32. Drug Mechanism Side effect Glucocorticoids Binds cytosolic receptors and heat shock proteins. Blocks transcription of IL-1,-2,-3,-6, TNF- α , and IFN- γ Hypertension, glucose intolerance, dyslipidemia, osteoporosis Cyclosporine (CsA) Trimolecular complex with cyclophilin and calcineurin block in cytokine (e.g., IL-2) production; however, stimulates TGF- production Nephrotoxicity, hypertension, dyslipidemia, glucose intolerance, hirsutism/hyperplasia of gums Tacrolimus (FK506) Trimolecular complex with FKBP-12 and calcineurin block in cytokine (e.g., IL-2 ) production; may stimulate TGF- production Similar to CsA, but hirsutism/hyperplasia of gums unusual, and diabetes more likely Azathioprine Hepatic metabolites inhibit purine synthesis Marrow suppression (WBC > RBC > platelets) Mycophenolate mofetil (MMF) Inhibits purine synthesis via inosine monophosphate dehydrogenase Diarrhea/cramps; dose-related liver and marrow suppression is uncommon Sirolimus Complexes with FKBP-12 and then blocks p70 S6 kinase in the IL-2 receptor pathway for proliferation Hyperlipidemia, thrombocytopenia
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41. Infections The Most Common Opportunistic Infections in the Renal Transplant Recipient Peritransplant (<1 month) Early (1–6 months) Late (>6 months) Wound infections Pneumocystis carinii Aspergillus Herpesvirus Cytomegalovirus Nocardia Oral candidiasis Legionella BK virus (polyoma) Urinary tract infection Listeria Herpes zoster Hepatitis B Hepatitis B Hepatitis C Hepatitis C
42. Prophylactic therapy for recipients of renal transplants comments Trimethoprim-sulfamethoxazole (TMP/SMX) Routine use eliminates the incidence of pneumocysits carinii, listeria monocytogenes, nocardia asteroides and toxoplasmosis gondii. Also reduces the incidence of UTI from 30-80% to <5-10% Monthly intravenous or aresolized pentamidine or dapsone or atovaquone Replaces TMP/SMX for patients with sulfa allergies Nystatin 4ml after meals and before bedtime For fungal prophylaxis Acyclovir, valgancyclovir, gancyclovir For CMV prophylaxis
43. Recommended immunization before and after transplantation Vaccine Before After MMR Yes - DPT Yes dT Varicella Yes Controversial Polio Yes - Hemophillus influenzae B Yes Yes Influenza yes Yes Pneumococcus Yes Yes Hepatitis B Yes Yes Hepatitis A Yes Yes
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50. Risk factors for CAN Alloantigen-Dependent (immune) risk factors Alloantigen-Independent (non-immune) risk factors Acute rejection (incl subclinical) Kidney size mismatch MHC antigen mismatches Proteinuria Previous transplantation Older donor age Cadaver donor Hypertension Younger recipient age Dyslipidemia Delayed graft function Smoking CMV infection
51. Alloantigen dependent (oval shaded) and independent factors (rectangular shaded) thought to be involved in the pathogenesis of chronic allograft nephropathy.
54. References: Brenner and rector’s The Kidney 8 th ed. Comprehensive Clinical Nephrology by John Feehally 3 rd ed. Harrison’s Principles of Internal Medicine 17 th ed.