| MeSH term | MeSH ID | Detail |
|---|---|---|
| Inflammatory Bowel Diseases | D015212 | 9 associated lipids |
| Reperfusion Injury | D015427 | 65 associated lipids |
| Colitis | D003092 | 69 associated lipids |
| Colonic Neoplasms | D003110 | 161 associated lipids |
| Diabetes Mellitus, Type 1 | D003922 | 56 associated lipids |
| Diabetes Mellitus, Type 2 | D003924 | 87 associated lipids |
| Fatty Liver | D005234 | 48 associated lipids |
| Cataract | D002386 | 34 associated lipids |
| Diabetes Mellitus, Experimental | D003921 | 85 associated lipids |
| Body Weight | D001835 | 333 associated lipids |
tacrolimus
Tacrolimus is a lipid of Polyketides (PK) class. Tacrolimus is associated with abnormalities such as Renal glomerular disease. The involved functions are known as inhibitors, Fungicidal activity, Metabolic Inhibition, Excretory function and Dephosphorylation. Tacrolimus often locates in Hepatic, Mitochondrial matrix and Inner mitochondrial membrane. The associated genes with Tacrolimus are RHOA gene and BGN gene.
Cross Reference
Introduction
To understand associated biological information of tacrolimus, we collected biological information of abnormalities, associated pathways, cellular/molecular locations, biological functions, related genes/proteins, lipids and common seen animal/experimental models with organized paragraphs from literatures.
What diseases are associated with tacrolimus?
tacrolimus is suspected in Renal glomerular disease, Candidiasis, Mycoses, PARKINSON DISEASE, LATE-ONSET, Morphologically altered structure, Skin Diseases, Infectious and other diseases in descending order of the highest number of associated sentences.
Related references are mostly published in these journals:
- Antimicrob. Agents Chemother. (2)
- Am. J. Physiol. Renal Physiol. (1)
- Drug Metab. Dispos. (1)
- Others (1)
| Disease | Cross reference | Weighted score | Related literature |
|---|
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Possible diseases from mapped MeSH terms on references
We collected disease MeSH terms mapped to the references associated with tacrolimus
PubChem Associated disorders and diseases
What pathways are associated with tacrolimus
There are no associated biomedical information in the current reference collection.
PubChem Biomolecular Interactions and Pathways
Link to PubChem Biomolecular Interactions and PathwaysWhat cellular locations are associated with tacrolimus?
Visualization in cellular structure
Associated locations are in red color. Not associated locations are in black.
Related references are published most in these journals:
| Location | Cross reference | Weighted score | Related literatures |
|---|
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What functions are associated with tacrolimus?
Related references are published most in these journals:
| Function | Cross reference | Weighted score | Related literatures |
|---|
What lipids are associated with tacrolimus?
Related references are published most in these journals:
| Lipid concept | Cross reference | Weighted score | Related literatures |
|---|
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What genes are associated with tacrolimus?
Related references are published most in these journals:
| Gene | Cross reference | Weighted score | Related literatures |
|---|
What common seen animal models are associated with tacrolimus?
There are no associated biomedical information in the current reference collection.
NCBI Entrez Crosslinks
All references with tacrolimus
Download all related citations| Authors | Title | Published | Journal | PubMed Link |
|---|---|---|---|---|
| Kanda J et al. | Effects of the calcineurin inhibitors cyclosporine and tacrolimus on bone metabolism in rats. | 2018 | Biomed. Res. | pmid:29899188 |
| De Lemos-Bonotto M et al. | A systematic review and meta-analysis of second-line immunosuppressants for autoimmune hepatitis treatment. | 2018 | Eur J Gastroenterol Hepatol | pmid:29227329 |
| Huo T et al. | Preparation and comparison of tacrolimus-loaded solid dispersion and self-microemulsifying drug delivery system by in vitro/in vivo evaluation. | 2018 | Eur J Pharm Sci | pmid:29222025 |
| Gao CJ et al. | Oxymatrine Sensitizes the HaCaT Cells to the IFN-γ Pathway and Downregulates MDC, ICAM-1, and SOCS1 by Activating p38, JNK, and Akt. | 2018 | Inflammation | pmid:29218605 |
| Nakahara T et al. | Mechanistic insights into topical tacrolimus for the treatment of atopic dermatitis. | 2018 | Pediatr Allergy Immunol | pmid:29205511 |
| Watanabe N et al. | The possible clinical impact of risperidone on P-glycoprotein-mediated transport of tacrolimus: A case report and in vitro study. | 2018 | Biopharm Drug Dispos | pmid:29055041 |
| Gupta PC and Ram J | Comparative Evaluation of Tacrolimus Versus Interferon Alpha-2b Eye Drops in the Treatment of Vernal Keratoconjunctivitis: A Randomized, Double-Masked Study. | 2018 | Cornea | pmid:29040120 |
| Banovic F et al. | Tacrolimus therapy for dermal arteritis of the nasal philtrum refractory to surgery and anti-inflammatory therapy (doxycycline/niacinamide and topical fluocinolone) in a dog. | 2018 | Vet. Dermatol. | pmid:28990239 |
| Nakamura K et al. | Prevention of chronic renal allograft rejection by AS2553627, a novel JAK inhibitor, in a rat transplantation model. | 2018 | Transpl. Immunol. | pmid:28988984 |
| Ixtlapale-Carmona X et al. | Graft immunologic events in deceased donor kidney transplant recipients with preformed HLA-donor specific antibodies. | 2018 | Transpl. Immunol. | pmid:28974434 |
| Sakai R et al. | Efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for lupus nephritis: a prospective, single-arm, single-centre, open label pilot study in Japan. | 2018 | Lupus | pmid:28683654 |
| Guan XF et al. | Population Pharmacokinetic Modeling of Diltiazem in Chinese Renal Transplant Recipients. | 2018 | Eur J Drug Metab Pharmacokinet | pmid:28646274 |
| Almeida-Paulo GN et al. | Weight of ABCB1 and POR genes on oral tacrolimus exposure in CYP3A5 nonexpressor pediatric patients with stable kidney transplant. | 2018 | Pharmacogenomics J. | pmid:28094348 |
| Liu Y et al. | Delayed Initiation of Tacrolimus Is Safe and Effective in Renal Transplant Recipients With Delayed and Slow Graft Function. | 2018 | Transplant. Proc. | pmid:30316359 |
| Nordheim E et al. | Preserved insulin secretion and kidney function in recipients with functional pancreas grafts 1 year after transplantation: a single-center prospective observational study | 2018 | Eur. J. Endocrinol. | pmid:30299895 |
| Kandula P et al. | Plantar ulcerative lichen planus: rapid improvement with a novel triple-therapy approach. | 2018 | Cutis | pmid:30235362 |
| Jiang JW et al. | Optimal immunosuppressor induces stable gut microbiota after liver transplantation. | 2018 | World J. Gastroenterol. | pmid:30228781 |
| Park S et al. | Reduced Tacrolimus Trough Level Is Reflected by Estimated Glomerular Filtration Rate (eGFR) Changes in Stable Renal Transplantation Recipients: Results of the OPTIMUM Phase 3 Randomized Controlled Study. | 2018 | Ann. Transplant. | pmid:29891834 |
| Gu B et al. | Exploration of Fecal Microbiota Transplantation in the Treatment of Refractory Diarrhea After Renal Transplantation. | 2018 | Transplant. Proc. | pmid:29880353 |
| Lee H et al. | Thymoglobulin Versus Basiliximab Induction Therapy in Low-Risk Kidney Transplant Recipients: A Single-Center Experience. | 2018 | Transplant. Proc. | pmid:29880348 |
| Majeed A et al. | A 20-year experience with nocardiosis in solid organ transplant (SOT) recipients in the Southwestern United States: A single-center study. | 2018 | Transpl Infect Dis | pmid:29668074 |
| Mah A et al. | Graft loss attributed to possible transfusion-transmitted ehrlichiosis following cord blood stem cell transplant. | 2018 | Transpl Infect Dis | pmid:29668040 |
| Ma D et al. | Manipulating the expression of SARP family regulator BulZ and its target gene product to increase tacrolimus production. | 2018 | Appl. Microbiol. Biotechnol. | pmid:29666890 |
| Ichinose K et al. | The efficacy of adjunct tacrolimus treatment in pregnancy outcomes in patients with systemic lupus erythematosus. | 2018 | Lupus | pmid:29665758 |
| Ishikawa S et al. | Management of Juvenile Idiopathic Arthritis in ABO-incompatible Kidney Transplantation: A Case Report. | 2018 | Transplant. Proc. | pmid:29661455 |
| Hu T et al. | Tacrolimus decreases proteinuria in patients with refractory IgA nephropathy. | 2018 | Medicine (Baltimore) | pmid:29718866 |
| Mei S et al. | Simultaneous determination of cyclosporine and tacrolimus in human whole blood by ultra-high performance liquid chromatography tandem mass spectrometry and comparison with a chemiluminescence microparticle immunoassay. | 2018 | J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. | pmid:29704799 |
| Stanton BZ et al. | Chemically induced proximity in biology and medicine. | 2018 | Science | pmid:29590011 |
| Shi D et al. | CYP3A4 and GCK genetic polymorphisms are the risk factors of tacrolimus-induced new-onset diabetes after transplantation in renal transplant recipients. | 2018 | Eur. J. Clin. Pharmacol. | pmid:29546446 |
| Mina M et al. | Comparison between the efficacy of microneedling combined with 5-fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo. | 2018 | J Cosmet Dermatol | pmid:29532621 |
| Zhong J et al. | Tacrolimus interacts with voriconazole to reduce the severity of fungal keratitis by suppressing IFN-related inflammatory responses and concomitant FK506 and voriconazole treatment suppresses fungal keratitis. | 2018 | Mol. Vis. | pmid:29527115 |
| Okada K et al. | EBV-positive PEL-like lymphoma that developed in the course of antisynthetase syndrome treated with tacrolimus. | 2018 | Int. J. Hematol. | pmid:29516290 |
| Sano H et al. | T-cell-replete haploidentical stem cell transplantation using low-dose antithymocyte globulin in children with relapsed or refractory acute leukemia. | 2018 | Int. J. Hematol. | pmid:29508228 |
| Wan Q et al. | Therapeutic Effect of 0.1% Tacrolimus Eye Drops in the Tarsal Form of Vernal Keratoconjunctivitis. | 2018 | Ophthalmic Res. | pmid:28803239 |
| Takeuchi T et al. | Post-marketing surveillance study of the long-term use of mizoribine for the treatment of lupus nephritis: 2-Year results. | 2018 | Mod Rheumatol | pmid:28722500 |
| Vosough M and Tehrani SM | Development of a fast HPLC-DAD method for simultaneous quantitation of three immunosuppressant drugs in whole blood samples using intelligent chemometrics resolving of coeluting peaks in the presence of blood interferences. | 2018 | J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. | pmid:29241087 |
| Hashemian MN et al. | Topical Tacrolimus as Adjuvant Therapy to Corticosteroids in Acute Endothelial Graft Rejection After Penetrating Keratoplasty: A Randomized Controlled Trial. | 2018 | Cornea | pmid:29215395 |
| Charnaya O et al. | Results of early treatment for de novo donor-specific antibodies in pediatric kidney transplant recipients in a cross-sectional and longitudinal cohort. | 2018 | Pediatr Transplant | pmid:29356221 |
| Yamada K et al. | Correlation between disease activity and serum ferritin in clinically amyopathic dermatomyositis with rapidly-progressive interstitial lung disease: a case report. | 2018 | BMC Res Notes | pmid:29338781 |
| Jin L et al. | Effect of Conversion to CTLA4Ig on Tacrolimus-Induced Diabetic Rats. | 2018 | Transplantation | pmid:29319618 |
| Oetting WS et al. | Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients. | 2018 | Pharmacogenomics | pmid:29318894 |
| Rayar M et al. | High Intrapatient Variability of Tacrolimus Exposure in the Early Period After Liver Transplantation Is Associated With Poorer Outcomes. | 2018 | Transplantation | pmid:29315140 |
| Niioka T et al. | Impact of the CYP3A5 genotype on the distributions of dose-adjusted trough concentrations and incidence of rejection in Japanese renal transplant recipients receiving different tacrolimus formulations. | 2017 | Clin. Exp. Nephrol. | pmid:28271256 |
| Kurzawski M et al. | Analysis of common polymorphisms within NR1I2 and NR1I3 genes and tacrolimus dose-adjusted concentration in stable kidney transplant recipients. | 2017 | Pharmacogenet. Genomics | pmid:28777242 |
| Wang C et al. | Combining metabolomics and network analysis to improve tacrolimus production in Streptomyces tsukubaensis using different exogenous feedings. | 2017 | J. Ind. Microbiol. Biotechnol. | pmid:28776273 |
| Béland MA et al. | Higher calcineurin inhibitor levels predict better kidney graft survival in patients with de novo donor-specific anti-HLA antibodies: a cohort study. | 2017 | Transpl. Int. | pmid:28186642 |
| Lim SW et al. | Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress. | 2017 | Cell Death Dis | pmid:28771227 |
| Gupta AK and Versteeg SG | Topical Treatment of Facial Seborrheic Dermatitis: A Systematic Review. | 2017 | Am J Clin Dermatol | pmid:27804089 |
| Kumai Y et al. | Reversible Cerebral Vasoconstriction Syndrome After Heart Transplantation: A Case Report. | 2017 | Transplant. Proc. | pmid:29198694 |
| Nazmul MN et al. | Severe Hyperkalemia Complicating Voriconazole Treatment in a Kidney Transplant Recipient With Histoplasmosis: A Case Report. | 2017 | Transplant. Proc. | pmid:29198681 |
| Miyake M et al. | Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. | 2017 | PLoS ONE | pmid:28644884 |
| Song L et al. | ASP2409, A Next-Generation CTLA4-Ig, Versus Belatacept in Renal Allograft Survival in Cynomolgus Monkeys. | 2017 | Am. J. Transplant. | pmid:27598231 |
| Zizzo AN et al. | Second-line Agents in Pediatric Patients With Autoimmune Hepatitis: A Systematic Review and Meta-analysis. | 2017 | J. Pediatr. Gastroenterol. Nutr. | pmid:28644343 |
| Sopko NA et al. | Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology. | 2017 | Eur. Urol. | pmid:27432525 |
| Al-Uzri A et al. | Longitudinal study on the use of dried blood spots for home monitoring in children after kidney transplantation. | 2017 | Pediatr Transplant | pmid:28635157 |
| Ruiz S et al. | Tacrolimus rescues the signaling and gene expression signature of endothelial ALK1 loss-of-function and improves HHT vascular pathology. | 2017 | Hum. Mol. Genet. | pmid:28973643 |
| Dorr CR et al. | CRISPR/Cas9 Genetic Modification of in HuH-7 Human Hepatocyte Cell Line Leads to Cell Lines with Increased Midazolam and Tacrolimus Metabolism. | 2017 | Drug Metab. Dispos. | pmid:28533324 |
| Saburi M et al. | Effects of calcineurin inhibitors on sodium excretion in recipients of allogeneic hematopoietic stem cell transplantation. | 2017 | Int. J. Hematol. | pmid:28516402 |
| Ferreira A et al. | Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and Everolimus. | 2017 | Am. J. Nephrol. | pmid:28511172 |
| Kim YJ et al. | Two cases of hydroa vacciniforme-like lymphoproliferative disease controlled by anti-inflammatory agents. | 2017 | Photodermatol Photoimmunol Photomed | pmid:28543883 |
| Zhang HJ et al. | Tacrolimus population pharmacokinetics according to CYP3A5 genotype and clinical factors in Chinese adult kidney transplant recipients. | 2017 | J Clin Pharm Ther | pmid:28401703 |
| Zanjani H et al. | Comparative Evaluation of Tacrolimus Versus Interferon Alpha-2b Eye Drops in the Treatment of Vernal Keratoconjunctivitis: A Randomized, Double-Masked Study. | 2017 | Cornea | pmid:28399035 |
| Piñana JL et al. | A Time-to-Event Model for Acute Kidney Injury after Reduced-Intensity Conditioning Stem Cell Transplantation Using a Tacrolimus- and Sirolimus-based Graft-versus-Host Disease Prophylaxis. | 2017 | Biol. Blood Marrow Transplant. | pmid:28396159 |
| Gnarra M et al. | Low-Dose Cyclosporine A in the Treatment of Severe Atopic Dermatitis Complicated by Chronic Hepatitis C Virus Infection. | 2017 | Pediatr Dermatol | pmid:28382768 |
| Zhang H et al. | Multitarget Therapy for Maintenance Treatment of Lupus Nephritis. | 2017 | J. Am. Soc. Nephrol. | pmid:28760751 |
| Salgüero Fernández I et al. | Rapidly progressive infiltrated plaques in a transplant recipient. | 2017 | Actas Dermosifiliogr | pmid:27677210 |
| Hettiarachchi PVKS et al. | Comparison of topical tacrolimus and clobetasol in the management of symptomatic oral lichen planus: A double-blinded, randomized clinical trial in Sri Lanka. | 2017 | J Investig Clin Dent | pmid:27633647 |
| Wen Y et al. | Inhibition of Calcineurin A by FK506 Suppresses Seizures and Reduces the Expression of GluN2B in Membrane Fraction. | 2017 | Neurochem. Res. | pmid:28299629 |
| Forns X et al. | Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study. | 2017 | Transpl Infect Dis | pmid:28295849 |
| Dhakal P et al. | Eculizumab in Transplant-Associated Thrombotic Microangiopathy. | 2017 | Clin. Appl. Thromb. Hemost. | pmid:26259912 |
| Albaghdadi AJ et al. | Tacrolimus in the prevention of adverse pregnancy outcomes and diabetes-associated embryopathies in obese and diabetic mice. | 2017 | J Transl Med | pmid:28193233 |
| Wojciechowski D et al. | Early post-transplant conversion from tacrolimus to belatacept for prolonged delayed graft function improves renal function in kidney transplant recipients. | 2017 | Clin Transplant | pmid:28190259 |
| Lum EL et al. | Acute Kidney Allograft Rejection Precipitated by Lenalidomide Treatment for Multiple Myeloma. | 2017 | Am. J. Kidney Dis. | pmid:28189378 |
| Xie Y et al. | Delayed Donor Bone Marrow Infusion Induces Liver Transplant Tolerance. | 2017 | Transplantation | pmid:28187014 |
| Koster RA et al. | Dried blood spot validation of five immunosuppressants, without hematocrit correction, on two LC-MS/MS systems. | 2017 | Bioanalysis | pmid:28300419 |
| Chapman WC et al. | Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation. | 2017 | Transplantation | pmid:28121741 |
| Sepaskhah M et al. | Comparative efficacy of topical application of tacrolimus and clotrimazole in the treatment of pityriasis versicolor: A single blind, randomised clinical trial. | 2017 | Mycoses | pmid:28120351 |
| Arroyo Hornero R et al. | CD45RA Distinguishes CD4+CD25+CD127-/low TSDR Demethylated Regulatory T Cell Subpopulations With Differential Stability and Susceptibility to Tacrolimus-Mediated Inhibition of Suppression. | 2017 | Transplantation | pmid:28118317 |
| Liu MZ et al. | IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients. | 2017 | Acta Pharmacol. Sin. | pmid:28112181 |
| Zhao YT et al. | Sensitized signalling between L-type Ca2+ channels and ryanodine receptors in the absence or inhibition of FKBP12.6 in cardiomyocytes. | 2017 | Cardiovasc. Res. | pmid:28077437 |
| Dun H et al. | ASP0028 in combination with suboptimal-dose of tacrolimus in Cynomolgus monkey renal transplantation model. | 2017 | Transpl. Immunol. | pmid:28077266 |
| Herskovitz J et al. | Immune Suppression During Preclinical Drug Development Mitigates Immunogenicity-Mediated Impact on Therapeutic Exposure. | 2017 | AAPS J | pmid:28070711 |
| Noguchi A et al. | Differences in therapeutic effects of topically applied corticosteroid and tacrolimus on atopic dermatitis-like symptoms in NC/Nga mice. | 2017 | J. Dermatol. Sci. | pmid:28069324 |
| Størset E et al. | Bodyweight-adjustments introduce significant correlations between CYP3A metrics and tacrolimus clearance. | 2017 | Br J Clin Pharmacol | pmid:28008657 |
| Segal JP et al. | Systematic review with meta-analysis: the management of chronic refractory pouchitis with an evidence-based treatment algorithm. | 2017 | Aliment. Pharmacol. Ther. | pmid:28008631 |
| Ishida R et al. | The Tissue-Reconstructing Ability of Colon CSCs Is Enhanced by FK506 and Suppressed by GSK3 Inhibition. | 2017 | Mol. Cancer Res. | pmid:28710230 |
| Bauer JS et al. | dRNA-seq transcriptional profiling of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis NRRL18488 and general analysis of the transcriptome. | 2017 | RNA Biol | pmid:28665778 |
| Kalam MA and Alshamsan A | Poly (d, l-lactide-co-glycolide) nanoparticles for sustained release of tacrolimus in rabbit eyes. | 2017 | Biomed. Pharmacother. | pmid:28772219 |
| Kapoor A et al. | Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy. | 2017 | Tex Heart Inst J | pmid:28761402 |
| Goldsmith PM et al. | Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol. | 2017 | BMJ Open | pmid:28756385 |
| Lewis DJ et al. | Oral bexarotene for post-transplant cutaneous T-cell lymphoma. | 2017 | Dermatol Ther | pmid:28748653 |
| Parrow NL and Fleming RE | Releasing the FKBP12 brake on hepcidin. | 2017 | Blood | pmid:29122771 |
| Kalt DA | Tacrolimus: A Review of Laboratory Detection Methods and Indications for Use. | 2017 | Lab Med | pmid:29096030 |
| Andrews LM et al. | Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients. | 2017 | Expert Opin Drug Metab Toxicol | pmid:29084469 |
| Noceti O et al. | Activity of the Calcineurin Pathway in Patients on the Liver Transplantation Waiting List: Factors of Variability and Response to Tacrolimus Inhibition. | 2017 | Clin. Chem. | pmid:29054923 |
| Barau C et al. | Pharmacokinetics of Mycophenolic Acid and Dose Optimization in Children After Intestinal Transplantation. | 2017 | Ther Drug Monit | pmid:27898598 |
| Kobayashi I et al. | Tacrolimus in combination with methotrexate and corticosteroid for the treatment of child-onset anti-signal recognition particle antibody-positive necrotizing myopathy. | 2017 | Scand. J. Rheumatol. | pmid:27897449 |
| Theile D et al. | Clementine juice has the potential for drug interactions - In vitro comparison with grapefruit and mandarin juice. | 2017 | Eur J Pharm Sci | pmid:27890698 |
| Iwayama T et al. | Granulomatous reaction to permanent eyebrow makeup successfully treated with topical steroids in combination with topical tacrolimus. | 2017 | Eur J Dermatol | pmid:29311043 |
| Grinyó JM et al. | Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial. | 2017 | Am. J. Kidney Dis. | pmid:27889299 |