Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients: Perspectives on Long-Term Outcomes

Abstract

After decades of pioneering and improvement, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Where focus has traditionally been on surgical techniques and immunosuppressive treatment with prevention of rejection and infection in relation to short-term outcomes, nowadays, so many people are long-living with a transplanted kidney that lifestyle, including diet and exposure to toxic contaminants, also becomes of importance for the kidney transplantation field. Beyond hazards of immunological nature, a systematic assessment of potentially modifiable—yet rather overlooked—risk factors for late graft failure and excess cardiovascular risk may reveal novel targets for clinical intervention to optimize long-term health and downturn current rates of premature death of kidney transplant recipients (KTR). It should also be realized that while kidney transplantation aims to restore kidney function, it incompletely mitigates mechanisms of disease such as chronic low-grade inflammation with persistent redox imbalance and deregulated mineral and bone metabolism. While the vicious circle between inflammation and oxidative stress as common final pathway of a multitude of insults plays an established pathological role in native chronic kidney disease, its characterization post-kidney transplant remains less than satisfactory. Next to chronic inflammatory status, markedly accelerated vascular calcification persists after kidney transplantation and is likewise suggested a major independent mechanism, whose mitigation may counterbalance the excess risk of cardiovascular disease post-kidney transplant. Hereby, we first discuss modifiable dietary elements and toxic environmental contaminants that may explain increased risk of cardiovascular mortality and late graft failure in KTR. Next, we specify laboratory and clinical readouts, with a postulated role within persisting mechanisms of disease post-kidney transplantation (i.e., inflammation and redox imbalance and vascular calcification), as potential non-traditional risk factors for adverse long-term outcomes in KTR. Reflection on these current research opportunities is warranted among the research and clinical kidney transplantation community.

Serum uric acid is associated with increased risk of posttransplantation diabetes in kidney transplant recipients: a prospective cohort study

“…Although kidney transplantation aims to recover kidney function, it incompletely mitigates mechanisms of disease such as inflammation, oxidative stress and impaired metabolic homeostasis [16]. In the current study, we found that most patients had hyperuricemia, which is in line with previous studies [21,50].…”

“…Also similar to type 2 diabetes, oxidative stress and chronic low-grade inflammation have been proposed to play an important role in pathophysiological mechanisms underlying development of PTDM in KTR [13][14][15]. Although kidney transplantation aims to restore kidney function, it incompletely abolishes ongoing chronic low-grade inflammation, oxidative stress and impaired metabolic homeostasis [16]. In outpatient KTR, several factors inherent to this clinical setting, including chronic use of calcineurin inhibitors and corticosteroid therapy, and well-documented elevation of serum uric acid (SUA), contribute to perpetuate redox imbalance and low grade of systemic inflammation [16][17][18][19][20], all converging to resemblance of the type 2 diabetes milieu.…”

Aorto-Iliac Artery Calcification and Graft Outcomes in Kidney Transplant Recipients

“…This risk reduction, pre- and post-transplantation, could be achieved by focusing on prevention of new-onset diabetes, preventive measures for mineral and bone disorders, and reduction of hyperlipidaemia and hypertension [ 34 ]. Medical strategies in line with these focus points are age-adapted immunosuppressive therapy, stringent use of statins and antihypertensive medication, and general lifestyle interventions [ 35 , 36 , 37 ].…”

Neutrophil-to-lymphocyte ratio in relation to the risk of all-cause mortality and cardiovascular events in patients with chronic kidney disease: a systematic review and meta-analysis

“…The combination of elevated neutrophil counts and low levels of lymphocytes, detected as a single comprehensive marker of inflammation can provide more information. Previous studies mentioned that treatment to reduce vascular calcification patients with renal disease may offset the excessive risk of cardiovascular disease [41,42]. NLR outperformed other white blood cells in predicting both short-and long-term mortality.…”