Post-transplant medications and complications


Anemia. Nearly every CKD or ESRD patient is anemic and most are iron deficient or functionally iron deficient. Even if a patient has a hemoglobin level of 11 mg/dL and adequate iron stores (with a normal hemoglobin being 15 mg/dL), the patient is still 1 g iron depleted. Each unit of blood should raise the hemoglobin by 1 mg/dL and each unit contains approximately 250 mg of iron. Additionally, the estimated blood loss over the first three months is 750 mL.24

Thus, most patients at our center receive iron dextran 1 g IV prior to discharge. Reactions are uncommon, perhaps because of concomitant steroid use. We do not use oral iron as it may bind to mycophenolate and other drugs, is not very effective, and is associated with gastrointestinal side effects. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are useful for treating post-transplant erythrocytosis, which usually does not occur in the first three months.


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However, their introduction early after transplant may perpetuate anemia, cause hyperkalemia and raise the serum creatinine.


Hypertension. The first-line antihypertensive at our center is the calcium channel blocker amlodipine. It is a long-acting agent that has only minimal interference with cytochrome P-450 system, particularly (CYP3A4), and thus, does not affect CNI or mTOR levels dramatically. Its vasodilatory properties may counteract some of the vasoconstriction caused by CNIs and mTORs. We avoid using diltiazem or verapamil because they are potent inhibitors of CYP3A4 and raise CNI and mTOR levels.


Most patients have CVD and will require a beta blocker such as metoprolol or nebivolol or a combination alpha and beta blocker such as carvedilol. Nebivolol increases nitric oxide, which is vasodilatory and may be particularly useful for patients on a CNI. Most patients will have left ventricular hypertrophy or a history of coronary artery disease for which an ACEI or ARB are indicated. We prefer to delay introduction of these agents until after three months, when much of the anemia should have resolved and the patient is relatively stable and on lower CNI doses. The patient is less likely to experience hyperkalemia or an elevated serum creatinine with introduction of an ACEI or ARB.


Dyslipidemia. Many patients will have dyslipidemia with either high total or low-density lipoprotein (LDL) cholesterol or low high-density lipoprotein (HDL) and high triglyceride levels. The use of the statin, fluvastatin, a relatively week statin, was shown to be associated with less Major Adverse Cardiac Events (MACE) after five years.25

We usually use atorvastatin because it is commonly effective at lowering LDL to goal with the initial starting dose. We have not found pravastatin to be effective, and the FDA has recently issued a warning contraindicating the use of simvastatin with concomitant use of cyclosporine, but not tacrolimus, and not to exceed 20 mg with concomitant amlodipine.26 The FDA drug safety page also has a table of the relative potencies of the various statins.26 If patients are at goal and asymptomatic with any agent and any dose, we have not felt obliged to change therapy, but put a note in the medical record of our awareness of 
the FDA warning and why we are continuing therapy. 


Fever. Fever is a common complication after transplant. The most common causes are bacterial infections and most commonly urinary tract infections and less commonly pneumonia and sepsis. We routinely admit patients with a fever greater than 102°F, pan culture them, and begin empiric antibiotics. Pan culture includes obtaining a CMV-PCR and BK-PCR, although BK is uncommonly associated with fever. Many bacterial infections can be identified and treated according to sensitivities.

We commonly use ciprofloxacin or azithromycin for outpatient treatment. Although azithromycin is a macrolide antibiotic similar to erythromycin or clarithromycin, it does not interfere with the CYP 3A4 system and does not interfere with CNIs or mTOR inhibitors. For bacterial infections, we do not routinely decrease immunosuppression unless they are recurrent or life threatening. However, we do routinely stop the antimetabolite for CMV or BK infections because we recognize these viral infections as an 
in vivo biomarker of excessive immunosuppression. This approach seems to be successful and does not increase the rates of rejection or graft loss.27, 28

Conclusion


Transplant management is complex and requires diligence and communication among the patient, the transplant center, and other treating physicians and allied health care personnel. It is hard work that is necessary but rewarding.

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