The Forgotten Vasculature: How Microvascular Rarefaction in Chronic Kidney Disease Shapes Kidney Transplant Outcomes

Abstract

Introduction: Systemic microvascular rarefaction and dysfunction are important hallmarks of chronic kidney disease (CKD), and are associated with clinical outcomes post kidney transplantation. This systematic review synthesizes the evidence linking microvascular health in CKD to post-transplant graft adaptation, function, and survival.

Methods: We conducted a comprehensive systematic review of 80 studies, including systematic reviews, meta-analyses, randomized controlled trials, and observational studies. Screening was based on predefined criteria focusing on CKD patients or kidney transplant recipients, microvascular assessment methods, and transplant-related outcomes. Data were extracted on assessment methodologies, microvascular abnormalities in CKD, recipient microvascular status, graft outcomes, post-transplant hypertension, and interventions affecting the microvasculature.

Results: Microvascular abnormalities, such as capillary rarefaction, endothelial dysfunction, and reduced reactivity, are well-known outcomes of CKD and worsen with disease progression. These changes can be seen by various methods such as retinal imaging, near-infrared spectroscopy, and Doppler ultrasound. Pre-transplant microvascular status, particularly elevated renal resistive index (RI >0.85), is a strong predictor of adverse outcomes, including graft failure and mortality (Kolonko et al., 2012). Post-transplant, microvascular health is affected by immunosuppressive regimens, with calcineurin inhibitors exacerbating dysfunction. Post-transplant hypertension (>90% prevalence) is closely linked to microvascular dysfunction and sympathetic overactivity. Interventions such as calcium channel blockers, renin-angiotensin system inhibitors, aerobic exercise, and targeted therapies (e.g., eculizumab) show promise in improving microvascular parameters and graft outcomes.

Discussion: The evidence consistently demonstrates that microvascular dysfunction is a systemic marker of cardiovascular and renal risk in CKD that persists after transplantation, affecting graft adaptation. The heterogeneity in assessment methods and study designs presents challenges, but the prognostic value of microvascular evaluation is clear. Calcineurin inhibitor-free regimens and non-pharmacological interventions like exercise training improve microvascular function and may enhance long-term prognosis.

Conclusion: Microvascular rarefaction and dysfunction are fundamental to CKD pathophysiology and have profound implications for kidney transplantation outcomes. Integrating microvascular assessment into pre- and post-transplant care could improve risk stratification and guide personalized therapeutic strategies. Future research should focus on standardizing assessment methods and conducting randomized trials of microvascular-targeted interventions.