Patterns of Drug-induced Lesions
Tubulointerstitium
Acute tubular injury
- Osmotic nephrosis
- Nephrocalcinosis
- Chrystal NP
Acute interstitial nephritis
Chronic tubulointer-stitial nephropathy
Glomeruli
Minimal change disease
Focal segmental glomerulosclerosis
Membranous GN
Crescentic GN
Thrombotic micro-angiopathy
Blood vessels
Hyalinosis
Thrombotic micro-angiopathy
Vasculitis
Patterns of Drug-induced Lesions
Tubulointerstitium
Acute interstitial nephritis
Chronic tubulointer-stitial nephropathy
Acute tubular injury
- Osmotic nephrosis
- Nephrocalcinosis
- Chrystal NP
Glomeruli
Minimal change disease
Focal segmental glomerulosclerosis
Membranous GN
Crescentic GN
Thrombotic micro-angiopathy
Blood vessels
Hyalinosis
Thrombotic micro-angiopathy
Vasculitis
NSAID CNINSAID
Bisphosphonates
PenicillamineCaptopril
Propylthiouracil
Hydralazin
Rifampicin
Gemcitabine
Cisplatin
Bucillamine
Tamoxifen
Anti-VEGF
Lithium
Sirolimus
Interferon
CNI
Mitomycine C
ACE-I
Antibiotics
DiazepamLithium
Thiazids
CNI COX2-I
BarbituratesVirostatics
OSPS
Bisphosphonates
HES
Cisplatin
Quinolones
IfosfamideMethotrexate
Ranitidin
ClopidogrelCNIAnti-VEGF
Quinine Mitomycine C
PhenytoinPropylthiouracilPenicillamine
Sulfasalazine
Problems
• Case reports or small case series
• Incomplete clinical data at time of biopsy
• Difficulty establishing cause - effect relationships
• Patterns are usually not specific for a certain drug
• Some drugs may cause various patterns
Example: Zoledronate
• Intravenous nitrogen-containing BP
• Hypercalcemia, esp. multiple myeloma and bone metastasis in solid tumors
• Binding to bone, osteoclast inhibition after localized release
• Inhibition of farnesyl diphospha-tate synthase inhibition of small GTPases involved in cell signaling
Glomerular pathology in BPs
• FSGS, collapsing variant, also NOS
• minimal change disease
PamidronateZoledronateAlendronate
Renal Zoledronate Toxicity
ATN
Risk factors for kidney injury:• Multiple myeloma or RCC
vs. other basic diseases• Increased age• Number of doses• Current use of NSAID• Current or prior use of
cisplatin
McDermott et al., J Support Oncol 4:524, 2006
time (h)
tubular damage
bisphosphonate
regeneration signal
cisplatin
proliferation
proliferation blocked
abortive regeneration
back leak syndrome renal insufficiency
renal recovery
Summary
• Multiple drugs cause common patterns of renal pathology
• Tubules are most frequently affected due to tubular secretion
• Important risk factors are preexisting renal diseases and concomitant use of other potentially nephrotoxic drugs
• Alertness and awareness of the renal patho-logist are a key prerequisite for identification
Drugs & Kidney: Literature
• Perazella MA, Markowitz GS: Bisphosphonate nephrotoxicity. Kidney Int 74:1385-1393, 2008
• Markowitz GS, Perazella MA: Drug-induced renal failure: a focus on tubulo-intestitial disease. Clin Chim Acta 351:31-47, 2005
• John R, Herzenberg AM: Renal toxicity of therapeutic drugs. J Clin Pathol 62:505-515, 2009