332.3 ð¥ å §ç§å°ç§èåç
332.3.1 Mechanistic Deep Dive
332.3.1.1 Renal Blood Flow
- ~ 20-25% of cardiac output
- 1200 mL/min total
- Filtration fraction ~ 20%
- Autoregulation maintains stable GFR (myogenic + tubuloglomerular feedback)
332.3.1.2 Tubuloglomerular Feedback (TGF)
- Macula densa senses Cl- delivery
- Adenosine + others modulate afferent arteriole
- Maintains GFR
332.3.1.3 RAAS in Detail
- Renin (JG cells) â angiotensinogen â Ang I â ACE â Ang II
- Ang II: vasoconstriction (efferent > afferent), aldosterone
- Aldosterone: Na retention, K excretion, fibrosis
- AT1R (vasoconstriction, growth) vs AT2R (vasodilation, anti-proliferation)
332.3.1.4 Acid-Base in Kidney
- HCO3 reabsorption (PCT, 90%)
- NH4 excretion (distal acidification)
- Acid base disorders â urine pH, urine anion gap
332.3.1.5 Solute Handling
Sodium: - Filtered ~ 26,000 mEq/d - 65% PCT, 25% LoH, 5-10% DCT, <5% CD - Aldosterone in CD
Potassium: - Reabsorbed mostly PCT + LoH - Distal CD: secretion or reabsorption (depending on K state) - Aldosterone â K secretion
Calcium: - 70% PCT, 20% LoH, 5-10% DCT, 5% CD - PTH â DCT reabsorption - Vitamin D â absorption
332.3.2 Recent Trials & Updates
332.3.2.1 CKD-EPI 2021 Race-Free Equation
- Adopted by ASN/NKF 2021
- Removes race coefficient
- More equitable
- Combined Cr + cystatin C even better
332.3.2.2 SGLT2i in CKD (FLOW, DAPA-CKD, EMPA-KIDNEY)
- Beyond DM
- Dapagliflozin DAPA-CKD: CKD with or without DM
- Empagliflozin EMPA-KIDNEY: similar
- FLOW (2024): semaglutide for CKD
332.3.3 High-Yield Specialist Points
332.3.3.1 Drug Dosing in CKD
- Use Cockcroft-Gault for many drugs (FDA historical)
- eGFR (CKD-EPI) for newer labels
- Some drugs require dose adjustment
332.3.3.2 Vitamin D in CKD
- 25-OH vitamin D (storage form)
- 1,25-OH vitamin D = calcitriol (active)
- 1α-hydroxylase in kidney
- Deficiency in CKD â 2° hyperparathyroidism â CKD-MBD
332.3.3.3 Anemia in CKD
- Reduced EPO production
- Iron deficiency
- Erythropoiesis-stimulating agents (ESAs)
- Iron supplementation
- HIF-PHI (roxadustat, vadadustat, daprodustat) â newer
332.3.3.4 CKD-MBD (Mineral Bone Disorder)
- Hyperphosphatemia
- â Vitamin D
- â PTH (secondary hyperparathyroidism)
- â FGF-23
- Vascular calcification
- Treatment: phosphate binders, calcitriol or analog, cinacalcet, etelcalcetide
332.3.3.5 Cardiovascular in CKD
- CKD = CHD risk equivalent
- HF, stroke, MI very common
- Top cause of death in CKD
332.3.4 Pearls
- eGFR: CKD-EPI 2021 race-free preferred
- UACR: A1 (< 30), A2 (30-300), A3 (> 300 mg/g)
- Nephrotic: > 3.5 g protein + hypoalbuminemia + edema + hyperlipidemia
- Nephritic: hematuria + RBC casts + HTN + AKI variable
- Casts: muddy brown (ATN), RBC (GN), WBC (AIN/pyelo), waxy (chronic), fatty (nephrotic)
- MUDPILES for anion gap acidosis
- APOL1: African ancestry risk genotype for nephropathy
- 2024 CKD therapies: SGLT2i + finerenone + GLP-1 RA (FLOW)