The Northwest School:

Pioneering a Partnership for

Education and Advocacy

David G Reuter MD PhD FAAPHeart Center, Seattle Children’sPediatrician: Allegro Pediatrics

Two Goals:

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1. Understand how kidney controls blood pressure1. Renin – Angiotensin – Aldosterone System (RAAS)

2. Understand Relationship between “Page Kidney” and Preeclampsia.

Clinical Problem: Preeclampsia

• Definition: • High Blood Pressure During Pregnancy

• Magnitude of Problem:• Occurs in 8% of pregnancies (10 Million Women)• 50,000 Moms / year die• 500,000 babies / year die

• Cause:• Unknown

• Our Goal:• Identify Cause of Preeclampsia• Refine Solution• Communicate our Insights to Families Worldwide

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Terminology

Medical

• Erythematous• Supine• Prone• Renal• Hypertension

Normal

• Red• Rest (On your Back)• Rest (Tummy Down)• Kidney• High Blood Pressure

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My Goal: Use normal words

Your Responsibility: Ask if I use unfamiliar words.

Note: All the topics are straightforward as long as we understand words.

Three Clues to Contemplate over the Summer:

• Clue #1:• Increased pressure in the kidney causes high blood pressure

• Clue #2:• Left Renal Vein Anatomy is Important

• Clue #3:• Renin and Ischemia are involved.

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Kidney

Anatomy and Function

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Kidney Anatomy

Clue: Note how IVC is on right, left kidney is on left

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IVC – Inferior Vena CavaBrings blood back to heart

“All Things Properly Understood Are Simple”

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Halloween Maze

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WRen

Sylvester Stallone

Angie Twins I and II

Kids (Wander)

Halloween Maze - Responsibilities

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WRen Ensure Constant Kid Flow Thru Maze

Sylvester Redirect kids into maze as needed Stallone

Angie Twins Adjust diameter of lane leading into maze I and II

Kids Wander thru maze; Return periodically

Halloween Maze – Normal Number of Kids

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Halloween Maze – Too Many People

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Halloween Maze – Too Few People

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Halloween Maze - Responsibilities

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Renin Ensure Constant Blood Flow Thru Kidneys

Aldosterone Redirect Fluid back into kidney as needed

Angiotensin II Adjust diameter of blood vesselAngiotensin I

Blood Wander thru kidney; Return periodically

Glomerulus – Kidney’s Maze for Blood.

CLUE: Note blood flow in and out of “MAZE”

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Questions

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How Does Kidney Control Blood Pressure / Volume?

Three Choices:

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Renin

High VolumeNormal VolumeLow Volume

Aldo Angi Angi AldoAngiAldo

H2O BP H2O BPH2O BP

Goal #2: Introduce Page Kidney

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Page Kidney Increased Kidney Pressure Hypertension

Page Kidney:

Wrap Kidney in Cellophone Increase Pressure Hypertension

Source• Page. Production of persistent arterial

hypertension. JAMA. 1939

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Group Discussion:Application of Knowledge

Anatomy and Function

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Group Discussion / Challenge

• Page Kidney:• Identify 3 ways to increase pressure in kidney

• 1) External compression• 2) • 3)

• High Blood Pressure:• Explain how Page Kidney Causes High Blood Pressure

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Clinical Page Kidney

• Case Report:• 33 yo male kidney surgery blood accumulation in kidney high blood

pressure

• Acute Page Kidney: Renin Mediated• Chronic Page Kidney: Ischemia Mediated

• Source: • McCune. Page Kidney. Am J Kidney Dz. 1991

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Acute Renal Vein Constriction:Leads to Increased Renin, Aldosterone, Proteinuria

• Purpose: • Evaluate effect of increased renal venous

pressure (RVP).

• Methods:• Renal vein constriction x 2 hours.• 8 swine (4 control; 4 tx).• RVP increased 0-30 mmHg.

• Results:• Increased renin.• Increased aldosterone.• Increased proteinuria.

Source: Doty JM, et al. Effect of increased venous pressure on renal function. J Trauma 1999.

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Blood Flow In and Out of Kidney

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Clue: Note how Vein (Blue) is weaker than artery (Red)

Blood Flow to Kidneys

Clue: Note where blood vessels cross spine

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RIGHT LEFT

Answer Key:

• Page Kidney:• Identify 3 ways to increase pressure in kidney

• 1) External compression• 2) Internal Pressure (e.g., bruise)• 3) Outflow Obstruction (Note effect of baby on renal vein)

• High Blood Pressure:• Explain how Page Kidney Causes High Blood Pressure

• Incr Renal Pressure Decrease flow of blood into kidney renin released angiotensin I/II released (Incr BP) Aldosterone release (Incr Fluid).

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Three Phases to Collaboration

• Introduction

• Renin / Page Kidney

• Renal Vein Anatomy

• Ischemia

• Supine Pressor Test

• Assimilate Clues

• Responders v Non-responders

• Risk Stratify Moms

• Optimize Therapy

• Design Next Trial

• SIDS Model

• Smallpox Model

• Preempt Model

• Days for Girls

• Social Media Strategy

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Study Solve Analyze Iterate Advocate

Next Lecture

Questions:• Why does preeclampsia occur in ~8% of pregnancy• Why is preeclampsia severe in ~3% of pregnancies• Why does severe preeclampsia recur?

Clue:• Understand variable anatomy of Left Renal Vein.

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Left Renal Vein Anatomy

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Back-up Slides

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Timeline of Collaboration

• Fall 2015:• Learn / Understand biology to sufficient degree to solve puzzle of

preeclampisa (Study the Problem)

• Spring 2016:• Knowing the etiology (cause) of preeclampsia, analyze data from

clinical trial conducted at Seattle Childrens to refine new therapy (Iterate Towards Excellence).

• Fall 2016:• Initiate grass roots, global health, adolescent driven, pediatric

advocacy campaign. (Advocacy and Communication)

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Three Goals

• Seek your collaboration to solve important problem in medicine regarding children / families.

• Share example of how to solve problem• Study• Iterate• Advocate

• Set Stage For Collaboration• Share insights on preeclampsia (Study Problem)• Courses Prepare You to Collaborate (Iterate / Analyze)• Consider Grass Roots Global Health Initiate (Advocate)

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Preeclampsia and Prematurity

Karumanchi et al. Kidney Intl 200537

Infant Symptoms:• Brain• Eyes• Ears• Heart • Lungs• Gut• Muscles

Goal #1: Explain how kidney controls blood pressure and fluid volume.

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