1 / 17

Drugs & Kidney

Drugs & Kidney. Helmut Hopfer Basel, Switzerland. Patterns of Drug-induced Lesions. Tubulointerstitium Acute tubular injury - Osmotic nephrosis - Nephrocalcinosis - Chrystal NP Acute interstitial nephritis Chronic tubulointer- stitial nephropathy. Glomeruli

gari
Download Presentation

Drugs & Kidney

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drugs & Kidney Helmut Hopfer Basel, Switzerland

  2. 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

  3. Virostatics Quinolones Bisphosphonates Bisphosphonates Propylthiouracil Propylthiouracil Methotrexate Bucillamine Anti-VEGF Anti-VEGF Tamoxifen Ifosfamide Phenytoin Interferon Sirolimus Cisplatin Cisplatin Quinine NSAID OSPS HES Thiazids COX2-I Lithium Lithium Captopril Mitomycine C Mitomycine C Penicillamine Penicillamine Sulfasalazine Gemcitabine Barbiturates Clopidogrel Hydralazin Rifampicin Ranitidin ACE-I NSAID CNI CNI CNI CNI Antibiotics Diazepam 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

  4. 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

  5. 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 Example: Zoledronate

  6. tubular secretion Renal Handling of Bisphosphonates glomerular filtration

  7. Glomerular pathology in BPs • FSGS, collapsing variant, also NOS • minimal change disease • Pamidronate • Zoledronate • Alendronate

  8. Nach: Kino et al., Biopharm Drug Dispos 20: 193, 1999 T. Pfister, Roche

  9. Nach: Kino et al., Biopharm Drug Dispos 20: 193, 1999

  10. KI67 NaK-ATPase Markowitz et al., Kidney Int 64:281, 2003

  11. Goscinny and Uderzo, 1969

  12. ATN Renal Zoledronate Toxicity • 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

  13. time (h) bisphosphonate tubular damage regeneration signal renal recovery proliferation proliferation blocked abortive regeneration back leak syndrome renal insufficiency cisplatin

  14. 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

  15. 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

More Related