Oncologic Outcomes of Post–Kidney Transplantation Superficial Urothelial Carcinoma

Purpose

To analyze the oncologic effect of post–kidney transplantation (KT) immunosuppressive status for end-stage renal disease (ESRD) patients with superficial urothelial carcinoma.

Usefulness of Monitoring Cell-Mediated Immunity for Predicting Post–Kidney Transplantation Viral Infection

Background

Monitoring cell-mediated immunity (CMI) can be used to estimate the risk of viral infections in kidney transplant recipients. The Immuknow (IMK) assay measures CD4⁺ T-cell adenosine triphosphate activity, assesses patient CMI status, and assists clinicians in determining the risk of viral infection.

Methods

We retrospectively analyzed 224 IMK values in 39 kidney transplant recipients at our institution from April 2012 to January 2013. We analyzed the relationship between IMK value and viral infection during the early and late post-transplantation periods. Multiple regression analyses were performed, to determine which factors impacted the results of the IMK assay.

Results

Eight patients developed viral infections, including BK virus, cytomegalovirus, herpes simplex, and shingles. Five infections occurred in the early post-transplantation period (<50 d) and 3 in the late period (>120 d). The IMK levels in patients who developed an infection in the early period were within normal limits; however, those in the late period were significantly lower than 200 ng/mL (421.0 ± 062.6 for early vs 153.7 ± 72.7 for late; P = .02).Our multiple regression analyses indicated that peripheral white blood cell and neutrophil counts affected IMK values (P = .03 and P = .02, respectively).

Conclusions

The IMK assay is a useful test for identifying patients at risk for post-transplantation viral infections in the late transplant period.     

A Multicenter Cohort Study From India of ABO-Incompatible Kidney Transplantation in Post–COVID-19 Patients

BackgroundThere is a dearth of data regarding the consequences of ABO-incompatible kidney transplant (ABOiKTx) among post–COVID-19 candidates.MethodsThe study was designed as a retrospective, multicentric cohort study across 11 sites in India, from August 2020 to December 2021. The data for ABOiKTx conducted for post–COVID-19 candidates were investigated. The primary outcome of biopsy-proven acute rejection was compared with the ABO protocol implemented through Kaplan-Meier analysis. The secondary outcomes were graft loss, patient survival, and infections.ResultsA total of 38 ABOiKTx with candidates of median (interquartile range) age of 38.5 (31.25-47.5) years were performed. Nineteen cases had mild COVID-19 severity, while 9 cases (23.6%) had an oxygen requirement. Six (15.7%) donors also were post–COVID-19. The most common ABO incompatibility reported was A to O in 14 (36.8%) pairs followed by B to O in 10 (26.3%) pairs. The maximum isoagglutinin titer cutoff was 1:2048 and 1:64 for baseline and pretransplant levels, respectively. The median time from COVID-19 infection to surgery was 130 (63.2-183) days. Biopsy-proven acute rejection, graft loss, and mortality were 13.1%, 2.6%, and 2.6%, respectively. The Breslow-Wilcoxon's P value in Kaplan-Meier plots were 0.57 and 0.93 for thymoglobulin-based induction and high dose rituximab-based regimen, respectively. The incidence of reinfection was 2.6%. Two (5.2%) urinary tract infections were reported. No cytomegalovirus or BK polyomavirus infection was reported. The median serum creatinine at 1 year of follow-up was 1.1 (0.8-1.3) mg/dL.ConclusionsOur report implies that ABOiKTx in post–COVID-19 candidates can be successfully performed with no major deviation from standard ABO protocol.     

Serum MicroRNAs as New Diagnostic Biomarkers for Pre– and Post–Kidney Transplantation

BackgroundIn the present study, we compared the expression levels of 3 microRNAs (miRNAs) between patients who had undergone kidney transplantation and healthy individuals in a search for a new diagnostic biomarker after kidney transplantation.MethodsWe used real-time quantitative polymerase chain reaction to investigate the expression levels of miR-181a, miR-483-5p, and miR-557 in the serum of 15 kidney transplantation patients before transplantation on the first, third, and seventh days after transplantation. The study was performed in the Guilin 181st Hospital between 2010 and 2012. The results of this study may assist with early diagnosis and treatment and contribute to our understanding of the pathological parameters. Receiver operating characteristic (ROC) analysis was performed to determine the area under the curve of each equation to predict evolution to rejection.ResultsROC curves were performed to explore miRNAs to predict rejection occurrence after transplantation showed pre-transplantation expression levels of miR-181a to be a potential factor with a significant area under the curve (AUC = 0.985, P < .05). The expression of miR-181a before kidney transplantation was also significantly different on days 1 and 3 after kidney transplantation, the area under the curve (AUC) was, respectively, 0.980 (P < .05) and 0.830 (P < .05). Predictors on days 1, 3, and 7 show that miR-483-5p and miR-557 are also predictive factors for rejection. Predictors for miR-483-5p and miR-557 were significantly under the area ROC, respectively (AUC = 0.920, P < .05), and (AUC = 0.990, P < .005) on day 1 (AUC = 0.920, P < .05) and (AUC = 0.960, P < .005) on day 3, (AUC = 0.845, P < .05) and (AUC = 0.889, P < .05) on day 7.ConclusionsThis study of miRNAs was unrelated to age, sex, histological classification, and metastasis (all P > .05). Serum miR-181a, miR-483-5p, and miR-557 could serve as circulating biomarkers for the early diagnosis of active situations of before and after kidney transplantation.     

Safety of Kidney Transplantation Using Anti-HBc–Positive Donors

BackgroundProspective studies evaluating the risk of hepatitis B virus (HBV) transmission in transplants of kidneys from hepatitis B core antibody (anti-HBc)–positive/hepatitis B surface antibody (anti-HBs)–negative donors are still lacking. The objective of this study was to assess the safety of kidney transplantation with the use of anti-HBc–positive donors.MethodsThis prospective case series study included 50 kidney transplant recipients from anti-HBc–positive donors with or without anti-HBs positivity. Recipients were required to test positive for anti-HBs (titers >10 mUI/mL), regardless of anti-HBc status, and negative for hepatitis B surface antigen (HBsAg). Recipient and donor data were retrieved from medical records, databases, and organ procurement organization sheets. Liver function tests were performed at progressively increasing post-transplantation intervals. Complete serologic tests for HBV were performed before transplantation, 3 and 6 months after transplantation, and annually thereafter.ResultsSix months after transplantation, all recipients were negative for HBsAg, HBeAg, anti-HBe, and anti-HBcIgM. No seroconversion was observed among the 20 patients who received kidneys from anti-HBc–positive/anti-HBs–negative donors. No patient showed elevated liver enzymes during follow-up.ConclusionsKidney transplantation using organs from anti-HBcIgG–positive donors (even when they are concurrently anti-HBs negative) in anti-HBs–positive recipients is a safe procedure and may be considered as a way to expand the donor pool.     

Urinary Tract Infections in the First Year Post–Kidney Transplantation: Potential Benefits of Treating Asymptomatic Bacteriuria

Background

Urinary tract infections (UTIs) are the commonest infectious complication in kidney transplant recipients (KTRs). No recommendations exist regarding treatment of asymptomatic bacteriuria. We aimed to identify potential risk factors and microbiological profile for UTIs, the role of treatment of asymptomatic bacteriuria, and effects on graft outcomes of bacteriuria within the first year post-transplantation.

Transplantation Opportunities of Hepatitis C Virus–Seropositive Patients on the Kidney Waiting List

Objective

Besides severe organ shortage, hepatitis C virus (HCV) infection is an important obstacle for kidney transplantation because of long waiting times on deceased kidney donor waiting lists. We aimed to evaluate calling number of candidates according to HCV serology.

Effect of Early Immunosuppression Therapy on De Novo Anti–Human-Leukocyte-Antigen Antibody After Kidney Transplantation

The aim of the study was to investigate the effect of immunosuppression therapy early after kidney transplantation, particularly exposure of mycophenolic acid (MPA) and calcineurin inhibitor (CNI), on posttransplantation de novo HLA antibody production.

Comparison of RIFLE and AKIN Criteria in the Evaluation of the Frequency of Acute Kidney Injury in Post–Liver Transplantation Patients

BackgroundAcute renal dysfunction is presented quite often after orthotopic liver transplantation (LT), with a reported incidence of 12–64%. The “RIFLE” criteria were introduced in 2004 for the definition of acute kidney injury (AKI) in critically ill patients, and a revised definition was proposed in 2007 by the Acute Kidney Injury Network (AKIN), introducing the AKIN criteria. The aim of this study was to record the incidence of AKI in patients after LT by both classifications and to evaluate their prognostic value on mortality.MethodsWe retrospectively evaluated the records of patients with LT over 2 years (2011–2012) and recorded the incidence of AKI as defined by the RIFLE and AKIN criteria. Preoperative and admission severity of disease scores, duration of mechanical ventilation, intensive care unit length of stay, and 30- and 180-day survivals were also recorded.ResultsSeventy-one patients were included, with an average age of 51.78 ± 10.3 years. The incidence of AKI according to the RIFLE criteria was 39.43% (Risk, 12.7%; Injury, 12.7%; Failure, 14.1%), whereas according to the AKIN criteria it was 52.1% (stage I, 22.5%; stage II, 7%; stage II 22.55%). AKI, regardless of the classification used, was related to the Model for End-Stage Liver Disease score, the volume of transfusions, the duration of mechanical ventilation, and survival. The presence of AKI was related to higher mortality, which rose proportionally with the severity of AKI as defined by the stages of either the RIFLE or the AKIN criteria.ConclusionsAKI classifications according to the RIFLE and AKIN criteria are useful tools in the recognition and classification of the severity of renal dysfunction in patients after LT, because they are associated with higher mortality, which rises proportionally with the severity of renal disease.     

Clinical Challenges of Tacrolimus for Maintenance Immunosuppression Post–Lung Transplantation

Lung transplantation (LTx) is a successful treatment option for end-stage lung disease, and immunosuppressant regimens, utilized to prevent rejection of the transplanted graft, are paramount to maintaining long-term graft survival. Immunosuppression can be classified as induction, maintenance, and antirejection therapy. This article focuses on maintenance immunosuppression that includes a combination of a calcineurin inhibitor (CNI), cell cycle inhibitor, and corticosteroid. CNIs remain the cornerstone of immunosuppression following LTx, and tacrolimus is now the preferred CNI, based on a better adverse effect profile and some limited evidence for enhanced efficacy. Tacrolimus is associated with a number of unique challenges post-LTx, with erratic and highly variable absorption making it difficult to achieve and maintain therapeutic levels. Current methods of therapeutic drug monitoring are extrapolated from models in liver and kidney transplants and are not validated in the LTx population. Alternative methods of delivering tacrolimus can address some of the issues associated with their use and can be utilized in particular clinical scenarios. Long-term toxicities attributed to tacrolimus, such as nephrotoxicity and neurotoxicity, can limit the long-term success of tacrolimus in preventing allograft rejection. This article emphasizes the current clinical challenges faced when managing LTx recipients with tacrolimus, offers strategies to manage these issues, and highlights the areas that need further research.     

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell–related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group—namely, the tolerant recipients—were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS‐independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross‐validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.     

Impact of Donor Age on Outcome of Intestinal Transplantation in Japan

Background

Donor age for intestinal transplantation (ITx) is somewhat younger than that for other solid organs. Clear criteria for adequate donors have not been established. There is a donor scarcity for ITx in Japan due to the shortage of young donors.

Comparison of Surgical Correction Techniques for Post–Renal Transplantation Vesicoureteral Reflux

Background

Symptomatic urinary tract infection (UTI) after renal transplantation (RT) is an important morbidity in transplant recipients and may cause pyelonephritis and sepsis. Surgical correction of high-grade vesicoureteral reflux (VUR) after RT is suggested, performing ureteral reimplantation or pyelo-ureteral/uretero-ureteral anastomosis. Recently, extravesical seromuscular tunnel lengthening techniques have been reported with favorable results and low complication rates.

Impact of Peritoneal Dialysis Versus Hemodialysis on Incidence of Intra-abdominal Infection After Simultaneous Pancreas–Kidney Transplant

Background  

Whether peritoneal dialysis is a risk factor for the development of intra-abdominal infection after simultaneous pancreas–kidney (SPK) transplantation is controversial.     

Association Between the Fertile Period and Live Birth Post–Kidney Transplantation: A Retrospective Single-Center Cohort Study

Background

Despite restoration of fertility after kidney transplantation, the benefit is limited in female kidney recipients. Our objective is to determine the reasons for this discrepancy.

Negative Impact of Underlying Non–Insulin-dependent Diabetes Mellitus Nephropathy on Long-term Allograft Survival in Kidney Transplantation: A 10-Year Analysis From a Single Center

IntroductionWe analyzed the relationship between underlying nephropathy and long-term outcomes in kidney transplant recipients.MethodsWe retrospectively analyzed data from 678 patients who underwent kidney transplantation (KTx) between 1998 and 2011. Recipients with 13 major nephropathies were evaluated for graft and patient survival, and causes of graft loss.ResultsThe best 10-year graft survival rates (100%) were in the patients with autosomal-dominant polycystic kidney disease, preeclampsia, Alport syndrome, and purpura nephritis. The worst rate (50.8%) was in patients with non–insulin-dependent diabetes mellitus nephropathy (NIDDMN; P = .039). Causes of graft-loss in the NIDDM patients included chronic rejection (6 cases), acute rejection (3 cases), infection (2 cases), and cardiovascular event (2 cases). Significant risk factors for graft loss were donor age (P < .01) and NIDDMN (P < .01).ConclusionUnderlying NIDDMN before KTx was a significant risk factor for long-term graft function. Immunologic factors and nonimmunologic factors influenced the long-term outcomes in patients with underlying NIDDMN.     

Case Report of Multiple Bilobar Hepatic Arterio-Portal Fistulas Post–Liver Transplantation Managed Conservatively

Multiple intrahepatic arterio-portal fistulas are rare. The majority are isolated and occur secondary to liver trauma including iatrogenic interventions such as liver biopsy. Post–liver transplantation 18 cases have been reported, all secondary to an interventional radiological procedure. We report multiple bi-lobar arterio-portal fistulas in a liver transplant recipient recognized 1 year after transplantation. The donor died due to intracerebral bleeding following blunt head and abdominal trauma. In the present case, the etiology is not very clear. The patient was managed conservatively and to date has not required intervention.     

Obstacles of Non–heart-beating Donor Kidney Transplantation in Japan to Date and Future Perspectives

In Japan, multiple organ retrieval from brain-dead heart-beating donors has been gradually increasing since the law was adopted in 1997 and amended in 2009. However, almost more than 90% of total deceased donor kidney transplantation (DDKT) in Japan are still obtained from non–heart-beating donors (NHBD). The majority of NHBD are Maastricht categories IV and III. In category IV, we usually place a double balloon arterial and a venous drainage catheter via the femoral vessels after the diagnosis of clinical brain death and acquisition of informed consent from the family. After controlled cardiac arrest, the double balloons are inflated and in situ cold perfusion started as soon as possible to minimize warm ischemic time (WIT), seeking to achieve a zero to within a few minutes WIT in most cases. In category III, it is impossible to place the device prior to cardiac arrest. In these cases, after declaration of cardiac death, cardiopulmonary compression is accompanied by systemic heparinization, immediate laparotomy, and insertion of a cold perfusion catheter at the aortic and caval bifurcations to minimize WIT. NHBD kidney retrieval is critical; extirpation must be performed as rapidly as possible. The results of NHBD kidney transplantation in Japan are excellent, according to the advancement and utilization of in situ cannulation, organ perfusion, and sophisticated retrieval techniques. The patient and graft survival rates of DDKT at 1, 3, and 5 years in most recent 2001 to 2007 era were 95.4%, 92.2%, 89.1% (n = 945) and 89.2%, 83.7%, 77.8% (n = 919), respectively.