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Information

Editors

MaijaHeiro
IlkkaHelanterä

Organ Transplant Recipient in Primary Health Care

Essentials

  • Immunosuppressive (anti-rejection) medication must not be altered in primary health care.
  • Drugs used in immunosuppression have significant interactions with other medicines, and this must always be taken into account before prescribing new medication.
  • If acute rejection is suspected, the patient must be referred immediately to an appropriate hospital.
  • During the first months after transplantation, all symptoms, however small, warrant referral to specialist care for further investigation and treatment.
  • Antimicrobial prophylaxis is recommended, with the same principles as for patients with prosthetic heart valves, before interventions such as certain dental procedures.
  • Early specialist consultation

Organisation

  • The organs usually transplanted are kidney, liver, heart, lung, combined heart-lung and pancreatic islet cells.
  • The outcomes of organ transplants have markedly improved over the years.
  • Most complications occur during the first post-transplantation year.
  • If the transplanted organ functions well, many health problems may be managed in primary care after the first year.

Monitoring after transplantation

  • A transplant recipient usually remains in the transplant unit for 1-4 weeks after the surgery.
  • After discharge, the patient's health, the functioning of the graft and the concentration of the immunosuppressive medication in the blood are checked at the local hospital. The checks are initially carried out at least once every week for one month, then every 1-2 weeks for 2 months, then usually monthly for the first post-transplantation year and finally every 2-6 months.

Immunosuppressive medication and associated problems Interleukin 2 Receptor Antagonists for Kidney Transplant Recipients, Sirolimus and Everolimus for Primary Immunosuppression in Kidney Transplant Recipients, Maintenance Immunosuppression for Liver Transplanted Patients, Mycophenolic Acid for Kidney Transplant Recipients, Glucocorticosteroid Avoidance for Liver Transplanted Patients

  • Medication must continue for as long as the functioning of the transplanted organ remains satisfactory.
  • Immunosuppressive medication is prescribed by a specialist physician.
  • The commonly used triple immunosuppressive regimen consists of ciclosporin or tacrolimus combined with mycophenolate mofetil or azathioprine and also a concomitant small dose of a glucocorticoid.
  • Immunosuppressive medication often increases the patient's glucose and lipid values, as well as blood pressure, to the point where medication is needed.
  • In order to prevent cardiac events, all patients should be prescribed aspirin.
  • Glucocorticoids reduce bone density, and consequently supplemental vitamin D, often supplemental calcium and sometimes bisphosphonates Prevention of Bone Disease in Kidney Transplant Recipients, are recommended to transplant recipients.
  • Immunosuppressive medication predisposes the patient to infections and, over the years, also to malignancies and arteriosclerosis.

Calcineurin inhibitors Maintenance Immunosuppression for Liver Transplanted Patients, Calcineurin Inhibitor Withdrawal or Tapering for Kidney Transplant Recipients

Ciclosporin and tacrolimus

  • Ciclosporin and tacrolimus are the corner stones of immunosuppression Calcineurin Inhibitor Withdrawal or Tapering for Kidney Transplant Recipients.
  • T-lymphocyte activity is suppressed as the expression of the gene IL-2 is inhibited.
  • The dose is determined according to the blood concentrations (mass spectrometric blood cyclosporin A / tacrolimus).
  • Adverse effects are often dose dependent and include nephrotoxicity (increased plasma creatinine), hypertension, neurotoxicity (tremor, paraesthesia), diabetes and headache.

The most significant drug interactions of ciclosporin and tacrolimus

The concentration of ciclosporin and tacrolimus is
increased by:decreased by:
FluconazolePhenytoin
ItraconazoleCarbamazepine
KetoconazoleBarbiturates
ErythromycinRifampicin
Clarithromycin
Diltiazem
Verapamil
Ethinyloestradiol
Metronidazole
The nephrotoxicity of ciclosporin and tacrolimus is increased by:
Amphotericin B
Aminoglycosides
NSAIDs
Diuretics

Purine antagonists Mycophenolic Acid for Kidney Transplant Recipients

Mycophenolate

  • Inhibition of lymphocyte activity
  • Dose: mycophenolate mofetil 1-2 g/day, mycophenolic acid 720-1 440 mg/day
  • Not nephrotoxic
  • Adverse effects include gastrointestinal complaints, diarrhoea, hepatopathy and myelosuppression

Azathioprine

  • An alternative to mycophenolate
  • The usual dose of azathioprine is 75-150 mg/day. It may be necessary to reduce the dose due to adverse effects (myelosuppression, hepatotoxicity).

mTOR inhibitors Sirolimus and Everolimus for Primary Immunosuppression in Kidney Transplant Recipients

Sirolimus and everolimus

Glucocorticoids Glucocorticosteroid Avoidance for Liver Transplanted Patients, Steroid Avoidance or Withdrawal for Kidney Transplant Recipients, Maintenance Immunosuppression for Liver Transplanted Patients

Interactions with immunosuppressive medication

  • Ciclosporin and tacrolimus in particular have significant interactions (table T1).
  • Before prescribing new medication possible interactions with the immunosuppressive therapy must be checked. Check locally available database(s) on interactions and adverse effects.
  • Grapefruit juice increases the concentration of both ciclosporin and tacrolimus, and it should be avoided.
  • Hypericum (St. John's wort) may decrease the concentration of at least ciclosporin and it should be used with caution.
  • If possible, antifungal drugs and macrolide antimicrobials should be avoided.
  • Allopurinol inhibits the metabolism of azathioprine and the two drugs must not be used concomitantly.
    • If the patient has severe gout, changing azathioprine to mycophenolate may be considered in the hospital, in which case allopurinol may be used.

Examples of safe medicines for organ transplant recipients

Antimicrobial drugsPenicillins
Cephalosporins1)
Sulphonamides1)
Trimethoprim1)
Fluoroquinolones1)
Clindamycin
Aciclovir1)
Cardiovascular drugs1) Beta-blockers
Calcium-channel blockers
ACE inhibitors1) and angiotensin-II receptor antagonists1)
Analgesic drugsTramadol1)
Paracetamol, except for liver transplant patients
Psychotropic drugsUsually safe
1) Reduced renal function to be taken into account
Infections in organ transplant recipients
  • Immunosuppressive medication predisposes the patient both to bacterial and viral infections (cytomegalovirus, Herpes simplex virus, Epstein-Barr virus, polyomaviruses) as well as to opportunistic infections (Pneumocystis jirovecii, listeria, fungi).
  • The risk of infection is highest during the first few months after transplantation.
  • Immunosuppression may mask the signs of infection.
  • After organ transplantation the recipient is often given valganciclovir or aciclovir prophylactically for 3-12 months against cytomegalovirus (CMV) and herpes infections Cytomegalovirus Prophylaxis with Antiviral Agents for Solid Organ Transplantation. The duration and choice of drug is dependent on the transplanted organ and the CMV antibody status of the recipient.
  • Both CMV and herpes infections may recur, particularly during the first post-transplantation year.
  • The first-line treatment of a CMV infection is either oral valganciclovir or intravenous ganciclovir and that of herpes infection acyclovir or valacyclovir.
  • BK polyomavirus may cause so-called polyomavirus nephropathy in a kidney transplant. It is treated by reduction of immunosuppressive therapy.
  • Prophylaxis against Pneumocystis jirovecii pneumonia in lung transplant recipients consists of lifelong co-trimoxazole or pentamidine inhalations; in other transplant recipients the duration of prophylaxis is 6 months.
  • During the first post-transplantation year all infections require specialist management.
  • When more than one year has lapsed from the transplantation and the function of the transplanted organ is stable, mild infections (afebrile urinary tract infection, upper respiratory tract infection, maxillary sinusitis) may be treated in primary care according to the same principles as in the overall population.
  • Pneumonia, febrile urinary tract infection and febrile skin infection always require specialist management.
  • Not even during infectious episodes must immunosuppressive medication be reduced in primary care without consulting a physician experienced in the treatment of transplant patients.

Dental care

  • Regular dental care is particularly important in organ transplant recipients in order to avoid infections.
  • Ciclosporin causes gingival hyperplasia which is exacerbated by calcium-channel blockers used to treat hypertension.
  • Antimicrobial prophylaxis is recommended, with the same principles as for patients with prosthetic heart valves, before procedures that involve the risk of bacteraemia Prevention of Bacterial Endocarditis.

Travelling

  • Travel abroad is not recommended during the first 6 months after transplantation.
  • After this, there is no reason why not to travel, but particular attention should be paid to hygiene and protection from the sun.
  • The treating specialist centre will provide information regarding vaccinations.

Vaccinations

Recommended vaccinations

Contraindicated vaccinations

Vaccinations that may be individually considered

Organ-specific information and complications

Renal transplantation Interleukin 2 Receptor Antagonists for Kidney Transplant Recipients, Statins for Kidney Transplant Recipients, Antihypertensive Treatment for Kidney Transplant Recipients

  • The most common indications are diabetic nephropathy, chronic glomerulonephritis, cystic kidney disease and nephrosclerosis.
  • The majority of transplants are from anonymous brain-dead patients. The number of kidney transplants from living donors has increased in recent years.
  • Rejection
    • The only indicator is usually a symptomless increase in plasma creatinine concentration.
    • Diagnosis is based on clinical picture and histological findings of a graft biopsy.
    • Acute treatment usually consists of high-dose i.v. glucocorticoids.
    • The possibility of increasing the maintenance dose of immunosuppressive medication should be considered.
  • The most common infection in renal transplant recipients is urinary tract infection Urinary Tract Infections.
    • Asymptomatic bacteriuria is common. It is not necessary to treat it routinely.
    • The treatment period of cystitis is in women 1-2 weeks and in men 2-3 weeks.
    • The initial treatment of acute pyelonephritis consists of intravenous antimicrobials, and the treatment should continue for 3 weeks in order to prevent recurrence.
  • Chronic scarring of the graft for an unclear reason is the main cause of renal graft failure. It encompasses chronic rejection, calcineurin inhibitor toxicity, atherosclerosis and infection (including changes caused by CMV and polyomavirus).
  • Renal disease, for example focal segmental glomerulosclerosis, may recur in the transplanted kidney. De novo glomerulonephritis may also develop in the graft.
  • Immunosuppression increases the risk of malignancy. Certain post-transplant viral infections have also been associated with the development of cancers. Skin cancer is the most common type of malignancy.
  • Cost effectiveness of renal transplantation
    • From the health economic point of view, renal transplantation is very economic. In a Finnish study, transplant surgery repaid itself before the end of the second year.
    • Statistically it may be expected that of the transplanted kidneys that function 12 months after transplantation about half will still function after 20 years.

Liver transplantation

  • The most common chronic liver diseases leading to transplantation are primary biliary cirrhosis Primary Biliary Cholangitis and primary sclerosing cholangitis Primary Sclerosing Cholangitis. An increasing number of transplant surgery is carried out for alcoholic cirrhosis of the liver Cirrhosis of the Liver.
  • In 20% of the cases, the cause of liver transplantation is acute liver failure in a previously healthy liver (unknown aetiology, drugs, toxic substances, circulatory disorder).
  • Often the only indication of graft failure are the increasing concentrations of aminotransferases.
  • In liver transplant recipients, the most common cause of death is infection. The most serious infections are usually diagnosed in hospital soon after transplantation.

Heart and lung transplantation Exercise-Based Cardiac Rehabilitation in Heart Transplant Recipients

  • The most common indications
    • Heart transplantation: dilating cardiomyopathy and coronary heart disease
    • Lung transplantation: alpha1-antitrypsin deficiency and idiopathic pulmonary fibrosis
  • Rejection of a heart transplant should be suspected in the presence of unexplained fever, hypotension, fatigue and dyspnoea. Rejection of a lung transplant may also include worsening home readings of the FEV1 (forced expiratory volume in one second) and PEF (peak expiratory flow rate).
  • Infections are the main cause of morbidity and death at the initial phase.
  • The main cause of death 5 years post-transplantation is due to chronic rejection, which will manifest itself as small airway blockage in the transplanted lung or as coronary artery occlusion in the transplanted heart.

Organ transplantation in children

  • The treatment responsibility belongs to a physician with expertise in paediatric organ transplantation.
  • During the early post-transplantation months, the main cause of morbidity and mortality is infection.
  • After the initial post-transplantation months bacterial infections are not very common in children, except urinary tract infections in children who have received a kidney transplant.

Referral to specialist care

  • If acute rejection is suspected, the patient must be referred immediately to an appropriate hospital.
  • If treatment compliance is questioned, specialist staff must be consulted.
  • During the first months after transplantation, all symptoms, however small, warrant referral to specialist care for further investigation and treatment.
  • After the first post-transplantation year, many problems may be managed in primary care, but specialist centres must be consulted whenever in doubt.

Organ transplant recipient and health care

  • The main cause of graft failure after the first post-transplantation year is chronic rejection/chronic scarring of the graft. In many cases, a functioning graft is lost as the patient dies prematurely of cardiovascular disease, malignancy or infection, all of which are more prevalent in organ transplant recipients than in the general population.
  • Particular attention must be paid to the risk factors of arteriosclerosis.
  • Smoking is particularly harmful for all organ recipients.
  • Alcohol consumption should be totally forbidden after liver transplantation, and should be only moderate after other organ transplantation.
  • Pregnancy is possible 1-2 years after transplantation, provided that the transplanted organ functions well. Pregnancy will require careful planning.
  • Successful future management relies on the seamless co-operation between the primary care physician and the specialist.

    References

    • Friman TK, Jäämaa-Holmberg S, Åberg F, et al. Cancer risk and mortality after solid organ transplantation: A population-based 30-year cohort study in Finland. Int J Cancer 2022;150(11)1779-1791. [PubMed]
    • Hariharan S, Israni AK, Danovitch G. Long-Term Survival after Kidney Transplantation. N Engl J Med 2021;385(8)729-743. [PubMed]
    • Helanterä I, Isola T, Lehtonen TK, et al. Association of Clinical Factors with the Costs of Kidney Transplantation in the Current Era. Ann Transplant 2019;24()393-400. [PubMed]
    • Kotton CN, Kumar D, Caliendo AM, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 2013;96(4):333-60. [PubMed]
    • Shirali AC, Bia MJ. Management of cardiovascular disease in renal transplant recipients. Clin J Am Soc Nephrol 2008;3(2):491-504. [PubMed]
    • McKay DB, Josephson MA. Pregnancy after kidney transplantation. Clin J Am Soc Nephrol 2008;3 Suppl 2():S117-25. [PubMed]
    • Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;357(25):2601-14. [PubMed]
    • Weisinger JR, Carlini RG, Rojas E et al. Bone disease after renal transplantation. Clin J Am Soc Nephrol 2006;1(6):1300-13. [PubMed].
    • Kotton CN, Ryan ET, Fishman JA. Prevention of infection in adult travelers after solid organ transplantation. Am J Transplant 2005 Jan;5(1):8-14. [PubMed]
    • Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004 Dec 23;351(26):2715-29. [PubMed]
    • Briggs JD. Causes of death after renal transplantation. Nephrol Dial Transplant 2001 Aug;16(8):1545-9. [PubMed]
    • Cohen D, Galbraith C. General health management and long-term care of the renal transplant recipient. Am J Kidney Dis 2001 Dec;38(6 Suppl 6):S10-24. [PubMed]