Chronic Kidney Disease Pharmacology
Renoprotection, Anemia Management, and Mineral Bone Disease
Renoprotection — Three Complementary Strategies
RAAS Blockade
ACE Inhibitors / ARBs
- Dilate efferent arteriole
- Reduce intraglomerular pressure
- Reduce proteinuria independently of BP
- Acute GFR fall up to 30% — acceptable
- Do NOT combine ACE inhibitor + ARB (ONTARGET)
- Hold: GFR <30, K >5.5, volume depletion
SGLT2 Inhibitors
Canagliflozin / Dapagliflozin
- Block proximal tubule Na-glucose cotransporter
- Restore macula densa Na delivery
- Tubuloglomerular feedback → afferent constriction
- Reduces intraglomerular pressure
- Works in diabetic AND non-diabetic CKD
- CREDENCE / DAPA-CKD trial evidence
Finerenone
Nonsteroidal MR Antagonist
- Blocks aldosterone-driven fibrosis in kidney
- Reduces proteinuria and CKD progression
- FIDELIO-DKD: diabetic CKD outcomes
- Complement to SGLT2 inhibitors
- Monitor potassium — hyperkalemia risk
CKD Anemia — Treatment Comparison
| Feature |
Epoetin Alfa / Darbepoetin |
HIF-PHI (Daprodustat) |
IV Iron |
| Mechanism |
Exogenous EPO receptor agonist |
Stabilizes HIF-1α → endogenous EPO |
Replenishes iron for erythropoiesis |
| Route |
Subcutaneous or IV injection |
Oral |
Intravenous infusion |
| Key warning |
Hgb target <11.5 g/dL — higher targets increase CV risk |
Cardiovascular safety under evaluation |
Anaphylaxis risk (rare); test dose with some formulations |
| Role |
Standard of care for CKD anemia |
Alternative when ESA response inadequate |
Required co-therapy with ESAs |
CKD–Mineral Bone Disease
Phosphate Binders
- Calcium carbonate / acetate — low cost; vascular calcification risk
- Sevelamer — non-calcium polymer; lowers LDL
- Lanthanum carbonate — non-calcium metal binder
- All: take with meals to bind dietary phosphate
PTH Suppression
Vitamin D and Cinacalcet
- Calcitriol / paricalcitol — suppress PTH via VDR; risk of hypercalcemia
- Cinacalcet — activates CaSR; lowers PTH without raising Ca
- Use cinacalcet when hypercalcemia limits vitamin D use
- Cinacalcet adverse effects: nausea, hypocalcemia
ESA Hyporesponsiveness Rule
When hemoglobin fails to rise despite adequate erythropoiesis-stimulating agent dosing, check iron first. Functional iron deficiency — inadequate iron mobilization despite normal total body stores — is the most common cause. Intravenous iron overcomes the hepcidin-mediated block on gastrointestinal iron absorption that accompanies chronic kidney disease inflammation. Replete iron before escalating the erythropoiesis-stimulating agent dose.