Chronic Kidney Disease Final - Handout

2/11/2021

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CKD for the PCP

Khaled Boubes, MD, FASN, FASDIN Assistant Professor of Medicine & Biomedical Engineering

Director of Interventional Nephrology Division of Nephrology, Department of Internal Medicine

The Ohio State University Wexner Medical Center

Disclosures

None

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OutlineCKD prevalence Is CKD a risk factor?

CKD basics

Decided to refer? What to do next?CKD work-up Things to AVOIDThings that we follow Treatments

New Treatments

2020 USRDS Annual Data Report: Epidemiology of kidney disease in the US. NIH, NIDDK

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Prevalence of CKD in adults within sex, 2003-2018


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CKD Basics

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CKD Heat-map

Source: Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppls. 2013;3:1-150.

Prognosis of CKD by GFR and albuminuria category

Persistent albuminuria categoriesDescription and range

A1 A2 A3Normal to

mildlyincreased

Moderatelyincreased

Severelyincreased

<30 mg/g<3 mg/mmol

30-300 mg/g3-30 mg/mmol

>300 mg/g>30 mg/mmol

G1

G2

Normal or high

Mildly decreased

≥90

60-89

G3a

G3b

Mildly to moderatelydecreased

Moderately toseverely decreased

45-59

30-44

G4Severely decreased 15-29

G5Kidney failure

<15

Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk;Orange: high risk; Red, very high risk.

Prognosis of CKD by GFRand Albuminuria Categories:

KDIGO 2012

GF

R c

ateg

ori

es (

ml/m

in/

1.7

3 m

2)D

escr

ipti

on

an

d

ran

ge

CKD Heat-map


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What is Creatinine?!

Metabolic by-product mainly produced by muscles

In steady-state; production = excretion

Is a serum Cr of 1.5mg/dL normal?

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What should I order?

CKD work-upChemistry

Rule out DM-2

Urine analysis with microscopic evaluation Blood is a red flag

Protein: Urine albumin to creatinine

Renal US Look for structural abnormalities, bladder obstruction,

etc…

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CKD work-up

Chemistry

Urine

Protein

Ultrasound

CKD Heat-map

Source: Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppls. 2013;3:1-150.

Prognosis of CKD by GFR and albuminuria category

Persistent albuminuria categoriesDescription and range

A1 A2 A3Normal to

mildlyincreased

Moderatelyincreased

Severelyincreased

<30 mg/g<3 mg/mmol

30-300 mg/g3-30 mg/mmol

>300 mg/g>30 mg/mmol

G1

G2

Normal or high

Mildly decreased

≥90

60-89

G3a

G3b

Mildly to moderatelydecreased

Moderately toseverely decreased

45-59

30-44

G4Severely decreased 15-29

G5Kidney failure

<15

Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk;Orange: high risk; Red, very high risk.

Prognosis of CKD by GFRand Albuminuria Categories:

KDIGO 2012

GF

R c

ateg

ori

es (

ml/m

in/

1.7

3 m

2)D

escr

ipti

on

an

d

ran

ge

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CKD work-up - Management

Review medications: “We are Medicine!” NSAID’s, NSAID’s, and NSAID’s! Avoid dual RAAS blockade Preferably avoid PPI’s

Maximize DM control

Maximize BP control

Appropriate dosing of medications

time

NSAID for Gout

Gentamicin forUTI

Contrast forcoronary cath

CHF with diuresisleading to AKIand low BP

GFR

Baseline rate of decline in GFR

ESRD

Fink, et al, AJKD, 2009

CKD progression: biology vs “us”?

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time

NSAID for Gout

Gentamicin forUTI

Contrast forcoronary cath

CHF with diuresisleading to AKIand low BP

GFR

Baseline rate of decline in GFR

ESRD

CKD progression: biology vs “us”?

Fink, et al, AJKD, 2009

Things that Nephrologists will follow

Excretory functions:

Remove from the body Toxic and waste products Excess water

Maintain the balance of Various electrolytes

Endocrine functions:

Erythropoietin

Active Vitamin D Bone metabolism

Renin BP control

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Things that Nephrologists will follow

CKD Etiology–

HTN– rule out secondary causes

Anemia–

Bone mineral disease– Ca, PO4, PTH and Vit D

Acidosis–

Treatments

Target the cause

Minimize proteinuria

Support “other” renal functions

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Figure 2 Kidney International 2020 98839-848DOI: (10.1016/j.kint.2020.06.024)

Executive summary of 2020 KDIGO DM Management in CKD Guideline

Antiplatelet therapies

SGLT2 inhibitors RAS blockade

Glycemic control Blood pressure control Lipid management

Exercise Nutrition Smoking cessation

Diabetes with CKD

Some patients

Most patients

All patients

Kidney International 2020 98839-848DOI: (10.1016/j.kint.2020.06.024)

Primary outcome Kidney outcomes

Drug Trial Kidney-related eligibility criteria

Primary outcome

Effect on primary outcome

Effect on albuminuria or albuminuria-containing composite outcome

Effect on GFR loss

Adverse effects

SGLT2 inhibitors

Empagliflozin EMPA-REG OUTCOME

eGFR ≥30 ml/min per 1.73 m2

MACE Genital mycoticinfections, DKA

Canagliflozin CANVAS trials CREDENCE

eGFR ≥30 ml/min per 1.73 m2

ACR >300 mg/g [30 mg/mmol] and eGFR30–90 ml/min per 1.73 m2

MACE

Progression of CKDb

Genital mycoticinfections, DKA,

amputation

Genital mycoticinfections, DKA

Dapagliflozin DECLARE-TIMI 58

CrCl ≥60 ml/min Dual primary outcomes: MACE and the composite of hospitalization for heart failure or CV deathc

Genital mycoticinfections, DKA

Executive summary of 2020 KDIGO DM Management in CKD Guideline

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Kidney International 2020 98839-848DOI: (10.1016/j.kint.2020.06.024)

Executive summary of 2020 KDIGO DMManagement in CKD Guideline

New kids on the block!

28 |

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New Therapies

Potassium binders

SGLT2-i

Finerenone

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The effect was sustained over 4 weeks

Well tolerated

JAMA. 2015;314(2):151-161. doi:10.1001/jama.2015.7446

Mild Hyperkalemia

Moderate Hyperkalemia

4 12 20 28 36 44 521 3

42

5.8

5.4

5.0

4.6

4.2

Serum Potassium, m

Eq/L

Weeks

Treatment Follow‐up

Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney DiseaseThe AMETHYST‐DN Randomized Clinical TrialBakris GL, et. al.

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January 15, 2015 N Engl J Med 2015; 372:222-231

Placebo1.25 g

2.5 g

5 g

10 g

5.4

5.2

5.0

4.8

4.6

4.46 12 18 24 36 40 44 48

Time (hours)

Serum Potassium (mmol/L)

Doses given:

P < 0/05

January 15, 2015 N Engl J Med 2015; 372:222-231

Sodium Zirconium Cyclosilicate in Hyperkalemia

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Editorial commentary

“Given the gastro- intestinal side effects, unpleasant taste, and risk for colonic necrosis with sodium polystyrene sulfonate, its days as the primary treatment option for hyperkalemia are likely numbered.”

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Comparison Patiromer

Exchanges Ca for K

Can cause low Mg

On market since 2015

Binds K in the colon

Can be used in ESRD

Cost: $700-800/month

ZS-9

Exchanges Na for K

Can cause edema

On market since 2019

Binds K throughout the GI tract Can be used in ESRD

Cost: $600-700/month

SGLT2- inhibitors

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100%

50%

0%0 12 24 36 48

Placebo

Empagliflozin

P < 0.001

Incident or Worsening Nephropathy

Month

Cumulative

probab

ility

0 12 24 36 48

Placebo

Empagliflozin

P < 0.001

Month

8

4

0

Hazard Ratio

Post‐Hoc Renal Composite Outcome

Wanner C et al. N Engl J Med 2016;375:323‐334.

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0 12 24 360

1200

600

Months

Geo

metric Mean Placebo

Canagliflozin

Urinary Albumin‐to‐Creatinine Ratio

0 12 24 36

Months

Placebo

Canagliflozin

0

‐10

‐20

Mean

Chan

ge(m

l/min/1.73 m

2)

Change from Baseline in Estimated GFR

V Perkovic et al. N Engl J Med 2019;380:2295‐2306.

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0 8 16 24 32

24

12

0Cumulative Inciden

ce (%)

P<0.001 Placebo

Dapagliflozin

Primary Composite Outcome

0 8 16 24 32

Months

12

6

0Cumulative Inciden

ce (%)

P=0.004 Placebo

Dapagliflozin

Death From Any Cause

0 8 16 24 32

20

10

0Cumulative Inciden

ce (%)

P<0.001 Placebo

Dapagliflozin

Renal‐Specific Composite Outcome

0 8 16 24 32

Months

12

6

0Cumulative Inciden

ce (%)

P=0.009

Placebo

Dapagliflozin

Composite Death from Cardiovascular Causes or Hospitalization for Heart Failure

Heerspink HJL et al. N Engl J Med 2020;383:1436‐1446

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0 12 24 36

Months Since Randomization

0

‐15

‐10

‐5

Chan

ge in

GFR

(m

l/min/1.73 m

2)

Placebo

Dapagliflozin

Heerspink HJL et al. N Engl J Med 2020;383:1436‐1446

SGLT2-Inhibitors

Kang, A., Jardine, M.J. SGLT2 inhibitors may offer benefit beyond diabetes. Nat Rev Nephrol 17, 83–84 (2021).

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Finerenone

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In Summary…• CKD is common

• CKD = higher risk

• CKD basics.• Heat map

• Decided to refer? • CKD work-up- Chemistry, UA with micro, UPC, renal US• Avoid NSAIDs

• New Treatments are available:• K binders • SGLT2-I• Finerenone

Chronic Kidney Disease Final - Handout

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