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Mechanistic Deep Dive
AIN Pathophysiology
- T-cell mediated hypersensitivity (Type IV)
- Drug-T-cell interaction â activation
- Cytokine release
- Interstitial inflammation
- Tubular damage (tubulitis)
PPI-Induced AIN
- Mechanism: drug-T-cell interaction
- Hypersensitivity may not be apparent
- Often subtle Cr rise
- Increasing recognition; long-term PPI exposure
Lithium Nephrotoxicity
- Cellular damage to collecting duct cells
- Inhibits aquaporin-2 insertion
- Impaired urine concentration
- Chronic interstitial nephritis
Aristolochic Acid Mechanism
- DNA adduct formation
- Tubular cell apoptosis
- Progressive interstitial fibrosis
- AA-DNA adducts in renal tissue
- Promotes urothelial carcinoma
Recent Trials & Updates
ICI Nephritis Increasing
- 2-5% of ICI patients
- More with combination ICI
- Earlier ICI use â earlier nephritis
- Outcomes generally good with treatment
Sjögren Renal Treatment
- HCQ
- Steroids for active
- Rituximab + MMF for refractory
Lithium Alternative
- For NDI from lithium
- Amiloride mechanism
- May allow continued lithium
High-Yield Specialist Points
ICI-Associated AIN
- Typically 2-3 months after ICI start
- May have multi-organ irAEs
- Treatment: hold ICI + prednisone 1 mg/kg
- Re-challenge possible after recovery (Cr improvement)
- Steroid taper over 4-6 weeks
Drug-Induced Crystals
- Acyclovir crystals
- Methotrexate crystals
- Sulfa crystals
- Indinavir crystals
- Reversible with hydration + dose adjustment
Vancomycin AKI
- Trough > 20 increases risk
- Concurrent nephrotoxins worsen
- AUC-based dosing newer recommended
Aminoglycoside Toxicity
- Cumulative dose + duration
- Once-daily extended-interval dosing reduces
- Monitor: peak + trough
- Renal recovery often
Pigment Nephropathy
- Rhabdomyolysis (myoglobin)
- Hemolysis (Hb)
- ATN + tubular obstruction
- Aggressive fluids
Crystal Nephropathy Workflow
- Identify crystal type
- Hydration
- Specific treatment (e.g., rasburicase for TLS)
Mesoamerican Nephropathy
- Sugarcane / agricultural workers
- Heat stress + dehydration + occupational toxins
- Central American epidemic
- Multifactorial
Chronic Lithium Management
- Monitor renal function annually
- Switch if Cr rises
- Amiloride for NDI
- Lower lithium levels may help
Sjögren Renal Workup
- Anti-SSA / Ro, anti-SSB / La
- Schirmer test
- Lip biopsy
- Manage symptomatic
- IS for severe
Cystinosis (Hereditary)
- Pediatric
- Cystine accumulation in lysosomes
- Multisystem (kidney, eye, thyroid, gonads)
- Treatment: cysteamine + supportive
- Eventual transplant
Pearls
- AIN: drug-induced most common; PPI, NSAID, ICI, penicillins
- CIN: chronic; lithium, analgesics, aristolochic acid, reflux, hereditary
- RTA Type 1: distal, Sjögren most common
- RTA Type 2: proximal, Fanconi often, MM
- RTA Type 4: hyperK, DKD, drug-induced
- Fanconi syndrome: proximal tubular dysfunction (cystinosis, MM, tenofovir)
- Nephrogenic DI: lithium, hyperCa, hypoK
- ICI nephritis: 2-5%, AIN typically, steroid responsive
- Aristolochic acid: äžèè¥ history (Taiwan); urothelial cancer risk