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Chronic Kidney Disease Edward Barnes, MD, FACP
Assistant Dean, COMP Chief, Nephrology & Hypertension
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
Filter Erythropoietin
Acid-Base
Sodium-Water
Vitamin D
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
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
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
Causes of ESRD
NKF; Kidney.org/general/new/problem
Growing ESRD Population
USRDS ADR 2010
21%
79%
Cost of CKD to Medicare CKD patient related costsNon CKD patient costs
Economic Burden of CKD in the U.S.
11
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
12
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
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
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
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
Therapy- Slowing the Progression of CKD
• RAAS suppression/Albuminuria therapy
– ACE inhibitors – Angiotensin Receptor Blockers
• Hypertension Control • Diabetes Management • Hyperlipidemia Control
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.
Guidelines Precision Medicine
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
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
• 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
ESRD 5 year Risk
• 0-5% Low Risk
• 5-15% Intermediate Risk
• >15% High Risk
Progression and Biomarkers
EGF and CKD progression
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
Proteomics
Pathway driven biomarker discovery
Data Analysis, Validation, & Translation
Profiling biomarker discovery
Proteomics
Traditional Biochemistry
Proteomics
Select Targeted Therapies
• Endothelin Receptor Antagonists
• Advanced Glycosylated End-product (AGE) Inhibitors
• Renal Repair
– Stem Cell Therapy Micro-Chinese Therapies
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
Avosentan vs. Albuminuria ET-1 inhibitor
Mann et al. J Am Soc Nephrol 21: 527–535, 2010
X
X
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;
Pyridoxamine AGE inhibitor
• Derivative of Vitamin B6
• Inhibits AGE Formation
TP Degenhardt et al. KI (2002) 61, 939–950;
Pyridoxamine
F Zheng et. al. KI (2006) 70, 507–514.
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,
Now that is some Sci-Fi S@#!
• Nano-technology
• Renal Assist Device (RAD) – Artificial Kidney
QUESTIONS?