The Impact of Transforming Growth Factor-β1 Gene Polymorphism on End-Stage Renal Failure After Heart Transplantation

Wetering, Jacqueline van de; Weimar, C.H.E.; Balk, A. H. M. M.; Roodnat, Joke I.; Holweg, Cécile; Baan, Carla C.; Domburg, Ron T. van; Weimar, Willem

doi:10.1097/01.tp.0000250360.78553.5e

Cited by 36 publications

(28 citation statements)

References 30 publications

(37 reference statements)

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“…1,[10][11][12][13][14][15][16][17] However, the results were not consistent among the reported studies. Meta-analysis is a good way to summarize the available data to provide robust results.…”

Section: Introductioncontrasting

confidence: 47%

“…Of these, 169 papers were excluded according to the inclusion and exclusion criteria. Nine studies 1,[10][11][12][13][14][15][16][17] were enrolled in our analysis for the association between TGF-b1 gene +869 T/C, À800 G/A, À509 T/C and +915 G/C polymorphisms and CKD risk (Figure 1). Among the enrolled nine studies, six for +869 T/C, one for À800 G/A, three for À509 T/C and five for +915 G/C (Figure 1).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Six studies [12][13][14][15][16][17] were identified for the analysis of the association between TGF-b1 gene +869 T/C polymorphism and CKD risk (Table 1). Three studies 12,13,15 were performed in Caucasians, while three 14,16,17 in Asians.…”

Section: Study Characteristics For Tgf-b1 Gene +869 T/c Polymorphism mentioning

confidence: 99%

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Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

2015

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The association of transforming growth factor-b1 (TGF-b1) polymorphisms with the risk of chronic kidney diseases (CKD) remains elusive. We aimed to perform a meta-analysis to evaluate the relationship between TGF-b1 polymorphisms and the susceptibility to CKD. Association studies were searched according to a defined criteria using electronic databases. The strength of association between TGF-b1 polymorphisms and CKD risk was evaluated by odds ratio (OR) with the corresponding 95% confidence interval (CI). Nine case-control studies were identified. T allele at the +869 T/C polymorphism was associated with a lower risk of CKD in Asians (p ¼ 0.003). TT genotype at the +869 T/C polymorphism was associated with a lower risk of CKD in overall populations and Asians (p ¼ 0.007 and 510 À4

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Section: Introductioncontrasting

confidence: 47%

Section: Study Characteristicsmentioning

confidence: 99%

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Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

2015

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“…It was demonstrated that a TGF-␤ polymorphism in codon 10 was associated with renal function in both adult and pediatric heart transplant recipients (333)(334)(335), although a study in liver transplant recipients could not confirm this association (336). In renal transplantation, TGF-␤ variants in the recipient were not associated with renal allograft outcome in a very large study (337), but this could be explained by the possibility that local TGF-␤ production could depend more on donor genotype than on recipient genotype.…”

Section: Local Renal Susceptibility Factors For Cni Nephrotoxicitymentioning

confidence: 99%

Calcineurin Inhibitor Nephrotoxicity

Naesens

Kuypers²,

Sarwal³

2009

Clinical Journal of the American Society of Nephrology

1,266

1,000

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The use of the calcineurin inhibitors cyclosporine and tacrolimus led to major advances in the field of transplantation, with excellent short-term outcome. However, the chronic nephrotoxicity of these drugs is the Achilles' heel of current immunosuppressive regimens. In this review, the authors summarize the clinical features and histologic appearance of both acute and chronic calcineurin inhibitor nephrotoxicity in renal and nonrenal transplantation, together with the pitfalls in its diagnosis. The authors also review the available literature on the physiologic and molecular mechanisms underlying acute and chronic calcineurin inhibitor nephrotoxicity, and demonstrate that its development is related to both reversible alterations and irreversible damage to all compartments of the kidneys, including glomeruli, arterioles, and tubulo-interstitium. The main question-whether nephrotoxicity is secondary to the actions of cyclosporine and tacrolimus on the calcineurin-NFAT pathway-remains largely unanswered. The authors critically review the current evidence relating systemic blood levels of cyclosporine and tacrolimus to calcineurin inhibitor nephrotoxicity, and summarize the data suggesting that local exposure to cyclosporine or tacrolimus could be more important than systemic exposure. Finally, other local susceptibility factors for calcineurin inhibitor nephrotoxicity are reviewed, including variability in P-glycoprotein and CYP3A4/5 expression or activity, older kidney age, salt depletion, the use of nonsteroidal anti-inflammatory drugs, and genetic polymorphisms in genes like TGF-␤ and ACE. Better insight into the mechanisms underlying calcineurin inhibitor nephrotoxicity might pave the way toward more targeted therapy or prevention of calcineurin inhibitor nephrotoxicity.Clin J Am Soc Nephrol 4: 481-508, 2009. doi: 10.2215/CJN.04800908 T he introduction of the calcineurin inhibitor (CNI) cyclosporine in human kidney transplantation in the late 1970s revolutionized transplantation medicine, and made transplantation a preferable therapeutic intervention for end-stage renal diseases (1,2). In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered, and tacrolimus was used successfully in human liver, kidney, and heart allograft recipients (3,4). Currently, 94% of kidney transplant recipients are discharged after transplantation with a CNI-based immunosuppressive regimen (5).The immunosuppressive properties of cyclosporine and tacrolimus result from inhibition of calcineurin, a calcium-and calmodulin-dependent phosphatase (protein phosphatase 3 [PPP3C], formerly PP2B). Intracellularly, these completely different molecules bind to cyclophylin and FKBP12 for cyclosporine and tacrolimus, respectively (6 -9). The competitive binding of cyclosporine-cyclophylin and tacrolimus-FKBP12 complexes to calcineurin inhibits phosphatase activity of calcineurin. This inhibition then suppresses the transcription of IL-2 via inhibition of the dephosphorylation and impaired translocation of the nucl...

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“…Some other factors also represent risk for nephrotoxicity. Polymorphism of TGF-β in codon 10 was associated with progressive dysfunction of native kidneys in recipients of transplanted hearts treated with cyclosporine or tacrolimus 117 . In case of recipients of transplanted kidneys, this knowledge could help identify subjects who are more susceptible to CI nephrotoxicity because they received a graft from a carrier of this polymorphism and their immunosuppressive therapy could be adjusted accordingly.…”

Section: Local Factors Increasing Risk Of CI Toxicitymentioning

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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The Impact of Transforming Growth Factor-β1 Gene Polymorphism on End-Stage Renal Failure After Heart Transplantation

Cited by 36 publications

References 30 publications

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

Calcineurin Inhibitor Nephrotoxicity

Calcineurin Inhibitor-Induced Renal Allograft Nephrotoxicity

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