Cardiovascular Disease in Kidney Transplant Recipients

Leave No Stone Unturned

Steven Van Laecke; Daniel Abramowicz

Disclosures

Nephrol Dial Transplant. 2019;34(5):727-730. 

In This Article

CVD in KTRs: The Need to Move Away From a General Population-based Approach

As explicitly pointed out by the authors, one of the main concerns in KTRs remains the ongoing exposure to pre-existing or incident de novo risk factors, which explains the high prevalence of hypertension and dyslipidaemia in KTRs.[1] Therapeutic nihilism in treating transplant recipients might arise from the small number of RCTs, which target hard endpoints such as mortality and CVD in CKD patients, let alone KTRs.[6] Therefore, clinicians might wonder which therapeutic standards are applicable to their patients that no longer carry the burden of the uraemic milieu but still have the heritage of a sometimes long-lasting CKD history. Questions remain valid concerning the external validity of the evidence generated in the general population. The role of established antidiabetic drugs such as metformin or of novel promising drugs such as sodium-glucose transport-2 inhibitors remains undefined in the treatment approach of post-transplant diabetes mellitus (PTDM), although some studies are ongoing (https://clinicaltrials.gov/ct2/results? cond=kidney+transplantation&term=SGLT2+inhibitors&cntry=&state=&city=& dist=).

Recognized cardiovascular risk factors such as smoking, which have been extensively examined in the general population, remain underemphasized before and after transplantation despite a potential for synergistic, multifaceted and protracted toxicity.[7] Thus, although guidelines recommend to stop smoking before transplantation, smoking cessation programmes remain underused, resulting into a much too high prevalence of smoking after transplantation.[1,8,9] Both pharmacological and app-based options for smoking cessation, which have been extensively explored in the general population, were not separately evaluated in KTRs.[10,11] Nevertheless, KTRs, with their continuous exposure to immunosuppressive drugs, have the most stringent need to quit smoking.[7] Rangaswami et al.[1] are absolutely right in summarizing the necessary multidisciplinary approach for smoking cessation in this report, although the applicability and relative superiority of the proposed individual actions in KTRs is uncertain. Also, the effect of lifestyle measures, the implementation of exercise programmes and even the avoidance of physical inactivity are expected to be beneficial, although the necessary studies to support this premise are still lacking.

In some instances, KTRs behave seemingly differently than the general population. Renin–angiotensin–aldosterone system inhibitors, for instance, do not improve cardiovascular outcome nor renal survival,[12] rendering their risk–benefit profile—bearing the risk of hyperkalaemia in mind—less favourable than in people with CKD and especially those with diabetes and/or proteinuria. This translates into a recommendation in support of calcium channel blockers as the initial antihypertensive drug of choice in KTRs.[1] Also, the effects of β-blockers and mineralocorticoid receptor antagonists on cardiovascular outcome in KTRs remains undefined.[13] Quite the opposite, in some instances guidelines are in strong support of a treatment (statins) to prevent CVD in KTRs, irrespective of the presence of a risk factor (dyslipidaemia) and largely based on an extension study of a single trial.[14] This emphasizes that the present and future in-depth evaluation of therapeutic options to decrease cardiovascular morbidity and mortality should be performed specifically among KTRs. Unanswered questions also render the cardiovascular screening of potential KTRs particularly awkward. For instance, convincing data are still lacking showing that a more scrutinized screening of coronary artery disease by coronary arteriography will affect outcomes after transplantation.[1]

All in all, cardiovascular status did not draw much attention from researchers, who still tend to focus on mostly short-term graft outcome or rejection. This is remarkable as the rejection rate with currently available immunosuppressive drug regimens is historically low and graft outcome has improved despite the increasing proportion of lower-quality organs.[15] Moreover, death with functioning graft has become a major cause of graft failure and this is not expected to change in the future.

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