Primary care of the kidney transplant recipient

1. What are the risk factors for cardiovascular disease (CVD) in patients receiving a kidney transplant?

See Table 61.1 .

2. Are statins beneficial in patients receiving kidney transplant?

Statins are the treatment of choice, and studies show there is a benefit to using them in the kidney transplant population. The incidence of dyslipidemia is high in kidney transplant patients secondary to immunosuppressive medications, proteinuria, transplant dysfunction, and the higher incidence of metabolic syndrome and new-onset diabetes after transplant. Various trials have shown improved cardiovascular outcomes with the use of lipid therapy in patient with chronic kidney disease. The Assessment of Lescol in Renal Transplantation (ALERT) study aimed to see if statin therapy reduced the primary outcome of a major cardiovascular event, including cardiac death or a cardiac intervention. The trial did not reach this primary end point due to insufficient power but did show a reduction in nonfatal myocardial infarctions. In the extended follow-up of ALERT participants, the incidence of major adverse cardiac events was reduced in patients treated with statin; however, there was no difference in patient mortality or allograft function. A Cochrane Database review stated that statins may reduce cardiovascular events in kidney transplant patients. However, statin treatment had no clear benefit in affecting overall mortality, stroke rate, kidney function, and toxicity outcomes in kidney transplant patients.

Statin use is associated with decreased proteinuria, decreased C-reactive protein, and decreased interstitial fibrosis incidence in transplant protocol biopsies, all which may confer additional benefit.

3. Which patients should be started on a statin post transplant?

If a patient is younger than 30 years without established atherosclerotic cardiovascular disease (ACVD) or diabetes, then based on the benefit-to-risk ratio, the patient can start a statin. Ideally all kidney transplant patients older than 30 years should be considered for a statin.

4. How do we monitor lipid levels?

Patients should have an initial lipid profile checked. The American College of Cardiology recommends follow-up in 4 to 12 weeks for compliance and then at least yearly lipid profile checks. Kidney Disease Improving Global Outcomes (KDIGO) guidelines differ in that they do not require to repeat lipid profiles, because the indication for treatment is the higher cardiovascular risk, not the low-density lipoprotein (LDL) level.

5. What are the goals of lipid lowering therapy?

In the general population, target goals for the lipid profile have been replaced by the aim of therapy being to reduce ACVD risk. As mentioned earlier, KDIGO guidelines follow with this. However, although the KDIGO guidelines do not require repeat lipid profiles, it might be prudent to recheck a lipid profile after statin therapy to confirm compliance, response to therapy, and reevaluation ACVD risk.

6. Are there any risks of statin use in transplant recipients?

Yes. Most statins are metabolized by the same cytochrome P450 system (CP3A4) as calcineurin inhibitors (CNIs). As a consequence, CNIs (particularly cyclosporine) may accumulate in plasma and may be associated with a greater frequency of rhabdomyolysis. Data on tacrolimus are sparse, although pharmacokinetic studies on concomitant atorvastatin and tacrolimus therapy did not demonstrate significant interactions. Fluvastatin and pravastatin may be safer because they are metabolized through non-CP3A4 mechanisms. Fluvastatin, pravastatin, rosuvastatin, simvastatin, and atorvastatin have all been used in kidney transplant patients. These patients should be closely monitored for side effects from statin therapy. It is important to note that cyclosporine inhibits the metabolism of statins, and so the statin dose is usually kept low and not aggressively titrated up.