Pediatric Pediatric Hypertension Hypertension A Nephrologists View A Nephrologists View Jeremy Gitomer, MD Jeremy Gitomer, MD Pediatric Nephrology Pediatric Nephrology Alaska Kidney Consultants Alaska Kidney Consultants
May 25, 2015
Pediatric Hypertension Pediatric Hypertension A Nephrologists ViewA Nephrologists View
Jeremy Gitomer, MDJeremy Gitomer, MD
Pediatric NephrologyPediatric Nephrology
Alaska Kidney ConsultantsAlaska Kidney Consultants
Goal of LectureGoal of Lecture
Scary thought!Scary thought!
Think of pediatric hypertension as a Think of pediatric hypertension as a nephrologist doesnephrologist does
DefinitionDefinition
Pediatric hypertension is defined as a blood Pediatric hypertension is defined as a blood pressure greater than the 95pressure greater than the 95 thth percentile blood percentile blood pressure for age, sex and length for patients pressure for age, sex and length for patients without comorbidities. without comorbidities.
Patients with comorbidities are defined as Patients with comorbidities are defined as hypertensive when the blood pressure is greater hypertensive when the blood pressure is greater than the 90%.than the 90%.
ComorbiditiesComorbidities Diabetes, Renal disease, Cardiac disease, Obesity, Diabetes, Renal disease, Cardiac disease, Obesity,
Family historyFamily history
Who Cares?Who Cares?
Cardiovascular disease is the number one Cardiovascular disease is the number one cause of death in the United States.cause of death in the United States.
Hypertension poses a significant risk for Hypertension poses a significant risk for the development of cardiovascular related the development of cardiovascular related mortality or morbidity.mortality or morbidity.
ArteriosclerosisArteriosclerosis
Cause for ConcernCause for Concern
Metabolic syndrome is increasing at an Metabolic syndrome is increasing at an alarming rate.alarming rate. Insulin resistanceInsulin resistanceObesityObesityHypertensionHypertension
Obesity is rampantObesity is rampantHypertension prevalence is increasing Hypertension prevalence is increasing
rapidlyrapidly
Cause for ConcernCause for Concern
Improvements in Improvements in neonatal survival will neonatal survival will impact the incidence impact the incidence of hypertensionof hypertension
N Engl J Med 2003; 348:101-108, Jan 9, 2003.
Preventive MedicinePreventive Medicine
Treatment of pediatric hypertension is Treatment of pediatric hypertension is actually preventive medicine.actually preventive medicine.
Patients don’t die of heart attacks or Patients don’t die of heart attacks or strokes in their pediatric years. strokes in their pediatric years.
Likely will have cardiovascular events at a Likely will have cardiovascular events at a younger age than expected.younger age than expected.
Diagnosis of HypertensionDiagnosis of Hypertension
3 office blood pressure readings greater 3 office blood pressure readings greater than the upper limit of normalthan the upper limit of normal
20 mm Hg higher than the limit on any one 20 mm Hg higher than the limit on any one reading is considered diagnostic of reading is considered diagnostic of hypertensionhypertension
White Coat HypertensionWhite Coat Hypertension
Defined as a normal blood pressure at Defined as a normal blood pressure at home but elevated in the office.home but elevated in the office. Increased sympathetic toneIncreased sympathetic toneNo evidence of increased cardiovascular No evidence of increased cardiovascular
mortalitymortality
Problem with Office BP Problem with Office BP MeasurementsMeasurements
Ziac Drug StudyZiac Drug StudyPatients enrolled diagnosed with Patients enrolled diagnosed with
hypertensionhypertensionRepeat screening SBP at visit 1 Repeat screening SBP at visit 1 129+/-129+/-
8 mm Hg8 mm HgSBP at visit 2 123+/-7 mm Hg SBP at visit 2 123+/-7 mm Hg SBP at visit 3 121+/-8 mm HgSBP at visit 3 121+/-8 mm Hg
Screening termination occurred in 15% Screening termination occurred in 15% with isolated SBP hypertensionwith isolated SBP hypertension
Am J Hypertens. 2001 Aug;14(8 Pt 1):783-7.Am J Hypertens. 2001 Aug;14(8 Pt 1):783-7.
ABPMABPM
Ambulatory blood pressure monitors Ambulatory blood pressure monitors New technologyNew technologyMeasure blood pressure every 15 minutes Measure blood pressure every 15 minutes
while awakewhile awakeMeasure blood pressure every 30 minutes Measure blood pressure every 30 minutes
while asleepwhile asleepNight time blood pressure drops 10% Night time blood pressure drops 10%
normallynormally
0 3 6 9 12 15 18 21 24100
120
140
160
180
Awake SBPload = 80%
Sleep SBPload = 60%
Time of Day
Example of ABPMExample of ABPM
ABPMABPM
American Journal of Kidney Diseases (1999) 33: 667-674
ABPMABPM
30% of patients with office hypertension 30% of patients with office hypertension have normal blood pressures by ABPMhave normal blood pressures by ABPM
White Coat HypertensionWhite Coat HypertensionIncidence reported from 31-50%Incidence reported from 31-50%
Hornsby: J Fam Prac 1991;33:617-23Hornsby: J Fam Prac 1991;33:617-23Reusz: Arch Dis Child 1994;70:90-4Reusz: Arch Dis Child 1994;70:90-4Lingens: Ped Neph 1995;9:167-72Lingens: Ped Neph 1995;9:167-72Gillerman: Ped Neph 1997;11:707-10Gillerman: Ped Neph 1997;11:707-10
White Coat HypertensionWhite Coat Hypertension
These patients do not need a work upThese patients do not need a work upObviously there are significant financial Obviously there are significant financial
and psychosocial incentives for identifying and psychosocial incentives for identifying these patients.these patients.The workup is expensiveThe workup is expensiveChronic medication is expensiveChronic medication is expensive
Hypertension Less than 1 Year OldHypertension Less than 1 Year Old
Age GroupAge Group Most CommonMost Common Less CommonLess Common
Infants and NeonatesInfants and Neonates Renal artery Renal artery thrombosis after thrombosis after umbilical artery umbilical artery catheterizationcatheterization
Bronchopulmonary Bronchopulmonary DysplasiaDysplasia
Coarctation of the Coarctation of the aortaaorta
Patent ductus Patent ductus arteriosusarteriosus
Congenital renal Congenital renal diseasedisease
Intraventricular Intraventricular hemorrhagehemorrhage
Renal artery stenosisRenal artery stenosis Neurogenic tumorsNeurogenic tumors
Causes of HypertensionCauses of HypertensionAge GroupAge Group Most CommonMost Common Less CommonLess Common1-101-10 Renal DiseaseRenal Disease Renal artery stenosisRenal artery stenosis
Coarctation of the aortaCoarctation of the aorta HypercalcemiaHypercalcemiaEssentialEssential NeurofibromatosisNeurofibromatosis
PheochromocytomaPheochromocytomaPrimary hyperaldosteronismPrimary hyperaldosteronism1111ββ hydroxylase deficiency hydroxylase deficiency1717αα hydroxylase deficiency hydroxylase deficiencyApparent mineralocorticoid excessApparent mineralocorticoid excessLiddle’s syndromeLiddle’s syndromeGlucocorticoid remediable Glucocorticoid remediable hypertensionhypertensionHypertension induced by Hypertension induced by immobilizationimmobilizationSleep apnea associated hypertensionSleep apnea associated hypertensionHead trauma associatedHead trauma associated
11 and older11 and older Renal DiseaseRenal Disease All diagnosis listed aboveAll diagnosis listed aboveEssential hypertensionEssential hypertension
Typical WorkupTypical Workup
Renal PanelRenal PanelPlasma Aldosterone/Renin Plasma Aldosterone/Renin Urine analysisUrine analysisUrine protein/creatinineUrine protein/creatinineRenal ultrasoundRenal ultrasound4 point blood pressure readings 4 point blood pressure readings CBCCBCTSHTSH
Renal PanelRenal Panel
Low potassium, High bicarbonateLow potassium, High bicarbonateHigh potassium, Low BicarbonateHigh potassium, Low BicarbonateRenal FunctionRenal FunctionCalcium levelCalcium level
Hypokalemic Metabolic AlkalosisHypokalemic Metabolic Alkalosis
HyperaldosteronismHyperaldosteronismLiddle’s SyndromeLiddle’s SyndromeApparent Mineralocorticoid ExcessApparent Mineralocorticoid ExcessGlucocorticoid Remediable HypertensionGlucocorticoid Remediable HypertensionRenal Artery StenosisRenal Artery StenosisReninomaReninoma
Mechanism of Hypokalemia and Mechanism of Hypokalemia and Metabolic AlkalosisMetabolic Alkalosis
Aldosterone Aldosterone increases ENaC increases ENaC densitydensity
Negative luminal Negative luminal charge developscharge develops
K+ and H+ secreted K+ and H+ secreted to maintain to maintain electroneutralityelectroneutrality
We don’t PEE We don’t PEE LIGHTNINGLIGHTNING
Liddle’s SyndromeLiddle’s Syndrome
Gain of function abnormality of ENaCGain of function abnormality of ENaCResults in sodium retentionResults in sodium retentionLow levels of aldosteroneLow levels of aldosteroneFormerly known as Formerly known as
pseudohyperaldosteronismpseudohyperaldosteronism
Apparent Mineralocorticoid ExcessApparent Mineralocorticoid Excess
Mutation in gene encoding for 11Mutation in gene encoding for 11ββ hydroxysteroid dehydrogenasehydroxysteroid dehydrogenaseCortisol is not converted to cortisone Cortisol is not converted to cortisone
intracellularlyintracellularlyCortisol binds to the mineralocorticoid Cortisol binds to the mineralocorticoid
receptor because the concentration is 100 receptor because the concentration is 100 times greater than mineralocorticoidstimes greater than mineralocorticoids
Mineralocorticoid receptors are activated Mineralocorticoid receptors are activated by cortisolby cortisol
Apparent Mineralocorticoid ExcessApparent Mineralocorticoid Excess
Associated withAssociated withLicoriceLicoriceChewing tobaccoChewing tobaccoCarbenoxolone Carbenoxolone
Glycyrrhetinic acid is the active componentGlycyrrhetinic acid is the active componentLow reninLow reninLow aldosterone levelLow aldosterone levelAutosomal RecessiveAutosomal Recessive
Apparent Mineralocorticoid ExcessApparent Mineralocorticoid Excess
Mineralocorticoid Receptor
Normal Cortisol
11β-hydroxysteroid dehydrogenase Type 2
Corticosterone
Aldosterone
Cortisol
11β-hydroxysteroid dehydrogenase Type 2
Corticosterone
Cortisol Mineralocorticoid Receptor
AME
Glucocorticoid Remediable Glucocorticoid Remediable HypertensionHypertension
Duplication of genes encoding aldosterone Duplication of genes encoding aldosterone synthase and 11synthase and 11ββ hydroxylase hydroxylase
Ectopic production of aldosterone occurs Ectopic production of aldosterone occurs under ACTH controlunder ACTH control
Glucorticoid Remediable Glucorticoid Remediable HypertensionHypertension
Glomerulosa Fasciculata
Progesterone ProgesteroneProgesterone
Deoxycorticosterone Deoxycorticosterone17 hydroxyprogesterone
CYP11β1 CYP11β1
CorticosteroneCorticosterone 11-deoxycortisol
CYP11β1
Cortisol
18-hydroxycorticosterone18-hydroxycorticosterone
CYP11β2Chimeric CYP11β2
Aldosterone Aldosterone
Hyperkalemic Metabolic AcidosisHyperkalemic Metabolic Acidosis
Gordon’s SyndromeGordon’s SyndromeAKA Pseudohypoaldosteronism Type 2AKA Pseudohypoaldosteronism Type 2Gain of function of the thiazide sodium Gain of function of the thiazide sodium
chloride cotransporterchloride cotransporterAutosomal dominantAutosomal dominant
Renal FunctionRenal Function
Normal ValuesNormal Values1 – 5 years old1 – 5 years old 0.3-0.5 mg/dL0.3-0.5 mg/dL6-11 years old6-11 years old 0.5-0.7 mg/dL0.5-0.7 mg/dLGirls > 11 yearsGirls > 11 years 0.7-0.9 mg/dL0.7-0.9 mg/dLBoys > 11 yearsBoys > 11 years 0.7-1.2 mg/dL0.7-1.2 mg/dL
Normal creatinine is determined by the Normal creatinine is determined by the muscle mass of the patient and their renal muscle mass of the patient and their renal functionfunction
Renal FunctionRenal Function
Schwartz EquationSchwartz Equation
CreCL = constant * Height / creatinineCreCL = constant * Height / creatinine
ConstantConstant 0.25 micropremie0.25 micropremie 0.33 Term neonate0.33 Term neonate 0.45 Infants0.45 Infants 0.55 Children 1-12, Adolescent girls 0.55 Children 1-12, Adolescent girls 0.70 Adolescent boys >120.70 Adolescent boys >12
Urine AnalysisUrine Analysis
HematuriaHematuriaGlomerular diseaseGlomerular disease
PyuriaPyuria Interstitial nephritisInterstitial nephritis
ProteinuriaProteinuriaGlomerular diseaseGlomerular diseaseHyperfiltration syndromeHyperfiltration syndromeReflux nephropathyReflux nephropathy
Red Blood Cell CastRed Blood Cell Cast
Urine Protein/CreatinineUrine Protein/Creatinine
More sensitive than albustix in detecting More sensitive than albustix in detecting proteinuriaproteinuria
Microalbumin detection sticks can be usedMicroalbumin detection sticks can be used
Renal UltrasoundRenal Ultrasound
Urologic abnormalitiesUrologic abnormalitiesUreteropelvic junction obstructionUreteropelvic junction obstructionMulticystic dysplastic kidneysMulticystic dysplastic kidneys
Polycystic kidney diseasePolycystic kidney diseaseRenal scarringRenal scarringDiscordant kidney size Discordant kidney size
Reflux nephropathyReflux nephropathyRenal artery stenosisRenal artery stenosis
4 Extremity BP4 Extremity BP
Screen for coarctationScreen for coarctationNot 100% sensitiveNot 100% sensitiveEchocardiogram is the diagnostic test of Echocardiogram is the diagnostic test of
choicechoice
If Workup is Negative?If Workup is Negative?
Start treatment with antihypertensive Start treatment with antihypertensive medication under the following medication under the following circumstancescircumstancesComorbid conditionsComorbid conditionsEvidence of end organ damageEvidence of end organ damage
Echocardiogram with LVHEchocardiogram with LVH
Systolic blood pressure 10 mm Hg greater Systolic blood pressure 10 mm Hg greater than 95%than 95%
Failure of lifestyle modificationsFailure of lifestyle modifications
Lifestyle ModificationsLifestyle Modifications
Salt restrictionSalt restrictionExercise 20 minutes 5 days a weekExercise 20 minutes 5 days a week
HR should achieve 85% of maximumHR should achieve 85% of maximumWeight lossWeight loss
Lifestyle ModificationsLifestyle Modifications
Why don’t they work?Why don’t they work?Entire family needs to participateEntire family needs to participateTime is an issueTime is an issue
CookingCookingExerciseExercise
Parents are frequently obeseParents are frequently obese
When to Perform More TestingWhen to Perform More Testing
Any abnormality of primary screeningAny abnormality of primary screeningAldosterone/Renin > 30Aldosterone/Renin > 30
HyperaldosteronismHyperaldosteronism
Abnormal Urine analysisAbnormal Urine analysisDiscordant kidney sizeDiscordant kidney sizeSevere hypertensionSevere hypertensionFamily historyFamily history
NF, MENNF, MENEarly strokes in familyEarly strokes in family
Renal Artery Stenosis?Renal Artery Stenosis?
Usually renin and aldosterone elevatedUsually renin and aldosterone elevatedMore than 1 medications required for BP More than 1 medications required for BP
controlcontrol20% incidence of RAS20% incidence of RAS
BP greater than 99%BP greater than 99%43% incidence of RAS43% incidence of RAS
Pediatr Nephrol. 2000 Aug;14(8-9):816-9.
Renal Scan And AngiogramRenal Scan And Angiogram
RAS on AngiogramRAS on Angiogram
Screen for Pheochromocytoma?Screen for Pheochromocytoma?
Family history of pheochromocytomaFamily history of pheochromocytoma MENMEN von Hippel Lindauvon Hippel Lindau Neurofibromatosis is unlikely to be associated with Neurofibromatosis is unlikely to be associated with
pheochromocytoma prior to age 25pheochromocytoma prior to age 25
SymptomsSymptoms FlushingFlushing HeadachesHeadaches ParoxysmsParoxysms TachycardiaTachycardia
Testing for PheochromocytomaTesting for Pheochromocytoma
No pediatric normal valuesNo pediatric normal valuesMetanepherines are higher in childrenMetanepherines are higher in children
Biochemical Biochemical testtest
SensitivitySensitivity SpecificitySpecificity Sensitivity at Sensitivity at 100% 100% SpecificitySpecificity
Plasma Plasma MetanepherineMetanepherine
9999 8989 8282
Plasma Plasma CatecholamineCatecholamine
8585 8080 3838
Urinary Urinary CatecholamineCatecholamine
8383 8888 6464
Urinary Urinary MetanepherineMetanepherine
7676 9494 5353
Urinary VMAUrinary VMA 6363 9494 4343
Ann Intern Med, Feb 2001; 134: 315 - 329.
Testing for PheochromocytomaTesting for Pheochromocytoma
Plasma metanepherines is the best screenPlasma metanepherines is the best screenSend out to Mayo clinicSend out to Mayo clinic
Hypertension in office
Correct size cuff Wait 5 minutes and repeat Still high Check 2 more visits
Home BP Monitoring Ambulatory BPM
BP Normal
White Coat HTN
BP Abnormal
Family History Physical Exam CBC Urine Analysis Renal Panel Aldosterone/Renin Urine Protein/creatinine
Comorbid Conditions Diabetes, Renal Disease, Cardiac Disease, Obesity
Treat with Antihypertensives
No Comorbid Conditions
Lifestyle Modifications
Consider Echocardiogram
No LVH
LVH Present
HTN after 1 year
HTN Resolved
BP check every 6 months
Workup Negative
Workup Positive Treat
Why No EKG?Why No EKG?
Sensitivity < 20% to detect LVHSensitivity < 20% to detect LVHSpecificity 88% to detect LVHSpecificity 88% to detect LVHEKG is a poor screening test for LVHEKG is a poor screening test for LVH
If the EKG demonstrates LVH criteria the If the EKG demonstrates LVH criteria the patient likely has LVHpatient likely has LVH
Am Heart J. 2003 Apr;145(4):716-23.
Medication AlgorithmMedication AlgorithmHypertension
IHSS Renal DiseaseNo ComorbiditiesObesity
Beta Blocker
Cardizem
ACE Inhibitor
ACE Inhibitor
Angiotensin Receptor Blocker
Diuretic
Calcium Channel Blocker
ACE Inhibitor
Calcium Channel Blocker
Second Calcium Channel Blocker
Diuretic
Second Calcium Channel Blocker
Calcium Channel Blocker
ACE Inhibitor
Second Calcium Channel Blocker
Angiotensin Receptor Blocker
Calcium Channel BlockersCalcium Channel Blockers
AmlodipineAmlodipineStudied in childrenStudied in children54 hour half life54 hour half life
Missing a dose is not an issueMissing a dose is not an issueOnce a day dosingOnce a day dosingDrops BP effectivelyDrops BP effectively
CardizemCardizemOnce daily dosingOnce daily dosingNegative ionotropeNegative ionotrope
ACE InhibitorsACE Inhibitors
LisinoprilLisinoprilGeneric- 7 dollars a monthGeneric- 7 dollars a monthOnce daily doseOnce daily dosePediatric studiesPediatric studies
CaptoprilCaptopril3 times a day3 times a day
VasotecVasotec2 times a day2 times a day
ACE Inhibitors CautionACE Inhibitors Caution
Nephrogenesis occurs until 2 years of ageNephrogenesis occurs until 2 years of ageACE Inhibitors decrease TGF-ACE Inhibitors decrease TGF-ββ and TNF- and TNF-
αα expression expressionThis may lead to a decrease in nephron This may lead to a decrease in nephron
massmass
Consider not using ACE Inhibitors until Consider not using ACE Inhibitors until after 2 years of ageafter 2 years of age
Angiotensin Receptor BlockersAngiotensin Receptor Blockers
All have been studied in childrenAll have been studied in children IrbesartanIrbesartanCandesartanCandesartanLosartanLosartanTelmesartanTelmesartan
ConclusionConclusion
Hypertension in children is increasing in Hypertension in children is increasing in incidenceincidence
Most children have essential hypertensionMost children have essential hypertensionThe workup is simple and inexpensiveThe workup is simple and inexpensiveAngiogram indicated for severe Angiogram indicated for severe
hypertensionhypertensionPlasma metanepherines is the best screen Plasma metanepherines is the best screen
for pheochromocytomafor pheochromocytomaOnce a day medications for complianceOnce a day medications for compliance