Patient Encounter Part 3

Identify your treatment goals for JJ in terms of antimicrobial prophylaxis.

Create a plan for JJ's antimicrobial prophylaxis, making sure to compare and contrast the pros and cons of the different agents.


© Controlling hypertension post-transplant is essential in preventing cardiac morbidity and mortality and prolonging graft survival. The target blood pressure in kidney transplant recipients should be less than 130/80 mm Hg. This goal blood pressure may not be suitable for all organ transplant recipients. In such cases, the Joint National Committee Seventh Report (JNC7) guidelines should be followed.

Lifestyle Modifications

In order to achieve a goal blood pressure, lifestyle modifications including diet, exercise, sodium restriction, and smoking cessation are recommended.67 Unfortunately, lifestyle modifications alone are often inadequate to control hypertension in this high-risk population and antihypertensive medications are usually initiated early after transplant.

Immunosuppressive Regimen Modification

Because tacrolimus has shown the propensity to cause less severe hypertension when compared to cyclosporine, conversion from cyclosporine-based immunosuppression to tacrolimus-based immunosuppression may be one way to help reduce the severity of hypertension in transplant recipients. Conversion to sirolimus, which is not associated with increases in blood pressure, may also be an alternative to the calcineurin inhibitors in patients with difficult-to-treat hypertension. Corticosteroid taper or withdrawal are effective strategies for lowering blood pressure, but are not warranted in all clinical situations.

Antihypertensive Agents

There is no single class of antihypertensive medications recognized as the ideal agent. Numerous factors must be considered when determining appropriate treatment for a given patient, including the safety and efficacy data of the available agents, patient-specific situations, and potential comorbidities, and medication cost. A large majority of patients often require multiple medications to achieve their goal blood pressure. This conclusion is supported by the recommendations of JNC-VII, where combination therapy is regarded as an appropriate first-line therapy.

^-Blockers and thiazide diuretics have proven benefits in reducing cardiovascular disease-associated morbidity and mortality59 Tolerability permitting, these agents are to be considered first-line therapies in most transplant recipients. The angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) have definite benefits in patients with nephropathy and are believed to have renoprotective effects in most patients. However, due to their ability to cause an initial increase in serum creatinine, these agents should be used cautiously when used in combination with the calcineurin inhibitors. The dihydropyridine calcium channel blockers have demonstrated an ability to reverse the nephrotoxicity associated with cyclosporine and tacrolimus. In general, antihypertensive therapy should focus on agents with proven benefit in reducing the pro59gression of cardiovascular disease and should be chosen on a patient-specific basis.5


G Hyperlipidemia is seen in up to 60% of heart, lung, and renal transplant patients and greater than 30% of liver transplant patients.68- 0 As a result of elevated cholesterol levels, transplant recipients are not only at an increased risk of atherosclerotic events, but emerging evidence also shows an association between hyperlipidemia and allograft vasculopathy.70 Hyperlipidemia, along with other types of cardiovascular disease, is now one of the primary causes of morbidity and mortality in long-term transplant survivors.71

Elevated cholesterol levels in transplant patients are due to a culmination of factors such as age, genetic disposition, renal dysfunction, DM, proteinuria, body weight, and immunosuppressive therapy. Many of the immunosuppressive agents can produce elevations in serum lipid levels.


© Lowering cholesterol has shown to significantly decrease severe rejection and

transplant vasculopathy, and improve 1-year survival in heart transplant recipients. Although these results cannot be extrapolated to the other transplant populations, they do demonstrate the potential benefits of aggressive cholesterol lowering in organ transplant recipients. Due to high prevalence of cardiovascular disease among organ transplant recipients, most health care practitioners consider these patients to fall in the highest risk category for lipid lowering as established by the National Cholesterol Education Panel (NCEP) III guidelines. These guidelines call for a calculated LDL (LDL-C) target level of less than 100 mg/dL (2.59 mmol/L)73

Lifestyle Modifications

Generally, lowering cholesterol in patients begins with therapeutic lifestyle changes. These changes are initiated either alone or in conjunction with lipid-lowering drug therapy depending on baseline cholesterol levels and other risk factors. Therapeutic lifestyle changes entail a reduction in saturated fat and cholesterol intake and an in-

crease in moderate physical activity. As with hypertension, lifestyle modifications

alone rarely are effective enough to achieve a goal LDL-C level. Modifications of the immunosuppressive regimen and use of cholesterol-lowering medications are often warranted in this patient population.

Immunosuppressive Regimen Modifications

Tacrolimus has shown the propensity to cause less severe hyperlipidemia when compared to cyclosporine. Conversion from cyclosporine-based immunosuppression to tacrolimus-based immunosuppression may be one way to counteract this disease in 70

transplant recipients.

In past studies, steroid withdrawal in renal transplant patients did lower total cholesterol by 17% and LDL cholesterol by 16%; unfortunately, an 18% decrease in high-

density lipoproteins (HDL) levels was also noted in these patients. Cholesterol-Lowering Agents

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins, are considered to be first-line therapy for hyperlipidemia in the general popula-

70 74-77

tion. ' However, there is some uncertainty about the pathogenesis of cardiovascular disease in transplant recipients and whether statin therapy will have similar effectiveness in organ transplant recipients. Statins have shown definite advantages when used in heart transplantation, including a reduction in LDL-C and major adverse cardiac outcomes (MACE), as well as an apparent cardioprotective effect. In renal transplant recipients, statins are known to lower LDL-C levels and reduce the incidence of some cardiac events, however, the ability to lower MACE may not be evident in this patient population. Despite these mixed results, statins are still considered the

primary therapeutic option for hyperlipidemia in all organ transplant recipients.

Fibric acid derivatives are an excellent choice for lowering triglycerides, but are not as effective as statins at lowering the LDL-C.70 These agents may play a role in conjunction with statins in patients with both elevated cholesterol and triglycerides. Nicotinic acid is very effective at improving the lipid panel, with excellent results in lowering LDL-C, as well as increasing HDL. However, patient tolerability issues are of concern with this agent. The bile acid sequestrants should be avoided in organ transplant recipients due to their high incidence of GI adverse events, as well as their propensity for pharmacokinetic DDIs with the immunosuppressants. Future studies are needed to establish ideal regimens involving the antihyperlipidemic and immun-osuppressive medications in order to decrease morbidity and mortality, and ultimately prevent cardiovascular events.70

New-Onset DM After Transplantation

© New-onset DM after transplantation (NODAT) is a serious complication that is often underestimated by transplant practitioners. 8 Kasiske and colleagues attempted to quantify the cumulative incidence of NODAT in renal transplant recipients and found that 8.3% of patients developed NODAT at 3 months post-transplant, 12.9%

at 12 months, and 22.3% at 36 months. Even more alarming is that recent studies have revealed an overwhelming prevalence of impaired glucose tolerance, which is

also accepted as a risk factor for long-term morbidity and mortality. NODAT is associated with increases in cardiovascular events, with an approximately 22% higher risk of mortality. Patients with NODAT are also more likely to suffer acute rejection episodes and infectious complications than patients without this complication.78


© NODATprevention mainly consists of identifying patients at risk pretransplant

and controlling modifiable risk factors both pre- and post-transplantation. The major modifiable risk factors are choice of immunosuppressive therapy and body mass index. For example:

• Immunosuppressive medications: steroid minimization and possibly withdrawal are effective strategies for the prevention of NODAT. Also, patients with worsening blood sugars after transplantation who are receiving tacrolimus may benefit from

conversion to cyclosporine.

• Body mass index: a reduction in body weight is always recommended in obese pa-

tients prior to the transplant procedure to help lower their NODAT risks. Treatment

Lifestyle modifications are always in order in patients who have developed or those who are at increased risk of developing NODAT.78 Insulin therapy and oral hy-poglycemic agents are often utilized in those patients where lifestyle modifications alone have not controlled blood glucose. Please refer to the chapter on DM for proper instruction on choosing the appropriate treatment regimens in patients with DM.

Neoplasia Skin Cancer

Skin cancer remains the most common malignancy after organ transplantation. The rate of skin cancers occurs from as low as 3.4-fold (melanoma) up to as high as 84-fold

(Kaposi's sarcoma) higher in organ transplant recipients when compared to the gen-

eral population. The incidence of these types of cancers increases with time post-transplant, with one study showing a prevalence rate of 35% among patients within 10 years after transplant.80 More alarming than the high prevalence is the activity of these cancers in the patient on maintenance immunosuppression. Skin cancers in transplant

recipients tend to grow more rapidly and are more likely to metastasize.

The most common risk factors for skin cancer development after transplant include increased age, excessive UV light exposure, high degree of immunosuppression, Fitzpatrick skin types I, II, and III, history of skin cancers, and infection by human papillomavirus.7

It is of the utmost importance that transplant practitioners be vigilant about educating

their patients about excessive exposure to the sun. Patients should be warned about the risk of skin cancer and be advised on simple methods to limit their risk:

• Use of protective clothing (i.e., long-sleeved shirts and long pants, dark-colored clothing)

• Use of sunscreen daily that is applied to all sun-exposed skin • Sun protection factor (SPF) 30 or higher is recommended

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