The Japanese Society of Therapeutic Drug Monitoring (JSTDM) and the Japanese Society of Transplantation (JST) have developed and launched the first TDM guideline to standardize the routine TDM practice for immunosuppressive drugs (ISD) used in kidney, liver and heart transplantations. This guideline describes a consensus document among transplantation experts of JST and TDM experts of the JSTDM. The Japanese version was published November 20, 2014, and its English version for publication in the TDM Journal, an official journal of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), is in preparation. The guideline is made up of "STATEMENTS" reporting essential information about TDM practice for immunosuppressive drugs used in Japan, which can be used in clinical settings, and of "SUMMARIES," which includes explanations and references. SUMMARIES provides reference literature as well as evidence levels and recommendation grades. Based on limitation of space, the STATEMENTS part is summarized here.
The number of organ transplantations from donation from brain-dead (DBD) donors has recently increased because of the enforcement of the revised Organ Transplantation Law in 2010 in Japan. More than 500 kidney transplant recipients, more than 30 liver transplant recipients, and two recipients of simultaneous pancreas and kidney transplantations have already experienced pregnancy and childbirth in our country. Along with the increase of DBD donors, pregnancy and childbirth must be an important issue for the recipients of heart and lung transplantations as well as kidney and liver transplantations. The Japan Society for Transplantation has decided to make a guideline for pregnancy and childbirth in patients after organ transplantation. The contents of this guideline are planned to be classified into two chapters. One concerns common problems after organ transplantations, such as the use of drugs, including immunosuppressive agents and vaccines. The second chapter is planned to focus on problems particular to reach organ transplantation. Furthermore, this guideline will include the problems of living donors for kidney and liver transplantations and male recipients who underwent organ transplantations.
Cytomegalovirus (CMV) infection is generally diagnosed by the antigenemia method in Japan. CMV infection frequently occurs within 3 months after renal transplantation. Therefore, antigenemia should be studied once a week or 2 weeks within 3 months of postrenal transplantation. The standard level of positive cells depends on the renal transplant center; however, the high-risk recipients, irrespective of being asymptomatic, should be treated as soon as a positive cell appears. In particular, a CMV seronegative recipient transplanted from a seropositive donor tends to suffer from serious infection and disease as a primary infection. In such a case, valganciclovir (VGCV) is prophylactically administered for 3 months postrenal transplantation abroad. Preemptive treatment is preferred in most Japanese renal transplant centers because prophylactic use of VGCV is not covered by medical insurance in Japan. Ganciclovir (GCV) should be intravenously administered at first if a recipient is seriously symptomatic with positive antigenemia. The dose and term of VGCV and GCV are decided in terms of renal function.
Guidelines for clinical practice of kidney transplant donors and recipients are pivotal to perform quality-controlled kidney transplantation. The guidelines for both renal transplant donors and recipients have recently been developed during a recent 3-year-period in Japan. A joint study by the Japanese Society for Transplantation and the Japanese Renal Transplant Society led to these important results. Guidelines for the care of live renal transplant donors were partially determined by reference to the Amsterdam Forum as an international authority on such standards. A society member who consents to be a donor should be competent, willing to donate, free of coercion, medically and psychosocially suitable, and fully informed of the risks and benefits as a live donor. Details of the criteria are modified to reflect the current situation in Japan. The standard list of criteria and the marginal list of criteria are prescribed as the result of studying past records. The precise criteria of donor age, renal function, hypertension, body mass index (BMI), and diabetes of Japanese guidelines are different from the Amsterdam Forum criteria. Kidney Disease: Improving Global Outcomes (KDIGO) published guidelines for the care of renal transplant recipients. The Japanese Society for Clinical Renal Transplantation also presented guidelines in some selected fields. The development of guidelines regarding renal transplants is expected to result in high-quality clinical transplantation.
Many medical complications, including hypertension, diabetes, and dyslipidemia, appear after kidney transplantation. These complications significantly affect the grafts and the patient survivals; thus the control of posttransplant medical complications is absolutely essential. Unfortunately, steroid and immunosuppressive agents induce or impair the medical complications, which are a special condition after kidney transplantation. The Japanese Society of Clinical Renal Transplantation (JSCRT) has already published "Guidelines for medical and pediatric complications after kidney transplantation" in 2011. Earlier, in 2009, "KDIGO Clinical Practice Guidelines for Kidney Disease" for the care of kidney transplant patients was published in the American Journal of Transplantation. The contents of recommendations are not always the same between two guidelines. Referring to these two guidelines, the author summarized the points and problems and posttransplant hypertension, posttransplant diabetes, and post transplant dyslipidemia.
The risk of invasive pneumococcal disease (IPD) among kidney transplant recipients is about 9 times higher than in the general population. IPD in solid-organ transplant recipients has a mortality rate of about 30%. Pneumococcal vaccine is significantly effective to prevent IPD and is currently recommended for solid-organ transplant recipients. We vaccinated all blood-group-incompatible living-donor kidney transplant recipients who needed a splenectomy with 23-valent pneumococcal polysaccharide vaccine (PPV23) in 2006. Since 2007, we have vaccinated all living-donor kidney transplant recipients before transplantation. Two cases of IPD occurred in our department from January 1, 2000, to May 31, 2014. Case 1, who was not vaccinated, died the next day after the onset of IPD in spite of intensive care, and the pneumococcal serotype was type 18C. Case 2, who was vaccinated only once, eventually involved severe neurological sequelae and the pneumococcal serotype was type 24. PPV23 contains 85.4% pneumococcal serotypes responsible for IPD in Japan. It contains type 18C but not type 24. We consider pneumococcal vaccination to be extremely important to all kidney transplant recipients.
The availability of a regional team may facilitate the organization and coordination of organ procurement. As a result, regional organ procurement has been reported to reduce costs, streamline logistics, and increase safety for the teams. We herein report a case of brain-dead donor liver transplantation with regional organ procurement. Because of the collaboration between the transplant team and the donor surgery team, the latter being was comprised of a liver transplant team in the local area of the donor hospital, a smooth brain-dead donor liver transplantation was successfully performed. Regional organ procurement is considered achievable in the future with the standardization of organ procurement by the establishment of an educational system for donor surgery.