium nephrotoxicity. However, the attributable incidence remains uncertain given the paucity of observational studies including a control group. This study assessed acute kidney injury incidence attributable to iodinated contrast media in critically ill patients based on new data accounting for sample and effect size and including a control group.MethodsSystematic review of studies measuring incidence of acute kidney injury in critically ill patients following contrast medium exposure compared to matched unexposed patients. Patient-level meta-analysis implementing a Bayesian nested mixed effects multiple logistic regression model.ResultsTen studies were identified; only four took into account the baseline acute kidney injury risk, three by patient matching (560 patients). Objective meta-analysis of these three studies (vague and impartial a priori hypothesis concerning attributable acute kidney injury risk) did not find that iodinated contrast media increased the incidence of acute kidney injury (odds ratio 0.95, 95% highest posterior density interval 0.45–1.62). Bayesian analysis demonstrated that, to conclude in favor of a statistically significant incidence of acute kidney injury attributable to contrast media despite this observed lack of association, one’s a priori belief would have to be very strongly biased, assigning to previous uncontrolled reports 3–12 times the weight of evidence strength provided by the matched studies including a control group.ConclusionsMeta-analysis of matched cohort studies of iodinated contrast medium exposure does not support a significant incidence of acute kidney injury attributable to iodinated contrast media in critically ill patients.

Race and Obesity in Adolescent Hypertension

By using data collected from school-based screenings, this study reveals unique relationships between body mass and hypertension amongst adolescents of different races and ethnicities. BACKGROUND AND OBJECTIVES: The overall prevalence of essential hypertension in adolescents may be growing. Differences in blood pressure (BP) are well established in adults, but are less clear in adolescents. We hypothesize that the prevalence of hypertension differs by race/ethnicity among adolescents at school-based screenings. METHODS: We performed school-based BP screening in over 20 000 adolescents from 2000 to 2015. Race/ethnicity was self-reported. Height and weight were measured to determine BMI, and BP status was confirmed on 3 occasions to diagnose sustained hypertension according to Fourth Working Group Report criteria. RESULTS: We successfully screened 21 062 adolescents aged 10 to 19 years (mean, 13.8 years). The final prevalence of sustained hypertension in all subjects was 2.7%. Obesity rates were highest among African American (3.1%) and Hispanic (2.7%) adolescents. The highest rate of hypertension was seen in Hispanic (3.1%), followed by African American (2.7%), white (2.6%), and Asian (1.7%) adolescents (P = .019). However, obese white adolescents had the highest prevalence of sustained hypertension (7.4%) compared with obese African American adolescents (4.5%, P < .001). At lower BMI percentiles (<60th percentile), Hispanic adolescents actually had the lowest predicted prevalence of hypertension among the 4 groups. CONCLUSIONS: The prevalence of hypertension varies among different race/ethnicities. Although obesity remains the strongest predictor of early hypertension, the strength of this relationship is intensified in Hispanic and white adolescents, whereas it is lessened in African American adolescents.

Ambulatory blood pressure status in children: comparing alternate limit sources

The American Heart Association has included alternate ambulatory blood pressure (ABP) limits for children published by Wühl in 2002. These updated limits employ the same pediatric cohort data as the previous ABP limits published by Soergel in 1997 but differ in analysis technique. The implications of changing ABP limit source on the diagnosis of hypertension has yet to be examined in a large pediatric cohort. We reviewed 741 ABP monitorings performed in children referred to our hypertension clinic between 1991–2007. Hypertension was defined as 24-h mean blood pressure ≥ 95th percentile or 24-h blood pressure load ≥25%, by Soergel and Wühl limits separately. Six hundred seventy-three (91%) children were classified the same by both limit sources. Wühl limits were more likely than Soergel to classify a child as hypertensive (443 vs. 409, respectively). There was an increased classification of prehypertension and decreased white-coat hypertension by the Wühl method, whereas ambulatory and severe hypertension counts remained relatively the same by both limits sources. The use of either limit source will not significantly affect most clinical outcomes but should remain consistent over long-term research projects. Collection of new normative data from a larger, multiethnic population is needed for better measurement of ABP in children.

Prevalence of Pancreatic Steatosis at a Pediatric Tertiary Care Center.

Objectives Pancreatic steatosis in adults has been proposed to be associated with obesity; however, data on pancreatic steatosis in children are lacking. Our study aimed to measure the prevalence of pancreatic steatosis in children and to examine its association with obesity and nonalcoholic fatty liver disease. Methods This is a retrospective chart review study of 232 patients 2 to 18 years old who underwent abdominal computed tomographic imaging in the emergency department or inpatient ward within a 1-year time span and from whom demographics, anthropometrics, and medical history were obtained. Our radiologist determined mean Hounsfield unit (HU) measurements for the pancreas, liver, and spleen. A difference of −20 between the pancreas and spleen (psHU) and between the liver and spleen was used to determine fatty infiltration. Results Of the 232 patients, 11.5% had a psHU less than −20. The prevalence of pancreatic steatosis was more than double among obese children (19%) than that in nonobese groups (8%). There is a significant correlation between the psHU and liver-spleen HU (r = 0.50, P < 0.001). Conclusions Pancreatic steatosis was identified in 10% of the study population and is associated with obesity. Also, pancreatic steatosis is significantly associated with nonalcoholic fatty liver disease. This is the first study assessing the prevalence of pancreatic steatosis in children.