Kam Kalantar-Zadeh, MD, MPH, Kam Kalantar-Zadeh, MD, MPH, PhD Twitter/Facebook/LinkedIn: @KamKalantar

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Text of Kam Kalantar-Zadeh, MD, MPH, Kam Kalantar-Zadeh, MD, MPH, PhD Twitter/Facebook/LinkedIn:...

  • 5/15/2020

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    Fundamentals of Chronic Kidney Disease (CKD) for Basic and Clinical Neuroscientists

    Kam Kalantar-Zadeh, MD, MPH, PhD Twitter/Facebook/LinkedIn: @KamKalantar

    Professor of Medicine, Pediatrics, Public Health, and Nursing Sciences Chief, Division of Nephrology and Hypertension and Kidney Transplantation

    University of California Irvine (UCI) School of Medicine Harold Simmons Center for Kidney Disease Research & Epidemiology, Orange, CA Tibor Rubin Veteran

    Administrations’ Long Beach Healthcare System, Long Beach, CA Professor of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA

    World Kidney Day (WKD) Steering Committee www.WorldKidneyDay.org

    Past President The International Society of Renal Nutrition & Metabolism (ISRNM)

    www.RenalNutrition.com

    ISN Council member (2016-2019) International Society of Nephrology (ISN) Council

    www.RenalNutrition.com

    Editor-in-Chief Journal of Renal Nutrition (JREN)

    www.JRNjournal.org

    University of California Irvine Medical Center, Orange, CA

    University of California Irvine Medical Center, Orange, CA

    University of California Irvine Medical Center In the heart of Disneyland

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    Dr. K. Kalantar‐Zadeh has received honoraria and/or support in  different forms from Abbott, Abbvie, Alexion, Amgen, ASN 

    (American Society of Nephrology), Astra‐Zeneca, Aveo, Chugai,  DaVita, Dr. Schaer, Fresenius, Genentech, Haymarket Media,  Hofstra Medical School, IFKF (International Federation of 

    Kidney Foundations), ISH (International Society of  Hemodialysis), International Society of Renal Nutrition &  Metabolism (ISRNM), JSDT (Japanese Society of Dialysis  Therapy), Hospira, Kabi, Keryx, Novartis, NIH (National 

    Institutes of Health), NKF (National Kidney Foundations), Pfizer,  Relypsa, Reata, Resverlogix, Sandoz, Sanofi, Shire, US Renal 

    Care, Vifor, UpToDate, ZS‐Pharma.

    Kamyar Kalantar-Zadeh, MD, MPH, PhD

    Objectives: 1. Review the symptoms, screening and diagnosis

    of CKD

    2. Evaluate the major risk factors and causes of CKD: Diabetes and HTN

    3. Examine Poor Outcomes in CKD

    4. Assess the major complications associated with CKD

    5. Review management of CVD in CKD patient including evaluation and treatment options

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    Section 1

    CKD Diagnosis and Classification

    Glomerular Filtration & Creatinine Clearance Glomerular Damage  CKD

    CKD Epidemiology Diabetic Nephropathy

    Proteinuria  CKD progression CKD  Cardiovascular Risk

    Beyond serum creatinine Management of CKD Nephrology Referral

    CKD Comorbid DisordersDO N

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    Glomerular Filtration & Creatinine Clearance Glomerular Damage  CKD

    CKD Epidemiology Diabetic Nephropathy

    Proteinuria  CKD progression CKD  Cardiovascular Risk

    Beyond serum creatinine Management of CKD Nephrology Referral

    CKD Comorbid Disorders

    Glomerulus

    Mesangial Matrix

    Efferent Renal Arteriole

    Mesangial Cells

    Renal Sympathetic

    Nerves

    Bowman’s Capsule

    Distal Convoluted Tubule

    Proximal Convoluted Tubule

    Adventitial Mast Cell/Macrophage

    Components of the Normal Nephron

    Vascular Smooth Muscle Cells

    Afferent Renal Arteriole

    Macula DensaDO

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    Glomerular Filtration

    Glomerular Filtration Rate (GFR): 90-130 ml/min

    Creatinine Clearance

    Equation to estimate Creatinine Clearance (CrCl)  eGFR

    • If 24 hr urine can be collected:

    CrCl = (Vu x Ucr ) / Pcr

    • If no urinary data available (only serum creatinine is available): Cockroft-Gault (0.85 for women)

    eGFR = 0.85 * ( Wt x [140-age] ) / Pcr x 72

    • Other equations: MDRD eGFR = 170 * Pcr-0.999 * age-0.176 * sex * race * BUN-0.170 *albumin0.318

    (Female: 0.762, AA:1.18)

    • Other equations: CKD-EPI

    100 eGFR ~ ------

    Pcr

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    MDRD Equation

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    Diabetes 50%

    Hypertension 27%

    Glomerulonephritis 13%

    Other 10%

    Primary Diagnoses for Patients Who Start Dialysis

    United States Renal Data System (USRDS) 2016-2019 Annual Data Report • WWW.USRDS.ORGDO N

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    Diabetes Complications

    • A. Macro-angiopathies – CAD (Coronary artery dis.) – PVD (Peripheral vascular dis.) – CVD (Cerebro-vascular dis.)

    • B. Microangiopathies – Retinopathy – Neuropathy – Nephropathy

    – Diabetic Foot ulcer

     CKD  ESRD

    © JH

    U 2

    00 5.

    Natural History of Diabetic Nephropathy

    0

    20

    40

    60

    80

    100

    120

    140

    0 5 10 15 20 25 30

    Duration of Diabetes (y)

    0

    100

    200

    300

    400

    500

    600

    U rin

    ar y

    A lb

    um in

    (m g/

    24 h

    )

    Microalbuminuria

    Albuminuria

    eGFR Albumin

    Courtesy of Mark E. Molitch, MD.

    eG FR

    (m L/

    m in

    /1 .7

    3 m

    2 )

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    Glomerular Filtration & Creatinine Clearance Glomerular Damage  CKD

    CKD Epidemiology Diabetic Nephropathy

    Proteinuria  CKD progression CKD  Cardiovascular Risk

    Beyond serum creatinine Management of CKD Nephrology Referral

    CKD Comorbid Disorders

    •Glomerular HTN

    •Hyperfiltration

    •Glomerular barrier dysfunction

    •Proteinuria

    •Mesangial cell hyperplasia

    •Intrarenal inflammatory processes

    •Endothelial dysfunction

    Normal Kidney

    Mechanisms of Kidney Damage in CKD ( GFR)

    B l o o d P r e s s u r eDO N

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    Mechanism of Kidney Damage in CKD: Glomerular Hypertension

    Increased intra-glomerular pressure

    Loss of nephrons or irreversible damage

    Compensatory hyperfiltrationDamage to

    glomerulus structure

    CKD is a progressive disorder  ESRD

    vicious cycle

    Hostetter T H, Olson J L, Rennke H G, Venkatachalam M A & Brenner B M. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Amer. J. Physioi. 241:F85-93, 1981

    Natural Progression of CKD (Chronic Kidney Disease)

    The rate of progression of GFR is usually predictable.

    GFR

    Time

    01/18 3/19 5/20 7/21 1/22

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    Natural Progression of CKD (Chronic Kidney Disease)

    Previous record of S-creatinine: 1/18: 1.8 9/19: 2.1 4/20: 2.0 8/20: 2.2 11/20: 2.9 9/21: 3.4 1/22: 3.3

    eGFR [1/crea]

    Time 01/18 3/19 5/20 7/21 1/22

    1/crea curve can help identify Acute-Kidney Injury: 1/22: S-creat 5.2 mg/dL

    Target for Feb 2022: S-creat ~ 3.5 mg/dL

    100 CrCl ~ ------

    Pcr

    Definition of Acute Kidney Injury (AKI) based on “Acute Kidney Injury Network” (AKIN Criteria)

    Stage Increase in Serum Creatinine

    Urine Output

    1 1.5-2 times baseline OR 0.3 mg/dl increase from baseline

    6 h

    2 2-3 times baseline 12 h 3 3 times baseline

    OR 0.5 mg/dl increase if baseline>4mg/dl OR Any RRT given

    24 h OR Anuria for >12 h

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    Glomerular Filtration & Creatinine Clearance Glomerular Damage  CKD

    CKD Definition & Epidemiology Diabetic Nephropathy

    Proteinuria  CKD progression CKD  Cardiovascular Risk

    Beyond serum creatinine Management of CKD Nephrology Referral

    CKD Comorbid Disorders

    Definition of CKD (Chronic Kidney Disease)

    The presence of kidney damage, or  level of kidney function

    for 3 months or more, irrespective of diagnosis

    National Kidney Foundation K/DOQI, 2001DO N

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    Definition of Chronic Kidney Disease (CKD)

    • Criterion 1. Kidney damage for 3 months, as defined by structural of functional abnormalities of the kidney, with or without decreased GFR, manifest by either:

    – Pathological abnormalities; or

    – Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests

    • Criterion 2. GFR (or Creatinine Clearance) 90(with CKD risk factors) >Screening >CKD risk reduction

    1 Kidney Damage withNormal or ↑GFR >90 >Diagnosis and treatment. >Treatment of comorbid conditions, >Slowing progression, >CVD risk reduction

    2 Kidney Damage withMild ↓GFR 60-89 >Estimating progr