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.     

Impact of Immunosuppressive Strategies on Post–Kidney Transplantation Thrombocytopenia

BackgroundThrombocytopenia after kidney transplantation is a common complication, partly induced by immunosuppressive therapies. Peritransplant thrombocytopenia may cause serious hemorrhages. We assessed the incidence of early posttransplantation thrombocytopenia (defined as a platelet count of <150,000 mm³ or <150 G/L) in de novo kidney transplant recipients (KTRs) across 4 immunosuppressive regimens.MethodsThis was a single-center observational study that included all consecutive KTRs who received either Thymoglobulin (THY) or Grafalon (GRA) and maintenance therapy of either mycophenolate-mofetil (MMF) or everolimus (EVR), associated with tacrolimus/corticosteroids.ResultsBetween July 27, 2016, and September 7, 2018, 237 KTRs were included; 64.6% experienced thrombocytopenia within the first week. Thrombocytopenia was significantly more frequent (P = .004) among GRA-treated patients (73.4%) compared to THY-treated patients (61.3%). These patients also had lower nadir platelet count (120 ± 52 vs 142 ± 48 G/L; P = .002) and lower platelet count at discharge (227 ± 94 vs 243 ± 92 G/L; P = .25). More of the GRA-EVR group had thrombocytopenia (81.0% vs 61.4% in THY-MMF, 60.9% in THY-EVR, and 69.8% in GRA-MMF; P = .081) and a worse nadir platelet count (109 ± 41 in GRA-EVR vs 141 ± 47G/L in THY-MMF, 145 ± 52 G/L in THY-EVR, and 125 ± 56 G/L in GRA-MMF; P = .011) but GRA was the only risk factor for thrombocytopenia in multivariate analyses (P = .002). Rates of hemorrhage, red blood cell transfusions, reoperations needed within the first week, delayed graft function, acute rejection, graft loss, and death did not differ between the groups after a mean follow-up of 25 ± 8 months.ConclusionsGRA associated with EVR led to more frequent and severe thrombocytopenia, although we found no significant clinical consequences.     

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.

Serum αKlotho as a Predictor of Graft Dysfunction After Kidney Transplantation

Objective

To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time.

Urinary Tissue Inhibitor of Metalloproteinase and Insulin-like Growth Factor–7 as Early Biomarkers of Delayed Graft Function After Kidney Transplantation

Background

Recently, urinary tissue inhibitor of metalloproteinase–2 (TIMP-2) and insulin-like growth factor–7 (IGFBP-7), markers for G1 cell cycle arrest, have been identified and validated in predicting the development of acute kidney injury in critically ill patients. It is unknown, however, whether these two biomarkers could predict the development of delayed graft function (DGF) after kidney transplantation (KT).

A New Formula as a Predictive Score of Post–Liver Transplantation Outcome: Postoperative MELD-Lactate

Introduction

Liver transplantation (OLT) involves a 5% to 10% 30-day mortality rate. Multiple scores have been used as predictors of early postoperative mortality, such as the original Model for End-stage Liver Disease (MELD) and MELD sodium. Investigations have been conducted over the last 5 years to find new predictors of early post-OLT mortality.

Objective

The aim of this study was to develop a new mathematical model to predict the individual chance of 30-day mortality after OLT.

Methods

The study was conducted on 58 patients submitted to OLT at the University Hospital, between October 2008 and March 2012. The 29 latest survivor and 29 latest nonsurvivor cases were selected. Arterial blood sodium, lactate, international normalized ratio, total bilirubin, and creatinine values were determined 1 hour after the end of surgery. The MELD original equation, MELD sodium, and new MELD lactate were also elaborated. The results were analyzed by the Mann-Whitney and Wilcoxon tests. The level of significance was set at .05.

Results

The new formula elaborated was as follows: MELD lactate = 5.68 × log_e (lactate) + 0.64 × (Original MELD) + 2.68. The MELD lactate values were significantly higher than the MELD sodium and original MELD values (P < .05). The area under the receiver operating characteristic curve of MELD lactate in predicting the outcome of patients submitted to OLT was 0.80, as opposed to 0.71 for the original MELD and 0.72 for MELD sodium (P < .05).

Conclusion

The postoperative MELD lactate score proved to be more specific and sensitive than the original MELD and MELD sodium as a predictive model of the outcome of patients submitted to OLT.     

Post–Covid-19 Cholangiopathy—A New Indication for Liver Transplantation: A Case Report

Liver injury is one of the nonpulmonary manifestations described in coronavirus disease 2019 (COVID-19). Post–COVID-19 cholangiopathy is a special entity of liver injury that has been suggested as a variant of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). In the general population, the outcome of SSC-CIP has been reported to be poor without orthotopic liver transplantation (OLT). However, the role of OLT for post–COVID-19 cholangiopathy is unknown. We present a case report of a 47-year-old man who recovered from acute respiratory distress syndrome from COVID-19 and subsequently developed end-stage liver disease from post–COVID-19 cholangiopathy. The patient underwent OLT and is doing well with normal liver tests for 7 months. To our knowledge, this is the first case report of a patient who underwent successful liver transplantation for post–COVID-19 cholangiopathy.     

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.

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.     

Similar Results With Solitary Pancreas Transplantation Compared With Simultaneous Pancreas–Kidney Transplantation in the New Millennium

Introduction

The purpose of this study was to analyze our single-center outcomes according to pancreas transplant (PT) category in the new millennium by using standardized management protocols.

Patients and Methods

We retrospectively studied 202 consecutive PTs (179 with portal-enteric drainage) in 192 patients; all received either rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and tapered corticosteroids or early steroid withdrawal. Unlike simultaneous pancreas/kidney (SPK) transplant, solitary PT (SPT) recipients were managed with routine perioperative anticoagulation and surveillance pancreas biopsies.

Results

From November 2001 to March 2013, we performed 162 SPK transplants, 35 pancreas after kidney transplants, and 5 pancreas-alone transplants (40 SPTs). Demographic characteristics were mostly comparable; however, the SPT group had younger donors, shorter waiting time, fewer HLA mismatches, and fewer African-American recipients but more retransplants (all, P < .05). With a mean follow-up of 5.5 versus 7.5 years, overall patient (86.4% SPK vs 86.8% SPT), kidney graft (74% SPK vs 80% SPT), and pancreas graft (both 65%) survival rates were comparable. Although mortality rates were similar, mortality patterns differed because no SPT recipients died early, whereas the 1-, 3-, and 5-year mortality rates after SPK transplant were 4%, 9% and 12%, respectively (P < .05). The most common causes of pancreas graft loss were death with functioning grafts in SPK recipients and acute/chronic rejection in SPT recipients. Rates of early thrombosis were 8.6% in SPK patients and 5% in SPT patients. Cumulative clinical acute rejection rates were similar between groups (SPK 29% vs SPT 27.5%; P = NS).

Conclusions

In the setting of depleting antibody induction and tacrolimus-based therapy, HLA matching, careful donor and recipient selection, portal-enteric drainage, selective perioperative anticoagulation, and surveillance SPT biopsy monitoring, similar medium-term outcomes can be achieved in SPK transplants and SPTs in the new millennium.     

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.

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.     

MicroRNAs: Novel Diagnostic and Therapeutic Tools for Pancreatic Ductal Adenocarcinoma?

Pancreatic ductal adenocarcinoma (PDAC) is known for its very poor overall prognosis, making tools for early diagnosis and new therapeutic modalities urgently needed. MicroRNAs (miRNAs), endogenous noncoding RNA molecules of ~22 nt, have gained attention as an epigenetic component involved in the development of many cancers, including PDAC. miRNA expression profiles of varying pancreatic tissues have identified a number of differentially expressed miRNAs and seem to be able to differentiate between three tissues of clinical importance: normal pancreas, chronic pancreatitis, and PDAC. This article gathers our current knowledge of differentially expressed miRNAs in pancreatic tissues with relevance to PDAC and presents potential diagnostic and therapeutic opportunities.     

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.     

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.