CKD + CKD Progression

Question 1

CKD Definition

Answer 1

• Abnormalities in kidney structure or function present for 3 months or more, WITH IMPLICATIONS FOR HEALTH
• OR eGFR < 60 mL/min/1.73 m^2 via the MDRD or CKD-EPI equation

Question 2

Kidney Structural Abnormalities

Answer 2

1. Albuminuria >= 30 mg/day
2. Presence of hematuria or red cell casts in urine
3. Electrolyte and other abnormalities due to tubular disorders
4. Abnormalities detected by histology (biopsy)
5. Abnormalities detected by imaging
6. History of kidney transplant

Question 3

Steps for Delaying CKD Progression

Answer 3

• Reduce proteinuria
• Control BP
• Glycemic Control (patients with DM)
• Other interventions

Question 4

Albuminuria/Proteinuria Assessment

Answer 4

• Albumin is a subtype of protein

- 24-Hr Urine Creatinine to calculate Albumin excretion rate (AER) and protein excretion rate (PER)

Question 5

Ratios with Creatinine

Answer 5

• Single urine sample collected from patient
• Albumin: Creatinine ratio (ACR)
• Protein:Creatinine Ratio (PCR)

Question 6

Urine Dipstick

Answer 6

• Single urine sample collected from patient
• Protein reagent strip
• Results considered qualitative
• Follow-up with quantitative measure (ACR, AER, PCR, PER)

Question 7

A1 Albumin/Protein Levels

Answer 7

• ACR/AER: <30
• PCR/PER: <150
• Normal to mild

Question 8

A2 Albumin/Protein Levels

Answer 8

• ACR/AER: 30-300
• PCR/PER: 150-500
• Moderate

Question 9

A3 Albumin/Protein Levels

Answer 9

• ACR/AER: >300
• PCR/PER: >500
• Severe

Question 10

BP Control - Lifestyle Modification

Answer 10

• Achieve/maintain health body weight: BMI 20-25
• Lowering sodium intake unless C/I: <2g per day
• Exercise program compatible with CV health and tolerance: at least 30 minutes 5x/week
• Limit alcohol intake: Women =<1 drink/day, Men =<2 drinks/day

Question 11

NON-DM + CKD BP Targets

Answer 11

• A1: <140/90

- A2/A3: <130/80

Question 12

NON-DM + CKD BP Agents

Answer 12

• A1: Any agent except loop diuretics

- A2/A3: ACE-I/ARBs

Question 13

DM + CKD BP Targets

Answer 13

• A1: <140/90

- A2/A3: <130/80

Question 14

DM + CKD BP Agents

Answer 14

• A1: Any agent except loop diuretics

- A2/A3: ACE-I/ARBs

Question 15

BP Agents + Decreasing Proteinuria/Albuminuria

Answer 15

• 1st line: ACE-I or ARBs (DON’T COMBINE)

- Alternative agent: NDP CCB

Question 16

BP + CKD Goals of Therapy

Answer 16

• Decrease amount of protein/albumin in urine
• Prevent progression from A2 to A3
• Slow GFR loss

Question 17

Monitoring ACEI/ARB

Answer 17

• Monitor K+ and SCr within 1-2 weeks of starting or increasing dose
• Discontinue if SCr increased more than 50% or eGFR decreases more than 50% from baseline
• Optimizing BP is also beneficial for proteinuria

Question 18

Serum K+ and ACEI/ARBs

Answer 18

• If K+ 5-5.5 mEq/L, decrease ACEI/ARB by 50% and recheck

- If K+ is >5.5 mEq/L, discontinue the ACEI/ARB and recheck

Question 19

eGFR + ACEI/ARB

Answer 19

• If eGFR decreases by 30-50%, decrease ACEI/ARB by 50%, repeat process until eGFR is within 30% of baseline
• If eGFR has decreased by more than 50%, discontinue the ACEI/ARB and recheck

Question 20

CKD + BP 1st Principles

Answer 20

• Considered high risk for CV disease
• Most will require 2+ antihypertensive agents to achieve target blood pressure
• With exception of ARB or ACEI in CKD patients with albuminuria, no strong evidence to support preferential use of any particular antihypertensive agent
• Consider half-life of drug and dose adjustment according to CKD stage

Question 21

Thiazide Diuretics

Answer 21

• Hydrochlorothiazide: CrCl < 30 mL/min, decreased diuretic efficacy (BP may be preserved)
• Chlorthalidone: Longer half life than HCTZ, may contribute to better BP control, may be effective at lowering renal function more than HCTZ
• Metolazone: effective at CrCl < 30 mL/min
• Often used in combination with loop diuretics for additive diuresis (dual nephron blockage)

Question 22

Loop Diuretics

Answer 22

• Considered when fluid overload also present
• Can be used in all stages of CKD (decreased diuresis with lower eGFR)
• Typically larger doses required with decreased renal function

Question 23

Calcium Channel Blockers

Answer 23

• NDP: antiproteinuric activity

- Amlodipine: AE of edema is a concern

Question 24

Beta-Blockers

Answer 24

• Masks signs and symptoms of hypoglycemia

- Atenolol and bisoprolol renally eliminated: initiate at smaller doses

Question 25

Aldosterone Antagonists

Answer 25

- Shown to decrease urine albumin excretion when added to ACEI or ARB - USE WITH CAUTION

Question 26

Potassium Sparing Diuretics

Answer 26

-Usually avoided due to hyperkalemia risk

Question 27

Direct Renin Inhibitors

Answer 27

-Limited data in CKD

Question 28

HTN + Proteinuria in CKD

Answer 28

- HTN associated with a faster rate of CKD decline - Proteinuria associated with faster rate of GFR decline - Proteinuria and decreased GFR can worsen BP - Agents used to decrease proteinuria are also BP agents - BP lowering itself may decrease protein excretion

Question 29

Glycemic Control

Answer 29

- Diabetic Nephropathy (CKD + DM) - microvascular complication of DM - Intensive DM management with goal of achieving near normoglycemia (A1c =<7%) has been shown to delay onset/progression of urinary albumin excretion and slow GFR loss

Question 30

DM + CKD First Line

Answer 30

- Metformine - Effective and safe, inexpensive, and may reduce risk off CV events and death - C/I if eGFR < 30 mL/min/1.73 m^2 - If already on therapy and eGFR is 30-45 mL/min/1.73 m^2 then consider cutting the dose in half - Initiating Metformin when eGFR is 30-45 is not recommended - Calculate eGFR at least annually - Patients have increased risk of hypoglycemia with these disease combinations

Question 31

DM + CKD 2nd Line Options

Answer 31

1. SGLT2i | 2. GLP-1RA

Question 32

GLP-1RA

Answer 32

- Dulaglutide (Trulicity), Liraglutide (Victoza), Semaglutide (Ozempic) - Demonstrated direct renal benefits (appear to possibly slow CKD progression) - Reduced risk of CVD events - No renal dose adjustments needed

Question 33

SGLT2i

Answer 33

- Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance) - Independent of glycemia benefits, demonstrated direct renal benefits - Decreases intraglomerular pressure, decreases albuminuria, slows GFR loss - Reduced risk of CVD events - C/I in patients with eGFR < 30 mL/min/1.72 m^2, EXCEPT with Invokana, if they are already on the medication, and patient has A3 albuminuria, then may continue with therapy - C/I with dialysis

Question 34

Blood Glucose Optimization Summary

Answer 34

- Tight glycemic control - delays onset/progression of diabetic nephropathy - Metformin is 1st line, but be cautious with eGFR - Preferred second lines are GLP-1RA and SGLT2i due to direct renal benefits and reduced CVD events - Consider how oral agents are eliminated - Insulin is appropriate at all levels of CKD - Patients with CKD and DM are at an increased risk of hypoglycemia, so ensure they are aware of the signs/symptoms and how to treat this - Encourage self blood glucose monitoring when appropriate