Duck Jong Han

Objective: We analyzed the efficacy and safety of an everolimus with reduced‐exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard‐exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study.Methods: In this 24‐month, open‐label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids.Results: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m² or treated biopsy‐proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m², P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m², P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm.Conclusion: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).

Laboratory biomarkers that can differentiate non‐infectious fever from infectious fever after pancreas transplantation have yet to be discovered. Non‐infectious fever was defined as the presence of fever (>38.3°C) in the absence of a documented clinical diagnosis of infection or a positive culture. Among 184 consecutive recipients, a total of 91 recipients developed fever within 1‐month post‐transplant, of whom 46 had infectious fever and 45 had non‐infectious fever at our center between August 2014 and July 2019. The onset of fever was earlier in the non‐infectious fever group (14.4 ± 3.7 post‐transplant days) compared with the infectious fever group (16.5 ± 5.8 post‐transplant days; p = .033). Multivariate analysis showed that serum procalcitonin at the peak of fever could significantly differentiate infectious fever from non‐infectious fever (OR 53.378, 95% CI: 6.819‐417.802, p < .001). The area under the curve for differentiating between the two groups was 0.853 (95% CI, 0.780‐0.926) for procalcitonin and 0.667 (95% CI, 0.549‐0.785) for CRP. The best cutoff values of serum procalcitonin and CRP were 0.405 ng/ml (sensitivity, 77.1%; specificity, 80.8%) and 7.355 mg/dl (sensitivity, 66.7%; specificity, 67.3%), respectively. Serum procalcitonin may be useful for differentiating non‐infectious fever from infectious fever after pancreas transplantation.

Minjae Kim, Shin Hwang, Chul-Soo Ahn, Deok-Bog Moon, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Sung Shin, Young Hoon Kim, Hea-Seon Ha, Jung-Ja Hong, In-Ok Kim, Duck Jong Han, and Sung-Gyu Lee. Ann Hepatobiliary Pancreat Surg 2020;24:454-9. https://doi.org/10.14701/ahbps.2020.24.4.454

The 30-Year Experience of a Single Center Objectives: We aimed to investigate the incidence, manifestations, and outcomes of malignancy after pediatric kidney transplantation (KT) at our center over 30 years. Methods: We retrospectively reviewed the medical records of 155 patients under 18 years of age who underwent KT between January 1990 and February 2020 at Asan Medical Center. Results: Twelve patients (7.7%) were diagnosed with a malignancy after KT. Malignancy was diagnosed after a mean period of 6.4±5.9 years (median 4.6, range 0.5-20.6 years) after KT. Nine (75.0%) of the 12 cancer patients were diagnosed with post-transplant lymphoproliferative disease (PTLD), and the other three had papillary thyroid cancer, mucoepidermoid cancer of the hard palate, and T-cell acute lymphoblastic leukemia, respectively. PTLD was diagnosed within a mean of 3.7±3.4 years (median 3.7, range 0.5-9.8 years) after KT. Five patients diagnosed with PTLD were cured without recurrence. Three patients with PTLD died from the disease, and one patient with mucoepidermoid cancer from a non-PTLD malignancy died after progression, despite surgical resection and chemotherapy. Three (33.3%) of the nine survivors progressed to end-stage renal disease (ESRD) after completing cancer treatment. No patient with post-transplant malignancy (PTM) experienced critical renal deterioration during cancer treatment. Conclusion: PTLD was the most common PTM, occurring at 5.8% of the pediatric KT patients after KT in our center. Careful follow up is needed particularly considering the risk of PTLD after KT in children.

Sensitization to human leukocyte antigens (HLAs) has been one of the major clinical challenges for successful kidney transplantation. In end-stage renal disease, kidney transplantation provides benefits compared with dialysis in terms of improved patient survival better quality of life, and lower ongoing costs after the first year. Living donor kidney transplantation has an advantage with improved allograft survival, and performed earlier and electively compared with deceased donor transplantation. However sensitized patients are increasing in number on transplant waiting lists, and their prospect of getting a transplant is less than nonsensitized patients due to immunological incompatibility with the donor. Strategy for sensitized patients are listing for a compatible deceased donor transplant or, if they have a living donor, either selecting a kidney exchange program or undergoing a desensitization procedure. Desensitization procedures may be undertaken to increase access to either living or deceased donor transplants, and in some situations may also be employed to facilitate participation in a kidney exchange, in less immunological barrier to be overcome. The question of whether individuals are better off with a desensitization treatment followed by HLA-incompatible living donor transplantation or waiting on the deceased donor kidney transplant list for a compatible transplant has recently been addressed by two large multicenter studies, with conflicting results. A multicenter study from the United States published in the New England Journal of Medicine [365;318 326.2011] concluded that there was a strong survival benefit for sensitized patients undergoing desensitization followed by HLA-incompatible living donor kidney transplant compared with those remaining on the waiting list. Of interest, a second study, published in the Lancet, [389;727 734.2017] found no significant survival advantage for desensitized patients compared with similar patients remaining on the waiting list in the United Kingdom. Controversies still remain regarding how desensitization can be achieved and which techniques are effective and safe. In this chapter various complications from the desensitization will be dealt with in current use of medications or armamentum. Keywords Desensitization Adverse effects Kidney transplantation

Background: A multicenter, randomized, open-label, parallel group, pilot, 52-week study in Asian countries that assessed the renal function, efficacy, and safety of reduced-exposure versus standard-exposure prolonged-release tacrolimus (PR-T) in adult kidney transplant recipients (KTRs). Methods: Posttransplantation, KTRs received PR-T from weeks 0 to 4 (initial dose, 0.2–0.3 mg/kg; target trough level, 6–10 ng/mL). At week 4, KTRs were randomized (1:1) to receive reduced-exposure PR-T (target 4–6 ng/mL, weeks 4–12; 3–5 ng/mL, weeks 12–52) or standard-exposure PR-T (target: 6–10 ng/mL, weeks 4–52). Primary end point: estimated glomerular filtration rate (eGFR) over 52 weeks. Secondary end points (week 52) included creatinine clearance, serum creatinine, graft/patient survival, biopsy-confirmed acute rejection (AR), composite of graft loss/patient death/biopsy-confirmed AR, and steroid-resistant AR. Treatment-emergent adverse events were recorded. Results: Sixty-six KTRs received PR-T (reduced-exposure, n = 32; standard-exposure, n = 34) and were analyzed. After per-protocol dose adjustment, mean ± standard deviation tacrolimus trough level was lower with reduced- versus standard-exposure PR-T (week 52, 4.5 ± 1.1 ng/mL vs 8.0 ± 2.2 ng/mL). In the reduced- versus standard-exposure group, eGFR was similar at weeks 8 to 52 (overall least-square mean difference, –2.82; 95% confidence interval, −7.91 to 2.27; P = 0.272). At week 52, there was no significant difference in creatinine clearance (P = 0.375) or serum creatinine (P = 0.547) between groups. All grafts/patients survived, no steroid-resistant AR was reported, and 4 and 3 patients had AR in reduced- and standard-exposure groups, respectively. Drug-related treatment-emergent adverse events were reported in 34.4% and 38.2% of patients, respectively. Conclusions: Reducing exposure to PR-T resulted in a clinically acceptable short-term safety profile and was generally as effective as standard tacrolimus exposure for Asian patients.