Pregnancy Outcomes After Liver Transplantation: A Systematic Review

Purpose

Liver transplantation (LT) constitutes a major therapeutic option for a number of patients suffering from liver pathologies. Pregnancy outcomes in patients who have undergone LT are assessed by a number of studies. The aim of our systematic review was to present the currently available evidence concerning the results of pregnancy in patients with LT.

Liver Transplantation for Giant Hepatic Hemangioma: A Systematic Review

Introduction

Despite their benign nature, liver hemangiomas (LH) are lesions that can cause major complications requiring intervention. Liver transplantation (LT) has been suggested as an effective treatment option in selected patients with giant LHs causing severe symptoms and cannot be treated otherwise. The aim of our study was to investigate the indications, aspects and post-operative outcomes of patients with a LH who underwent LT.

Chronic allograft injury: Mechanisms and potential treatment targets

Improving long-term graft survival remains one of the critical challenges facing kidney transplantation since a great portion of kidney grafts are lost by 10 years after transplantation. Understanding the causes of chronic allograft injury and providing timely therapeutic interventions are essential for improving these outcomes. In this review, we will discuss the recent data that emerged turning down calcineurin inhibitors as the primary cause of long-term graft injury and highlighting the increased importance of non-compliance, antibody-mediated injury, disease recurrence, and BK nephropathy as culprits. We suggest a number of different strategies to better manage kidney transplant recipients that, ultimately, may improve long-term graft survival.     

Optimizing everolimus exposure when combined with calcineurin inhibitors in solid organ transplantation

The mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C₀) measurement to be an appropriate and reliable index for therapeutic drug monitoring (TDM). Exposure-response analyses of data from early fixed-dose trials demonstrated that rates of biopsy-proven acute rejection (BPAR) are significantly higher if everolimus C₀ declines below 3 ng/mL, an observation confirmed in subsequent concentration-controlled trials. Evidence for the most favorable upper limit is less clear but with reduced-exposure calcineurin inhibitor (CNI) therapy, an upper limit of 8 ng/mL appears to balance efficacy and safety outcomes. The recommended C₀ range is 3–8 ng/mL in kidney, liver and heart transplantation patients, based on LC–MS/MS monitoring in whole blood. Randomized clinical trials based on this target range have demonstrated rates of BPAR comparable to a regimen of mycophenolic acid with standard-exposure CNI. Everolimus exhibits moderate intrapatient pharmacokinetic variability, and it can be challenging to maintain stable concentrations within target range in some individuals. Many factors can influence everolimus exposure for a given dose, including hepatic function, activity of the drug efflux pump P-glycoprotein, the rate of everolimus metabolism, drug–drug interactions (predominantly with CYP3A4 and P-glycoprotein inhibitors, including cyclosporine), intake of fatty food, and patient adherence to the prescribed regimen. Trough concentration levels should be monitored 4–5 days after the first dose and after any change in everolimus dose, with additional monitoring in response to any change in concomitant medication or other clinical circumstances which could alter everolimus exposure. Although LC–MS/MS is the gold standard for everolimus monitoring, various immunoassays are widely used due to their relative simplicity and lower cost, and results can show considerable discrepancies with reference methods due to issues such as interassay variability and cross-reactivity. Method standardization will be important in the future to improve the consistency and reproducibility of results between centers. In conclusion, based on an extensive program of clinical trials, the optimal exposure range for everolimus in combination with reduced-exposure CNI therapy has been established and can be achieved in most transplant recipients through careful, planned TDM.     

The clinical course of IgA nephropathy after kidney transplantation and its management

Immunoglobulin (Ig) A nephropathy is one of the most common primary glomerulonephritides worldwide causing end stage renal disease in up to 20–40% of affected patients, nearly two decades post diagnosis. Kidney transplantation is the treatment of choice for patients with renal failure, secondary to glomerular diseases. However, IgA nephropathy has a strong tendency to recur in the graft, and although initially thought to be a benign condition, several reports of graft loss, due to recurrent IgA nephropathy, there have been over the last three decades. Overall graft survival has been significantly improved in kidney transplantation, as a result of reduced incidence of acute rejection, as more potent and more specific immunosuppressive agents are now available in clinical practice. Thus, the rates of IgA nephropathy and other glomerulonephritides recurrence are expected to increase, since graft survival has been improved. However, the reported incidence of IgA nephropathy recurrence in the graft varies substantially across centers, as a consequence of different levels of interest, diverse biopsy policies and differing durations of follow up, of the published studies. Notably, recurrence rates of patients receiving graft biopsies by clinical indication only, ranges from 13% to 50% with graft loss being between 1.3% and 16%. The aim of this review is to underline important pathogenetic insights of IgA nephropathy, describe the clinical course of the disease after kidney transplantation, with emphasis on the incidence of recurrence and the associated risk factors, and finally provide all available options for its management in transplant recipients.     

Successful Treatment of Focal Segmental Glomerulosclerosis Recurrence in a Second Kidney Transplant Patient: A Case Report

Background

Recurrence of focal segmental glomerulosclerosis (FSGS) in renal allograft recipients after first transplant occurs in the second graft in virtually all patients. There is little evidence regarding optimal treatment.

Acute Kidney Injury Secondary to Hypercalcemia in a Kidney Transplant Patient With Pneumocystis jirovecii Pneumonia: A Case Report

Background

Persistent hyperparathyroidism is one of the main causes of hypercalcemia following kidney transplantation; differential diagnosis is required.

Is social support associated with post-transplant medication adherence and outcomes? A systematic review and meta-analysis

Although social support is used to determine transplant eligibility, the relationship between social support, medication adherence, and survival among transplant recipients remains unclear. We estimated the relationship between social support and post-transplant medication adherence and outcomes using 10 electronic databases from inception to January 2016. Study quality was assessed and all review stages were conducted independently by 2 reviewers. Systematic review and meta-analysis were conducted. Thirty-two studies (9102 participants) met inclusion criteria: 21 assessed medication adherence (5197 participants), and 13 assessed clinical outcomes (3905 participants). Among high quality studies, neither social support nor marital status was predictive of medication adherence or post-transplant outcomes. Social support was not associated with medication adherence. It was associated with superior post-transplant outcomes, but the relationship was not significant among high quality studies. Compared to unmarried recipients, married recipients were more likely to adhere to medication post-transplant, but this relationship was not significant among high quality studies. Marital status was not significantly associated with transplant success. Social support is weakly and inconsistently associated with post-transplant adherence and outcomes. Larger prospective studies using consistent and validated measures are needed to justify the use of inadequate social support as a contraindication to transplantation.