Pediatric Hypertension Nephrologist View

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Pediatric Hypertension Nephrologist View

  1. 1. Pediatric Hypertension A Nephrologists View Jeremy Gitomer, MD Pediatric Nephrology Alaska Kidney Consultants
  2. 2. Goal of Lecture <ul><li>Scary thought! </li></ul><ul><li>Think of pediatric hypertension as a nephrologist does </li></ul>
  3. 3. Definition <ul><li>Pediatric hypertension is defined as a blood pressure greater than the 95 th percentile blood pressure for age, sex and length for patients without comorbidities. </li></ul><ul><li>Patients with comorbidities are defined as hypertensive when the blood pressure is greater than the 90%. </li></ul><ul><li>Comorbidities </li></ul><ul><ul><li>Diabetes, Renal disease, Cardiac disease, Obesity, Family history </li></ul></ul>
  4. 4. Who Cares? <ul><li>Cardiovascular disease is the number one cause of death in the United States. </li></ul><ul><li>Hypertension poses a significant risk for the development of cardiovascular related mortality or morbidity. </li></ul>
  5. 5. Arteriosclerosis
  6. 6. Cause for Concern <ul><li>Metabolic syndrome is increasing at an alarming rate. </li></ul><ul><ul><li>Insulin resistance </li></ul></ul><ul><ul><li>Obesity </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><li>Obesity is rampant </li></ul><ul><li>Hypertension prevalence is increasing rapidly </li></ul>
  7. 7. Cause for Concern <ul><li>Improvements in neonatal survival will impact the incidence of hypertension </li></ul>N Engl J Med 2003; 348:101-108, Jan 9, 2003.
  8. 8. Preventive Medicine <ul><li>Treatment of pediatric hypertension is actually preventive medicine. </li></ul><ul><li>Patients don’t die of heart attacks or strokes in their pediatric years. </li></ul><ul><li>Likely will have cardiovascular events at a younger age than expected. </li></ul>
  9. 9. Diagnosis of Hypertension <ul><li>3 office blood pressure readings greater than the upper limit of normal </li></ul><ul><li>20 mm Hg higher than the limit on any one reading is considered diagnostic of hypertension </li></ul>
  10. 10. White Coat Hypertension <ul><li>Defined as a normal blood pressure at home but elevated in the office. </li></ul><ul><ul><li>Increased sympathetic tone </li></ul></ul><ul><ul><li>No evidence of increased cardiovascular mortality </li></ul></ul>
  11. 11. Problem with Office BP Measurements <ul><li>Ziac Drug Study </li></ul><ul><li>Patients enrolled diagnosed with hypertension </li></ul><ul><li>Repeat screening SBP at visit 1 129+/-8 mm Hg </li></ul><ul><ul><li>SBP at visit 2 123+/-7 mm Hg </li></ul></ul><ul><ul><li>SBP at visit 3 121+/-8 mm Hg </li></ul></ul><ul><li>Screening termination occurred in 15% with isolated SBP hypertension </li></ul>Am J Hypertens. 2001 Aug;14(8 Pt 1):783-7.
  12. 12. ABPM <ul><li>Ambulatory blood pressure monitors </li></ul><ul><ul><li>New technology </li></ul></ul><ul><ul><li>Measure blood pressure every 15 minutes while awake </li></ul></ul><ul><ul><li>Measure blood pressure every 30 minutes while asleep </li></ul></ul><ul><li>Night time blood pressure drops 10% normally </li></ul>
  13. 13. Example of ABPM 0 3 6 9 12 15 18 21 24 100 120 140 160 180 Awake SBP load = 80% Sleep SBP load = 60% Time of Day
  14. 14. ABPM American Journal of Kidney Diseases (1999) 33: 667-674
  15. 15. ABPM <ul><li>30% of patients with office hypertension have normal blood pressures by ABPM </li></ul><ul><li>White Coat Hypertension </li></ul><ul><li>Incidence reported from 31-50% </li></ul><ul><ul><li>Hornsby: J Fam Prac 1991;33:617-23 </li></ul></ul><ul><ul><li>Reusz: Arch Dis Child 1994;70:90-4 </li></ul></ul><ul><ul><li>Lingens: Ped Neph 1995;9:167-72 </li></ul></ul><ul><ul><li>Gillerman: Ped Neph 1997;11:707-10 </li></ul></ul>
  16. 16. White Coat Hypertension <ul><li>These patients do not need a work up </li></ul><ul><li>Obviously there are significant financial and psychosocial incentives for identifying these patients. </li></ul><ul><ul><li>The workup is expensive </li></ul></ul><ul><ul><li>Chronic medication is expensive </li></ul></ul>
  17. 17. Hypertension Less than 1 Year Old Neurogenic tumors Renal artery stenosis Intraventricular hemorrhage Congenital renal disease Patent ductus arteriosus Coarctation of the aorta Bronchopulmonary Dysplasia Renal artery thrombosis after umbilical artery catheterization Infants and Neonates Less Common Most Common Age Group
  18. 18. Causes of Hypertension All diagnosis listed above Renal Disease 11 and older Essential hypertension Head trauma associated Sleep apnea associated hypertension Hypertension induced by immobilization Glucocorticoid remediable hypertension Liddle’s syndrome Apparent mineralocorticoid excess 17 α hydroxylase deficiency 11 β hydroxylase deficiency Primary hyperaldosteronism Pheochromocytoma Neurofibromatosis Essential Hypercalcemia Coarctation of the aorta Renal artery stenosis Renal Disease 1-10 Less Common Most Common Age Group
  19. 19. Typical Workup <ul><li>Renal Panel </li></ul><ul><li>Plasma Aldosterone/Renin </li></ul><ul><li>Urine analysis </li></ul><ul><li>Urine protein/creatinine </li></ul><ul><li>Renal ultrasound </li></ul><ul><li>4 point blood pressure readings </li></ul><ul><li>CBC </li></ul><ul><li>TSH </li></ul>
  20. 20. Renal Panel <ul><li>Low potassium, High bicarbonate </li></ul><ul><li>High potassium, Low Bicarbonate </li></ul><ul><li>Renal Function </li></ul><ul><li>Calcium level </li></ul>
  21. 21. Hypokalemic Metabolic Alkalosis <ul><li>Hyperaldosteronism </li></ul><ul><li>Liddle’s Syndrome </li></ul><ul><li>Apparent Mineralocorticoid Excess </li></ul><ul><li>Glucocorticoid Remediable Hypertension </li></ul><ul><li>Renal Artery Stenosis </li></ul><ul><li>Reninoma </li></ul>
  22. 22. Mechanism of Hypokalemia and Metabolic Alkalosis <ul><li>Aldosterone increases ENaC density </li></ul><ul><li>Negative luminal charge develops </li></ul><ul><li>K+ and H+ secreted to maintain electroneutrality </li></ul><ul><li>We don’t PEE LIGHTNING </li></ul>
  23. 23. Liddle’s Syndrome <ul><li>Gain of function abnormality of ENaC </li></ul><ul><li>Results in sodium retention </li></ul><ul><li>Low levels of aldosterone </li></ul><ul><li>Formerly known as pseudohyperaldosteronism </li></ul>
  24. 24. Apparent Mineralocorticoid Excess <ul><li>Mutation in gene encoding for 11 β hydroxysteroid dehydrogenase </li></ul><ul><ul><li>Cortisol is not converted to cortisone intracellularly </li></ul></ul><ul><ul><li>Cortisol binds to the mineralocorticoid receptor because the concentration is 100 times greater than mineralocorticoids </li></ul></ul><ul><li>Mineralocorticoid receptors are activated by cortisol </li></ul>
  25. 25. Apparent Mineralocorticoid Excess <ul><li>Associated with </li></ul><ul><ul><li>Licorice </li></ul></ul><ul><ul><li>Chewing tobacco </li></ul></ul><ul><ul><li>Carbenoxolone </li></ul></ul><ul><li>Glycyrrhetinic acid is the active component </li></ul><ul><li>Low renin </li></ul><ul><li>Low aldosterone level </li></ul><ul><li>Autosomal Recessive </li></ul>
  26. 26. Apparent Mineralocorticoid Excess Mineralocorticoid Receptor Normal Cortisol 11 β -hydroxysteroid dehydrogenase Type 2 Corticosterone Aldosterone Cortisol 11 β -hydroxysteroid dehydrogenase Type 2 Corticosterone Cortisol Mineralocorticoid Receptor AME
  27. 27. Glucocorticoid Remediable Hypertension <ul><li>Duplication of genes encoding aldosterone synthase and 11 β hydroxylase </li></ul><ul><li>Ectopic production of aldosterone occurs under ACTH control </li></ul>
  28. 28. Glucorticoid Remediable Hypertension Glomerulosa Fasciculata Progesterone Progesterone Progesterone Deoxycorticosterone Deoxycorticosterone 17 hydroxyprogesterone CYP11 β 1 CYP11 β 1 Corticosterone Corticosterone 11-deoxycortisol CYP11 β 1 Cortisol 18-hydroxycorticosterone 18-hydroxycorticosterone CYP11 β 2 Chimeric CYP11 β 2 Aldosterone Aldosterone
  29. 29. Hyperkalemic Metabolic Acidosis <ul><li>Gordon’s Syndrome </li></ul><ul><ul><li>AKA Pseudohypoaldosteronism Type 2 </li></ul></ul><ul><ul><li>Gain of function of the thiazide sodium chloride cotransporter </li></ul></ul><ul><ul><li>Autosomal dominant </li></ul></ul>
  30. 30. Renal Function <ul><li>Normal Values </li></ul><ul><ul><li>1 – 5 years old 0.3-0.5 mg/dL </li></ul></ul><ul><ul><li>6-11 years old 0.5-0.7 mg/dL </li></ul></ul><ul><ul><li>Girls > 11 years 0.7-0.9 mg/dL </li></ul></ul><ul><ul><li>Boys > 11 years 0.7-1.2 mg/dL </li></ul></ul><ul><li>Normal creatinine is determined by the muscle mass of the patient and their renal function </li></ul>
  31. 31. Renal Function <ul><li>Schwartz Equation </li></ul><ul><li>CreCL = constant * Height / creatinine </li></ul><ul><ul><li>Constant </li></ul></ul><ul><ul><ul><li>0.25 micropremie </li></ul></ul></ul><ul><ul><ul><li>0.33 Term neonate </li></ul></ul></ul><ul><ul><ul><li>0.45 Infants </li></ul></ul></ul><ul><ul><ul><li>0.55 Children 1-12, Adolescent girls </li></ul></ul></ul><ul><ul><ul><li>0.70 Adolescent boys >12 </li></ul></ul></ul>
  32. 32. Urine Analysis <ul><li>Hematuria </li></ul><ul><ul><li>Glomerular disease </li></ul></ul><ul><li>Pyuria </li></ul><ul><ul><li>Interstitial nephritis </li></ul></ul><ul><li>Proteinuria </li></ul><ul><ul><li>Glomerular disease </li></ul></ul><ul><ul><li>Hyperfiltration syndrome </li></ul></ul><ul><ul><li>Reflux nephropathy </li></ul></ul>
  33. 33. Red Blood Cell Cast
  34. 34. Urine Protein/Creatinine <ul><li>More sensitive than albustix in detecting proteinuria </li></ul><ul><li>Microalbumin detection sticks can be used </li></ul>
  35. 35. Renal Ultrasound <ul><li>Urologic abnormalities </li></ul><ul><ul><li>Ureteropelvic junction obstruction </li></ul></ul><ul><ul><li>Multicystic dysplastic kidneys </li></ul></ul><ul><li>Polycystic kidney disease </li></ul><ul><li>Renal scarring </li></ul><ul><li>Discordant kidney size </li></ul><ul><ul><li>Reflux nephropathy </li></ul></ul><ul><ul><li>Renal artery stenosis </li></ul></ul>
  36. 36. 4 Extremity BP <ul><li>Screen for coarctation </li></ul><ul><li>Not 100% sensitive </li></ul><ul><li>Echocardiogram is the diagnostic test of choice </li></ul>
  37. 37. If Workup is Negative? <ul><li>Start treatment with antihypertensive medication under the following circumstances </li></ul><ul><ul><li>Comorbid conditions </li></ul></ul><ul><ul><li>Evidence of end organ damage </li></ul></ul><ul><ul><ul><li>Echocardiogram with LVH </li></ul></ul></ul><ul><ul><li>Systolic blood pressure 10 mm Hg greater than 95% </li></ul></ul><ul><ul><li>Failure of lifestyle modifications </li></ul></ul>
  38. 38. Lifestyle Modifications <ul><li>Salt restriction </li></ul><ul><li>Exercise 20 minutes 5 days a week </li></ul><ul><ul><li>HR should achieve 85% of maximum </li></ul></ul><ul><li>Weight loss </li></ul>
  39. 39. Lifestyle Modifications <ul><li>Why don’t they work? </li></ul><ul><ul><li>Entire family needs to participate </li></ul></ul><ul><ul><li>Time is an issue </li></ul></ul><ul><ul><ul><li>Cooking </li></ul></ul></ul><ul><ul><ul><li>Exercise </li></ul></ul></ul><ul><ul><li>Parents are frequently obese </li></ul></ul>
  40. 40. When to Perform More Testing <ul><li>Any abnormality of primary screening </li></ul><ul><ul><li>Aldosterone/Renin > 30 </li></ul></ul><ul><ul><ul><li>Hyperaldosteronism </li></ul></ul></ul><ul><ul><li>Abnormal Urine analysis </li></ul></ul><ul><ul><li>Discordant kidney size </li></ul></ul><ul><ul><li>Severe hypertension </li></ul></ul><ul><ul><li>Family history </li></ul></ul><ul><ul><ul><li>NF, MEN </li></ul></ul></ul><ul><ul><ul><li>Early strokes in family </li></ul></ul></ul>
  41. 41. Renal Artery Stenosis? <ul><li>Usually renin and aldosterone elevated </li></ul><ul><li>More than 1 medications required for BP control </li></ul><ul><ul><li>20% incidence of RAS </li></ul></ul><ul><li>BP greater than 99% </li></ul><ul><ul><li>43% incidence of RAS </li></ul></ul>Pediatr Nephrol. 2000 Aug;14(8-9):816-9.
  42. 42. Renal Scan And Angiogram
  43. 43. RAS on Angiogram
  44. 44. Screen for Pheochromocytoma? <ul><li>Family history of pheochromocytoma </li></ul><ul><ul><li>MEN </li></ul></ul><ul><ul><li>von Hippel Lindau </li></ul></ul><ul><ul><li>Neurofibromatosis is unlikely to be associated with pheochromocytoma prior to age 25 </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Flushing </li></ul></ul><ul><ul><li>Headaches </li></ul></ul><ul><ul><li>Paroxysms </li></ul></ul><ul><ul><li>Tachycardia </li></ul></ul>
  45. 45. Testing for Pheochromocytoma <ul><li>No pediatric normal values </li></ul><ul><li>Metanepherines are higher in children </li></ul>Ann Intern Med, Feb 2001; 134: 315 - 329. 43 94 63 Urinary VMA 53 94 76 Urinary Metanepherine 64 88 83 Urinary Catecholamine 38 80 85 Plasma Catecholamine 82 89 99 Plasma Metanepherine Sensitivity at 100% Specificity Specificity Sensitivity Biochemical test
  46. 46. Testing for Pheochromocytoma <ul><li>Plasma metanepherines is the best screen </li></ul><ul><li>Send out to Mayo clinic </li></ul>
  47. 47. 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
  48. 48. Why No EKG? <ul><li>Sensitivity < 20% to detect LVH </li></ul><ul><li>Specificity 88% to detect LVH </li></ul><ul><li>EKG is a poor screening test for LVH </li></ul><ul><li>If the EKG demonstrates LVH criteria the patient likely has LVH </li></ul>Am Heart J. 2003 Apr;145(4):716-23.
  49. 49. Medication Algorithm Hypertension IHSS Renal Disease No Comorbidities Obesity 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
  50. 50. Calcium Channel Blockers <ul><li>Amlodipine </li></ul><ul><ul><li>Studied in children </li></ul></ul><ul><ul><li>54 hour half life </li></ul></ul><ul><ul><ul><li>Missing a dose is not an issue </li></ul></ul></ul><ul><ul><li>Once a day dosing </li></ul></ul><ul><ul><li>Drops BP effectively </li></ul></ul><ul><li>Cardizem </li></ul><ul><ul><li>Once daily dosing </li></ul></ul><ul><ul><li>Negative ionotrope </li></ul></ul>
  51. 51. ACE Inhibitors <ul><li>Lisinopril </li></ul><ul><ul><li>Generic- 7 dollars a month </li></ul></ul><ul><ul><li>Once daily dose </li></ul></ul><ul><ul><li>Pediatric studies </li></ul></ul><ul><li>Captopril </li></ul><ul><ul><li>3 times a day </li></ul></ul><ul><li>Vasotec </li></ul><ul><ul><li>2 times a day </li></ul></ul>
  52. 52. ACE Inhibitors Caution <ul><li>Nephrogenesis occurs until 2 years of age </li></ul><ul><li>ACE Inhibitors decrease TGF- β and TNF- α expression </li></ul><ul><li>This may lead to a decrease in nephron mass </li></ul><ul><li>Consider not using ACE Inhibitors until after 2 years of age </li></ul>
  53. 53. Angiotensin Receptor Blockers <ul><li>All have been studied in children </li></ul><ul><ul><li>Irbesartan </li></ul></ul><ul><ul><li>Candesartan </li></ul></ul><ul><ul><li>Losartan </li></ul></ul><ul><ul><li>Telmesartan </li></ul></ul>
  54. 54. Conclusion <ul><li>Hypertension in children is increasing in incidence </li></ul><ul><li>Most children have essential hypertension </li></ul><ul><li>The workup is simple and inexpensive </li></ul><ul><li>Angiogram indicated for severe hypertension </li></ul><ul><li>Plasma metanepherines is the best screen for pheochromocytoma </li></ul><ul><li>Once a day medications for compliance </li></ul>

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