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1.  Left ventricular geometry in children and adolescents with primary hypertension 
Objective
Children with hypertension (HTN) are at increased risk for left ventricular hypertrophy (LVH). Increased LV mass by the process of remodeling in response to volume or pressure loading may be eccentric (increased LV diameter) or concentric (increased wall thickness). Our objective was to classify LV geometry among children with primary HTN and examine differences in ambulatory blood pressure (ABP).
Study design
Subjects aged 7-18 years with suspected HTN were enrolled in this cross-sectional study. ABP and LVM index (LVMI) and were measured within the same 24 hour period. LV geometry was classified as normal, concentric remodeling, concentric LVH or eccentric LVH.
Results
Children with LVH had significantly higher ambulatory systolic and diastolic BP levels and BMI z-score. Sixty-eight children had HTN based upon ABPM. Thirty-eight percent of the hypertensive subjects had LVH, with equal distribution in the concentric and eccentric groups. There were significant differences in the 24-hour diastolic BP (DBP) parameters when the eccentric LVH group was compared to the normal geometry and concentric LVH groups. Relative wall thickness was inversely associated with nighttime DBP parameters. These relationships persisted after controlling for BMI Z-score.
Conclusions
While the risk for LVH is associated with increased systolic BP and BMI Z-score, those with eccentric LVH had significantly higher DBP.
doi:10.1038/ajh.2009.164
PMCID: PMC2795788  PMID: 19851297
Hypertension; left ventricular hypertrophy; concentric LVH; eccentric LVH; relative wall thickness
2.  Renal Late Effects in Patients Treated for Cancer in Childhood: A Report from the Children’s Oncology Group 
Pediatric blood & cancer  2008;51(6):724-731.
Background
Improvements in childhood cancer therapy have led to increasing numbers of long-term survivors. These survivors are at risk for a variety of late effects due to the disease itself, treatment exposures (surgery, chemotherapy, and radiotherapy), underlying medical problems, and health behaviors. The COG LTFU Guidelines are risk-based, exposure-related recommendations for the identification and management of late effects due to therapies utilized in the treatment of childhood cancer, and are designed for asymptomatic survivors presenting for routine medical follow-up two or more years after completion of cancer therapy.
Procedure
The COG Guidelines Task Force on Urinary Tract Complications conducted an extensive review of the medical literature via MEDLINE. Specific treatment exposures which were reviewed include nephrectomy, chemotherapy regimens known to be nephrotoxic (cisplatin, carboplatin, ifosfamide, and methotrexate) and renal irradiation. Literature sources were ranked according to the strength of evidence and are cited in the review.
Conclusions
This review summarizes the literature that supported the recommendations for cancer survivors at risk for nephrotoxicity previously outlined in the Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers (COG LTFU Guidelines).
doi:10.1002/pbc.21695
PMCID: PMC2734519  PMID: 18677764
Wilms’ tumor; ifosfamide; cisplatin; methotrexate; radiotherapy; nephrectomy; chronic kidney disease; proteinuria; hypertension
3.  Serum Uric Acid and Ambulatory Blood Pressure in Children with Primary Hypertension 
Pediatric research  2008;64(5):556-561.
Hyperuricemia is associated with primary hypertension (HTN) in adults and children. Furthermore, uric acid levels during childhood are associated with blood pressure (BP) levels in adulthood. We measured 24-h ambulatory BP and serum uric acid (SUA) in 104 children referred for possible hypertension. Mean age was 13.7 ± 2.6 y (range 7-18y) with 67 males and 37 females; 74 were African-American, 29 Caucasian and one Asian. SUA was associated with age (r=0.38, P=0.0001) and BMI Z-score (r=0.23, P=0.021). SUA was significantly associated with mean ambulatory systolic (S) and diastolic (D) BP. Mean ambulatory BP was normalized to gender- and height-specific reference standards using BP index. SUA was significantly associated with 24-h DBP index and nocturnal DBP index after adjusting for age, gender, race, BMI Z-score and urinary sodium excretion. SUA was also significantly associated with 24-h DBP load and nocturnal DBP load. Uric acid was significantly associated with increased likelihood for diastolic HTN (OR 2.1, CI 1.2, 3.7; P=0.0063) after adjusting for other co-variables. Among children at risk for HTN, the likelihood for diastolic HTN (as defined by ambulatory blood pressure monitoring) increases significantly as SUA increases. SUA may be associated with increased severity of HTN during youth.
doi:10.1203/PDR.0b013e318183fd7c
PMCID: PMC2621196  PMID: 18596575
Hypertension; ambulatory blood pressure; uric acid
4.  Ambulatory Blood Pressure and Increased Left Ventricular Mass in Children at Risk for Hypertension 
The Journal of pediatrics  2007;152(3):343-348.
Objective
To relate ambulatory blood pressure (ABP) to cardiac target organ measurement in children at risk for primary hypertension (HTN).
Study design
Left ventricular mass index (LVMI) and ABP were measured concomitantly in children (6 to 18 years) at risk for hypertension using a cross-sectional study design.
Results
LVMI showed a significant positive correlation with 24-hour systolic blood pressure (SBP) load, SBP index (SBPI), and standard deviation score (SDS). When subjects were stratified by LVMI percentile, there were significant differences in SBP load, 24-hour SBPI, and 24-hour SSDS. The odds ratio (OR) of having elevated LVMI increased by 54% for each incremental increase of SDS in 24-hour SSDS after controlling for race and BMI (OR = 1.54, unit = 1 SDS, CI = 1.1, 2.15, P = .011) and increased by 88% for each increase of 0.1 in BPI (OR = 1.88, CI = 1.03, 3.45, P = .04). Subjects with stage 3 HTN had significantly greater mean LVMI compared with normal subjects (P = .002 by ANOVA; LMVI, 31.6 ± 7.9 versus 39.5 ± 10.4).
Conclusions
As systolic ABP variables increase, there is greater likelihood for increased LVMI. Staging based on ABPM allows assessment of cardiovascular risk in children with primary hypertension.
doi:10.1016/j.jpeds.2007.07.014
PMCID: PMC2763428  PMID: 18280838
5.  Comparison of ambulatory blood pressure reference standards in children evaluated for hypertension 
Blood pressure monitoring  2009;14(3):103-107.
Objective
The purpose of this study was to systematically compare methods for standardization of blood pressure levels obtained by ambulatory blood pressure monitoring (ABPM) in a group of 111 children studied at our institution.
Methods
Blood pressure indices, blood pressure loads and standard deviation scores were calculated using he original ABPM and the modified reference standards. Bland—Altman plots and kappa statistics for the level of agreement were generated.
Results
Overall, the agreement between the two methods was excellent; however, approximately 5% of children were classified differently by one as compared with the other method.
Conclusion
Depending on which version of the German Working Group’s reference standards is used for interpretation of ABPM data, the classification of the individual as having hypertension or normal blood pressure may vary.
doi:10.1097/MBP.0b013e32832ce11e
PMCID: PMC2755509  PMID: 19433980
ambulatory blood pressure monitoring; blood pressure; hypertension; reference standards
6.  VALIDATION OF THE AM5600 AMBULATORY BLOOD PRESSURE MONITOR IN CHILDREN AND ADOLESCENTS 
Blood pressure monitoring  2008;13(6):349-351.
We measured ambulatory blood pressure using the AM5600 in children and adolescents participating in a research study to assess the relationship of BP to risk factors for cardiovascular disease. Although this use of this monitor has been previously reported in adults, it has not been validated in pediatric subjects. In this study, we assess the accuracy of the monitor as compared to the mercury sphygmomanometer in children ages 7-18 years of age. We found that the mean of the difference between the monitor and the mercury device was 0.29 ± 3.5 and 0.045 ± 3.7 mmHg for systolic and diastolic BP respectively, which fulfills the AAMI standard for use of a device. The cumulative percent of readings between the two devices which differed assigned the device a grade of A according to the British Hypertension Society..
doi:10.1097/MBP.0b013e3283102cfe
PMCID: PMC2754039  PMID: 19020426
hypertension; ambulatory blood pressure monitoring; Blood pressure measuring device
7.  Early Volume Expansion During Diarrhea and Relative Nephroprotection During Subsequent Hemolytic Uremic Syndrome 
Objectives
To determine if interventions during the pre–hemolytic uremic syndrome (HUS) diarrhea phase are associated with maintenance of urine output during HUS.
Design
Prospective observational cohort study.
Settings
Eleven pediatric hospitals in the United States and Scotland.
Participants
Children younger than 18 years with diarrhea-associated HUS (hematocrit level <30% with smear evidence of intravascular erythrocyte destruction), thrombocytopenia (platelet count <150 × 103/mm3), and impaired renal function (serum creatinine concentration>upper limit of reference range for age).
Interventions
Intravenous fluid was given within the first 4 days of the onset of diarrhea.
Outcome Measure
Presence or absence of oligoanuria (urine output ≤0.5 mL/kg/h for >1 day).
Results
The overall oligoanuric rate of the 50 participants was 68%, but was 84% among those who received no intravenous fluids in the first 4 days of illness. The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% confidence interval, 1.1–2.4; P=.02). Children with oligoanuric HUS were given less total intravenous fluid (r = −0.32; P = .02) and sodium (r=−0.27; P=.05) in the first 4 days of illness than those without oligoanuria. In multivariable analysis, the most significant covariate was volume infused, but volume and sodium strongly covaried.
Conclusions
Intravenous volume expansion is an underused intervention that could decrease the frequency of oligoanuric renal failure in patients at risk of HUS.
doi:10.1001/archpediatrics.2011.152
PMCID: PMC4064458  PMID: 21784993
8.  The Tumor Lysis Syndrome 
The New England journal of medicine  2011;364(19):1844-1854.
doi:10.1056/NEJMra0904569
PMCID: PMC3437249  PMID: 21561350
9.  Impact of Continuous Renal Replacement Therapy on Oxygenation in Children with Acute Lung Injury after Allogeneic Hematopoietic Stem Cell Transplantation 
Pediatric blood & cancer  2010;55(3):540-545.
Background
Acute lung injury (ALI) continues to carry a high mortality rate in children after allogeneic hematopoietic stem cell transplant (HSCT). Continuous renal replacement therapy (CRRT) is often used for these patients for various indications including renal failure and fluid overload, and may have a beneficial effect on oxygenation and survival. Therefore, we sought to determine the effect of CRRT on oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI, and to document survival to intensive care unit discharge in this at-risk population receiving both mechanical ventilation and CRRT.
Procedure
Retrospective analysis of a pediatric allogeneic HSCT cohort admitted to intensive care unit of a single pediatric oncology center from 1994 to 2006 who received CRRT during a course of mechanical ventilation for ALI.
Results
Thirty post-HSCT mechanically ventilated children with ALI who underwent CRRT were included. There was a significant improvement in PaO2/FiO2 with median increase of 31 and 43 in the 24 and 48 hour intervals after initiation of CRRT compared with the 24 hour interval before CRRT (p = 0.0008 and 0.0062, respectively). This improvement in PaO2/FiO2 correlated significantly with reduction of fluid balance achieved after initiation of CRRT (p=0.0001). There was a trend not reaching statistical significance in improvement in mean airway pressure 48 hours after CRRT in survivors compared to non-survivors.
Conclusions
CRRT improved oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI.
doi:10.1002/pbc.22561
PMCID: PMC3214656  PMID: 20658627
Hematopoietic stem cell transplantation; Critically ill; Acute lung injury; Pediatrics; Renal replacement therapy; Oxygenation
10.  Blood Aldosterone to Renin Ratio, Ambulatory Blood Pressure and Left Ventricular Mass in Children 
The Journal of pediatrics  2009;155(2):170-175.
Objectives
To assess blood aldosterone-renin ratio (ARR) and its relationship to ambulatory blood pressure (ABP) and left ventricular mass (LVM) in children.
Study design
A cross-sectional clinical study was conducted in 102 children (71.6% African American and 62.7% male) aged 7-18 years (mean=13.6, median=14). ABP (24-hour monitoring) was expressed as blood pressure index (BPI = mean BP/95th percentile by sex and height). LVM was measured by echocardiography and expressed as an index (LVMI=grams/ht2.7). Regression analyses were used to estimate associations.
Results
African American children had significantly lower serum aldosterone concentration and plasma renin activity compared with European American children (aldosterone: 5.9 ng/dl vs. 11.4 ng/dl, P = <0.0001 and renin: 1.6 ng/ml/h vs. 2.8 ng/ml/h, P = 0.01 respectively). However, ARR was not significantly different by race. ARR was not associated with 24-hour ABP, but was significantly associated with LVMI (β = 0.4 g/m2.7, P = 0.02) after adjustment for the ratio of 24-hour urine Na to creatinine excretion, BMI-z score, and ABPI.
Conclusion
The study observed a significant association between ARR and LVMI but not ABP in children, which suggested early cardiac remodeling associated with a high ARR.
doi:10.1016/j.jpeds.2009.02.029
PMCID: PMC2726743  PMID: 19464027
renin; aldosterone; aldosterone-renin ratio; ambulatory blood pressure; left ventricular mass; pediatrics
11.  Renal Function After Ifosfamide, Carboplatin, and Etoposide (ICE) Chemotherapy, Nephrectomy, and Radiotherapy in Children With Wilms Tumour 
We prospectively evaluated tumour response and renal function in 12 newly-diagnosed children with high-risk Wilms tumour receiving ifosfamide, carboplatin, and etoposide (ICE) chemotherapy. Two cycles of ICE were followed by 5 weeks of vincristine, dactinomycin, and doxorubicin (Adriamycin) (VDA), and nephrectomy, radiotherapy, additional VDA, and a third ICE cycle. Carboplatin dosage was based on glomerular filtration rate (GFR) to achieve targeted systemic exposure (6 mg/ml × min). Mean GFR (measured by technetium 99m-DTPA clearance) declined by 7% after 2 cycles of ICE and by 38% after nephrectomy; the mean carboplatin dose was reduced 32% after nephrectomy. Mean GFR remained stable after the third ICE cycle. Although urinary β2-microglobulin excretion increased during therapy, no patient had clinically significant renal tubular dysfunction at the end of treatment.
Treatment with ICE, nephrectomy, and radiotherapy significantly reduces GFR, largely as the result of nephrectomy. Adjustment of carboplatin dosage on the basis of GFR and careful monitoring of renal function may alleviate nephrotoxicity.
doi:10.1016/j.ejca.2008.09.017
PMCID: PMC2682543  PMID: 18996004
ifosfamide; carboplatin; nephrectomy; renal function; creatinine; glomerular filtration rate; kidney neoplasms
12.  BK VIRUS–INDUCED TUBULOINTERSTITIAL NEPHRITIS IN A CHILD WITH ACUTE LYMPHOBLASTIC LEUKEMIA 
The Journal of pediatrics  2007;151(2):215-217.
We report a case of BK virus–induced tubulointerstitial nephritis in a child with acute lymphoblastic leukemia. Primary BKV infection was exacerbated by chemotherapy-induced immunodeficiency. Careful administration of chemotherapy and anti-viral therapy prevented further damage. This diagnosis should be considered in children who experience renal dysfunction during cancer treatment.
doi:10.1016/j.jpeds.2007.05.005
PMCID: PMC2077844  PMID: 17643782

Results 1-12 (12)