Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: Evidence from the symphony study
Abstract
BACKGROUND: The metabolic syndrome (MS) is an important risk factor for graft dysfunction and patient death after renal transplantation. The aim of this sub-analysis of the Symphony study was to assess the progression of the laboratory parameters associated with MS in the first year after transplantation. METHODS: Data collected from the Symphony study were used; 1645 patients were randomized to receive standard-dose cyclosporine (Stand-CsA), low-dose cyclosporine (Low-CsA), tacrolimus (Low-Tac) or sirolimus (Low-SRL), in addition to mycophenolate mofetil (MMF) and corticosteroids. Data were collected for levels and progression over the first year post-transplantation of systolic and diastolic blood pressure, uric acid, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and fasting glucose levels by treatment arm. RESULTS: The low-SRL group had significantly higher levels of triglycerides and LDL. The two CsA arms were associated with the highest uric acid levels at each time point. There were no significant differences in overall levels or changes in glucose or HDL. Patients in the standard-CsA arm had significantly higher diastolic blood pressure than those in the Low-SRL and Low-Tac arms. Systolic blood pressure was higher in the Low-CsA arm than in the Low-Tac arm. The use of antihypertensive and antidiabetic agents was similar between the treatment arms. In the Low-SRL arm, more patients were treated with lipid-lowering therapy. Mean daily steroid doses were the highest in the Low-SRL arm. CONCLUSIONS: This sub-analysis demonstrates that there is a difference in metabolic parameters between immunosuppressive groups. CsA therapy was associated with the highest values of uric acid and systolic and diastolic blood pressure. Patients on SRL therapy had the worst lipaemic control. A possible effect of Tac on new-onset diabetes could not be excluded.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Testosterone replacement improves glycemia, dyslipidemia, hepatic steatosis, body composition, and cardiovascular risk.
“testosterone replacement improves glycemia, dyslipidemia, hepatic steatosis, body composition, and CVD risk”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1574]
The Discussion and Cholesterol sections examine glucose, lipids, blood pressure and BMI in kidney-transplant recipients receiving different immunosuppressive regimens. A search for testosterone replacement, and for testosterone, androgen and hepatic steatosis, found no passage addressing its effects on the claimed outcomes. The copy therefore cannot verify the attributed claim. (LLM, conf=0.78)
Experimental — accuracy not yet measuredTestosterone replacement prevents progression from prediabetes to type 2 diabetes.
“and also prevents progression from prediabetes to T2D.1571–1574”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1574]
The Discussion addresses new-onset diabetes and glucose tolerance after renal transplantation under different immunosuppressive regimens. Searches for testosterone replacement and progression from prediabetes found no passage addressing that claim; the paper’s findings about immunosuppression do not establish or contradict it. The indexed passages provide no page numbers. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThree modestly sized trials and the large randomized SEAS trial (1,873 patients treated with simvastatin 40 mg plus ezetimibe 10 mg or placebo) failed to show a reduction in clinical progression of aortic stenosis in patients with mild-to-moderate native valve aortic stenosis.
“Three modestly sized trials [479-481] and one large randomized trial (SEAS, which included 1873 patients treated with simvastatin 40 mg plus ezetimibe 10 mg or placebo) [266] failed to show a reduction in the clinical progression of aortic stenosis in patients with mild-to-moderate native valve aortic stenosis.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [479]
Randomized controlled trials and meta-analyses of observational and randomized trials have not confirmed that lipid lowering slows aortic stenosis progression.
“However, this has not been confirmed in RCTs [266,479-481], or in meta-analyses of observational and randomized trials [482,483].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [479]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944 · see citing works
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011 · see citing works
Grundy, S. M., Brewer, H. B., Cleeman, J. I., Smith, S. C., & Lenfant, C. (2004) · Circulation · doi:10.1161/01.cir.0000111245.75752.c6 · Cited by 5,982 · see citing works
Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation
Ekberg, H., Junior, H. T. S., Demirbas, A., Vitko, S., Nashan, B., Gürkan, A., Margreiter, R., Hugo, C., Grinyo, J. M., Frei, U. A., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa067411 · Cited by 1,814 · see citing works
Self-citationDiabetes Mellitus after Kidney Transplantation in the United States
Kasiske, B. L., Snyder, J. J., Gilbertson, D. T., & Matas, A. J. (2003) · American Journal of Transplantation · doi:10.1034/j.1600-6143.2003.00010.x · Cited by 1,286 · see citing works
Pirsch, J. D., Miller, J., Deierhoi, M. H., Vincenti, F. G., & Filo, R. S. (1997) · Transplantation · doi:10.1097/00007890-199704150-00013 · Cited by 1,120 · see citing works
Kahan, B. D. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02480-6 · Cited by 911 · see citing works
SIROLIMUS (RAPAMYCIN)-BASED THERAPY IN HUMAN RENAL TRANSPLANTATION
GROTH, C. G., Bäckman, L., Morales, J.-M., Calne, R., Kreis, H., Lang, P., Touraine, J. L., Claesson, K., Campistol, J. M., Durand, D., et al. (1999) · Transplantation · doi:10.1097/00007890-199904150-00017 · Cited by 878 · see citing works
Mayer, A. D., Dmitrewski, J., Squifflet, J.-P., Besse, T., Grabensee, B., Klein, B. C., Eigler, F. W., Heemann, U. W., Pichlmayr, R., Behrend, M., et al. (1997) · Transplantation · doi:10.1097/00007890-199708150-00012 · Cited by 724 · see citing works
Self-citationVincenti, F. G., Friman, S., Scheuermann, E., Rostaing, L. P. E., Jenssen, T. G., Campistol, J. M., Uchida, K., Pescovitz, M. D., Marchetti, P., Tuncer, M. A., et al. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01749.x · Cited by 618 · see citing works
Montori, V. M., Basu, A., Erwin, P. J., Velosa, J. A., Gabriel, S. E., & Kudva, Y. C. (2002) · Diabetes Care · doi:10.2337/diacare.25.3.583 · Cited by 528 · see citing works
Margreiter, R. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07875-3 · Cited by 451 · see citing works
Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients
Johnston, O., Rose, C., Webster, A. C., & Gill, J. S. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007111202 · Cited by 425 · see citing works
(2019) · Journal of Human Hypertension · doi:10.1038/41371.1476-5527 · Cited by 389 · see citing works
Flechner, S. M., Goldfarb, D. A., Modlin, C. S., Feng, J., Krishnamurthi, V., Mastroianni, B., Savas, K., COOK, D. J., & Novick, A. C. (2002) · Transplantation · doi:10.1097/00007890-200210270-00002 · Cited by 374 · see citing works
Larson, T. S., Dean, P. G., Stegall, M. D., Griffin, M. D., Textor, S. C., Schwab, T. R., Gloor, J. M., Cosío, B. G., Lund, W. J., Kremers, W. K., et al. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.01177.x · Cited by 299 · see citing works
Morrisett, J. D., Abdel-Fattah, G., Hoogeveen, R., Mitchell, E., Ballantyne, C. M., Pownall, H. J., Opekun, A. R., Jaffe, J. S., Oppermann, S., & Kahan, B. D. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m100392-jlr200 · Cited by 295 · see citing works
Johnson, C. P., Ahsan, N., Gonwa, T. A., et al. (2000) · Transplantation · doi:10.1097/00007890-200003150-00028 · Cited by 295 · see citing works
Knight, S. R., & Morris, P. J. (2010) · Transplantation · doi:10.1097/tp.0b013e3181c518cc · Cited by 265 · see citing works
Glucose Metabolism in Renal Transplant Recipients
Teutonico, A., Schena, P. F., & Paolo, S. D. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005050487 · Cited by 238 · see citing works
Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation
Trompeter, R. S., Filler, G., Webb, N. J. A., et al. (2002) · Pediatric Nephrology · doi:10.1007/s00467-001-0795-9 · Cited by 226 · see citing works
Long-Term Benefits with Sirolimus-Based Therapy after Early Cyclosporine Withdrawal
Kreis, H., Oberbauer, R. W., Campistol, J. M., et al. (2004) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000113248.59077.76 · Cited by 225 · see citing works
de Vries, A. P. J., Bakker, S. J. L., van Son, W. J., van der Heide, J. J. H., Ploeg, R. J., The, H. T., de Jong, P. E., & Gans, R. O. B. (2004) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2004.00558.x · Cited by 213 · see citing works
Cyclosporine-Induced Hypertension After Transplantation
Textor, S. C., Canzanello, V. J., Taler, S. J., et al. (1994) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(12)65772-3 · Cited by 197 · see citing works
Sirolimus Does Not Exhibit Nephrotoxicity Compared to Cyclosporine in Renal Transplant Recipients
Morales, J. M., Wramner, L., Kreis, H., Durand, D., Campistol, J. M., Andrés, A., Arenas, J., Nègre, E., Burke, J. T., & GROTH, C. G. (2002) · American Journal of Transplantation · doi:10.1034/j.1600-6143.2002.20507.x · Cited by 188 · see citing works
Gonwa, T. A., Mendez, R., Yang, H. C., Weinstein, S., Jensik, S. C., & Steinberg, S. (2003) · Transplantation · doi:10.1097/01.tp.0000062837.99400.60 · Cited by 187 · see citing works
Charpentier, B., Rostaing, L. P. E., Berthoux, F. C., et al. (2003) · Transplantation · doi:10.1097/01.tp.0000056635.59888.ef · Cited by 163 · see citing works
Glucose Metabolism in Renal Transplant Recipients on Tacrolimus
Boots, J. M. M., van Duijnhoven, E. M., Christiaans, M. H. L., Wolffenbuttel, B. H. R., & van Hooff, J. P. (2002) · Journal of the American Society of Nephrology · doi:10.1681/asn.v131221 · Cited by 163 · see citing works
Cardiovascular Risk Factors in Renal Transplant Patients
Ligtenberg, G., Hené, R. J., Blankestijn, P. J., et al. (2001) · Journal of the American Society of Nephrology · doi:10.1681/asn.v122368 · Cited by 161 · see citing works
Impact of Metabolic Syndrome on Graft Function and Survival After Cadaveric Renal Transplantation
Porrini, E., Delgado, P., Bigo, C., et al. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2006.04.078 · Cited by 155 · see citing works
Klein, I. H. H. T., Abrahams, A. C., van Ede, T., et al. (2002) · Transplantation · doi:10.1097/00007890-200203150-00012 · Cited by 149 · see citing works
Artz, M. A., Boots, J. M. M., Ligtenberg, G., Roodnat, J. I., Christiaans, M. H. L., Vos, P. F., Moons, P., Borm, G. F., & Hilbrands, L. B. (2004) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2004.00427.x · Cited by 143 · see citing works
Chueh, S., & Kahan, B. D. (2003) · Transplantation · doi:10.1097/01.tp.0000074310.40484.94 · Cited by 100 · see citing works
van den Ham, E. C. H., Kooman, J. P., Christiaans, M. H. L., Nieman, F. H. M., & van Hooff, J. P. (2003) · Transplant International · doi:10.1111/j.1432-2277.2003.tb00304.x · Cited by 91 · see citing works
Tacrolimus reversibly reduces insulin secretion in paediatric renal transplant recipients
Filler, G., Neuschulz, I., Vollmer, I., et al. (2000) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/15.6.867 · Cited by 89 · see citing works
Pascual, J., van Hooff, J. P., Salmela, K. T., Lang, P., Rigotti, P., & Budde, K. (2006) · Transplantation · doi:10.1097/01.tp.0000225806.80890.5e · Cited by 87 · see citing works
van den Ham, E. C. H., Kooman, J. P., Christiaans, M. H. L., et al. (2003) · PubMed · doi:10.1007/s00147-002-0502-1 · Cited by 83 · see citing works
Saudek, F., Malaise, J., Bouček, P., et al. (2005) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfh1076 · Cited by 79 · see citing works
Roland, M., Gatault, P., Doute, C., Büchler, M., Al-Najjar, A., Barbet, C., Châtelet, V., Marliere, J.-F., Nivet, H., Lebranchu, Y., et al. (2008) · Transplant International · doi:10.1111/j.1432-2277.2008.00640.x · Cited by 63 · see citing works
Luan, F. L., Zhang, H., Schaubel, D. E., Miles, C. D., Cibrik, D. M., Norman, S. P., & OJO, A. O. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02328.x · Cited by 43 · see citing works
Wissing, K. M., Unger, P., Ghisdal, L., Broeders, N., Berkenboom, G. M., Carpentier, Y., & Abramowicz, D. (2006) · Transplantation · doi:10.1097/01.tp.0000235446.50715.ef · Cited by 34 · see citing works
Charpentier, B., Groth, C. G., Bäckman, L., et al. (2003) · Transplantation Proceedings · doi:10.1016/s0041-1345(03)00213-6 · Cited by 28 · see citing works
Dmitrewski, J., Krentz, A. J., Mayer, A., BUCKELS, J. A. C., Barnes, A., Smith, J., & Nattrass, M. (2001) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2001.00132.x · Cited by 24 · see citing works
Hoitsma, A. J., & Hilbrands, L. B. (2006) · Clinical Transplantation · doi:10.1111/j.1399-0012.2006.00535.x · Cited by 21 · see citing works
Sharif, A., Ravindran, V. K., Dunseath, G. J., Luzio, S. D., Owens, D. R., & Baboolal, K. (2010) · Transplantation · doi:10.1097/tp.0b013e3181bd06d2 · Cited by 19 · see citing works
Campos, H. H., & Filho, M. A. (2002) · Transplantation Proceedings · doi:10.1016/s0041-1345(02)02968-8 · Cited by 16 · see citing works
Hypertension in transplant recipients.
Singer, D., & Jenkins, G. H. (1996) · PubMed · Cited by 15 · see citing works
Glucose Metabolic Disorder After Transplantation
van Hooff, J. P., Christiaans, M. H. L., & van Duijnhoven, E. M. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01832.x · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854 · see citing works
Blonde, L., Umpierrez, G. E., Reddy, S. S., McGill, J. B., Berga, S. L., Bush, M., Chandrasekaran, S., DeFronzo, R. A., Einhorn, D., Galindo, R. J., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.08.002 · Cited by 507 · see citing works
Metabolic consequences of modern immunosuppressive agents in solid organ transplantation
Bamgbola, O. (2016) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018816641580 · Cited by 85 · see citing works
- Authors
- Claes, K., Meier-Kriesche, H.-U., Schold, J. D., Vanrenterghem, Y., Halloran, P. F., & Ekberg, H.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Cleveland Clinic (US)
- University of Alberta (CA)
- Venue
- Nephrology Dialysis Transplantation
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-05-26
- Volume
- 27
- Issue
- 2
- Pages
- 850-857
- ISSN
- 0931-0509 (ISSN-L)
- 1460-2385
- OpenAlex
- W2164877125
- Cited by
- 75
- References
- 48
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 2 · 2019: 7 · 2017: 2 · 2016: 10 · 2015: 7 · 2014: 12 · 2013: 4 · 2012: 5
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nephrology Dialysis Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- F. Hoffmann-La Roche
- Topics
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- metabolic syndrome, kidney transplantation, immunosuppressive regimens, cyclosporine, tacrolimus, rapamycin, low-dose immunosuppression, blood pressure, uric acid, triglycerides, LDL cholesterol, HDL cholesterol, fasting blood glucose, lipid control, corticosteroid dose, new-onset diabetes
- MeSH terms
- Adrenal Cortex Hormones, Adult, Blood Chemical Analysis, Blood Pressure Determination, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Therapy, Combination, Female, Graft Rejection, Graft Survival, Humans, Hyperlipidemias, Immunosuppressive Agents, Kidney Failure, Chronic, Male, Middle Aged, Monitoring, Physiologic, Mycophenolic Acid, Prognosis, Reference Values, Transplantation Immunology, Body Mass Index, Kidney Transplantation, Tacrolimus, Cyclosporine, Risk Assessment, Sirolimus, Metabolic Syndrome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
