Association of High Pretransplant sIL-6R Plasma Levels with Acute Tubular Necrosis in Kidney Graft Recipients

Sadeghi, Mahmoud; Daniel, Volker; Naujokat, Cord; Mehrabi, Arianeb; Opelz, Gerhard

doi:10.1097/01.tp.0000226076.04938.98

Cited by 18 publications

(18 citation statements)

References 26 publications

(28 reference statements)

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“…High plasmatic levels of IL-6 production and urinary IL-6 concentration were associated with acute rejection episodes (1,25). High pretransplant soluble IL-6 receptor levels were associated with an increased risk of developing acute tubular necrosis (1). After reperfusion, gene expression of IL-6, amongst other cytokines, was significantly upregulated in renal tubuli compared to biopsies taken after cold ischemia (26).…”

Section: Il-6 Tnf-a Tgf-beta Platelet-derived Growth Factor (Pdgf)mentioning

confidence: 85%

“…They are expressed in the renal proximal tubular epithelial cells (RPTEC) upon activation, which play a major role in renal injury and dysfunction (21,22) and an increased production of IL-6 by RPTEC was detected in vitro in response to many diverse stimuli (23 (24). High plasmatic levels of IL-6 production and urinary IL-6 concentration were associated with acute rejection episodes (1,25). High pretransplant soluble IL-6 receptor levels were associated with an increased risk of developing acute tubular necrosis (1).…”

Section: Il-6 Tnf-a Tgf-beta Platelet-derived Growth Factor (Pdgf)mentioning

confidence: 99%

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High Weight Differences between Donor and Recipient Affect Early Kidney Graft Function—A Role for Enhanced IL-6 Signaling

Gong

Klöpfel

Reutzel‐Selke

et al. 2009

American Journal of Transplantation

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The frequency of delayed function of kidney transplants varies greatly and is associated with quality of graft, donor age and the duration of cold ischemia time. Furthermore, body weight differences between donor and recipient can affect primary graft function, but the underlying mechanism is poorly understood. We transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. Twenty-four hours posttransplantation, serum creatinine levels in H-WD recipients were significantly higher compared to L-WD recipients indicating impaired primary graft function. This was accompanied by upregulation of IL-6 transcription and increased tubular destruction in grafts from H-WD recipients. Using DNA microarray analysis, we detected decreased expression of genes associated with kidney function and an upregulation of other genes such as Cyp3a13, FosL and Trib3. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and cause tubular damage, whereas immediate neutralization of IL-6 receptor signaling in H-WD recipients rescued primary graft function with well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lowerweight donors could be used to improve primary graft function. † Both the authors contributed equally to this work.

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Section: Il-6 Tnf-a Tgf-beta Platelet-derived Growth Factor (Pdgf)mentioning

confidence: 85%

Section: Il-6 Tnf-a Tgf-beta Platelet-derived Growth Factor (Pdgf)mentioning

confidence: 99%

High Weight Differences between Donor and Recipient Affect Early Kidney Graft Function—A Role for Enhanced IL-6 Signaling

Gong

Klöpfel

Reutzel‐Selke

et al. 2009

American Journal of Transplantation

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“…Several studies have demonstrated that serum levels of sIL‐6R may offer prognostic information. The role of sIL‐6R as a prognostic factor has been recognized in multiple myeloma, kidney transplant, and primary hyperparathyroidism (25–27).…”

Section: Discussionmentioning

confidence: 99%

Serum interleukin‐6 receptor in polymyalgia rheumatica: A potential marker of relapse/recurrence risk

Pulsatelli¹,

Boiardi²,

Pignotti³

et al. 2008

Arthritis & Rheumatism

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Objective. To investigate the modulation of systemic levels of soluble interleukin-6 receptor (sIL-6R) and soluble gp130 (sgp130) in untreated and treated polymyalgia rheumatica (PMR) patients during a followup period of at least 24 months in order to evaluate the relationship of these molecules with clinical outcome and their feasibility to provide a prognostic tool in clinical practice. Methods. We analyzed sIL-6R and sgp130 serum levels in 93 PMR patients, and 46 age-matched normal controls, at disease onset and at 1, 3, 6, 12, and 24 months of followup during corticosteroid therapy by enzyme-linked immunosorbent assay. Results. No difference in sIL-6R and sgp130 levels was observed between PMR patients and normal controls at disease onset or during followup. A significant correlation was found between the number of relapses and sIL-6R concentrations at baseline and after 1, 3, and 12 months of therapy. No correlation was found between sgp130 levels and the number of relapses. Cox multivariate analysis indicated that the best model for predicting relapses was identified by sIL-6R levels and the hemoglobin value at baseline. We found that high sIL-6R levels combined with low hemoglobin values resulted in a 10.1-fold increased risk of relapse. Conclusion. Our data support the identification of a potential prognostic marker of PMR outcome that might have important implications in clinical practice. Because targeting sIL-6R with blocking antibodies has proven useful in other rheumatic disorders, our results could suggest the opportunity to evaluate sIL-6R-blocking treatment in patients with PMR and elevated levels of sIL-6R at disease onset.

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“…Other studies documented the association of recipient pretransplant levels of different cytokines as the soluble interleukin 6 receptor (sIL-6R)[25] and the low soluble gp130 with post-transplant DGF.…”

Section: Biomarkers Of Ischemia-reperfusion Syndrome and Dgfmentioning

confidence: 99%

Biomarkers in renal transplantation: An updated review

Salvadori

Tsalouchos

2017

WJT

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Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasive indicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment. Biomarkers predicting or diagnosing acute rejection either cell-mediated or antibody-mediated allow a risk stratification of the recipient, a prompt diagnosis in an early phase when the histology is still unremarkable. The kidney solid organ response test detects renal transplant recipients at high risk for acute rejection with a very high sensitivity and is also able to make diagnosis of subclinical acute rejection. Other biomarkers are able to detect chronic allograft dysfunction in an early phase and to differentiate the true chronic rejection from other forms of chronic allograft nephropathies no immune related. Finally biomarkers recently discovered identify patients tolerant or almost tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive therapy.

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Association of High Pretransplant sIL-6R Plasma Levels with Acute Tubular Necrosis in Kidney Graft Recipients

Abstract: High pretransplant sIL-6R plasma levels are associated with an increased risk of ATN and might contribute to the development of ATN early posttransplant. Our data suggest that preactivation of the recipient's immune system increases the risk of ATN.

Cited by 18 publications

References 26 publications

High Weight Differences between Donor and Recipient Affect Early Kidney Graft Function—A Role for Enhanced IL-6 Signaling

High Weight Differences between Donor and Recipient Affect Early Kidney Graft Function—A Role for Enhanced IL-6 Signaling

Serum interleukin‐6 receptor in polymyalgia rheumatica: A potential marker of relapse/recurrence risk

Biomarkers in renal transplantation: An updated review

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