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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Transplant Surgery · Calcineurin Inhibitor Toxicity and Post-Transplant Complications

Medication Side Effects: Kidneys, Blood Sugar, and Blood Pressure

At a Glance

Calcineurin inhibitors (CNIs) like tacrolimus prevent organ rejection but can cause high blood pressure, kidney stress, and new-onset diabetes. Your transplant team uses therapeutic drug monitoring to balance medication levels, maximizing organ protection while minimizing harmful side effects.

The medications that protect your transplant are powerful tools, but they often come with a “trade-off.” The most common class of transplant medications—Calcineurin Inhibitors (CNIs), which include tacrolimus (Prograf) and cyclosporine (Neoral/Gengraf)—can cause side effects that affect your kidneys, blood sugar, and blood pressure. Understanding these effects allows you and your care team to manage them proactively.

The CNI Paradox: Protecting the Organ, Stressing the Kidneys

It is ironic that the very drugs used to save a transplanted organ can sometimes cause nephrotoxicity (kidney damage).

  • How it happens: CNIs work by blocking specific pathways in your immune cells, but they also cause the small blood vessels in the kidneys to constrict (tighten) [1][2]. Over time, this reduced blood flow can lead to structural changes like scarring (fibrosis) and thinning of the kidney tubes (tubular atrophy) [3][4].
  • The Solution: Your team uses therapeutic drug monitoring to keep the medication in a “Goldilocks” zone—high enough to prevent rejection but low enough to minimize kidney stress. If damage is detected, they may lower the dose or switch you to a different type of medication [5][6].

New-Onset Diabetes After Transplant (NODAT)

Many patients develop high blood sugar for the first time after their transplant. This is called New-Onset Diabetes After Transplant (NODAT).

  • The Cause: CNIs, especially tacrolimus, can interfere with the “beta cells” in your pancreas that produce insulin. They can cause these cells to become stressed or produce less insulin [7][8]. When combined with corticosteroids (like prednisone), which make your body more resistant to insulin, your blood sugar can rise [5][9].
  • Risk Factors: You are at higher risk for NODAT if you are older, have high CNI “trough” levels (the lowest level of the drug in your blood before your next dose), or have low magnesium levels [10][8].

Managing High Blood Pressure

Hypertension (high blood pressure) is a very common side effect of CNIs.

  • The Mechanism: CNIs increase the activity of the sympathetic nervous system (your “fight or flight” response) and cause blood vessels throughout the body to constrict [2].
  • Treatment: Doctors often prescribe specific blood pressure medications, such as calcium channel blockers (like amlodipine), because they help counteract the vessel-tightening effects of CNIs [11].

Exploring Alternatives: Belatacept and CNI-Sparing

For some patients, the side effects of CNIs become too difficult to manage. In these cases, doctors may consider alternative “CNI-sparing” regimens.

  • Belatacept: Unlike CNIs, belatacept is an injectable medication that does not cause kidney constriction or significantly increase the risk of diabetes [12][13]. Patients who switch often see an improvement in their kidney function (eGFR) [14][15].
  • The Trade-off: While belatacept is gentler on the kidneys and metabolism, it may carry a slightly higher risk of acute rejection episodes compared to tacrolimus [16][17]. It is also only used in patients who have already been exposed to the Epstein-Barr Virus (EBV) due to safety concerns.

Your care team will constantly weigh these risks and benefits to ensure you have the best possible long-term outcome.

Common questions in this guide

Why do my transplant medications affect my kidneys?
Calcineurin inhibitors (CNIs) like tacrolimus work to prevent organ rejection but can also cause small blood vessels in the kidneys to constrict. Over time, this reduced blood flow can lead to kidney stress or scarring, which is why your care team carefully monitors your medication levels.
What is New-Onset Diabetes After Transplant (NODAT)?
NODAT is high blood sugar that develops after an organ transplant. It is often caused by anti-rejection medications, particularly tacrolimus and corticosteroids, which can interfere with insulin production and make your body more resistant to insulin.
How is high blood pressure from transplant medications treated?
Doctors frequently prescribe specific blood pressure medications, such as calcium channel blockers like amlodipine. These help counteract the vessel-tightening effects caused by your transplant medications without interfering with their ability to protect your new organ.
Are there alternatives to CNIs if the side effects are too severe?
Yes, for some patients, doctors may recommend a CNI-sparing regimen. Medications like belatacept are gentler on the kidneys and metabolism, though they carry their own specific risks and are only suitable for certain patients based on their viral history and rejection risk.
What is a CNI trough level and why is it checked?
A trough level is the lowest concentration of a medication in your bloodstream just before you take your next dose. Doctors check this level to ensure your medication is high enough to prevent organ rejection but low enough to avoid causing kidney damage or diabetes.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is my current 'trough level' for my CNI, and is it in the range where it might be affecting my kidneys or blood sugar?
  2. 2.Are my blood pressure medications, like calcium channel blockers, interacting with my transplant meds in any way?
  3. 3.Based on my risk of rejection, am I a candidate for 'CNI-sparing' options like belatacept or mTOR inhibitors?
  4. 4.If my blood sugar stays high, will we change my transplant medications or start me on diabetes-specific treatments?
  5. 5.How often will we be checking my 'eGFR' (kidney function) to monitor for drug-related stress on my kidneys?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
  1. 1

    Immunosuppression with cyclosporine versus tacrolimus shows distinctive nephrotoxicity profiles within renal compartments.

    Demirci H, Popovic S, Dittmayer C, et al.

    Acta physiologica (Oxford, England) 2024; (240(8)):e14190 doi:10.1111/apha.14190.

    PMID: 38884453
  2. 2

    Calcineurin Controls Hypothalamic NMDA Receptor Activity and Sympathetic Outflow.

    Zhou JJ, Shao JY, Chen SR, Pan HL

    Circulation research 2022; (131(4)):345-360 doi:10.1161/CIRCRESAHA.122.320976.

    PMID: 35862168
  3. 3

    Pathophysiological mechanisms of calcineurin inhibitor-induced nephrotoxicity and arterial hypertension.

    Hošková L, Málek I, Kopkan L, Kautzner J

    Physiological research 2017; (66(2)):167-180 doi:10.33549/physiolres.933332.

    PMID: 27982677
  4. 4

    CD44 as a pathological marker for the early detection of calcineurin inhibitor-induced nephrotoxicity post kidney transplantation.

    Hayashi A, Okamoto T, Nio-Kobayashi J, et al.

    Biomedical research (Tokyo, Japan) 2022; (43(5)):181-186 doi:10.2220/biomedres.43.181.

    PMID: 36244796
  5. 5

    Twelve-Month and Five-Year Analyses of Risk Factors for New-Onset Diabetes After Transplantation in a Group of Patients Homogeneous for Immunosuppression.

    Dedinská I, Laca Ĺ, Miklušica M, et al.

    Transplantation proceedings 2015; (47(6)):1831-9.

    PMID: 26293059
  6. 6

    New-Onset Diabetes After Transplantation: Comparison Between a Cyclosporine-Based and a Tacrolimus-Based Immunosuppressive Regimen.

    Zolota A, Miserlis G, Solonaki F, et al.

    Transplantation proceedings 2018; (50(10)):3386-3391 doi:10.1016/j.transproceed.2018.08.037.

    PMID: 30577210
  7. 7

    Tacrolimus-induced acute pancreatitis and diabetic ketoacidosis (DKA) in pediatric kidney transplant recipient.

    Mazumder MA, Gulati S, Narula AS, et al.

    Pediatric transplantation 2022; (26(2)):e14194 doi:10.1111/petr.14194.

    PMID: 34854174
  8. 8

    Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein-1 are involved in tacrolimus-induced diabetes mellitus.

    Sun X, Wang H, Chi J, et al.

    Pharmacology research & perspectives 2023; (11(3)):e01081 doi:10.1002/prp2.1081.

    PMID: 37195045
  9. 9

    New-Onset Diabetes Mellitus (NODM) After Liver Transplantation (LT): The Ultimate Non-diabetogenic Immunosuppressive Therapy.

    Chaitou AR, Valmiki S, Valmiki M, et al.

    Cureus 2022; (14(3)):e23635 doi:10.7759/cureus.23635.

    PMID: 35510006
  10. 10

    Incidence and risk factors of post-transplant diabetes mellitus among kidney transplant recipients: a retrospective study from a tertiary center in Saudi Arabia.

    Alotaibi M, Almalki N, Alotaibi ME, et al.

    BMC nephrology 2025; (26(1)):460 doi:10.1186/s12882-025-04375-x.

    PMID: 40804369
  11. 11

    Targeting Calcineurin Inhibitor-Induced Arterial Hypertension in Liver Transplanted Children Using Hydrochlorothiazide.

    Hartleif S, Baier H, Kumpf M, et al.

    The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 2022; (27(5)):428-435 doi:10.5863/1551-6776-27.5.428.

    PMID: 35845561
  12. 12

    Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review.

    Kumar J, Reccia I, Virdis F, et al.

    World journal of transplantation 2021; (11(3)):70-86 doi:10.5500/wjt.v11.i3.70.

    PMID: 33816147
  13. 13

    From the Clinical to the Bench: Exploring the Insulin Modulation Effects of Tacrolimus and Belatacept.

    Perrier Q, Cottet-Rouselle C, de-Beaumont M, et al.

    Cell transplantation 2024; (33()):9636897241246577 doi:10.1177/09636897241246577.

    PMID: 38646716
  14. 14

    Costimulatory Blockade and Use of mTOR Inhibitors: Avoiding Injury Part 2.

    Wojciechowski D, Vincenti F

    Advances in chronic kidney disease 2016; (23(5)):306-311 doi:10.1053/j.ackd.2016.09.004.

    PMID: 27742385
  15. 15

    Belatacept rescue therapy of CNI-induced nephrotoxicity, meta-analysis.

    El Hennawy H, Safar O, Al Faifi AS, et al.

    Transplantation reviews (Orlando, Fla.) 2021; (35(4)):100653 doi:10.1016/j.trre.2021.100653.

    PMID: 34597943
  16. 16

    A Randomized Controlled Clinical Trial Comparing Belatacept With Tacrolimus After De Novo Kidney Transplantation.

    de Graav GN, Baan CC, Clahsen-van Groningen MC, et al.

    Transplantation 2017; (101(10)):2571-2581 doi:10.1097/TP.0000000000001755.

    PMID: 28403127
  17. 17

    Indirect treatment comparison of belatacept versus tacrolimus from a systematic review of immunosuppressive therapies for kidney transplant patients.

    Muduma G, Hart WM, Patel S, Odeyemi AO

    Current medical research and opinion 2016; (32(6)):1065-72 doi:10.1185/03007995.2016.1157463.

    PMID: 26907083

This page provides educational information on transplant medication side effects. Always consult your transplant coordinator or doctor before making any changes to your medication regimen.

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