Malignancy Diseases in Kidney Transplantation,Clinical Outcomes,Patient, and Allograft Survival: A Case-Control Study

BackgroundMalignancy is a well-known complication in patients after kidney transplantation (KT), but its effect on posttransplant outcomes, allograft, and patient survival remains unexplored. The aim of this study is to report the impact of the comorbidity on clinical outcome, function, and failure of an allograft kidney.MethodsThis case-control study included 101 KT patients. Twenty-six patients who developed cancer (CA) were assigned to the case group and 75 to the control group. Statistical analysis was performed using logistic regression models, and graft survival was analyzed using the Kaplan-Meier curve.ResultsNon-melanoma skin CA was the most common malignancy, accounting for almost 60% of cases, followed by stomach CA, prostate CA, and lymphoproliferative diseases (7.70% each). Difference in graft and patient survival was not significant between the two groups (P > .05). A tumor in nonfunctioning in the first nonfunctioning KT was identified in 1 KT patient with a second allograft and by anatomopathological was detect Fuhrman grade II renal cell carcinoma. This KT patient was in good clinical condition with serum creatinine level of 1.5 mg/dL.ConclusionsNo association was observed between CA development and risk factors, including family history and smoking habit, and no differences in allograft and patient survival were found. Nevertheless, in our data, CA in KT patients occurred early after transplantation. Renal cell carcinoma in allograft failure was identified in a patient; that suggested that nephrectomy of kidney failure must be performed to avoid patient allosensitization and neoplasia. Thus, we suggest continuous screening of malignancy diseases for KT patients.     

Similar Anemic Control Between Chronic Kidney Diseases in Patients With and Without Transplantation on Entry to Dialysis

Background

Transplant recipients are supposedly in a more anemic, catabolic, and even inflammatory state at re-entering hemodialysis due to chronic rejection. The goal of this study was to clarify how transplant recipients can re-enter dialysis safely by focusing on control of anemia.

Shared Decision Making Increases Living Kidney Transplantation and Peritoneal Dialysis

BackgroundHospital accreditation in Taiwan encourages greater use of shared decision making (SDM) in health care. This study aimed to explore the distribution change of treatment modalities for renal replacement therapy (RRT) before and after the use of SDM in newly diagnosed end-stage renal disease (ESRD) patients.MethodsThe processes of SDM for RRT were designed with Internet-based patient educational program and smart system. The project of SDM was reviewed by departmental consensus meeting and continuously executed since January 2017. Patients received long-term RRT between January 2016 and December 2017 were enrolled.ResultsIn 2017, 310 patients (187 male, average 63.9 years old) received long-term RRT. Of them, 220 (71%) patients completed SDM for RRT. Sixty-six patients received peritoneal dialysis (PD), 67 patients entered the evaluation of living related kidney transplantation (KT) program, while 18 patients finally received operation for living KT. Compared to 2016, execution of SDM for RRT was associated with drastically increase of the number of living KT (38.5%) and PD (112.9%) after the implementation of SDM for RRT in 2017. The number of preemptive living KT was also increased from 1 patient to 5 patients. Moreover, 91.3% patients were satisfied with the process of SDM for RRT.ConclusionOur findings suggest that the implementation of SDM before patients entering long term RRT lead to more ESRD patients receiving living KT and entering PD therapy. The increasing trend of living KT could be reasonably expected if SDM for RRT could be carried out nationwide.     

First Multicenter Clinical Trial on Machine Perfusion Preservation for Marginal Donor Kidney Transplantation in Japan

BackgroundMachine perfusion has not been widely used because of its low demand in Japan; however, we believe its advantages may increase the number of organ transplants.MethodsHere, we report the first clinical trial of machine perfusion for kidney transplantation in Japan. We used the CMP-X08 perfusion device (Chuo-Seiko Co, Ltd, Asahikawa, Hokkaido, Japan) to preserve the donated organs. The flow rate, perfusion pressure, renal resistance, and temperature were monitored during continuous hypothermic perfusion.ResultsFrom August 2020 to the present, 13 cases of perfusion-preserved kidney transplantation have been performed. Of these, ten and 3 cases were performed using organs donated after brain death (DBD) and cardiac death (DCD), respectively. The average age of the recipients was 55.9 ± 7.3 (45-66) years. The average dialysis period was 14.8 ± 8.4 (0-26) years. The donor's final creatinine level before organ retrieval was 1.58 ± 1.0 (0.46-3.07) mg/dL. The warm ischemic times of the 3 DCD donors were 3, 12, and 18 minutes. The average total ischemic time was 12.0 ± 3.7 (7.17-19.88) hours. The average MP time was 140 (60-240) minutes. A total of 7 cases had delayed graft function. The best creatinine level during hospitalization was 1.17 ± 0.43 (0.71-1.85) mg/dL. There were no primary non-functional cases, and perfusion preservation was safely performed in all cases.ConclusionsTherefore, we present this report as the first clinical trial on machine perfusion for kidney transplantation from marginal donors with DBD and DCD in Japan.     

Effects of Kidney Transplantation on Valvular Heart Diseases

IntroductionIn patients with end-stage renal failure, hypervolemia frequently causes increased cardiac output, especially in patients who are under-dialyzed and those with cardiac decompensation.ObjectiveThis study aimed to examined the effect of kidney transplantation on valvular heart diseases.Patients and methodsThis retrospective data analysis included adult patients (n = 180) who underwent kidney transplantation between February 2015 and June 2018 at the Division of Organ Transplantation, University of Debrecen, Hungary. This study examined the echocardiographic parameters and laboratory results preoperatively and postoperatively (at 6 and 12 months). Statistical analyses were performed using the χ²/Fisher exact tests and Kruskal-Wallis analysis of variance test. P < .05 was considered significant.ResultsNo mitral regurgitation (MR) was observed preoperatively in 27% of the patients, while 62% had grade 1 MR, and 11% had grade 2 MR. Grade 2 MR was reduced from 11% to 2% twelve months after kidney transplantation (P = .03). Valvular calcification was detected preoperatively in 21.5% of the study population but was detected in 25.8% 6 months postoperation and in 35.5% 12 months postoperation (P = .09). At 12-month follow-up, 30.8% of patients without diabetes and 60% (P = .03) of patients with diabetes had valvular calcification.ConclusionSignificant improvement was noted in patients with moderate-stage MR because renal transplantations decrease the volume overload on the heart. After surgical intervention, elevation in the incidence of calcified valves among patients with diabetes was significant compared to patients without diabetes.     

Influence of Long-term Dialysis on the Outcome of Kidney Transplantation: A Single-Center Study

Aim

We investigated clinical outcomes of patients in Japan with a history of long-term dialysis treatment.

肾移植围术期血流动力学的变化

目的和方法：４０例肾移植病人在硬膜外麻醉胶放置Ｓｗａｎ－Ｇａｎｚ导管行围术期血流动力学分析。结果：硬膜外阻滞３０分钟,ＭＡＰ、ＣＶＰ、体循环阻力（ＳＶＲ）下降明显（Ｐ〈０．０５）,而其他指标无明显变化。髂内动脉阻断后,ＭＡＰ、ＣＶＰ逐渐恢复麻醉前水平,而肺循环阻力（ＰＶＲ）则明显升高（Ｐ〈０．０５）。提供肾血流２０分钟内血流动力学变化较大。心输出量（ＣＯ）、心脏指数（ＣＩ）显著增加（Ｐ〈０．０１）     

Pharmacokinetics for Once- Versus Twice-Daily Tacrolimus Formulations in De Novo Kidney Transplantation: A Randomized, Open-Label Trial

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC_0–24 of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC_0–24 and C_min for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.     

Evaluation of Non-adherence in Patients Undergoing Dialysis and Kidney Transplantation: United States Transplantation Practice Patterns Survey

Introduction

We performed a survey of United States transplantation centers to evaluate practice patterns in the assessment of nonadherence before and after kidney transplantation.

Methods

An electronically administered, anonymous survey was sent to 181 United Network for Organ Sharing (UNOS) approved transplantation centers in 2012.

Results

Seventy-nine centers completed our survey. Of them, 51.3% had a protocol to evaluate medication/dialysis adherence before the listing; most common (36.4%) was the Simplified Medication Adherence Questionnaire. As an alternative to a questionnaire, the most common measure of nonadherence was the number of missed hemodialysis sessions (77.0%). The most common reason for poor adherence to dialysis regimens was difficulty with transportation (81.3%). Also, 94.4% noted the lack of a questionnaire to evaluate adherence to medications but relied on drug levels (73.4%) and self report. Only 12.9% used a questionnaire for the measurement of quality of life (Karnofsky performance scale). Of the participating centers, 27.1% used a formal cognitive testing for potential living donors. A social worker was used by most centers for nonadherent patients. Respondents indicated that patients (in the pretransplantation state) were more compliant with dialysis than with medication regimens. Finally, 37.7% of respondents noted graft failure due to medication nonadherence in 15% to 29% of their patients.

Conclusions

There was a significant variability in the methods of screening for nonadherence while the patient was on dialysis, during pretransplantation work up, and during post-transplantation follow-up examinations. We recommend that there should be a standardized technique to evaluate nonadherence to facilitate focused clinical trials to improve adherence.     

IL-18 and Urinary NGAL Predict Dialysis and Graft Recovery after Kidney Transplantation

Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.Kidney allograft function after transplantation varies from a rapid increase in GFR, causing brisk reductions in serum creatinine (Scr), to primary allograft failure. Defined as the need for dialysis within 1 wk of transplantation, delayed graft function (DGF) occurs in 20 to 33% of deceased-donor kidney transplants (DDKTs).^1–4 Recent strategies for increasing the donor pool include using “extended-criteria donor” (ECD) and “donation after cardiac death” (DCD) kidneys. Both types are associated with higher rates of DGF compared with standard-criteria kidneys.⁵ Thus, with more ECD/DCD transplants, as a strategy to reduce waiting lists, physicians will encounter DGF more frequently.DGF, predominantly caused by ischemia-reperfusion injury (IRI) from allograft procurement, occurs infrequently in living-donor kidney transplants (LDKTs).The role of IRI in graft survival was first highlighted by Terasaki et al.,⁶ who showed that graft survival was better in LDKTs than DDKTs, regardless of antigen mismatches. Moreover, they showed six-antigen mismatched grafts that functioned on day 1 had better 3-yr survival than perfectly matched grafts with delayed function. Investigators have actively sought preventative/therapeutic techniques aimed at reducing IRI and the need for post-transplant dialysis; however, apart from using hypothermic machine allograft perfusion and minimizing cold ischemia time,⁷ results have been disappointing.The deleterious effects of DGF in the immediate post-transplant period include increased lengths of stay and total hospital costs primarily because of the need for dialysis.^8,9 We examined the long-term role that DGF plays in patient and graft survival in a recent meta-analysis and showed more than 40% increased risk of graft loss at 1 yr with DGF.¹⁰ Even in patients not dialyzed after transplant, studies have shown poorer long-term outcomes with “slow graft function (SGF)” compared with “immediate graft function (IGF).”^3,11,12Although most studies agree that DGF is associated with poorer outcomes, multiple DGF definitions are used.^13–17 Current means of diagnosing DGF or SGF, using Scr and urine output (UOP), require knowledge of previous values to interpret, are affected by diuretic use, and can take a number of days to confirm.¹⁸ As in other forms of acute kidney injury (AKI) caused by IRI, this lag in diagnosis has greatly hampered efforts to prevent or treat renal injury in human trials.¹⁹ Additionally, with the exception of IGF, it is often impossible to predict recovery. Noninvasive measurement of accurate biomarkers near injury onset could make postoperative course prediction feasible and may ultimately promote advances in kidney transplantation and ischemic AKI.Ongoing studies of kidney IRI mechanisms have identified many potential biomarkers. Multiple translational studies have subsequently evaluated over 21 serum and urine biomarkers.²⁰ Three of the most intensely studied include neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1). Transplantation involves organ ischemia with eventual reperfusion. This makes DDKT a reliable model to evaluate the role of biomarkers in detecting IRI leading to DGF of variable severity/duration. We therefore conducted a multicenter, prospective-cohort study of patients receiving DDKTs to evaluate the timing and efficacy of using urinary NGAL, IL-18, and KIM-1 for predicting recovery of graft function and the need for dialysis within 1 wk after transplantation.