Abstract
Several studies have assessed clinical outcomes after steroid withdrawal (SW) in kidney transplant (KT) recipients, but little is known about its potential impact on lymphocyte subpopulations. We designed a prospective study to evaluate the long-term impact of SW in 19 KT recipients compared to 16 KT recipients without changes in immunosuppression (steroid maintenance, SM). We assessed renal function, presence of HLA antibodies and peripheral blood lymphocyte subsets at time of inclusion, and 3, 12 and 24 months later. The immunophenotype of 20 healthy subjects was also analyzed. Serum creatinine and proteinuria remained stable in SW and SM patients. SW did not associate with generation of de novo donor-specific antibodies. SW patients showed decreases in T-lymphocytes (p < 0.001), and in the CD4+ T cell subpopulation (p = 0.046). The proportion of B-lymphocytes (p = 0.017), and both naïve and transitional B cells increased compared to SM patients (p < 0.001). Changes in B cell subsets were detected 3 months after SW and persisted for 24 months. No changes were observed in NK cells related to steroid withdrawal. SW patients displayed significant changes in peripheral T and B cell subsets, transitioning to the phenotype detected in healthy subjects. This may be considered as a maintained positive effect of SW previously unnoticed.
Highlights
Kidney transplantation is the best therapeutic option for patients with end-stage renal disease, given the improvement in quantity and quality of life compared with long-term dialysis[1,2,3,4]
Steroid avoidance has been associated with increased risk of acute rejection[20,21,22,23,24], there is growing evidence that Steroid withdrawal (SW) may offer several advantages in low risk kidney transplant (KT) patients[22]
Our results support that SW can be accomplished in immunologically low-risk KT patients without compromising renal function the first two years after steroid withdrawal
Summary
Kidney transplantation is the best therapeutic option for patients with end-stage renal disease, given the improvement in quantity and quality of life compared with long-term dialysis[1,2,3,4]. Acute rejection in low-immunological risk KT recipients is below 15% with current immunosuppression, based on calcineurin inhibitors (CNI), antiproliferative agents such as mycophenolic acid (MPA) and steroids, and rarely produces graft-loss[8,9]. SW is not generalized, it is applied to selected immunological low-risk KT recipients[25] or in children, where advantage in growth is of utmost importance[26] The lack of both long-term follow-up studies and evaluation of this treatment strategy on the development of chronic www.nature.com/scientificreports/. A recent report that studies the association between potential tolerance biomarkers and immunosuppression, included the short-term results of a small cohort of patients who underwent steroid withdrawal early after KT for clinical reasons. We designed an exploratory prospective study to analyze the long-term influence of SW on immunological biomarkers
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