Follow-up of Kidney Graft Recipients With Cyclosporine-Associated Hemolytic-Uremic Syndrome and Thrombotic Microangiopathy

Bren, Andrej; Pajek, Jernej; Grego, K; Buturović, J; Ponikvar, Rafael; Lindič, Jelka; Knap, Bojan; Vizjak, Alenka; Ferluga, D; Kandus, A.

doi:10.1016/j.transproceed.2005.02.112

Cited by 41 publications

(30 citation statements)

References 7 publications

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“…[8] In the study of Bren and colleagues, blood CsA level ranged between 165-750 ng/mL in post-kidney transplant hemolytic uremic syndrome. [11] Roberts and colleagues also reported a CsA level greater than 480 ng/ mL in renal transplant recipients with CsA-induced TMA. [12] However, the possibility of CsA-induced TMA exists even with lower doses of CsA because of the potential idiosyncratic reactions.…”

Section: Discussionmentioning

confidence: 95%

Thrombotic Microangiopathy in the Early Post-Renal Transplant Period

et al. 2008

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Section: Discussionmentioning

confidence: 95%

Thrombotic Microangiopathy in the Early Post-Renal Transplant Period

et al. 2008

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“…Its use is associated with significant nephrotoxicity, ranging from acute vasoconstriction to chronic tubular and vascular injury, and less commonly, thrombotic microangiopathy (TMA). (AlMassarani et al, 2008;Al-Nouri et al, 2015;Bren et al, 2005;Cortina et al, 2015;Jiang et al, 2014;Lin et al, 2003;Naesens et al, 2009;Rodrigues-Diez et al, 2016;Zarifian et al, 1999) CNI toxicity negatively impacts allograft survival and may be a contributory factor to the lack of improvement in long-term allograft survival which has remained stagnant over the last few decades.…”

Section: Calcineurin Inhibitor Toxicity Impacts On Long-term Allografmentioning

confidence: 99%

“…(Al-Nouri et al, 2015;Bren et al, 2005;Cortina et al, 2015;Lin et al, 2003;Ponticelli, 2007) TMA associated with the use of CNIs can present with a clinical picture resembling acute hemolytic-uremic syndrome, which in severe cases can lead to transplant allograft loss. (Ali et al, 2013;Caires et al, 2012;Furmanczyk et al, 2009;Gray and Ameduri, 2016;Parissis et al, 2010;Said et al, 2010) However, TMA can also occur without overt systemic clinical manifestations.…”

Section: Calcineurin Inhibitor Use Associated With Thrombotic Microanmentioning

confidence: 99%

“…(Al-Nouri et al, 2015;Ali et al, 2013;Bren et al, 2005;Caires et al, 2012;Cortina et al, 2015;Furmanczyk et al, 2009;Gray and Ameduri, 2016;Lin et al, 2003;Parissis et al, 2010;Ponticelli, 2007;Said et al, 2010;Zarifian et al, 1999) The primary aim of this thesis is to examine whether cyclosporine exposure lead to complementmediated endothelial cell injury and to elucidate the mechanism by which complement dysregulation is induced. To achieve this, we used an in vitro model of disease that utilizes human blood outgrowth endothelial cells (BOEC), because they are an endothelial progenitor cell that can be isolated from patients.…”

Section: Complement Dysregulation Is Central To Thrombotic Microangiomentioning

confidence: 99%

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Calcineurin inhibitor-induced endothelial cell injury – A role for complement

Teoh

Riedl

Bruno

et al. 2018

Molecular Immunology

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Calcineurin inhibitor (CNI) use significantly reduced acute rejection rates and revolutionized early allograft and patient outcomes post-transplantation. However, known nephro-and vascular toxicity preclude its use and contribute to chronic allograft injury, negatively impacting longer term outcomes. Evolving evidence suggest a role for complement dysregulation in the pathogenesis of CNI-induced endothelial injury. In an in vitro model using Blood Outgrowth Endothelial Cells (BOEC) isolated from healthy donors and a donor with a pathogenic MCP/CD46 variant, we showed that cyclosporine resulted in a dose and time dependent increase in complement deposition, enhanced by anti-CD59 sensitization. We showed for the first time that MCP/CD46 deficient BOECs were genetically predisposed to be more susceptible to cyclosporine-induced complement deposition (multiple-hit hypothesis). We found complement factor H surface dysregulation to play a key role in cyclosporine-induced complement activation on BOEC surfaces, with glycocalyx abolishment possibly being the key mechanism leading to alternative pathway dysregulation.iii

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“…The main causative mechanism is endothelial damage due to ischemia caused by vasoconstriction; CI induced hyper-aggregation of platelets can also contribute as activation of prothrombotic factors 29,30 . Withdrawal of cyclosporine with conversion to tacrolimus or administration of sirolimus is usually a sufficient therapeutic measure 31,32 . In more severe cases, plasmapheresis, administration of intravenous immunoglobulins may be necessary and recently the positive effect of belatacept as a suitable maintenance immunosuppression in these patients has been reported 33 .…”

Section: Toxic Tubulopathymentioning

confidence: 99%

Calcineurin Inhibitor-Induced Renal Allograft Nephrotoxicity

Krejčí¹,

Tichý²,

Bachleda³

et al. 2010

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. The introduction of the calcineurin inhibitors (CI) cyclosporine and tacrolimus into immunosuppressive protocols initiated a new era in organ transplantation with excellent short-term graft survival. Nevertheless, the chronic nephrotoxicity of these drugs represents a significant adverse factor limiting their long-term use. Patients treated with a CI can be at risk for developing renal failure and this problem is especially pronounced in patients after renal transplantation.Methods and Results. In a review paper we summarize the clinical aspects, histological manifestations and pitfalls of diagnostics of acute and chronic CI nephrotoxicity in patients after kidney transplantation. We look in detail at the disputed relationship between blood concentrations of cyclosporine and tacrolimus and histological manifestation of toxicity and summarize data showing that for toxic effects, local renal exposure to CI and their metabolites can play a more significant role than systemic exposure. We also include recent views on the pathophysiologic and molecular mechanisms underlying these changes; factors influencing local susceptibility to CI nephrotoxicity are discussed, including variability of expression and activity of P-glycoprotein and cytochrome P450. Last but not least we summarize our own experience with clinically manifest and subclinical forms of nephrotoxicity and their impact on the progression of chronic graft changes.Conclusions. Owing to their unique effects, CI remain the cornerstone of most immunosuppressive protocols for renal transplantation. Together with optimization of local kidney exposure to CI and their metabolites, efforts to reduce systemic levels as much as possible are the most important preventive measure for reducing toxic renal graft damage.

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Follow-up of Kidney Graft Recipients With Cyclosporine-Associated Hemolytic-Uremic Syndrome and Thrombotic Microangiopathy

Cited by 41 publications

References 7 publications

Thrombotic Microangiopathy in the Early Post-Renal Transplant Period

Thrombotic Microangiopathy in the Early Post-Renal Transplant Period

Calcineurin inhibitor-induced endothelial cell injury – A role for complement

Calcineurin Inhibitor-Induced Renal Allograft Nephrotoxicity

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