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333.3.1 Mechanistic Deep Dive
333.3.1.1 ATN Pathophysiology
- Tubular epithelial cell apoptosis + necrosis
- Cytoskeletal disruption
- Loss of brush border + polarity
- Cast formation
- Tubular obstruction + back-leak
333.3.1.2 Ischemic vs Toxic ATN
- Ischemic: outer medullary stripe (S3 segment)
- Toxic: more diffuse
- Histologic distinction difficult
333.3.2 Recent Trials & Updates
333.3.2.1 Terlipressin for HRS (CONFIRM 2021)
- US Phase 3 trial
- FDA approval 2022
- More effective than placebo
- Risk of pulmonary edema (volume + vasoconstriction)
333.3.3 High-Yield Specialist Points
333.3.3.1 Drug-Induced AKI Mechanisms
Pre-Renal: - ACE/ARB: reduce efferent arteriole tone - NSAIDs: reduce afferent arteriole vasodilation - Diuretics: volume depletion
ATN: - Aminoglycosides: tubular cell accumulation - Vancomycin: oxidative + ischemic - Contrast: ischemia + direct toxicity - Cisplatin: tubular accumulation - Tenofovir: mitochondrial toxicity
AIN: - T-cell mediated hypersensitivity - Penicillins, NSAIDs, PPIs, ICIs - T1/T2 helper response
Crystal: - Acyclovir: crystals in tubules - Methotrexate: crystals - Sulfa: crystals
333.3.3.2 ICI-Associated AIN
- Pembrolizumab, nivolumab, ipilimumab, etc.
- T-cell driven nephritis
- Often AIN pattern
- Treatment: hold ICI + corticosteroids
- Can re-challenge after recovery in some
333.3.3.3 Atheroembolic AKI (Cholesterol Embolism)
- Post-arterial procedure (cath, AAA repair)
- Subacute (weeks)
- Livedo reticularis, blue toes, eosinophilia
- Treatment: supportive; statins; no specific
- Poor prognosis
333.3.3.5 TMA-AKI Differential
- TTP, HUS (typical/atypical), DIC, scleroderma renal crisis, malignant HTN, HELLP, drug-induced TMA
- Workup: peripheral smear, ADAMTS13, complement, etc.
333.3.3.6 Cardiorenal Syndrome
- Diuretic resistance common
- Acetazolamide (ADVOR), tolvaptan (TACTICS-HF)
- Ultrafiltration (UNLOAD, CARRESS-HF mixed)
- Heart-kidney transplant
333.3.4 Pearls
- KDIGO: Cr â 0.3 in 48 h OR 1.5à in 7 d OR UO < 0.5 mL/kg/h à 6 h
- Pre-renal: FENa < 1%, BUN/Cr > 20, U Osm > 500
- ATN: muddy brown casts, FENa > 2%, U Osm isothenuric
- AIN: WBC casts, ICI / NSAID / PPI / penicillin
- Post-renal: US for hydronephrosis
- HRS: terlipressin + albumin (FDA 2022); liver transplant cure
- Rhabdomyolysis: CK > 5000, aggressive IVF
- TLS: rasburicase prophylaxis + hydration
- Biomarkers: NGAL, KIM-1, Nephrocheck (TIMP-2 Ã IGFBP7)