Editing Renal Transplant (section)

== Post-transplant care ==

* '''The best predictor of immediate graft function following living donor renal transplantation is donor kidney output just prior to nephrectomy.'''
* Low-molecular-weight heparin is eliminated by the kidney and must be used cautiously in the setting of unpredictable metabolism to minimize bleeding complications.
* In patients with reasonable bladder capacity, the urinary catheter may be removed on postoperative day 3 and the closed suction drain removed later in the day if drain output remains low.
* '''The most common early complications of renal transplantation include (6):'''
*# '''Infection'''
*# '''Bleeding'''
*# '''Urinary leak'''
*#* '''Leaks manifest in the early post-operative period with decreased urine output from the urinary catheter and increased output from the closed suction drain.'''
*#* '''If the leak occurs after the urethral catheter has been removed, the catheter should be replaced immediately.'''
*#* '''Many anastomotic leaks will heal with the ureteral stent in place and catheter drainage.'''
*#** '''Leaks that do not heal with conservative measures may require placement of a percutaneous nephrostomy tube or open repair'''
*# '''Lymphatic leak'''
*#* Lymphoceles can originate from the transplant kidney or the lymphatic channels that surround the iliac vessels
*#* Incidence of lymphoceles can be reduced by routine placement of a closed suction drain that is removed when the output is < 50 mL/day.
*#* '''Many lymphoceles are small and inconsequential, but large lymphoceles may:'''
*#** '''Cause pain'''
*#** '''Become infected'''
*#** '''Compress the allograft, leading to dysfunction'''
*#* Lymphoceles are well visualized on ultrasound
*#* '''Management'''
*#*# '''If intervention required, initially treated with image-guided aspiration'''
*#*# '''If this fails, a closed suction drain is inserted'''
*#*# '''If this fails, sclerosing agents may be used'''
*#*# '''If this fails, creating of a peritoneal window can aid in reabsorption'''
*# '''Vascular thrombosis'''
*#* '''Transplant renal artery thrombosis'''
*#** '''Generally occurs within 3 days of the transplant'''
*#** '''Associated with hypercoagulable state or delayed graft function'''
*#*** Patients at risk for thrombosis should be given anticoagulation therapy
*#** '''Diagnosis and Evaluation'''
*#*** '''Sudden cessation of urine output'''
*#*** Doppler ultrasound reveals no blood flow to the graft
*#** '''Management'''
*#*** '''Emergent thrombectomy and antithrombolytics should be attempted, but rarely successful'''
*#* '''Transplant renal vein thrombosis'''
*#** '''Associated with hypercoagulable state, kinking or stenosis of the vein, acute rejection, and hypotension'''
*#** Diagnosis and Evaluation
*#*** Doppler ultrasound may reveal a clot in the vein and decreased blood flow to the graft
*#** '''Management'''
*#*** '''Emergent thrombectomy and antithrombolytics should be attempted, but rarely successful'''
*#* '''Reasons for elevated renal arterial resistive index in a transplant kidney (7): ARVOCAD'''
*#*# '''Renal Artery stenosis (if measured upstream from the stenosis)'''
*#*# '''Transplant Rejection (acute or chronic)'''
*#*# '''Renal Vein thrombosis'''
*#*# '''Ureteric Obstruction'''
*#*# '''Perinephric fluid Collection'''
*#*# '''Acute tubular necrosis (ATN)'''
*#*# '''Drug toxicity'''
*#** '''Resistive Index = (peak systolic velocity - end diastolic velocity) / peak systolic velocity; normal = 0.60-0.70'''
*# '''Rejection'''
*#* '''Classified by temporal occurrence of graft loss:'''
*#** '''Hyperacute (humoral) rejection'''
*#*** '''Occurs shortly after the reperfusion of kidney transplants'''
*#*** '''MOA: Recipient cytotoxic antibodies and complement react with donor vascular endothelial antigens, leading to a rapid activation of the coagulation cascade and graft thrombosis'''
*#*** Rarely seen clinically today because of sensitive crossmatch tests to detect DSA.
*#** '''Acute rejection'''
*#*** '''Classically occurs ≈5 days after an allogeneic organ transplant without immunosuppression.'''
*#*** '''Most common presentation is increasing serum creatinine and decreasing urine output'''
*#*** Needle biopsy of the kidney graft is the current standard diagnostic test
*#** '''Chronic rejection'''
*#*** '''Characterized by a gradual deterioration of kidney function'''
*#*** The histologic features of interstitial fibrosis, arteriolar sclerosis, and tubular atrophy rarely improve with augmented immunosuppression, and are in some cases the result of drug toxicity.
*#* Allograft nephrectomy
*#** Can be a technically challenging procedure and is reserved for few clinical situations.
*#** Removal of an allograft that has failed during the first year post-transplant can lower levels of anti-HLA antibodies that may make subsequent transplantation more difficult due to positive cross matches.
* '''Immunosuppression'''
** '''Advances in immunosuppressive drugs have improved early graft survival rates, but these improvements have had little impact on late graft loss, largely because of chronic rejection.'''
** '''Mechanisms of Action of Immunosuppressants'''
*** '''Glucocorticoids: Reduce transcription of cytokine genes'''
*** '''Azathioprine: Inhibits purine synthesis'''
*** '''Mycophenolate mofetil: Inhibits purine synthesis'''
*** '''Sirolimus: Inhibits cell cycle progression'''
*** '''Everolimus: Inhibits cell cycle progression'''
*** '''Tacrolimus: Inhibits calcineurin and IL-2 production'''
*** '''Cyclosporine: Inhibits calcineurin and IL-2 production'''
*** '''Rabbit antithymocyte globulin: Depletes T lymphocytes'''
*** '''Rituximab: Depletes B lymphocytes'''
*** Alemtuzumab: Depletes T and B lymphocytes
*** Bortezomib: Proteasome inhibitor
*** '''Basiliximab: Blocks IL-2 receptor'''
*** Belatacept: Costimulation blockade
*** Eculizumab: Complement inhibitor
** See CW11 Table 47-3 for Common Organ Targets for Toxicities of Immunosuppressant Therapy

** '''Corticosteroids most likely to impair wound healing'''
** '''Prednisone, cyclosporine, and sirolimus all result in hyperlipidemia'''
** '''Commonly used regimens to prevent infections and peptic ulcer disease include TMP/SMX for 3 months for prophylaxis against Pneumocystis pneumonia'''
** '''Prophylaxis against cytomegalovirus disease is possible with ganciclovir, acyclovir, valacyclovir, or cytomegalovirus immune globulin'''
** '''Cyclosporine and tacrolimus are metabolized by the cytochrome P450 system; doses may have to be adjusted with concomitant use medications that also involve the cytochrome P450 system (fluconazole, ketoconazole)'''
*** '''P450 Inducers'''  '''''B'''ull'''S'''hit '''CRAP GPS''' INDUCES my rage!''§
**** '''B'''arbituates
**** '''S'''t. John’s wort
**** '''C'''arbamazepine
**** '''R'''ifampin
**** '''A'''lcohol (chronic)
**** '''P'''henytoin
**** '''G'''riseofulvin
**** '''P'''henobarbital
**** '''S'''ulfonylureas
*** '''P450 Inhibitors''' '''''VICK'''’'''S''' '''FACE''' '''A'''ll '''O'''ver '''GQ''' STOPS ladies in their tracks.''§
**** '''V'''alproate
**** '''I'''soniazid
**** '''C'''imetidine
**** '''K'''etoconazole
**** '''S'''ulfonamides
**** '''F'''luconazole
**** '''A'''lcohol (acute)
**** '''C'''hloramphenicol
**** '''E'''rythromycin ''(macrolides EXCEPT azithromycin)''
**** '''A'''miodarone
**** '''O'''meprazole
**** '''G'''rapefruit juice
**** '''Q'''uinidine
** '''Diltiazem and ketoconazole have been used to reduce calcineurin inhibitor dosing and cost while maintaining blood levels and immunosuppressive effect'''
** '''Chronic immunosuppression increases the risk for malignancy'''
*** '''Skin cancer is the most common malignancy after solid-organ transplant'''
*** '''Malignancies associated with viral infection (4):'''
***# '''Kaposi sarcoma (human herpesvirus 8)'''
***# '''Non-Hodgkin lymphoma (EBV)'''
***# '''Vulvar (human papillomavirus)'''
***# '''Hepatocellular (Hepatitis C) carcinoma'''
*** '''The incidence of kidney, penile, and bladder cancers are also increased'''
**** '''Recall in HIV, increased risk of kidney, penile, and testis; metabolic syndrome has increased risk of kidney, bladder, and prostate'''
*** '''The incidence of prostate cancer is actually decreased in transplant recipients'''
*** '''Lymphoma may respond to a reduction in immunosuppression'''
* '''Fertility'''
** '''After successful kidney transplantation, levels of FSH, LH, and testosterone usually become normal and spermatogenesis improves'''.
** '''Among male recipients who have fathered children, there has been no increase in congenital abnormalities in the offspring. It is recommended, however, that impregnation be delayed for at least 1 year after transplantation.'''
** '''Successful renal transplantation usually restores fertility in premenopausal women'''
* '''Hemorrhagic cystitis in an immunosuppressed patient has been most commonly associated with adenovirus'''