Updated principles and clinical caveats in the management of infection in renal transplant recipients

Parasuraman, Ravi; Samarapungavan, Dilip; Venkat, K. K.

doi:10.1016/j.trre.2009.09.001

Cited by 12 publications

(13 citation statements)

References 20 publications

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“…(20)(21)(22)(23) Although this appears to be a result, at least in part, of vascular and atherogenic effects of FGF23, (24,25) infection is also a key cause of mortality in CKD patients. Aside from the increased risk of infection due to immunosuppressive therapies in CKD patients undergoing kidney transplantation, (26) CKD itself is a state of acquired immune deficiency. (27) The incidence of bacterial infections in CKD dialysis patients is higher than in the general population (28,29) and infections are the second leading cause of death in such patients.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes

Bacchetta

Sea

Chun

et al. 2012

Journal of Bone and Mineral Research

171

122

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Vitamin D is a potent stimulator of monocyte innate immunity, with this effect being mediated via intracrine conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25(OH)2D). In the kidney synthesis of 1,25(OH)2D is suppressed by fibroblast growth factor 23 (FGF23), via transcriptional suppression of the vitamin D-activating enzyme 1α-hydroxylase (CYP27B1). We hypothesized that FGF23 also suppresses CYP27B1 in monocytes, with concomitant effects on intracrine responses to 1,25(OH)2D. Monocytes from healthy donor peripheral blood mononuclear cells (PBMCm) and from peritoneal dialysate effluent from kidney disease patients (PDm) were assessed at baseline to confirm the presence of mRNA for FGF23 receptors (FGFRs), with Klotho and FGFR1 being more strongly expressed than FGFR2/3/4 in both cell types. Immunohistochemistry showed co-expression of Klotho and FGFR1 in PBMCm and PDm, with this effect being enhanced following treatment with FGF23 in PBMCm but not PDm. Treatment with FGF23 activated MAP kinase (MAPK) and Akt pathways in PBMCm, demonstrating functional FGFR signaling in these cells. FGF23 treatment of PBMCm and PDm decreased expression of mRNA for CYP27B1. In PBMCm this was associated with downregulation of 25OHD to 1,25(OH)2D metabolism, and concomitant suppression of intracrine induced 24-hydroxylase (CYP24A1) and antibacterial cathelicidin (LL37). FGF23 suppression of CYP27B1 was particularly pronounced in PBMCm treated with interleukin-15 to stimulate synthesis of 1,25(OH)2D. These data indicate that FGF23 can inhibit extra-renal expression of CYP27B1 and subsequent intracrine responses to 1,25(OH)2D in two different human monocyte models. Elevated expression of FGF23 may therefore play a crucial role in defining immune responses to vitamin D and this, in turn, may be a key determinant of infection in patients with CKD.

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Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes

Bacchetta

Sea

Chun

et al. 2012

Journal of Bone and Mineral Research

171

122

View full text Add to dashboard Cite

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“…During the first post-transplant month, the most frequent categories of infection are related to technical problems (including surgical site infections), urinary tract infections, vascular access infections, and pulmonary infections [7]. During this period, more than 90% of all infections are caused by bacteria and fungi and opportunistic infections are unusual [7] [8]. The greatest risk of life-threatening infection occurs between 1 and 6 months post transplantation, when the effects of immunosuppressive therapy peak [8] [9].…”

Section: Introductionmentioning

confidence: 99%

“…During this period, most common infections are opportunistic agents: virus like cytomegalovirus (CMV), polyomaviruses (BKV), Epstein-Barr Virus (EBV) and fungi (aspergillus). These opportunistic infections can occur with minimal epidemiological exposure and are related to the immunosuppression [7] [10]. CMV is the most common opportunistic organism encountered during this period [6] [9], and causes significant morbidity by direct infection and its immunomodulatory effects predispose to other infectious complications [5].…”

Section: Introductionmentioning

confidence: 99%

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Infections Following Kidney Transplant in Children: A Single-Center Study

Fernandes¹,

Rocha²,

Costa³

et al. 2014

OJNeph

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“…Apart from the special context of patients with renal transplants [32], CKD by itself is a state of acquired immune deficiency involving both cellular and humoral immunity [33]. The incidence of bacterial infections in dialysis patients is higher than in the general population and acute infections (not only bacterial, but also viral and fungal) substantially contribute to the high hospitalization rates and mortality in patients with end-stage renal disease (ESRD) [34, 35].…”

Section: Introductionmentioning

confidence: 99%

Beyond mineral metabolism, is there an interplay between FGF23 and vitamin D in innate immunity?

2012

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Fibroblast Growth Factor 23 (FGF23) is an ‘endocrine’ FGF acting in the kidney as a phosphaturic hormone and a suppressor of active vitamin D, through an inhibition of the 1α hydroxylase and a stimulation of the 24 hydroxylase. Beyond its well-known effects on the bone/kidney/parathyroid axis and its deregulation during chronic kidney disease (CKD), recent evidence has revealed its direct systemic effects on cardiovascular health. In the meantime, studies have highlighted health implications for vitamin D inside and outside CKD that also extend beyond its classical actions on mineral homeostasis and bone metabolism: vitamin D has indeed been shown to exert pluripotent non-classical effects as a modulator of immune function in monocytes, mainly through the stimulation of the antimicrobial cathelicidin. The aim of this review is to provide new insights on the interplay between FGF23 and vitamin D in innate immunity in the context of CKD.

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Updated principles and clinical caveats in the management of infection in renal transplant recipients

Cited by 12 publications

References 20 publications

Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes

Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes

Infections Following Kidney Transplant in Children: A Single-Center Study

Beyond mineral metabolism, is there an interplay between FGF23 and vitamin D in innate immunity?

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