336.1 🎓 醫孞生版

336.1.0.1 📌 䞀頁重點

336.1.0.1.1 Four Pillars of CKD Treatment (2024 Paradigm)

336.1.1 Pillar 1: ACE Inhibitors / ARBs

Mechanism: - Reduces glomerular hyperfiltration (efferent arteriolar dilation) - Reduces proteinuria - Anti-fibrotic effects - Anti-inflammatory

Indications: - CKD with proteinuria (UACR > 30 mg/g) - HTN in CKD - Especially DKD + non-DKD with proteinuria

Examples: - ACE: lisinopril, ramipril, enalapril, perindopril, captopril - ARB: losartan, valsartan, candesartan, irbesartan, telmisartan, olmesartan

Practical: - Start at maximum tolerated dose - Acute Cr ↑ up to 30% acceptable - Monitor K (hyperkalemia risk) - Avoid combination ACE + ARB (ONTARGET) - ACE cough → switch to ARB - Pregnancy: contraindicated

336.1.2 Pillar 2: SGLT2 Inhibitors (Major Game-Changer)

Mechanism: - Inhibit SGLT2 in proximal tubule → glucosuria + natriuresis - Reduces glomerular hyperfiltration (tubuloglomerular feedback) - Cardio-renal protective independent of glucose lowering

Examples + Doses: - Dapagliflozin 10 mg daily - Empagliflozin 10 mg daily - Canagliflozin 100 mg daily - (Ertugliflozin less common)

Indications: - DKD + non-DKD CKD (≥ albuminuria or low eGFR) - HF (HFrEF + HFpEF) - DM2 with CV/renal disease

Cutoff for Initiation: - eGFR ≥ 20-25 (varies by drug + indication) - Continue down to dialysis in some (current real-world)

Side Effects: - Genitourinary infections (yeast) - Euglycemic DKA (DM patients; hold during illness/surgery) - Hypovolemia (especially with diuretics) - Lower limb amputation (canagliflozin CANVAS — controversial) - Fournier’s gangrene (rare)

Key Trials: - CREDENCE (2019): canagliflozin in DKD - DAPA-CKD (2020): dapagliflozin in CKD ± DM - EMPA-KIDNEY (2022): empagliflozin in broader CKD - All show ↓ CKD progression + CV events

336.1.3 Pillar 3: Finerenone (Non-Steroidal Selective MRA)

Mechanism: - Highly selective MRA - Less hyperkalemia than spironolactone (steroidal) - Anti-inflammatory, anti-fibrotic - Reduces proteinuria

Indications: - DKD + albuminuria (UACR > 30 mg/g) - T2DM + CKD

Dose: - 10 mg daily; titrate to 20 mg - eGFR-based initiation (≥ 25)

Side Effects: - Hyperkalemia (less than spironolactone) - Hold if K > 5.5

Trials: - FIDELIO-DKD (2020): ↓ CKD progression - FIGARO-DKD (2021): ↓ CV events - Combined analyses positive

336.1.4 Pillar 4: GLP-1 RA (Newer Addition)

Mechanism: - ↑ Insulin, ↓ glucagon - Slow gastric emptying - Weight loss - Cardio-renal protective beyond DM

Examples: - Semaglutide (Ozempic, Wegovy) - Liraglutide (Victoza) - Dulaglutide (Trulicity) - Tirzepatide (GIP/GLP-1, Mounjaro / Zepbound)

Indications: - DM + ASCVD or CKD - Obesity ± ASCVD (SELECT)

Key Trials: - FLOW (2024) — semaglutide in T2DM + CKD → 24% ↓ composite renal endpoint - SUSTAIN-6: semaglutide CV benefit - LEADER: liraglutide CV benefit - AWARD-7: dulaglutide in CKD

336.1.5 Combined Effect of 4 Pillars

  • Each pillar independent benefit
  • Combined: ↓ CKD progression > 50% in DKD
  • Modeled studies suggest dramatic survival benefit
  • Real-world implementation lagging
336.1.5.0.1 Adjunctive Therapies

336.1.6 Blood Pressure Control

Target (KDIGO 2021): - < 130/80 (some recommend < 120 SBP based on SPRINT — controversial in CKD)

Strategy: - ACE/ARB first-line (proteinuric) - CCB or thiazide - Spironolactone for resistant - Multi-drug usually

336.1.7 Lipid Management

Statin Indications: - ASCVD: secondary prevention - Primary prevention if eGFR < 60 + albuminuria - DKD - General CKD ≥ 50 years

Targets: - ACC/AHA: high-intensity if multiple RF - Some recommend LDL < 70 (high-risk CKD)

336.1.8 Glycemic Control (DKD)

HbA1c: < 7% individualized (lower stricter, less elderly) - SGLT2i + GLP-1 RA preferred - Metformin OK until eGFR < 30 - Insulin for advanced - Avoid hypoglycemia (worse in CKD)

336.1.9 Nutrition

Protein Intake: - KDIGO: 0.6-0.8 g/kg/d (non-dialysis CKD) - 1.0-1.2 g/kg/d on HD - 1.2-1.5 g/kg/d on PD

Sodium: - < 2.3 g/d - Salt restriction

Potassium: - Restrict if hyperkalemic (avoid bananas, oranges, tomatoes, potatoes) - K binders (patiromer, sodium zirconium cyclosilicate) for chronic management

Phosphate: - Restrict (avoid processed foods, dairy excess, dark cola) - Phosphate binders with meals

Fluid: - Variable; restrict if overload or HD

336.1.10 Lifestyle

  • Smoking cessation
  • Exercise (moderate, supervised if cardiac)
  • Weight management
  • Stress + sleep
336.1.10.0.1 Management of Specific Complications

336.1.11 Anemia

First-Line: - Iron supplementation (oral or IV; IV preferred in HD) - Target ferritin > 100, TSAT > 20% - IV iron formulations: ferric carboxymaltose, iron sucrose, sodium ferric gluconate

Second-Line: - ESAs (epoetin, darbepoetin): target Hgb 10-11.5

Third-Line (NEW): - HIF-PHIs: roxadustat, vadadustat, daprodustat - Oral - Stabilize HIF → endogenous EPO + ↓ hepcidin

336.1.12 CKD-MBD

Phosphate Binders: - Calcium-based: Ca carbonate, Ca acetate (concerns: Ca load + vascular calcification) - Non-calcium: sevelamer, lanthanum, ferric citrate, sucroferric oxyhydroxide - Bile acid sequestrant: colestilan (rare)

Vitamin D: - Cholecalciferol / ergocalciferol if 25-OH < 30 - Active analogs (calcitriol, paricalcitol, doxercalciferol) for advanced CKD + hyperPTH

Calcimimetics: - Cinacalcet (oral) - Etelcalcetide (parenteral) - For severe 2° hyperPTH

Parathyroidectomy: - Refractory 2° hyperPTH - PTH > 800-1000 + symptoms - Calciphylaxis

336.1.13 Acidosis

Sodium Bicarbonate: - Target HCO3 22-26 - 0.5-1 g BID-TID typical - Slows CKD progression (some studies) - BICAR-ICU type evidence

336.1.14 Hyperkalemia

Acute Severe: - Calcium gluconate (membrane stabilizer) - Insulin + glucose - β2-agonist (albuterol) - Sodium bicarbonate (if acidotic) - K binders (patiromer, SZC) - Loop diuretic - RRT for refractory

Chronic: - K binders: patiromer, sodium zirconium cyclosilicate (SZC, Lokelma) - Dietary K restriction - Adjust K-retaining drugs (ACE/ARB/MRA)

336.1.15 CV Risk

  • Statin (primary prevention if albuminuria + eGFR < 60)
  • ASA for established ASCVD
  • BP control < 130/80
  • HbA1c control
  • Smoking cessation
  • AC for AF (CHA₂DS₂-VASc + bleeding risk)
336.1.15.0.1 Emerging Therapies

336.1.16 Endothelin Antagonists

Sparsentan (Atrasentan) for FSGS + IgA nephropathy: - Dual ETA + AT1R antagonist - DUPLEX trial (FSGS), PROTECT trial (IgA) positive

336.1.17 Complement Inhibitors

  • Iptacopan (factor B inhibitor) for C3 glomerulopathy + IgA
  • Eculizumab / ravulizumab for aHUS
  • Belimumab for lupus nephritis (BLISS-LN positive 2020)

336.1.18 APOL1-Targeted Therapy

  • Inaxaplin (VX-147) for FSGS + HIV-AN with APOL1 risk genotypes
  • Phase 3 trial AMPLITUDE

336.1.19 Anti-Fibrotic

  • Bardoxolone methyl — withdrawn (CV mortality concerns)
  • Pirfenidone, others investigational

336.1.20 Stem Cell + Cell Therapy

  • Investigational
  • Mesenchymal stem cells
  • Bioartificial kidney

336.1.21 Renal Microcirculation

  • Pentoxifylline (some studies)
  • Specific microcirculation modulation

336.1.21.1 🩺 床邊速查

  • 4 pillars CKD treatment: ACE/ARB + SGLT2i + finerenone + GLP-1 RA
  • Statin: eGFR < 60 + albuminuria or primary prevention CKD
  • BP: < 130/80 (KDIGO 2021)
  • HbA1c: < 7% individualized
  • Anemia: iron + ESA + HIF-PHI; target Hgb 10-11.5
  • Hyperkalemia chronic: patiromer, SZC + diet
  • CKD-MBD: phosphate binders (non-Ca preferred) + vit D + calcimimetics
  • Emerging: sparsentan (FSGS/IgA), iptacopan (C3G/IgA), inaxaplin (APOL1)