Chronic Kidney Disease · ESRD Care is Expensive . Other Medicare . ESRD + Late Stage Chronic...
Transcript of Chronic Kidney Disease · ESRD Care is Expensive . Other Medicare . ESRD + Late Stage Chronic...
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Chronic Kidney Disease Edward Barnes, MD, FACP
Assistant Dean, COMP Chief, Nephrology & Hypertension
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Objectives • Background– What’s the Problem?
– Definition and Staging – Epidemiology – Pathogenesis
• Current Management – Goals – Strategies
• To the future – Guideline Medicine Precision Medicine – A peek into New Tech
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Filter Erythropoietin
Acid-Base
Sodium-Water
Vitamin D
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Definition • Kidney damage for 3 months
– Defined by structural of functional abnormalities of the kidney, with or without decreased GFR, manifest by either:
– Pathological abnormalities – Markers of kidney damage
• Blood or protein in urine • Abnormal Imaging tests
• GFR <60 mL/min/1.73m2 for 3 months, with or without kidney damage
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How do we measure Kidney Function?
Estimated GFR (ml/min/1.73m2) MDRD
=186 x (SCr)-1.154x (Age)-0.203x(0.742 if female) x (1.210 if African- American) = exp(5.228-1.154xln(SCr)-0.203xln(Age)-(0.299 if female)+(0.192 if African-American
• Less Accurate in patients with eGFR near or >60mL/min per 1.73m2
• CKD-EPI GFR- Increased accuracy for eGFR >60mL/min per 1.73m2
•26 studies pooled data for validation
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Chronic Kidney Disease (CKD)
Stages of CKD
V End-Stage
Renal Disease
IV Severe
III Moderate
II Mild
I Kidney
Damage
Transplant
Dialysis
Hospice
> 90 60-89 30-59 15-29 <15
GFR mL/min/1.73 m2
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Causes of ESRD
NKF; Kidney.org/general/new/problem
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Growing ESRD Population
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USRDS ADR 2010
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21%
79%
Cost of CKD to Medicare CKD patient related costsNon CKD patient costs
Economic Burden of CKD in the U.S.
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Why Do CKD Patients Need Special Care?
eGFR & Mortality
0
2
4
6
8
10
12
14
16
>59 45-59 30-44 15-29 <15
Adjst
ed D
eath
Rat
e (D
eath
s / 1
00 p
t yea
rs a
t risk
)
eGFR (ml/min/1.73 m2)
eGFR Adjusted Mortality
No. of Events 25,803 11,603 7,802 4,408 1,842
eGFR < 60 ml/min/m2 Increase Risk of Death
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ESRD Care is Expensive
Other Medicare
ESRD + Late Stage Chronic Kidney Disease (CKD)
~ $30B per year
~1.5% of Patients ~10% of Federal Healthcare Costs
Other Medicare
Source: USRDS (publicly available comprehensive clinical and financial dataset reported to and used by CMS) ~375,000 ESRD + ~300,000 Stage 4 Chronic Kidney Disease
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Pathophysiology
• Susceptibility Factors – Older Age – Health illiteracy – Race and Ethnicity – Family History – Low Renal Mass
• Initiation Factors – Diabetes – Hypertension – Autoimmune – Systemic Infections – Lower Urinary Obstruction – Drug Toxicity
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Pathophysiology
• Progression Factors – High Level of Proteinuria – Uncontrolled Hypertension – Poor Glycemic Control – Smoking
• End-Stage Factors (Increasing Mortality) – Low dose Dialysis – Anemia – Low Albumin – Late referral to
Nephrologist
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What are the Guidelines?
• KDOQI Guidelines • Therapies for Slowing the Progression of CKD
– RAAS suppression/Albuminuria therapy • ACE inhibitors OR • Angiotensin Receptor Blockers
– Hypertension Control- BP <140/90 mmHg – Diabetes Management- HbA1C <7.0% – Hyperlipidemia Control –LDL <100 mg/dL – Low Protein Diet in Diabetics with macroalbuminuria – no more than 1.3g of
protein/day – Low Sodium diet- <2g/day
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Therapy- Slowing the Progression of CKD
• RAAS suppression/Albuminuria therapy
– ACE inhibitors – Angiotensin Receptor Blockers
• Hypertension Control • Diabetes Management • Hyperlipidemia Control
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What is Precision Medicine?
Precision Medicine: Medical care designed to optimize efficiency or therapeutic benefit for particular groups of patients, especially by using genetic or molecular profiling.
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Guidelines Precision Medicine
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Normal Increased Risk Damage Albuminuria GFR ESRD Death
CKD Conceptual Model
Ideal Biomarker
Creatinine
Pavlesky PM, Chief Renal Section VA Pittburgh
Increased GFR
Kidney Markers
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Chronic Kidney Disease (CKD)
Stages of CKD
V End-Stage
Renal Disease
IV Severe
III Moderate
II Mild
I Kidney
Damage
Transplant
Dialysis
Hospice
> 90 60-89 30-59 15-29 <15
GFR mL/min/1.73 m2
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• Gender Female • Age 67 • eGFR 44 mL/min • UACR 286 mg/g • Serum Ca 9.2 mg/dL • Serum Phos 4.5 mg/dL • Serum Bicarb 20 meq/L • Serum Albumin 3.1 meq/L • Score 10.3% risk of ESRD over 5yrs
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ESRD 5 year Risk
• 0-5% Low Risk
• 5-15% Intermediate Risk
• >15% High Risk
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Progression and Biomarkers
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EGF and CKD progression
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Proteomics
Advances in the fields of two-dimensional gel electrophoresis, protein analysis, and computer databases together make proteome analysis
possible.
The study of genetics which refers to all the proteins expressed by a genome; proteomics involves the identification of proteins in the body and the determination of their role in physiological and pathophysiological functions
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Proteomics
Pathway driven biomarker discovery
Data Analysis, Validation, & Translation
Profiling biomarker discovery
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Proteomics
Traditional Biochemistry
Proteomics
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Select Targeted Therapies
• Endothelin Receptor Antagonists
• Advanced Glycosylated End-product (AGE) Inhibitors
• Renal Repair
– Stem Cell Therapy Micro-Chinese Therapies
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Endothelin Receptor Antagonists
• Endothelin-1 (ET-1) levels are elevated in urine/plasma in patients with DM
• ET-1 levels correlate with:
– renal function – blood pressure – albuminuria
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Avosentan vs. Albuminuria ET-1 inhibitor
Mann et al. J Am Soc Nephrol 21: 527–535, 2010
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X
X
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AGE Inhibitors
Glucose & Proteins AGEs Cross-linked AGEs RAGE
Glucose Lowering Agents
AGE Formation Inhibitors
Pyridoxamine
AGE Crosslink Breakers
Receptor Blockers
TP Degenhardt et al. KI (2002) 61, 939–950;
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Pyridoxamine AGE inhibitor
• Derivative of Vitamin B6
• Inhibits AGE Formation
TP Degenhardt et al. KI (2002) 61, 939–950;
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Pyridoxamine
F Zheng et. al. KI (2006) 70, 507–514.
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Stem Cells • 1. Micro-Chinese Medicine Osmotherapy
ingredients in the medicines can help patients repair the damaged renal intrinsic cells and prevent the further renal damage. – Also used to manage Hypertension
• 2. Stem Cell Transplant combined application of
Stem Cell Transplant and Micro-Chinese Medicine Osmotherapy. – undifferentiated original cells, which can differentiate new
cells to replace their roles. – Stem Cell Transplant and Micro-Chinese Medicine
Osmotherapy has showed their enormous effect in the treatment of CKD,
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Now that is some Sci-Fi S@#!
• Nano-technology
• Renal Assist Device (RAD) – Artificial Kidney
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QUESTIONS?