Background and Basics
Define CKD
kidney damage for > or = 3 months (structural or functional abnormality of the kidney with or without decreased GFR
What is the main CKD management goal?
To slow the progression and prevent a CV event, complications, and need of dialysis
Progression: change in GFR category
Certain drop: drop in category and >25% eGFR decline
Rapid progression: decrease in eGFR> 5 mL per year
KDIGO recommendations for target SBP
SBP<120
What is the goal A1C?
6.5-8%
ertugliflozin
Steglatro
Stages of CKD (GFR categories)
G1: > or = 90
G2: 60-89
G3a: 45-59
G3b: 30-44
G4: 15-29
G5: < or = 15 or dialysis
4 ways to prevent progression
1. optimize blood pressure
2. treat proteinuria
3. intensive blood glucose control
4. non-pharmacologic
Significance of Aliskiren
risk outweighs benefits
*not commonly used
2. metformin + SGLT2 inhibitor
metformin: eGFR <45 (reduce dose), <30 (discontinue)
SGLT2 I: eGFR <30 do not initiate
3. additional drug therapy: GLP-1 receptor agonist preferred
Methoxy Polyethylene Glycol-Epoetin Beta
Mircera
Staging of CKD (albuminuria categories)
A1: <30
A2: 30-300
A3: >300
Non-pharm therapy
Protein restriction: restrict to 0.8 g/kg/day if CrCl <30 but not on dialysis
Smoking cessation
Role of ACEI/ARBs
What do we need to monitor
Renoprotective effects, want highest tolerable dose to achieve BP target
they decrease the glomerular capillary pressure, GFR, and Albminuria
Monitor BP, SCr, K at baseline and 2-4 weeks (reduce or D/C dose if SCr increases >30% within 4 weeks)
a Na+ glucose cotransporter located in proximal tubule, moves glucose against conc. gradient using energy from Na+ flux
Inhibitors block glucose transport into proximal tubule and lower blood glucose- leads to renoprotective effects
Epoetin Alfa
Epogen, Procrit
Risk Factors
*know the difference between susceptibility, initiation, and progression factors
Susceptibility: (not proved to cause, just increase risk) >60 years old, racial/ethnic minorities, reduced kidney mass, low income or education, low birth weight, fam history of CKD, inflammation, dyslipidemia
Initiation: (generally modifiable, directly cause CKD) DM and HTN are the most common, glomerulonephritis, polycystic kidney disease, drug toxicity
Progression: (faster decline of function, generally modifiable) uncontrolled BG and BP, proteinuria, hyperlipidemia, AKI, smoking, obesity
If AER > or = 30 mg/d: use ACEI/ARB even in normal BP (start with lowest recommended doses)
Alternative are aldosterone antagonists, direct renin inhibitors, non-DHP CCB
Other antihypertensive agents
CCB, beta blockers, alpha agonists, thiazide and loop diuretics
Therapeutic effects and adverse effects
reduce A1c by 0.7-1%, cause 2-4 kg weight loss, decrease BP 2-4 mmHg, uricosuric effect
GI infection, increased serum potassium, 2-fold increased risk of lower limb amputations
Darbepoetin alfa
Aranesp
Clinical signs, symptoms, and pertinent labs
Often asymptomatic until CKD 4 or 5
Symptoms: fatigue, weak, SOB, confusion, N/V, loss of appetite, etc.
Signs: edema, weight gain, change in urine output, foaming of urine, abdomen distension
Labs: decreased eGFR, bicarb, Hb/Hct and iron, vitamin D, Ca, albumin
increased: Scr, BUN, K, Phosphate, PTH, ACR, LDL
What class of drugs have shown nephroprotective effects?
SGLT2
Mineralocorticoid receptor antagonists
steroidal vs non-steroidal (what are Finerenone's DDI and AEs)
Steroidal (spironolactone, eplerenone): additive therapy to reduce BP for resistant HTN and to lower albuminuria, monitor K, SCr, gynescomastia (avoid in patients with hyperkalemia)
non-steroidal (finerenone): renoprotective for CKD pts with type II DM, increased risk for hyperkalemia, *blocks MR-mediated Na+ reabsorption reducing fibrosis and inflammation
**DDI: CYP3A4, AE: hyperkalemia, hypotension, hyponatremia
3 SGLT2 Inhibiting drugs with renoprotective effects and their CKD indications
empagliflozin and canagliflozin delay CKD progression in patients with type II DM
Dapagliflozin delay CKD progression in patients with or without DM
MOA of non-steroidal mineralocorticoid receptor antagonists
selectively blocks mineralocorticoid receptor (MR) in epithelial kidney tissues. MR over-activation is thought to contribute to fibrosis and inflammation worsening CKD
AE: hyperkalemia, hypotension, hyponatremia