335.1 🎓 醫孞生版

335.1.0.1 📌 䞀頁重點

335.1.0.1.1 Definition + Epidemiology
335.1.0.1.1.1 CKD Definition (KDIGO)
  • eGFR < 60 mL/min/1.73 m² OR
  • Kidney damage (any of):
    • Albuminuria (UACR ≥ 30 mg/g)
    • Persistent hematuria
    • Abnormal imaging
    • Pathology on biopsy
    • History of renal transplant
  • For ≥ 3 months
335.1.0.1.1.2 Epidemiology
  • Global ~ 10%
  • Taiwan ~ 12% adults
  • ESKD prevalence increasing (DM + HTN + aging)
  • Taiwan high prevalence (genetic + diet + medications + 䞭草藥)
335.1.0.1.1.3 Etiology
  • DM (most common) — diabetic kidney disease (DKD)
  • HTN — hypertensive nephropathy
  • GN (glomerulonephritis) — IgA, FSGS, lupus
  • PKD (polycystic kidney disease) — ADPKD common
  • Tubulointerstitial (analgesics, lead, NSAIDs)
  • Vascular (atheroembolic, RAS)
  • Reflux nephropathy, obstruction
  • Hereditary (Alport, Fabry, sickle cell)
  • Idiopathic
335.1.0.1.2 KDIGO Staging — G + A

335.1.1 G Stage (by eGFR)

  • G1: eGFR ≥ 90 (normal or high)
  • G2: 60-89 (mildly ↓)
  • G3a: 45-59 (mild-moderate ↓)
  • G3b: 30-44 (moderate-severe ↓)
  • G4: 15-29 (severely ↓)
  • G5: < 15 or RRT (kidney failure)

335.1.2 A Stage (by Albuminuria — UACR)

  • A1: < 30 mg/g (normal-mild ↑)
  • A2: 30-300 mg/g (moderately ↑, microalbuminuria)
  • A3: > 300 mg/g (severely ↑, macroalbuminuria)

335.1.3 Combined Risk

  • G3a + A1: low risk
  • G3a + A2: moderate
  • G3a + A3 OR G3b + A1-2: high
  • G3b + A3 OR G4 + any: very high
335.1.3.0.1 Pathophysiology

335.1.4 Glomerular Hypertension

  • Initial nephron injury → compensatory hypertrophy
  • Increased intraglomerular pressure → further injury
  • “Maladaptive hyperfiltration”
  • ACE/ARB reduce intraglomerular pressure → protective

335.1.5 Tubulointerstitial Damage

  • Common final pathway
  • Independent prognostic factor

335.1.6 Inflammation + Fibrosis

  • Multiple cytokines (TGF-β, CTGF)
  • Myofibroblast activation
  • Progressive scarring

335.1.7 Vascular + Endothelial

  • Common pathway → vascular calcification + atherosclerosis
335.1.7.0.1 Clinical Features

335.1.8 Early CKD (G1-G3a)

  • Often asymptomatic
  • Found on routine labs
  • Albuminuria may be only sign

335.1.9 Moderate CKD (G3b-G4)

  • Fatigue
  • Cognitive issues (mild)
  • Edema (variable)
  • Often comorbid issues

335.1.10 Severe CKD (G4-G5)

  • Uremic symptoms:
    • Anorexia, nausea, vomiting
    • Pruritus
    • Restless legs
    • Cognitive dysfunction
    • Sleep disturbance
  • Volume overload
  • Pulmonary edema
  • Pericarditis (uremic)
  • Encephalopathy
  • Bleeding (platelet dysfunction)
  • Anemia symptoms (fatigue, dyspnea)
  • Bone pain (CKD-MBD)
  • Muscle wasting
335.1.10.0.1 CKD Complications

335.1.11 Cardiovascular (Top Cause of Death)

Mechanisms: - Traditional RFs accumulated - CKD-specific: vascular calcification (CKD-MBD), uremic toxins, inflammation, anemia, BP - CKD = CHD risk equivalent

Manifestations: - CHD, MI - Stroke - HF - Arrhythmias (AF common; SCD elevated) - PAD

Management: - BP control (< 130/80) - Lipid management (statin for primary prevention if albuminuria) - ASA for established ASCVD - AC for AF (anticoagulation decision complex in CKD) - SGLT2i + GLP-1 RA (DM + ASCVD) - Finerenone (DKD + albuminuria)

335.1.12 Anemia of CKD

Mechanism: - Reduced EPO production (peritubular fibroblasts) - Iron deficiency (uremia + inflammation + hepcidin) - Inflammation-induced (anemia of chronic disease) - Blood loss (HD)

Diagnosis: - Hgb < 13 men, < 12 women (WHO) - Iron studies (ferritin, TSAT) - Other causes (B12, folate, hemolysis)

Treatment: - Iron supplementation: oral or IV - Erythropoiesis-stimulating agents (ESAs): - Epoetin alfa - Darbepoetin - Methoxy PEG-epoetin beta - Target Hgb 10-11.5 - CHOIR + TREAT trials: caution; higher targets ↑ CV events - HIF-PHIs (HIF prolyl hydroxylase inhibitors) — NEW: - Roxadustat (Evrenzo) - Vadadustat (Vafseo) - Daprodustat (Jesduvroq) - Oral, stabilize HIF → endogenous EPO - Approved for renal anemia - FDA approved 2023 (some restrictions for CKD non-dialysis)

335.1.13 CKD-MBD (Mineral Bone Disorder)

Components: 1. Hyperphosphatemia (early) 2. Hypocalcemia (later) 3. ↓ Vitamin D activation (impaired 1α-hydroxylase) 4. Secondary hyperparathyroidism (↑ PTH compensating) 5. ↑ FGF-23 (compensatory phosphaturic) 6. Vascular calcification (deposition of Ca-PO4)

Stages: - Stage 3-4 CKD: ↑ FGF-23, ↑ PTH - Stage 4-5 CKD: ↑ PO4, ↓ Ca, marked ↑ PTH

Treatment: - Phosphate binders: - Calcium-based (calcium carbonate, calcium acetate) — concerns of Ca load - Non-calcium (sevelamer, lanthanum, ferric citrate, sucroferric oxyhydroxide) - Active vitamin D analogs (calcitriol, paricalcitol, doxercalciferol) - Cinacalcet (calcimimetic) — for severe 2° hyperPTH - Etelcalcetide (parenteral calcimimetic, FDA 2017) - Parathyroidectomy for refractory severe 2° hyperPTH - Avoid excessive Ca (vascular calcification risk) - Magnesium supplementation if low

335.1.14 Fluid + Electrolyte

Hyperkalemia: - Risk with ACE/ARB/MRA - Avoid K-sparing diuretics - K binders (patiromer, sodium zirconium cyclosilicate) for chronic - Diet: K restriction

Hyponatremia: SIADH-like; fluid restriction

Hypocalcemia, Hyperphosphatemia: CKD-MBD management

Magnesium: hypo- (PPI long-term, diuretics) or hyper-

Acid-base: - Metabolic acidosis (impaired NH4 excretion + HCO3 wasting) - Treatment: sodium bicarbonate (target HCO3 22-26) - Some evidence: slows CKD progression

335.1.15 Hypertension

  • ~ 80% of CKD patients
  • Often resistant
  • Target < 130/80 (KDIGO 2021)
  • ACE/ARB first-line (especially with proteinuria)
  • Multi-drug usually needed

335.1.16 Uremia (Late)

  • Encephalopathy
  • Neuropathy
  • Pruritus
  • Bleeding (platelet dysfunction)
  • Pericarditis
  • Asterixis (severe)

335.1.17 Endocrine

  • Insulin resistance
  • Infertility (men + women)
  • Hypothyroidism (more common)
  • Hyperprolactinemia
  • Sex hormone abnormalities

335.1.18 Nutrition / Protein-Energy Wasting (PEW)

  • Common
  • Inflammation, anorexia, dialysis losses
  • Sarcopenia
  • Multidisciplinary

335.1.19 Acid-Base Disturbance

  • Metabolic acidosis with anion gap
  • Severe: bone disease, muscle wasting, CKD progression
  • Sodium bicarbonate supplementation

335.1.20 Bleeding Tendency

  • Platelet dysfunction (uremic)
  • Treatment: desmopressin (DDAVP), cryoprecipitate, blood transfusion if needed

335.1.21 Cognitive

  • Cognitive decline accelerated
  • Vascular dementia
  • Multifactorial

335.1.22 Skin

  • Pruritus (uremic)
  • Calcifying uremic arteriolopathy (calciphylaxis)
  • Bullous lesions
335.1.22.0.1 Differential Diagnosis (Important)

335.1.23 CKD vs AKI on CKD

  • AKI: acute Cr rise
  • CKD: chronic + may have AKI episodes
  • CKD often has: small kidneys on US, anemia, low Ca, high PO4 (chronic)
  • AKI: normal-size kidneys, no chronicity markers

335.1.24 Causes Workup

  • DM (HbA1c, history)
  • HTN duration + severity
  • Urinary findings (hematuria, proteinuria, casts → GN)
  • Family history (PKD, Alport)
  • Drug history (analgesics, lithium)
  • Imaging (size, stones, cysts, obstruction)
  • Renal biopsy for unclear cases

335.1.24.1 🩺 床邊速查

  • CKD: eGFR < 60 OR damage > 3 mo
  • KDIGO G stage: G1-G5 by eGFR
  • A stage: A1 < 30, A2 30-300, A3 > 300 mg/g UACR
  • Top causes: DM > HTN > GN > PKD
  • Complications: CV (top death), anemia, CKD-MBD, electrolytes, uremia
  • HIF-PHI new for anemia (roxadustat, daprodustat)
  • Cinacalcet / etelcalcetide for 2° hyperPTH
  • Phosphate binders: Ca-based (Ca load) vs non-Ca (sevelamer, etc.)