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

Kam Kalantar-Zadeh, MD, MPH, PhDTwitter/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 MedicineHarold Simmons Center for Kidney Disease Research & Epidemiology, Orange, CA Tibor Rubin Veteran

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

World Kidney Day (WKD) Steering Committeewww.WorldKidneyDay.org

Past PresidentThe 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-ChiefJournal 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 CenterIn 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 NOT

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CKD Epidemiology





Management of CKD

Nephrology Referral

CKD Comorbid Disorders

Glomerulus

Mesangial Matrix

Efferent Renal Arteriole

Mesangial Cells

Renal Sympathetic

Nerves

Bowman’s Capsule

DistalConvoluted Tubule

Proximal Convoluted Tubule

Adventitial Mast Cell/Macrophage

Components of the Normal Nephron

Vascular Smooth Muscle Cells

Afferent Renal Arteriole

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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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Diabetes50%

Hypertension27%

Glomerulonephritis13%

Other10%

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

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Natural History of Diabetic Nephropathy

0

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120

140

0 5 10 15 20 25 30

Duration of Diabetes (y)

0

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400

500

600

Uri

nar

y A

lbu

min

(m

g/2

4 h

)

Microalbuminuria

Albuminuria

eGFRAlbumin

Courtesy of Mark E. Molitch, MD.

eGF

R (

mL

/min

/1.7

3 m

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CKD Epidemiology





Management of CKD

Nephrology Referral


•Glomerular HTN

•Hyperfiltration

•Glomerular barrier dysfunction

•Proteinuria

•Mesangial cell hyperplasia

•Intrarenal inflammatory processes

•Endothelial dysfunction

Normal Kidney

Mechanisms of Kidney Damage in CKD ( GFR)

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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]

Time01/18 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 OR0.3 mg/dl increase from baseline

<0.5 ml/kg/h for >6 h

2 2-3 times baseline <0.5 ml/kg/h for >12 h

3 3 times baseline OR0.5 mg/dl increase if baseline>4mg/dlORAny RRT given

<0.3 ml/kg/h for >24 hORAnuria for >12 h

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CKD Definition & Epidemiology





Management of CKD

Nephrology Referral


Definition of CKD(Chronic Kidney Disease)

The presence of kidney damage, or level of kidney function

for 3 months or more, irrespective of diagnosis

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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, includingabnormalities in the composition of the blood or urine, or abnormalities in imaging tests

• Criterion 2. GFR (or Creatinine Clearance) <60mL/min/1.73m2 for 3 months, with or without kidney damage

National Kidney Foundation K/DOQI Guidelines 2001

Staging of CKDStage Description GFR

(mL/min/1.73m2)Action*

At increased risk >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 progression

3 Moderate ↓ GFR 30-59 >Evaluating and treating complications

4 Severe ↓ GFR 15-29 >Preparation for Kidney Replacement Rx

5 Kidney Failure <15(pre-ESRD or dialysis)

>Renal Replacement Rx (dialysis/Trsp)[if uremia present]

CKD = Chronic Kidney Disease National Kidney Foundation K/DOQIDO NOT

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Staging of CKDStage Description GFR

(mL/min/1.73m2)Action*

At increased risk >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 progression

3 Moderate ↓ GFR 30-59 >Evaluating and treating complications

4 Severe ↓ GFR 15-29 >Preparation for Kidney Replacement Rx

5 Kidney Failure <15(pre-ESRD or dialysis)

>Renal Replacement Rx (dialysis/Trsp)[if uremia present]

CKD = Chronic Kidney Disease National Kidney Foundation K/DOQI

2012 refinement/revision by KDIGO

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The Chronic Kidney Disease Epidemic

Coresh J et al. JAMA. 2007;298:2038-2047; United States Renal Data System (USRDS) 2005 Annual Data Report.

3.6

6.5

15.5

0.7 0.450

2

4

6

8

10

12

14

16

1 2 3 4 5

Mil

lio

ns

of P

eo

ple

≥90 60-89 30-59 15-29 <15

CKD StageeGFR(mL/min/1.73 m2)

CKD Affects ~16% of the US Population

USA: Dialysis Dependent Patients540,000 US Americans and growing680,000 ESRD = dialysis + Transplants

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Kovesdy & Kalantar-Zadeh. Enter the dragon: a Chinese epidemic of CKD?

Lancet 2012 Mar 3;379(9818):783-5

USA: 26 millions China: 119 millions

CKD-EPI EquationMatsushita … Levey, JAMA. 2012 May 9; 9;307(18):1941-51

EDITORIAL: Kalantar-Zadeh & Amin. JAMA. 2012 May 9;307(18):1976-7

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CKD-EPI EquationMatsushita … Levey, JAMA. 2012 May 9; 9;307(18):1941-51

EDITORIAL: Kalantar-Zadeh & Amin. JAMA. 2012 May 9;307(18):1976-7

• Estimating GFR based on filtration markers such as serum• creatinine or cystatin C concentration should serve as a screening tool

and should be interpreted conservatively to avoid labeling healthy individuals with the diagnosis of CKD stage 3 before timed-urine collection or other tests are assessed carefully.

• Although use of the CKD-EPI equation may mitigate this problem, and this equation should now replace the MDRD equation, the search for better filtration markers and estimated GFR equations continues. In the interim, a wiser cutoff level at which patients should be warned about possible kidney disease, such as an estimated GFR lower than 45 mL/min/1.73m2 by the CKD-EPI equation, would be prudent.

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CKD Cardio/cerebro-vascular Risk


Management of CKD

Nephrology Referral


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No EventsESRDDeath

Increased Mortality in Patients With Diabetes, CKD, or Both: 2-Y Clinical Outcomes

DM = diabetes mellitus; ICD-9-CM = International Statistical Classification of Diseases, 9th Revision, Clinical Modification.CKD identified as ICD-9-CM diagnosis code, includes CKD from diabetes, hypertension, obstructive uropathy, and other diagnosis codes reported to USRDS.Collins et al. Kidney Int. 2003;64(suppl 87):S24-S31.

Medicare Cohort

84.0

15.729.5 32.3

67.6 61.6

0

20

40

60

80

100

+ DM,- CKD

- DM,+ CKD

+ DM,+ CKD

Pat

ien

ts (

%)

0.3

2.96.1

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Patient population: health plan patients with estimated GFR <90 followed up until RRT, death, or disenrollment from health plan. N=27,998.

Keith et al. Arch Intern Med. 2004;164:659

0

20

40

60

80

100

Died RRT Event-free Disenrolled

5-Year Follow-UpP

erce

nt

of

Pat

ien

ts (

%)

10%

75%

15%

20% 24%

46%

63%

16% 10%

64%

7%

1.3%

28%

19%

1.1%

GFR 60-89No Proteinuria

GFR 60-89+ Proteinuria

GFR 30-59 GFR 15-29

†

DEATH IS MORE COMMON THAN DIALYSIS IN CKD

.1%

CKD 2 CKD 2 CKD 3 CKD 4

CKD and Age-Standardized Rates of Hospitalization, CV Events and Death in 1.1 Million Outpatients over 3 yrs

0

5

10

15

20

>60 45-59 30-44 15-29 < 15Age-

Sta

ndar

diz

ed R

ates

HOSPITALIZATIONS/10 person-yrs

CV EVENTS/50 person-yrs

ALL CAUSE DEATH/100 person-yrs

Go et al, New Engl J Med 351:1296, 2004

CKD-5D

Dialysis Pts

~18% /yrCKD-1 & 2 CKD-3a CKD3b CKD-4 CKD-5

b6

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b6 X and Y axis lines are blank. Y is labelled "age-standardized rates". X is not labelled.bnewsome, 10/8/2004

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Sarnak. Am J Kidney Dis. 2000;35(suppl 1):S117.

Cardiac and Cardiovascular Mortality

GP Male

GP Female

GP Black

GP White

DP Male

DP Female

DP Black

DP White

100

10

1

0.1

0

25–34 35–44 45–54 55–64 65–74 75–84 >85

Age (years)

An

nu

al M

ort

alit

y (%

)

General Population (GP)

Dialysis Population (DP)

What do people with CKD die from?Cardiovascular disease is a major cause

USRDS, 2010‐2019 ADRNational Vital Statistics Report, CDC 2010‐2018

Cardiovasculardisease42.0%

Infection3.6%

Withdrawal9%

All other33.0%

Malignancy4%

Cardiovasculardisease31.0%

All other33.1%

Malignancy23.2%

Lung disease5.3%

Self‐harm1.4%Alzheimers

3.1%

Infection12%

ESRD, USA General population, USA

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Management of CKD

Nephrology Referral


Creatinine Levels

Problems with Serum Creatinine?

• Insensitive for detecting kidney dysfunction• Product of muscle breakdown – so reflects nutritional status• This may be a problem particularly in the elderly

NutritionalStatus

KidneyFunction

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Cystatin C(0.53-0.95 mg/dL)

• Nonglycosylated, low molecular mass (13 kDa) protein produced by all nucleated cells.

• Its low molecular mass & its high isoeletric point (pI) allow it to be freely filtered by the glomeruli.

• Serum concentration of cystatin C correlates with GFR.

• Serum levels of cystatin C are independent of weight and height, muscle mass, age (>1 yr.) or sex, making GFR estimates much less variable than those with creatinine.

• Measurements can be made and interpreted from a single random sample.

• Jung et al, Nephron 1995

Mortality from all causes according to quintile of kidney function

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COST! (but much less expensive in recent years)More data is still needed re inflammation, thyroid

disease, HIV, etc)? Few reports suggested that cystatin C is affected

by: changes in thyroid function Inflammation (CRP) corticosteroids active HIV infection Certain malignancies?

Inker … Levey, NEJM 2012

BETTER than either of them? Combine both!

The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for CKD.

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Management of CKD

Nephrology Referral


Management of CKD (Chronic Kidney Disease)

• Can CKD be cured or reversed? • No!

• Can the progression of CKD be stopped?• No!

• Can the rate of progression of CKD be slowed down?• Yes!

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Can the rate of CKD progression be modified?

The rate of progression of CKD is usually predictable.

eGFR(1/Cr)

Time

01/13 3/14 5/15 7/16 10/17 12/18

with ACEI

without ACEI

Started on ACEI

Pathologic Processes Leading to Glomerular Injury and Proteinuria

afferent

Increasedglomerularpressure

efferent

Urinary protein

Efferent arteriolar

constriction

=angiotensin AT1receptor

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Many nephrologists are trained to learn that “MDRD Study” was a failure!

“Low Protein Diet has no effect” ???

Low Protein Low SaltDiet Therapy for the Management of CKD

Pathologic Processes Leading to Glomerular Injury and Proteinuria

afferent

Increasedglomerularpressure

efferent

Urinary protein

Efferent arteriolar

constriction

=angiotensin AT1receptor

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Amino acids (dietary protein intake) deliveryincreases intracapillary glomerular pressure and GFR

Aminoacids• Glom. flow • Cap. glom. pressure• GFR

Glomerular aff. arteriole

Glomerular eff. arteriole

Tubule

Glomerule

Studies in rats and healthy manhave shown vasodilation of the glomerular afferent arteriole

GFR

Kalantar-Zadeh & Foque, Nutritional Management of CKD. NEJM Nov 2, 2017

Amino acid (dietary protein intake) restrictiondecreases intracapillary glomerular pressure and GFR

Aminoacids • Glom. flow • Cap. glom. Pressure • GFR

Glomerular aff. arteriole Glomerular eff. arteriole

Tubule

Glomerule

GFR

vasoconstriction of the glomerular afferent arteriole

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2016/10/5 57

Observational studies about the effect of high protein (HP) diet on renal function

Ko, Obi, Tortorici and Kalantar-Zadeh, Curr Opin Clin Nutr Metab Care 2016

LPD to sVLPD: effect on CKD progression? MDRD study (CKD stage 3) NEJM 1994

MDRD: Modification of Diet in Renal Disease

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MDRD study 1: secondary analysis

Levey AS et al, J Am Soc Nephrol 1999; 10: 2426-2439



MDRD study 1: secondary analysis

Levey AS et al, J Am Soc Nephrol 1999; 10: 2426-2439

effect?

Kalantar-Zadeh & Fouque, NEJM, Nov 2017

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Low Protein Diet for 5 Categories of CKD Severity

Kalantar-Zadeh & Foque, Nutritional Management of CKD. NEJM Nov 2, 2017








Management of CKD

Nephrology Referral

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Management of CKD Comorbidities

• 1. Anemia• 2. Bone Disease• 3. Acidosis and electrolyte disarrays• 4. Hypertension• 5. Nutrition• 6. Medication Dose adjustment• 7. Preparation for Renal Replacement Therapy

Anemia of Renal Failure: Progression

• Hakim RM, Lazarus JM Biochemical parameters in chronic renal failure. Am J Kidney Dis 1988 Mar;11(3):238-47

Hematocrit vs. creatinine

0

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20

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50

1 2 3 4 5 6 7 8 9

serum creatinine

hem

ato

crit

ESRDCKD 1 → 2 →3→4→5normal

CKD

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• 3 N-linked (CHO) chains

• Maximum 14 sialic acids

• MW ~ 30,400 daltons

• 40% carbohydrate

• 5 N-linked (CHO) chains

• Maximum 22 sialic acids

• MW ~ 37,100 daltons

• 51% carbohydrate

Additional carbohydrate

side chains

Receptor 1

AranespTM

Receptor 2 Receptor 1

rHuEPO

Receptor 2

carbohydrate side chains

Molecular Comparison of EPO (erythropoietin alpha) and Aranesp (darbepoetin alfa)

Resistance to EPO Therapy

• 1. Iron deficiency• 2. Insufficient dialysis• 3. Aluminum intoxication • 4. Hyperparathyroidism • 5. Deficiency of folate or vitamin B12

• 6. Blood loss • 7. Inhibitory cytokines • Infections• Inflammation / Malnutrition• Neoplasms• 8. ACE inhibitors • 9. Hemoglobinopathies• 10. Antibodies against EPO• 11. Unknown factorsDO N

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• 1. Anemia• 2. Bone Disease• 3. Acidosis and electrolyte disarrays• 4. Hypertension• 5. Malnutrition• 6. Medication Dose adjustment• 7. Preparation for Renal Replacement Therapy

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Secondary Hyperparathyoridism

Ca = calcium; CVD = cardiovascular disease; P = phosphorus.

PTH

Bone DiseaseFracturesBone pain

Marrow fibrosisErythropoietin resistance

Serum P1,25D

Calcitriol

Renal Failure

PTH

Systemic ToxicityCVD

HypertensionInflammationCalcification

Immunological

25D

Ca++

Decreased Vitamin D Receptors and Ca-Sensing Receptors

FGF-23

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©JH

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50

100

150

200

250

300

>80 79-70 69-60 59-50 49-40 39-30 29-20 <20

eGFR Interval (mL/min/1.73 m2)

iPT

H L

evel

(p

g/m

L)

05101520253035404550

iPTH 1,25 Vitamin D 25(OH) Vitamin D

1,25

Vit

amin

D (

pg

/mL

)25

(OH

) V

itam

in D

(n

g/m

L)

Mean Values of iPTH, 1,25(OH)2D3, and 25(OH)D3 by eGFR

N = 1814

*P<0.001.Bakris et al. Poster presented at: American Society of Nephrology Renal Week 2005; November 8-13, 2005; Philadelphia, PA. Abstract F-PO732.

(n = 61) (n = 117) (n = 230) (n = 396) (n = 355) (n = 358) (n = 204) (n = 93)

*

*

Stage 2 Stage 4Stage 3

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Vitamin D3 25-Hydroxyvitamin D25(OH)D

1,25-Dihydroxyvitamin D3

1,25 (OH)2D3, Calcitriol

(Active Vitamin D)

Brown et al. Am J Physiol. 1999;277:F157-F175.

Liver and Kidney Function Are Essential for Vitamin D Precursor Activation to Calcitriol

HO

OH

OHHO

OH

HO

liver kidney

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Metabolic Acidosis

• Metabolic acidosis with moderate anion gap (AG: ~15 meq/L)

• Due to retention of sulfuric and phosphoric acids

• Treatment: NaBicarbonate 650-1300 mg po bid– Na Bicarbonate:

• better than citrate (aluminum absorption)– Newer agents: proton binders: veverimer

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Hyperkalemia

• K>5.3 meq/dL especially with ACEI/ARB• Etiology: distal nephron sodium delivery low, RTA 4

• Rx: 1. low K diet (avoid banana, avocado, etc): Not healthy diet2. furosemide 40-120 mg qd to tid3. Na-bicarb 650-1300 mg bid4. Florinef 0.1-0.5 mg qd (in HTN contraindicated!5. Lower ACEI/ARB dose 6. Older K binder: Kayexalate 15 gm qd or qod7. Newer K-binders:

1. Patiromer (Valtassa): 8.4 g qd2. Zerconium (Lokelma): 5 g qd


• 1. Anemia• 2. Bone Dz• 3. Acidosis and electrolyte disarrays• 4. Hypertension• 5. Malnutrition• 6. Medication Dose adjustment• 7. Preparation for Renal Replacement Therapy

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Recommendations for BP and RAS Management in CKD

BP = blood pressure; RAS = renin angiotensin system; CCB = calcium channel blocker; BB = -blocker; JNC 7 = The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.ADA. Diabetes Care. 2005;28(suppl 1); Chobanian et al. JAMA. 2003;289:2560-2572; Kidney Disease Outcomes Quality Initiatives (K/DOQI). Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.

PatientGroup

Goal BP(mm Hg) First Line Adjunctive

+ Diabetes <130/80 ACE-I or ARB Diuretics then CCB or BB

Diabetes + Proteinuria <130/80 ACE-I or ARB Diuretics then CCB or BB

Diabetes Proteinuria <130/80

No specific preference:

Diuretics then ACE-I, ARB, CCB, or BB

EXPECT TO NEED TO USE 3+ AGENTS TO ACHIEVE GOALSRecommendations largely consistent across JNC 7, ADA, and K/DOQI

Q13

JNC8 JAMA 2014

There is strong evidence to support treating HTN in persons >60 years to a BP

goal <150/90 mmHg and persons 30-59 years to a diastolic goal <90 mmHg

There is insufficient evidence in <60 years for a systolic goal, or in <30 years for a diastolic goal, so the panel recommends BP <140/90 based on expert opinion.

What is the best BP target in NDD-CKD pts?

Should sBP <120 mmHg be targeted in CKD?

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Observational modeling of strict vs. usual BP control‐association with all‐

cause mortalityCsaba P. Kovesdy, Jun L. Lu, Miklos Z. Molnar, Jennie Z. Ma, Robert B. Canada, Elani Streja, Kamyar Kalantar‐Zadeh, and Anthony J. Bleyer

JAMA Intern Med 2014

The Systolic Blood Pressure Interventional Trial (SPRINT) trial17 is the first major clinical trial of blood pressure lowering with a primary aim to prevent cardiovascular events and mortality that specifically enrolled patients with CKD, but its results will not be available for several years, and its strict inclusion/exclusion criteria may limit the generalizability of its findings to a narrow spectrum of the CKD population

Higher Death Hazardfor sBP<120:

1.70 (1.63‐1.78)

N=77,765 CKD veterans: N=5,760 sBP <120 mm HgN=72,005 sBP 120-139 mm Hg

Median follow-up: 6.0 years

Death: 19,517 patients: Death rates:

in sBP <120 mm Hg: 81/1000 patient-yrs

in sBP 120-139 mm Hg” 42/1000 patient-yrs)

(P < .001).

The mortality hazard ratio of sBP <120 vs. 120 to 139 mm Hg:

1.70 (95%CI: 1.63-1.78) after adjustment for propensity scores.DO N

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2013

N= 651,749 patients over 7 years

Kovesdy … Kalantar‐Zadeh,

Annals Int Med 2013


• 1. Anemia• 2. Bone Disease• 3. Acidosis and electrolyte disarrays• 4. Hypertension• 5. Nutrition: Plant Dominant Low Protein Diet• 6. Medication Dose adjustment• 7. Preparation for Renal Replacement Therapy

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Protein Intake Restriction• Mixed data (MDRD Study)

• Recommended: 0.6-0.8 g/kg/day

• Measure 24-hr urine urea nitrogen:

Estimated protein intake == 6.25 * UUN

Kopple et al. Kidney Int. 2000 Maroni et al. Kidney Int. 1985



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Who has higher mortality: Cancer or Dialysis?

High Risk for Death in ESRD Patients

Go et al. NEJM

• AIDS + HAART >95% five year survival

• Testicular cancer 95%

• Breast cancer 85%

• Bladder cancer 75%

• Kidney transplant 75%

• Rectal cancer 62%

• Cervix cancer 60%

• Colonic cancer 54%

• Dialysis 46% (10 yr survival <15%)

• Ovarian cancer 44%

• Stomach cancer 20%

• Lung cancer 10%

Sources;Cancer Research UK 2005UK Renal Registry 2006USRDS 2006

Courtesy Hutchison Alastair & Peter StenvinkelDO NOT

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Transition to ESRDprelude vintage

-5 -4 -3 -2 -1 +1 +2 +3 +4 +5 years

Annualized Mortality

40%

30%

20%

10%

Costs of Patient Care ($)

eGFR(ml/min)

25

20

15

10

5

↑UremiaCKD5 eGFR <15 eGFR <10 eGFR <5

• Watch for uremia Sx & Sx:

• Loss of appetite, nausea, vomiting• MS, ↓ concentration, seizure, coma• Camps, pruritus• Uremic pericarditis (rub)• Uremic bleeding tendency (Rx: dDAVP, estrogen)• Volume overload, CHF Sx & Sx without CHF• Electrolyte disarray (K, Ca) and acidosis

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Historical Background:In 1972 the US Congress extended Medicarecoverage to all persons under age 65 suffering from ESRD (End-Stage Renal Disease), i.e. individuals who cannot survive without kidney dialysis treatment, to cover all costs related to their dialysis Rx.

The intent of this law (PL 92-603, the Social Security Amendments of 1972) was to allow allAmericans access to an emerging and very expensive technology, regardless of their ability to pay.

The effectiveness of the ESRD program:

No Kidney Function = No Life Dialysis = Life (?)

550,000 Dialysis Patients in the USA

Fast growing population: ESRDAnd 120,000 new dialysis patients are added each year

Conclusions• Low GFR and proteinuria are independent risk factors for

development of CVD. Patients with CKD are likely to die from CVD

• Low protien-, low salt diet may help slow progression of CKD and improve proeinuria.

• BP control is important but too low BP values (sBP<100) in patients with established CKD should be avoided as hypotension may be assocaitated with worse CKD outcomes.

• There is a recent trend towards more conservative management of advanced CKD and later transition to dialysis esp. among the very old patients and multi-morbid patientsDO N

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Acknowledgement

Investigators and Staff• Elani Streja, MPH, PhD• Connie M. Rhee, MD, MSc• Hamid Moradi, MD• Wei Ling Lau, MD• Joline Chen, MD, MPH• Vanessa Ravel, MPH• Foad Ahamdi, MD• Paungpaga Lertdumrongluk, MD• Megha Doshi, MD• Sepideh Rezakhani, MD• Melissa Soohoo, MPH• Bryan Shapiro, MPH• Rochelle Roger, MPH• Amanda Brown, RD• Tracy Nakata • Nany Lopez• Catherine Guillen• Jennie Jing, MS• Kamyar Kalantar-Zadeh, MD, MPH,

PhD

Collaborators:• Csaba P. Kovesdy, MD• Rajnish Mehrotra, MD• Joel D Kopple, MD• Matthew Budoff, MD• Steven S. Jacobsen, MD,

PhD• Rajiv Saran, MD, MSc.• Miklos Z. Molnar, MD, PhD• Jongha Park, MD• Daniel Gillen, PhD• Danh Nguyen, PhD• Allen Nissenson, MD, • Steven Brunelli, MD, MS

The Harold Simmons Center for Kidney Disease Research & Epidemiology

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