Abstract
Despite advances in post-transplant management, the long-term survival rate of kidney grafts and patients has not improved as approximately forty percent of transplants fails within ten years after transplantation. Both immunologic and non-immunologic factors contribute to late allograft loss. Chronic kidney transplant rejection (CKTR) is often clinically silent yet progressive allogeneic immune process that leads to cumulative graft injury, deterioration of graft function. Chronic active T cell mediated rejection (TCMR) and chronic active antibody-mediated rejection (ABMR) are classified as two principal subtypes of CKTR. While significant improvements have been made towards a better understanding of cellular and molecular mechanisms and diagnostic classifications of CKTR, lack of early detection, differential diagnosis and effective therapies continue to pose major challenges for long-term management. Recent development of high throughput cellular and molecular biotechnologies has allowed rapid development of new biomarkers associated with chronic renal injury, which not only provide insight into pathogenesis of chronic rejection but also allow for early detection. In parallel, several novel therapeutic strategies have emerged which may hold great promise for improvement of long-term graft and patient survival. With a brief overview of current understanding of pathogenesis, standard diagnosis and challenges in the context of CKTR, this mini-review aims to provide updates and insights into the latest development of promising novel biomarkers for diagnosis and novel therapeutic interventions to prevent and treat CKTR.
Highlights
Chronic kidney transplant rejection (CKTR) is characterized by progressive decrease of renal graft function that starts to manifest at one-year after the transplantation and usually accompanied by hypertension and proteinuria [1]
B cell deficiency resulted in reduced transplant glomerulopathy, decreased microvascular inflammation, reduced macrophage infiltration and interferon g (IFNg) transcripts in the allograft [14], which underscores the importance of B cells in the pathogenesis of antibodymediated rejection (ABMR)
It has been shown in biopsyproven chronic active ABMR cases that T cells and macrophages are the dominant infiltrating cell types in glomerulus, whereas B cells are frequently observed in the tubulointerstitial compartment, indicating that both T cells and macrophages play a pivotal role in renal chronic ABMR [18]
Summary
Chronic kidney transplant rejection (CKTR) is characterized by progressive decrease of renal graft function that starts to manifest at one-year after the transplantation and usually accompanied by hypertension and proteinuria [1]. Recent advances in high-throughput cellular and molecular biotechnologies have allowed for in-depth analyses of cellular and molecular processes and deconvolutions of mechanisms underlying CKTR and have led to identification and validation of new molecular and cellular biomarkers through non-invasive or minimal-invasive approaches. The discovery of these biomarkers holds tremendous promise for early detection and development of promising novel therapies for improvement of kidney transplant outcomes. This review will first provide a brief summary on current understanding of pathogenesis and standard mothed challenges for the diagnosis of CKTR, and focus on more in-depth discussions to the area of biomarker discovery and novel therapeutic interventions to improve long term transplant outcome
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