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Mechanistic Deep Dive
FGF-23 Biology
- Phosphaturic hormone from osteocytes
- Elevated early in CKD
- â Phosphate excretion + â vitamin D
- Predictive of CV events + mortality
- Resistance to FGF-23 in advanced CKD
Hepcidin in CKD Anemia
- Iron homeostasis regulator
- â In inflammation + CKD
- Functional iron deficiency
- HIF-PHI â hepcidin â improved iron utilization
Vascular Calcification
- Active process (osteoblast-like vascular smooth muscle)
- Phosphate, Ca, FGF-23, klotho, inflammation
- Atherosclerotic + medial
- â Mortality
Klotho-FGF-23 Axis
- Klotho: co-receptor for FGF-23
- â Klotho in CKD progresses
- Aging marker
Recent Trials & Updates
CREDENCE (2019) â Canagliflozin DKD
- T2DM + CKD
- â ESKD, CV events
- Foundation of SGLT2i in DKD
DAPA-CKD (2020) â Dapagliflozin
- CKD with or without DM
- â ESKD progression
- Extended indication beyond DM
EMPA-KIDNEY (2022) â Empagliflozin
- Similar to DAPA-CKD
- â CKD progression + CV events
FIDELIO-DKD (2020), FIGARO-DKD (2021) â Finerenone
- Non-steroidal selective MRA
- DKD + albuminuria
- â CKD progression + CV events
- FDA approved
FLOW (2024) â Semaglutide
- CKD + DM
- â Composite renal outcome
- 24% reduction
- Adds GLP-1 RA to CKD armamentarium
CHOIR (2006), TREAT (2009) â ESAs
- Higher Hgb target â â CV events
- Practice: donât normalize Hgb (target 10-11.5)
Daprodustat (ASCEND-D, ASCEND-ND, 2021)
- FDA approval 2023
- Non-dialysis vs dialysis indications
- Non-inferior to ESAs
EVOLVE (2012) â Cinacalcet
- Mortality outcome neutral; reduced PTH, CaÃP
IMPACT-SHPT â Etelcalcetide
High-Yield Specialist Points
When to Refer to Nephrology
- eGFR < 30 (G4)
- A3 (> 300 mg/g)
- Rapid decline (> 5 mL/min/year)
- Difficult management (HTN, K, MBD)
- Cause unclear
- Prepare for RRT
Renal Replacement Therapy Preparation
- AV fistula 6-12 months before HD
- PD catheter 4-6 weeks before
- Transplant referral
- Conservative management option (kidney supportive care)
Patient Education
- Diet (Na, K, PO4, protein)
- Medication adherence
- Avoid nephrotoxins (NSAIDs)
- Foot care (DM)
- Vaccinations
- Mental health support
ACE/ARB in CKD
- First-line if proteinuria
- Acute Cr â acceptable up to 30% (still continue)
- Hyperkalemia monitoring
- Avoid combination ACE + ARB (ONTARGET)
SGLT2i in CKD
- â Glomerular hyperfiltration
- Cardio-renal protective
- Approved across CKD stages (eGFR ⥠20-25 various)
- Side effects: euglycemic DKA (DM), genital infections
Finerenone
- Non-steroidal selective MRA
- For DKD + albuminuria
- 10-20 mg daily
- Watch K+ (less than spironolactone)
GLP-1 RA in CKD
- Semaglutide (FLOW 2024)
- â Renal events
- CV benefit
- Weight loss
Avoiding Nephrotoxins
- NSAIDs
- Aminoglycosides
- Contrast (when possible)
- Herbal medicines (äžèè¥ â important in Taiwan)
- Tenofovir (consider alternatives)
Bone Mineral Disease Workflow
- Monitor: Ca, P, PTH, vit D, ALP
- Bone biopsy rarely
- Treatment: phosphate binders, active D, calcimimetics
- Parathyroidectomy for severe refractory
Vascular Calcification Imaging
- Kauppila score (lateral spine X-ray)
- CT calcium score
- Predicts mortality
Calciphylaxis
- Calcific uremic arteriolopathy
- Painful necrotic skin lesions
- High mortality
- Treatment: sodium thiosulfate, wound care, parathyroidectomy if hyperPTH
Pearls
- CKD: eGFR < 60 OR damage ⥠3 mo
- KDIGO G + A staging
- Top causes: DM > HTN > GN > PKD
- Top death cause: CV
- HIF-PHI (roxadustat, daprodustat) NEW for anemia
- Finerenone (FIDELIO/FIGARO) for DKD + albuminuria
- SGLT2i + GLP-1 RA + ACE/ARB for DKD
- Hgb target: 10-11.5 (CHOIR, TREAT)
- Phosphate binders: non-Ca preferred to avoid Ca load
- Vascular calcification: predicts mortality