The KHA-CARI Guidelines Caring for Australasians with Renal Impairment The Kidney Health Australia-Caring for Australasians with Renal Impairment (KHA-CARI) Guidelines Adaptation of the KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients

s and in relevant cases full text articles of additional literature identified by the update search were reviewed in addition to going through the full text of the relevant articles already mentioned in the KDIGO guidelines. Additional searches were done by the authors relevant to the topic. Databases searched: Medline, Central, Cochrane database of systematic reviews. Date of searches: November 2010. ADEQUACY OF KDIGO SEARCH STRATEGY The KDIGO search strategy used was not described sufficiently to be reproducible, but searched using terms for kidney transplant recipients, and terms for the interventions acyclovir, gancyclovir, reduce immunosuppression, intravenous immunoglobulin, anti-CD20 antibody, and limited the results to RCTs with ≥ 20 participants or cohort studies with ≥ 100 participants (Refer to Table 32 of the KDIGO guidelines). The authors felt excluding studies on the basis of number of participants had no evidence base, and so were prepared to consider any RCT or cohort papers. APPLICABILITY OF KDIGO RECOMMENDATIONS AND SUGGESTIONS There are no reasons why the source data and guidelines are not applicable to patients in an Australian context, and most of the recommendations and suggestions can be adopted without any significant changes to current practice. The only recommendation (IB) made in KDIGO– regarding the reduction or cessation of immunosuppression, is intuitively appealing and largely adaptable, though not based on RCT evidence. Since more robust evidence in this area is not likely to be forthcoming in the future, this has been retained, but as a suggestion. Other recommendations made in KDIGO without a sound evidence base are intuitively appealing, such as those regarding EBV viral load monitoring, however the basis for firm recommendations about frequency and duration of monitoring is questioned. Some additional suggestions have been included in the KHA-CARI adaptation. OVERVIEW OF THE EVIDENCE There was no high quality additional evidence to suggest any confident changes to the recommendations or suggestions for this chapter. Due to the lack of evidence some of the recommendations made in the KDIGO guidelines were softened, particularly those regarding EBV viral load monitoring. Additional literature review for this adaptation revealed one new relevant RCT of ganciclovir plus placebo versus ganciclovir plus IVIG in patients at high risk of primary EBV infection [350]. The results were inconclusive (no difference), and the design lacked a full placebo arm, so no meaningful conclusions could be drawn about the interventions to provide a useful recommendation. Other studies provided by the Adaptation Workgroup provide additional evidence, but no new concepts, interventions or prognostic information [351-355]. The KHA-CARI Guidelines – Caring for Australasians with Renal Impairment KHA-CARI Adaptation of KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients (February 2012) Page 104 SUMMARY OF EVIDENCE The recommendations and suggestions are based largely on low-quality evidence due to a paucity of relevant randomized trials in this field. WHAT DO THE OTHER GUIDELINES SAY? Kidney Disease Outcomes Quality Initiative: None UK Renal Association: None Canadian Society of Nephrology: None European Best Practice Guidelines: [356] A. In the first year after organ transplantation, recipients are at the greatest risk of developing lymphoproliferative diseases (PTLDs), which are induced most often by Epstein–Barr virus (EBV) infection, and patients should therefore be screened prior to or at the time of transplantation for EBV antibodies. (Evidence level B) B. In the rare cases (<5%) where the recipient is EBV seronegative, he or she has a 95% likelihood of receiving an organ from an EBV‐ seropositive donor, which translates into a high risk of primary EBV infection with seroconversion soon after transplantation. In such cases, the recipient should receive a prophylactic antiviral treatment with acyclovir, valacyclovir or ganciclovir, starting at the time of transplant and lasting for at least 3 months. The specific recommendations given for CMV prophylaxis could be applicable in this situation. (See also Guidelines in Part 1: III.8.1, p. 87.) (Evidence level C) C. The treatment of PTLD should be based on accurate pathology with extensive cell markers and phenotyping. The treatment modalities are as follows. Reduction of basal immunosuppression in all cases (either maintain only steroids, or decrease by at least 50% the anti-calcineurin drugs and stop other immunosuppressive drugs). (Evidence level B) In the case of EBV-positive B-cell lymphoma, antiviral treatment with acyclovir, valacyclovir or ganciclovir may be initiated for at least 1 month or according to the blood level of EBV replication when available. (Evidence level C) In the case of rare lymphomas from the mucosal-associated lymphoid tissue (MALT) with positive Helicobacter pylori, full eradication of H. pylori should be carried out with a validated protocol. Subsequent H. pylori prophylaxis should be implemented to avoid relapse. (Evidence level B) In the case of CD20-positive lymphomas, treatment with rituximab, a chimeric monoclonal antibody directed against CD20, should be carried out with one iv injection per week for 4 weeks. (Evidence level B) In the case of diffuse lymphomas or improper response to previous treatment, CHOP chemotherapy should be used alone or in combination with rituximab. The CHOP regimen is cyclophosphamide, doxorubicine, vincristine and prednisone. (Evidence level B) Complete cessation of immunosuppression with or without graft nephrectomy should also be considered. (Evidence level C) International Guidelines: None The KHA-CARI Guidelines – Caring for Australasians with Renal Impairment KHA-CARI Adaptation of KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients (February 2012) Page 105 SUGGESTIONS FOR FUTURE RESEARCH 1. RCT examining a protocol driven decrease of immunosuppression in response to increasing EBV titres in high-risk kidney transplant recipients 2. RCT examining a protocol driven anti-viral therapy in response to increasing EBV titres in high risk kidney transplant recipients. 3. Systematic summary of evidence for EBV viral load monitoring CONFLICT OF INTEREST A Webster and K Murali have no relevant financial affiliations that would cause a conflict of interest according to the conflict of interest statement set down by KHA-CARI. The KHA-CARI Guidelines – Caring for Australasians with Renal Impairment KHA-CARI Adaptation of KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients (February 2012) Page 106 Topic 13.4. Herpes Simplex Virus 1, 2 and Varicella Zoster Virus Author: Helen Pilmore and Paul Manley