›Dosing
›Maintenance 0.05 to 0.1 mg/kg/day PO divided every 12 hours, adjusted to trough level
›Trough target 5 to 10 ng/mL, higher target 8 to 12 ng/mL in the first three months
›Toxicity
›Nephrotoxicity
›Neurotoxicity, tremor, headache, and posterior reversible encephalopathy syndrome
›Hyperkalemia and hypomagnesemia
›Hyperglycemia and new-onset diabetes after transplant
›Hypertension and QT prolongation
›Cyclosporine
›Dosing
›Maintenance 3 to 5 mg/kg/day PO divided every 12 hours (modified formulation), adjusted to trough level
›Trough target 100 to 250 ng/mL, higher early after transplant
›Toxicity
›Nephrotoxicity and hypertension
›Hirsutism and gingival hyperplasia
›Hyperlipidemia and hyperuricemia
Other maintenance immunosuppressants
›Antimetabolites
›Mycophenolate mofetil PO
›1000 mg PO every 12 hours in most adult regimens
›Toxicity, diarrhea, leukopenia, and teratogenicity
›Azathioprine PO
›1 to 3 mg/kg/day PO
›Toxicity, leukopenia and hepatotoxicity
›Dangerous interaction with allopurinol from xanthine oxidase inhibition raises azathioprine toxicity risk
›mTOR inhibitors
›Sirolimus or everolimus
›Trough-adjusted dosing per transplant protocol
›Toxicity, impaired wound healing, mouth ulcers, hyperlipidemia, and interstitial pneumonitis
›Avoided in the immediate postoperative period because of wound healing impairment
›Corticosteroids
›Maintenance prednisone
›Low-dose maintenance, commonly 5 mg PO daily, per transplant protocol
›Stress dosing
›Hydrocortisone 50 to 100 mg IV for significant illness or procedure, cross-referenced under Approach to the Critical Patient
Dangerous drug interactions with calcineurin inhibitors
›Interactions that raise calcineurin inhibitor levels through CYP3A4 inhibition
›Azole antifungals
›Fluconazole, itraconazole, voriconazole, and posaconazole
›Can markedly raise tacrolimus or cyclosporine levels and precipitate acute nephrotoxicity
›Empiric calcineurin inhibitor dose reduction and close level monitoring when an azole is started
›Voriconazole additionally shares QT prolongation risk with tacrolimus
›Macrolide antibiotics
›Clarithromycin and erythromycin raise calcineurin inhibitor levels
›Azithromycin has minimal CYP3A4 effect and is the preferred macrolide when one is needed
›Non-dihydropyridine calcium channel blockers
›Diltiazem and verapamil raise calcineurin inhibitor levels
›Starting either for blood pressure or rate control in the ED without transplant team input risks unintended toxicity
›Dihydropyridine calcium channel blockers such as amlodipine have minimal interaction and are preferred for de novo blood pressure control
›Other CYP3A4 inhibitors
›Grapefruit juice and amiodarone
›Interactions that lower calcineurin inhibitor levels through CYP3A4 induction
›Rifampin and rifabutin
›Can dramatically reduce calcineurin inhibitor levels and precipitate acute rejection
›Requires major dose increase and close level monitoring, or avoidance, under transplant guidance
›Antiepileptics
›Phenytoin, phenobarbital, and carbamazepine
›St John's wort
›Potent inducer with reported rejection episodes after unsupervised use
›Additive toxicity without a level change
›NSAIDs
›Additive nephrotoxicity through afferent arteriolar vasoconstriction
›Trimethoprim-sulfamethoxazole
›Additive hyperkalemia and a spurious creatinine rise from reduced tubular creatinine secretion
Infection management principles
›Empiric therapy for suspected sepsis
›Broad-spectrum coverage per local antibiogram
›Antibiotic selection, dosing, and de-escalation follow Approach to fever in the immunocompromised patient
›First dose within 60 minutes of suspected sepsis recognition
›Transplant-specific antimicrobial therapy
›CMV disease
›Valganciclovir PO 900 mg every 12 hours, renally adjusted
›Ganciclovir IV 5 mg/kg every 12 hours, renally adjusted, for severe disease or when oral therapy is not tolerated
›Pneumocystis jirovecii pneumonia
›Trimethoprim-sulfamethoxazole IV or PO at treatment dose per weight, renally adjusted
›Corticosteroid adjunct for significant hypoxemia per standard PCP criteria
›BK virus nephropathy
›No proven direct antiviral therapy
›Reduction of immunosuppression is the primary strategy, guided by transplant nephrology
›Distinguishing BK nephropathy from rejection before adjusting immunosuppression is essential; increasing immunosuppression for presumed rejection would worsen unrecognized BK nephropathy
Surgical and urologic complication management
›Lymphocele
›Percutaneous drainage for symptomatic or compressive lymphocele
›Surgical marsupialization for recurrent cases
›Urine leak
›Diagnosis
›Drain fluid creatinine higher than serum creatinine confirms a urine leak
›Management
›Foley catheter drainage and urology or transplant surgery consultation
›Percutaneous nephrostomy and ureteral stenting or surgical repair depending on the defect
›Ureteric stenosis
›Percutaneous nephrostomy with antegrade stenting
›Surgical revision if endourologic management fails
Vascular complication management
›Renal artery stenosis
›Angioplasty with or without stenting after confirmatory imaging
›Blood pressure management in the interim under transplant guidance given the solitary-kidney physiology
›Graft thrombosis
›Emergent surgical or endovascular thrombectomy attempt
›Time-critical; delay increases the likelihood of graft nephrectomy
Supportive care and analgesia
›Antipyretics and analgesics
›Acetaminophen PO or IV
›650 to 1000 mg every 6 hours, maximum 3000 mg per day in chronic liver or graft dysfunction
›Opioid analgesia when needed
›Fentanyl or hydromorphone preferred for renal clearance predictability
›Avoid NSAIDs entirely
›Glucose management
›Monitor glucose in any patient who is lethargic or has reduced oral intake
›Corticosteroid and tacrolimus contribution to hyperglycemia
›Fasting glucose 7.0 mmol/l or greater or random glucose 11.1 mmol/l or greater prompts evaluation for new-onset diabetes after transplant
›Isolation precautions
›Contact and droplet precautions for suspected transmissible respiratory or gastrointestinal infection
›Applies given prolonged shedding and higher transmission consequence in an immunosuppressed unit