CKD (Pathophys and finerenone) Crash Course

What is a modifiable risk factor for CKD?

What is a modifiable risk factor for CKD?

HTN, Obesity, Diabetes

What are the guidelines related to kidney disease? (objective 1)

KDIGO, KDOQI, National Kidney Foundation

What are the top 4 causes/risk factors for ESRD?

Diabetes, HTN, Glomerulonephritis, Polycystic Kidney Dz (PKD)

What are the susceptibility factors of kidney damage?

adv age, fam hx of CKD, decr in kidney mass, low birth weight, minority, low income/edu, systemic inflamation, dyslipidemia

What are the initiation factors of kidney damage?

Diabetes, HTN, glomerulonephritis, polycystic kidney dz, vascular dz, HIV nephropathy, UTIs, Urinary stones, urinary obstruction

Those who are high-risk (Diabetes, HTN…) should be screened for CKD how often?

annually

What is the definition of CKD?

abnormalities in kidney FUNCTION or STRUCTURE for > 3 months

Kidney dysfunctions is ID’ed as what GFR?

< 60 mL/min/1.73m2

Kidney Structure Abnormalities are ID’ed as what?

1. imaging detection

2. urine sediment abnormalities

3. histology abnormalities

4. hx of kidney transplant

5. albuminuria (AER > 30 mg/24 hours or ACR > 30 mg/g)

Progression fo CKD is defined as _____________ ; rapid progression is eGFR ________________

defined as drop in GFR; rapid progession is eGFR decline of ≥ 5 mL/min/1.73 m2 per year

Which is better in estimating GFR in patients w/ eGFR ≥ 60 mL/min/m2, MDRD or CKD-EPI?

CKD-EPI

Why is albuminuria not seen in healthy patients?

basement membrane and capillary endothelial cells of the bowman’s capsule have small fenestrations that blocked charged molecules (albumin) and large molecules (RBCs) from passing with the filtrated into the Bowman’s capsule

Why is albumin found in the urine of CKD patients?

fenestrations and basement membrane of the Bowman’s capsule is damaged so larger and charged molecules can pass through and travel with the filtrate through the nephron

What condition is an independent risk factor for kidney fxn decline and CV disease?

proteinuria (albuminuria)

How is the severity of albuminuria determined?

based on ACR (albumin (mg)/creatine (g))

What ACR is A1?

< 30 mg/g (mild)

What ACR is A2?

30 - 300 mg/g (moderate)

What ACR is A3?

> 300 mg/g (severe)

Based on the KDIGO CKD prognosis based on GFR and Albuminuria chart, what indicates A1 patients to be very high risk?

GFR < 30 mL/min/1.73 m2

Based on the KDIGO CKD prognosis based on GFR and Albuminuria chart, what indicates A2 patients to be very high risk?

GFR < 45 mL/min/1.73 m2

Based on the KDIGO CKD prognosis based on GFR and Albuminuria chart, what indicates A3 patients to be very high risk?

GFR < 60 mL/min/1.73 m2

When is ACE-i and ARB only recommended and not indicated?

1. CKD w/ A3 w/ or w/o diabetes

2. CKD w/ A2 w/ diabetes

When is ACE-i and ARB only suggested and not indicated?

CKD w/ A2 w/o diabetes

In cases with CKD pts with normokalemia, how is the dosing of ACE-i or ARB changed after < 30% increase in creatine?

increase dose or continue on maximally tolerated dose

In cases with CKD pts with hyperkalemia, how what does the KDIGO guideline say to do after starting the pt on ACE-i/ARB?

1. review drug therapy in addition ot ACE-i/ARB

2. moderate K+ intake

3. consider: diuretics, sodium bicarbonate, or CI cation exchangers (phosphorus binders)

In cases with CKD pts with hyperkalemia, how what does the KDIGO guideline say to do after reviewing/adding concurrent tx to ACE-i/ARB and the patient’s K+ keep increasing?

reduce dose or stop ACEi/ARB as last resort

In cases with CKD pts with > 30% increase in creatine, how what does the KDIGO guideline say to do after initiating ACE-i/ARB?

1. review AKI cause

2. correct volume depletion

3. reassess concomitant meds (diuretics, NSAIDs)

4. consider renal artery stenosis

In cases with CKD pts with > 30% increase in creatine, how what does the KDIGO guideline say to do after initiating ACE-i/ARB → review AKI causes, correct volume depletion, etc.?

reduce dose or stop ACEi/ARB as last resort

What is the first line for albuminuria?

ACE-i and ARB

As per the ACC-AHA, what is the BP goal for pts w/ CKD?

< 130/80 mmHg

As per the 2024 KDIGO guidelines, what is the target SBP?

< 120 mmHg

What is the target A1c/HbA1c goal for pts w/ CKD and DM?

target range of <6.5% to < 8.0%

As per the KDIGO guidelines, when are SLGT-2 inhibitors indicated?

CKD AND at least one of the follwoing:

1. HF

2. eGFR ≥ 20 mL/min/1.73m2 AND type 2 DM

3. eGFR ≥ 20 mL/min/1.73m2 AND ACR ≥ 200 mg/g

4. eGFR 20-45 mL/min/1.73m2 AND ACR < 200 mg/g

What are the SGLT-2 inhibitors?

1. dapagliflozins

2. empagliflozin

3. canagliflozin

What is the MOA of finerenone?

nonsteroidal mineralcorticoid receptor antagonist w/ proven kidney and CV benefits

Finerenone is related to spironolactone, does it have the same indication as well?

no

Who is finerenone recommended for?

1. CKD and T2DM AND albuminuria > 30 mg/g despite being on max tolerated dose of RAAS inhbitor

2. CKD and HFrEF

Is finerenone a valid substitution for ACEi/ARB?

no, it is only added an ACEi/ARB

What is the major side effect of finerenone?

hyperkalemia (therefore, need to monitor K+ levels)

At what K+ level can you comfortably initiate finerenone?

≤ 4.8 mmol/l (monitor K+ at 1 month after initiation, then q4months)

Do you discontinue finerenone at K+ 4.9 - 5.5 mmol?

no, continue and monitor q4months

What level do you hold finerenone?

> 5.5 mmol/l

How often are regular risk factor reassessments?

q3-6 months

For non-pharm management of CKD, what is the recommended amount of exercise?

at least 150 min per week

What are the three CKD complications?

HTN, edema, hypervolemia, hyperkalemia, metabolic acidosis, anemia, hypoglycemia, CKD mineral and bone disorder

What does a GFR 30-50 mL/min (G3) affect?

decrease ability to dilute or concentrate urine

What does a GFR <30 mL/min (G4) affect?

decrease ability to adjust to abrupt changes in Na+ or H2O

CKD complications (HTN, edema, hypervolemia) can lead to (2)?

1. increase in total body Na+ and ECF vol

2. Decrease ability to make urine

In CKD, there is decrease secretion of K+ in which locations?

distal convoluted tubule and colon

Which drugs can worsen hyperkalemia?

1. ACEi or ARB

2. finerenone (aldosterone antagonist)

3. trimethoprim-sulfamethoxazole (Bactrim)

4. CNIs (cyclosporine, tacrolimus)

How can metabolic acidosis develop in CKD?

1. failure to reabsorb bicarbonate in proximal convoluted tubule

2. failure to excrete H+ in distal tubule

more acidic blood

How does anemia develop in CKD patients?

decrease in erythropoietin (hormone that promotes RBC) → decrease hemoglobin (anemia)

In patients in later stages of CKD, there is a decrease in _____ degradation and clearance by kidney that leads to….

decrease in insulin degradation and clearance → increase circulating insulin → hypoglycemia

In mineral and bone disorder, lab abnormalities can be found in which hormones/ions?

phosphorous (hyperphosphatemia), calcium, parathyroid hormone (PTH) (2ndry hyperparathyroidism) and Vitamin D

In mineral and bone disorder, what bone abnormalities can be found?

bone turnover, mineralization (due to abnormal PTH and Vitamin D) and strength (Renal Osteodystrophy)

In mineral and bone disorder, what can happen to vascular and other soft tissue?

calcification

What is the complete (bolded) complications of CKD?

1. Na+ H2O retention → incr BP (HTN) + edema

2. hypervolemia

3. hyperkalemia

4. incr hypoglycemia risk

5. metabolic acidosis

6. other electrolyte abnormality

7. vitamin deficiencies

8. anemia

9. 2ndry hyperparathyroidism

10. hyperphosphatemia

11. renal osteodystrophy

What is the normal range of calcium?

8.6 - 10.2

What is the normal range of phosphorous?

2.7 - 4.5

In CKD, which ions increase?

1. Na

2. Cl

3. K

4. BUN

5. Cr

6. Mg

7. Phos

In CKD, which ions decrease?

1. CO2

2. Glu

In CKD, change in what ion’s serum levels is dependent on CKD progression?

Ca

Hemoglobin increases or decreases in CKD?

decreases

Albumin increases or decreases in CKD?

decreases

Parathyroid hormone (PTH) increases or decreases in CKD?

increases