the kidney in pregnancy
DESCRIPTION
The Kidney in Pregnancy. Jeffrey J. Kaufhold, MD FACP Update 2010. Renal Physiology. Overview of Physiology 101 Nitric Oxide Physiology Endothelin Physiology Normal Changes in Pregnancy Pathophysiology in Pregnancy. Glomerular Physiology Blood flow determinants. Systemic. AT-II ANS. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/1.jpg)
1
The Kidney in Pregnancy
Jeffrey J. Kaufhold, MD FACP
Update 2010
![Page 2: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/2.jpg)
2
Renal Physiology
Overview of Physiology 101 Nitric Oxide Physiology Endothelin Physiology Normal Changes in Pregnancy Pathophysiology in Pregnancy.
![Page 3: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/3.jpg)
3
Glomerular PhysiologyBlood flow determinants
Afferent Efferent
Filtration
Systemic
PG'sTGF
Local
AT-IIANS
![Page 4: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/4.jpg)
4
Renal Physiology 201
Explosion of Research in NO and ET In the last 4 years, over 3000
publications each.
![Page 5: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/5.jpg)
5
Nitric Oxide
Functions:– Regulate BP– Neurotransmitter– Suppress Pathogens
Studies describe Pathophys. in:– Pregnancy/Pre-ecclampsia– HTN– Hepatic Failure
![Page 6: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/6.jpg)
6
Endothelin
Function: » Most potent vasoconstrictor
Studies describe broad range of Pathophysiologic conditions.
![Page 7: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/7.jpg)
7
Why is this Important?
Inhibitors and Antagonists being developed which you will use soon
You already use some:» Nitroprusside» Isordil/NTG» Viagra
![Page 8: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/8.jpg)
8
Nitric Oxide - NO
Uncharged molecule - can go anywhere Unpaired electron - highly reactive Chemical generation:
» Arginine + O2-----> NO + CitrullineNOS
![Page 9: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/9.jpg)
9
Enzyme Production
Nitric Oxide Synthase (NOS)» Two Types
– Constitutive vasodilator neurotransmitter
– Inducible Free radical scavenger Pathogen killer
![Page 10: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/10.jpg)
10
NITRIC OXIDE
![Page 11: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/11.jpg)
11
Nitric Oxide
Targets:» Vascular Smooth
Muscle» Neurons» Pathogenic bacteria
Effects:» Vasodilator» Feedback for ET-1» Neurotransmitter» Free Radical/Killer
![Page 12: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/12.jpg)
12
Progesterone
Stimulates Nitric Oxide Synthase» See below
Stimulates Relaxin » to soften Ligaments/ allow opening of Birth Canal» Hydroureter
Stimulates Ventilation» Chronic Resp Alkalosis,» Useful in Sleep apnea
![Page 13: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/13.jpg)
13
Normal Changes in Pregnancy
Systemic Vasodilation Lower BP Increased Aldosterone Volume expansion / edema Increased GFR / RBF Angiogenesis
![Page 14: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/14.jpg)
14
Normal Changes in Pregnancy
0
20
40
60
80
100
120
140
Normal 1st Trim 2ndTrim
3rdTrim
GFR
MAP
Volume
![Page 15: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/15.jpg)
15
Normal Changes in Pregnancy
0
2
4
6
8
10
12
14
16
Normal 1stTrim
2ndTrim
3rdTrim
Pulse change
TPR
Art.Compliance
CardiacOutput
Chapter 6, part 1, Medical Care of the Pregnant Patient
![Page 16: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/16.jpg)
16
Glomerular PhysiologyBlood flow determinants
Afferent Efferent
Filtration
Systemic
PG'sTGF
Local
AT-IIANS
Increase Calcium excretionDecrease uric acid reabsorptionDue to reduced filtration fraction
![Page 17: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/17.jpg)
17
Why do these Changes Occur?
![Page 18: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/18.jpg)
18
Progesterone
Stimulates Nitric Oxide Synthase Decreased response to Angiotensin
![Page 19: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/19.jpg)
19
Progesterone
Stimulates Nitric Oxide Synthase» Leads to systemic Vasodilation» Which causes lower BP,» Which stimulates Aldosterone» Which leads to volume expansion» Which increases GFR/RBF
Decreased response to Angiotensin
![Page 20: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/20.jpg)
20
NonVascular Functions of NO
Modulates immune response reduces toxicity of oxygen radicals reduces adhesion of neutrophils, etc inhibits mast cell degranulation
Pregnancy is an Immune Tolerant Condition
![Page 21: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/21.jpg)
21
Pathophysiology
Hypertension Proteinuria Pre-ecclampsia HELLP syndrome Pre-existing renal disease Pre-existing Hypertension
![Page 22: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/22.jpg)
22
Pathophysiology
Hypertension Proteinuria
Return of Responsiveness to Angiotensin
![Page 23: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/23.jpg)
23
Pathophysiology
Pre-ecclampsia» Severe HTN with risk for seizures» Vacuole formation in endothelial cells» Circulating Inhibitors of NOS
HELLP syndrome» Hepatic dysfunction due to underperfusion» Low platelets due to fibrin deposition and scything
of cells in capillaries » Increased Endothelin
![Page 24: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/24.jpg)
24
Normal Glomerulus
![Page 25: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/25.jpg)
25
Ecclampsia
Hyaline thrombus
vacuoles
![Page 26: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/26.jpg)
26
Pathophysiology
Pre-existing renal disease» General rule is
– 1/3 worsen– 1/3 stable– 1/3 improve
Pre-existing Hypertension» Tends to improve» Which drugs to use?
![Page 27: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/27.jpg)
27
Pathophysiology
Hypertension Which drugs?» First Line: Aldomet, Labetolol» Second Line: Hydralazine, Pindolol,
Acebutolol, Nifedipine.» Third Line: Atenolol, Inderal, clonidine,
diltiazem, verapamil, HCTZ
Contraindicated: ACE inhibitors
![Page 28: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/28.jpg)
28
ENDOTHELIN
Three Types Produced by endothelial cells, most
renal cell types. Two receptor types, A and B
![Page 29: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/29.jpg)
29
ENDOTHELIN
Stimulators:» Vasoconstrictors» Thrombin» Hypoxia» Low shear stress» Cytokines
![Page 30: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/30.jpg)
30
ENDOTHELIN
Inhibitors of production» Vasodilators» Heparin» High shear stress
![Page 31: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/31.jpg)
31
ENDOTHELIN
Feedback inhibition by Nitric Oxide, PGI2 (prostacyclin)
Also inhibited by activation of ET-B receptor on the endothelial cell
![Page 32: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/32.jpg)
32
ENDOTHELIN
![Page 33: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/33.jpg)
33
ENDOTHELIN
Vascular Smooth M. Renal Tubules Mesangial cells
Vasoconstriction Sodium excretion Proliferation,
accumulation of Matrix, and contraction.
Target Effect
![Page 34: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/34.jpg)
34
ENDOTHELINClinical Aspects
ATN Contrast nephrotoxicity Cyclosporine nephrotoxicity Endotoxic shock Hypertension Chronic renal failure
![Page 35: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/35.jpg)
35
Clinical Aspects of N.O.
Cirrhosis» decreased BP, low SVR, angiogenesis» NOS inhibitors work, sort of.
Pregnancy» reduced response to angiotensin » natural inhibitor found in pre-ecclampsia
![Page 36: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/36.jpg)
36
Pre-eclampsia Mediators
Soluble fms-like Tyrosine Kinase-1» sFLT1» Antagonizes VEGF, Placental Growth
Factor (PlGF) Soluble Endoglin
» sENG» Cleavage product of TGF-B receptor
– Maynard SE, Thadani R. Pregnancy and the Kidney. JASN Vol 20, 2009, p 14-22.
![Page 37: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/37.jpg)
37
Pre-eclampsia Mediators
Autoantibodies to Angiotensin I receptor» Found in pre-eclampsia and other condiitions» May play a role but are not specific
Deficiency of Catechol-O-Methyl Transferase (COMT) placental enzyme which breaks down catecholamines.
– Maynard SE, Thadani R. Pregnancy and the Kidney. JASN Vol 20, 2009, p 14-22.
![Page 38: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/38.jpg)
38
Future Markers for Pre-eclampsia
Placental Protein 13 (PP13) Placental artery doppler in 3rd trimester Genetic predisposition with certain Gene markers Uric Acid level increases. Why?
– Maynard SE, Thadani R. Pregnancy and the Kidney. JASN Vol 20, 2009, p 14-22.
![Page 39: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/39.jpg)
39
Glomerular PhysiologyBlood flow determinants
Afferent Efferent
Filtration
Systemic
PG'sTGF
Local
AT-IIANS
Due to increased filtration fraction Reduce Calcium excretion Increase uric acid reabsorption
![Page 40: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/40.jpg)
40
Future Treatments for Pre-eclampsia
VEGF » Vascular Endothelial Growth Factor
L-arginine» Substrate for Nitric Oxide Synthase
– Maynard SE, Thadani R. Pregnancy and the Kidney. JASN Vol 20, 2009, p 14-22.
![Page 41: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/41.jpg)
41
Summary
Physiology and Pathophysiology of» Nitric Oxide» Endothelin
Physiology and Pathophysiology of the kidney in Pregnancy
![Page 42: The Kidney in Pregnancy](https://reader035.vdocuments.us/reader035/viewer/2022062722/568139fd550346895da1c3cc/html5/thumbnails/42.jpg)
42
References Medical Care of the Pregnant Patient
» RV Lee, K Rosene-Montella et al. Published by the American College of Physicians (acponline.org), 2000
Kidney Disease and Pregnancy» Dr Phyllis August» www.kidneyatlas.org/book4/adk4-10.pdf
Pregnancy Outcomes after kidney Donation» www.nephrologynow.com/publications/pregnancy-outcom
es-after-kidney-donation» Ibrahim et al. Am J Transplant. 2009 Apr;9(4):825-34
Maynard SE, Thadani R. Pregnancy and the Kidney. JASN Vol 20, 2009, p 14-22.