Top

BMC Nephrology

Published in:

Open Access 01-12-2022 | Obesity | Research

The effect of calcineurin inhibitors on anthropometric measurements in kidney transplant recipients

Authors: Emel Isiktas Sayilar, Alparslan Ersoy, Canan Ersoy, Aysegul Oruc, Yavuz Ayar, Deniz Sigirli

Published in: BMC Nephrology | Issue 1/2022

Abstract

Background

This study was designed to investigate the effect of calcineurin inhibitors (CNIs), cyclosporine (CsA), and tacrolimus (Tac) on anthropometrics in kidney transplant recipients.

Methods

111 of 128 adult kidney transplant recipients who received post-transplant CNIs were included in this retrospective study. Anthropometrics were recorded in the pre-transplant and post-transplant 4-year follow-up periods (1^st, 3^rd, 6^th, 12^th, 24^th, 36^th and 48^th months).

Results

Compared to pre-transplant values, significant increases in body weight and body mass index (between 3^rd and 48^th months), waist and hip circumferences (between 1^st and 48^th months), waist-to-hip ratio (between 1^st and 3^rd or 6^th months) and neck circumference (between 1^st and 12^th or 24^th months) were observed in both CsA and Tac groups. A significant increase was noted in post-transplant body fat percentage values for the 3^rd to 24^th months in the CsA group, whereas for the 24^th to 48^th months in both CsA and Tac groups. Hip circumferences percentage changes from the pre-transplant period to the 1^st, 12^th and 24^th months were significantly higher in CsA than in the Tac group. At each time point, there was no significant difference in percentage changes for other anthropometric parameters between the CsA and Tac groups. De novo diabetes mellitus developed in 8.3% of the CsA group and 19.1% of the Tac group.

Conclusions

After a successful kidney transplant, anthropometric measurements increase in most recipients. Although the effect of calcineurin inhibitor type on weight gain is unclear, a regression analysis showed that CNI type was not a risk factor for the development of obesity in the 48^th month. However, it is helpful to be cautious about its dyslipidemic effect in patients using CsA and the potential hazards of using Tac in patients with a diabetic predisposition.

Neipp M, Karavul B, Jackobs S, et al. Quality of life in adult transplant recipients more than 15 years after kidney transplantation. Transplantation. 2006;81(12):1640–4. https://doi.org/10.1097/01.tp.0000226070.74443.fb.CrossRefPubMed

Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. New Engl J Med. 1999;341(23):1725–30. https://doi.org/10.1056/NEJM199912023412303.CrossRefPubMed

Hong JC, Kahan BD. Immunosuppressive agents in organ transplantation: past, present, and future. Semin Nephrol. 2000;20(2):108–25.PubMed

Malvezzi P, Rostaing L. The safety of calcineurin inhibitors for kidney-transplant patients. Expert Opin Drug Saf. 2015;14(10):1531–46. https://doi.org/10.1517/14740338.2015.1083974.CrossRefPubMed

Friedman AN, Miskulin DC, Rosenberg IH, Levey AS. Demographics and trends in overweight and obesity in patients at time of kidney transplantation. Am J Kidney Dis. 2003;41(2):480–7. https://doi.org/10.1053/ajkd.2003.50059.CrossRefPubMed

de Vries AP, Bakker SJ, van Son WJ, et al. Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally. Am J Transplant. 2004;4(10):1675–83. https://doi.org/10.1111/j.1600-6143.2004.00558.x.CrossRefPubMed

Ducloux D, Kazory A, Simula-Faivre D, Chalopin JM. One-year post-transplant weight gain is a risk factor for graft loss. Am J Transplant. 2005;5(12):2922–8. https://doi.org/10.1111/j.1600-6143.2005.01104.x.CrossRefPubMed

Gore JL, Pham PT, Danovitch GM, et al. Obesity and outcome following renal transplantation. Am J Transplant. 2006;6(2):357–63. https://doi.org/10.1111/j.1600-6143.2005.01198.x.CrossRefPubMed

Meier-Kriesche HU, Arndorfer JA, Kaplan B. The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death. Transplantation. 2002;73(1):70–4. https://doi.org/10.1097/00007890-200201150-00013.CrossRefPubMed

10.

Nagy K, Ujszaszi A, Remport A, et al. Association of abdominal circumference, body mass index, and inflammation in kidney transplant recipients. J Ren Nutr. 2016;26(5):325–33. https://doi.org/10.1053/j.jrn.2016.02.007.CrossRefPubMed

11.

Chang SH, Coates PT, McDonald SP. Effects of body mass index at transplant on outcomes of kidney transplantation. Transplantation. 2007;84(8):981–7. https://doi.org/10.1097/01.tp.0000285290.77406.7b.CrossRefPubMed

12.

Małgorzewicz S, Wołoszyk P, Chamienia A, Jankowska M, Dębska-Ślizień A. Obesity risk factors in patients after kidney transplantation. Transplant Proc. 2018;50(6):1786–9. https://doi.org/10.1016/j.transproceed.2018.02.099.CrossRefPubMed

13.

Kovesdy CP, Czira ME, Rudas A, et al. Body mass index, waist circumference and mortality in kidney transplant recipients. Am J Transplant. 2010;10(12):2644–51. https://doi.org/10.1111/j.1600-6143.2010.03330.x.CrossRefPubMed

14.

Sanches FM, Avesani CM, Kamimura MA, et al. Waist circumference and visceral fat in CKD: a cross-sectional study. Am J Kidney Dis. 2008;52(1):66–73. https://doi.org/10.1053/j.ajkd.2008.02.004.CrossRefPubMed

15.

Yusuf S, Hawken S, Ounpuu S, et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet (London, England). 2005;366(9497):1640–9. https://doi.org/10.1016/S0140-6736(05)67663-5.CrossRef

16.

American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl):S8–16.CrossRef

17.

Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12. https://doi.org/10.7326/0003-4819-150-9-200905050-00006.CrossRefPubMedPubMedCentral

18.

Ho-Pham LT, Campbell LV, Nguyen TV. More on body fat cutoff points. Mayo Clin Proc. 2011;86(6):584; author reply 584-5. https://doi.org/10.4065/mcp.2011.0097.CrossRefPubMed

19.

Elsayed EF, Sarnak MJ, Tighiouart H, et al. Waist-to-hip ratio, body mass index, and subsequent kidney disease and death. Am J Kidney Dis. 2008;52(1):29–38. https://doi.org/10.1053/j.ajkd.2008.02.363.CrossRefPubMedPubMedCentral

20.

de Mattos AM, Prather J, Olyaei AJ, et al. Cardiovascular events following renal transplantation: role of traditional and transplant-specific risk factors. Kidney Int. 2006;70(4):757–64. https://doi.org/10.1038/sj.ki.5001628.CrossRefPubMed

21.

Clunk JM, Lin CY, Curtis JJ. Variables affecting weight gain in renal transplant recipients. Am J Kidney Dis. 2001;38(2):349–53. https://doi.org/10.1053/ajkd.2001.26100.CrossRefPubMed

22.

Małgorzewicz S, Dębska-Slizień A, Czajka B, Rutkowski B. Adipokines and nutritional status in kidney transplant recipients. Transplant Proc. 2014;46(8):2622–6. https://doi.org/10.1016/j.transproceed.2014.09.014.CrossRefPubMed

23.

Jabłonowska-Lietz B, Wrzosek M, Włodarczyk M, Nowicka G. New indexes of body fat distribution, visceral adiposity index, body adiposity index, waist-to-height ratio, and metabolic disturbances in the obese. Kardiol Pol. 2017;75(11):1185–91. https://doi.org/10.5603/KP.a2017.0149.CrossRefPubMed

24.

Canoy D, Boekholdt SM, Wareham N, et al. Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation Into Cancer and Nutrition in Norfolk cohort: a population-based prospective study. Circulation. 2007;116(25):2933–43. https://doi.org/10.1161/CIRCULATIONAHA.106.673756.CrossRefPubMed

25.

Gnatiuc L, Tapia-Conyer R, Wade R, et al. Abdominal and gluteo-femoral markers of adiposity and risk of vascular-metabolic mortality in a prospective study of 150 000 Mexican adults. Eur J Prev Cardiol. 2022;29(5):730–8. https://doi.org/10.1093/eurjpc/zwab038.CrossRefPubMed

26.

Tokodai K, Amada N, Kikuchi H, et al. Body fat percentage as a marker of new-onset diabetes mellitus after kidney transplantation. Transplant Proc. 2013;45(4):1544–7. https://doi.org/10.1016/j.transproceed.2012.12.009.CrossRefPubMed

27.

Ersoy A, Baran B, Ersoy C, Kahvecioglu S, Akdag I. Calcineurin inhibitors and post-transplant weight gain. Nephrology (Carlton). 2008;13(5):433–9. https://doi.org/10.1111/j.1440-1797.2008.00916.x.CrossRef

28.

Esteva-Font C, Ars E, Guillen-Gomez E, et al. Ciclosporin-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2). Nephrol Dial Transplant. 2007;22(10):2810–6. https://doi.org/10.1093/ndt/gfm390.CrossRefPubMed

29.

Furhmann A, Lopes PC, Sereno J, et al. Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on glucose and lipid metabolism in liver, skeletal muscle and adipose tissue in an in vivo rat model. Biochem Pharmacol. 2014;88(2):216–28. https://doi.org/10.1016/j.bcp.2014.01.020.CrossRef

30.

Mohebi R, Mohebi A, Sheikholeslami F, Azizi F, Hadaegh F. Wrist circumference as a novel predictor of hypertension and cardiovascular disease: results of a decade follow up in a West Asian cohort. J Am Soc Hypertens. 2014;8(11):800–7. https://doi.org/10.1016/j.jash.2014.08.010.CrossRefPubMed

31.

Zampetti S, Campagna G, Lucantoni F, et al. Wrist circumference is associated with increased systolic blood pressure in children with overweight/obesity. Hypertens Res. 2018;41(3):193–7. https://doi.org/10.1038/s41440-017-0006-0.CrossRefPubMed

32.

Luordi C, Maddaloni E, Bizzarri C, et al. Wrist circumference is a biomarker of adipose tissue dysfunction and cardiovascular risk in children with obesity. J Endocrinol Invest. 2020;43(1):101–7. https://doi.org/10.1007/s40618-019-01086-7.CrossRefPubMed

33.

Namazi N, Djalalinia S, Mahdavi-Gorabi A, et al. Association of wrist circumference with cardio-metabolic risk factors: a systematic review and meta-analysis. Eat Weight Disord. 2020;25(1):151–61. https://doi.org/10.1007/s40519-018-0534-x.CrossRefPubMed

34.

Mueller NT, Johnson W, Odegaard AO, et al. Wrist breadth and homeostasis model assessment of insulin resistance in youth: the Fels Longitudinal Study. Am J Hum Biol. 2013;25(5):581–5. https://doi.org/10.1002/ajhb.22416.CrossRefPubMedPubMedCentral

35.

Bergrem HA, Valderhaug TG, Hartmann A, et al. Glucose tolerance before and after renal transplantation. Nephrol Dial Transplant. 2010;25(3):985–92. https://doi.org/10.1093/ndt/gfp566.CrossRefPubMed

36.

Gotti E, Perico N, Perna A, et al. Renal transplantation: can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol biopsy findings. J Am Soc Nephrol. 2003;14(3):755–66. https://doi.org/10.1097/01.asn.0000048717.97169.29.CrossRefPubMed

37.

Kockx M, Glaros E, Leung B, et al. Low-density lipoprotein receptor-dependent and low-density lipoprotein receptor-independent mechanisms of cyclosporin A-induced dyslipidemia. Arterioscler Thromb Vasc Biol. 2016;36(7):1338–49. https://doi.org/10.1161/ATVBAHA.115.307030.CrossRefPubMed

38.

Bloom RD, Crutchlow MF. New-onset diabetes mellitus in the kidney recipient: diagnosis and management strategies. Clin J Am Soc Nephrol. 2008;3 Suppl 2(Suppl 2):S38-48. https://doi.org/10.2215/CJN.02650707.CrossRefPubMed

39.

Dai C, Walker JT, Shostak A, et al. Tacrolimus- and sirolimus-induced human β cell dysfunction is reversible and preventable. JCI Insight. 2020;5(1):e130770. https://doi.org/10.1172/jci.insight.130770.CrossRefPubMedCentral

40.

Bays HE, González-Campoy JM, Bray GA, et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther. 2008;6(3):343–68. https://doi.org/10.1586/14779072.6.3.343.CrossRefPubMed

41.

Hjelmesaeth J, Hagen M, Hartmann A, et al. The impact of impaired insulin release and insulin resistance on glucose intolerance after renal transplantation. Clin Transplant. 2002;16(6):389–96. https://doi.org/10.1034/j.1399-0012.2002.02059.x.CrossRefPubMed

42.

Jørgensen MB, Hornum M, van Hall G, et al. The impact of kidney transplantation on insulin sensitivity. Transpl Int. 2017;30(3):295–304. https://doi.org/10.1111/tri.12907.38.CrossRefPubMed

43.

Drachenberg CB, Klassen DK, Weir MR, et al. Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation. Transplantation. 1999;68(3):396–402. https://doi.org/10.1097/00007890-199908150-00012.CrossRefPubMed

44.

Weir MR, Fink JC. Risk for posttransplant Diabetes mellitus with current immunosuppressive medications. Am J Kidney Dis. 1999;34(1):1–13. https://doi.org/10.1016/s0272-6386(99)70101-0.CrossRefPubMed

45.

Vaziri ND, Liang K, Azad H. Effect of cyclosporine on HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LDL receptor, HDL receptor, VLDL receptor, and lipoprotein lipase expressions. J Pharmacol Exp Ther. 2000;294(2):778–83.PubMed

46.

Allamani M, Sennesael J, Vendemeulenbroucke E. Posttransplantation diabetes mellitus: a long-term retrospective cohort study. Transplant Proc. 2010;42(10):4378–83. https://doi.org/10.1016/j.transproceed.2010.07.009.CrossRefPubMed

47.

Pham PT, Pham PM, Pham SV, Pham PA, Pham PC. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes. 2011;4:175–86. https://doi.org/10.2147/DMSO.S19027.CrossRefPubMedPubMedCentral

48.

Knoll GA, Bell RC. Tacrolimus versus cyclosporin for immunosuppression in renal transplantation: meta-analysis of randomised trials. BMJ (Clinical research ed). 1999;318(7191):1104–7. https://doi.org/10.1136/bmj.318.7191.1104.CrossRef

49.

Pereira MJ, Palming J, Rizell M, et al. Cyclosporine A and tacrolimus reduce the amount of GLUT4 at the cell surface in human adipocytes: increased endocytosis as a potential mechanism for the diabetogenic effects of immunosuppressive agents. J Clin Endocrinol Metab. 2014;99(10):E1885–94. https://doi.org/10.1210/jc.2014-1266.CrossRefPubMed

50.

Fonseca ACRG, Carvalho E, Eriksson JW, Pereira MJ. Calcineurin is an important factor involved in glucose uptake in human adipocytes. Mol Cell Biochem. 2018;445(1–2):157–68. https://doi.org/10.1007/s11010-017-3261-0.CrossRefPubMedPubMedCentral

51.

Forte CC, Pedrollo EF, Nicoletto BB, et al. Risk factors associated with weight gain after kidney transplantation: a cohort study. PLoS One. 2020;15(12):e0243394. https://doi.org/10.1371/journal.pone.0243394.CrossRefPubMedPubMedCentral

52.

Altheaby A, Alajlan N, Shaheen MF, et al. Weight gain after renal transplant: Incidence, risk factors, and outcomes. PLoS One. 2022;17(6):e0268044. https://doi.org/10.1371/journal.pone.0268044.CrossRefPubMedPubMedCentral

53.

Mihatsch MJ, Kyo M, Morozumi K, et al. The side-effects of cyclosporine-A and tacrolimus. Clin Nephrol. 1998;49(6):356–63.PubMed

54.

Alghamdi S, Nabi Z, Skolnik E, Alkorbi L, Albaqumi M. Cyclosporine versus tacrolimus maintenance therapy in renal transplant. Exp Clin Transplant. 2011;9(3):170–4.PubMed

55.

Kaplan B, Schold JD, Meier-Kriesche HU. Long-term graft survival with neoral and tacrolimus: a paired kidney analysis. J Am Soc Nephrol. 2003;14(11):2980–4. https://doi.org/10.1097/01.asn.0000095250.92361.d5.CrossRefPubMed

56.

Vincenti F, Jensik SC, Filo RS, Miller J, Pirsch J. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation. 2002;73(5):775–82. https://doi.org/10.1097/00007890-200203150-00021.CrossRefPubMed

Title: The effect of calcineurin inhibitors on anthropometric measurements in kidney transplant recipients
Authors: Emel Isiktas Sayilar
Alparslan Ersoy
Canan Ersoy
Aysegul Oruc
Yavuz Ayar
Deniz Sigirli
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Obesity
Obesity
Insulins
Insulins
Tacrolimus
Calcineurin Inhibitors
Published in: BMC Nephrology / Issue 1/2022
Electronic ISSN: 1471-2369
DOI: https://doi.org/10.1186/s12882-022-03004-1

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2022

The effect of two types of diet on apoptosis indexes, lipid profile and histopathological outcome in acute kidney injury during exercise

Associations of sodium and potassium intake with chronic kidney disease in a prospective cohort study: findings from the Hispanic Community Health Study/Study of Latinos, 2008–2017

SARS-CoV-2 in dialysis patients and the impact of vaccination

Intestinal dysbiosis featuring abundance of Streptococcus associates with Henoch-Schönlein purpura nephritis (IgA vasculitis with nephritis) in adult

Impact of telehealth interventions added to peritoneal dialysis-care: a systematic review

Patient-reported outcomes in a pilot clinical trial of twice-weekly hemodialysis start with adjuvant pharmacotherapy and transition to thrice-weekly hemodialysis vs conventional hemodialysis

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage