Petra Glander

Charité Universitätsmedizin Berlin | Charité · Department of Nephrology

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant...

Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of v...

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 wee...

Background and Aims Patients with chronic kidney disease suffer often from cardiovascular diseases, especially high blood pressure and its complications such as stroke and heart attack. After kidney transplantation, this condition persists and can in addition harm the graft. However, outpatient care surveillance is not ideal to treat high blood pre...

The MACCS (Medical Assistant for Chronic Care Service) platform enables secure sharing of key medical information between patients after kidney transplantation and physicians. Patients provide information such as vital signs, well-being, and medication intake via smartphone apps. The information is transferred directly into a database and electroni...

Aim: Calcineurin inhibitors (CNI) have a small therapeutic window, and drug monitoring is required. Pharmacokinetic monitoring does not correlate sufficiently with clinical outcome. Therefore, the expression of nuclear factor of activated T-cells (NFAT)-regulated genes in the peripheral blood has been suggested as a potentially useful immune monit...

Background: Mycophenolic acid (MPA) is a standard immunosuppressant in organ transplantation. A simple monitoring biomarker for MPA treatment has not been established so far. Here, we describe inosine 5'-monophosphate dehydrogenase (IMPDH) monitoring in erythrocytes and its application to kidney allograft recipients. Methods: IMPDH activity meas...

Background Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection. Methods This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infe...

Background: Limited data exist on the pharmacokinetic profile of novel direct acting antivirals in kidney transplant recipients. Daclatasvir is primarily eliminated via the biliary route and sofosbuvir via the renal route; here we report the pharmacokinetic profile of combined treatment with these compounds in a prospective study of hepatitis C vi...

Background Outcomes of patients with end-stage renal disease are mainly affected by their comorbidities. Detailed data evaluating the impact of pre-transplant comorbidities on long-term outcome after kidney transplantation are largely missing. Methods In a long-term retrospective analysis, we investigated 839 deceased donor kidney transplant recip...

The use of once‐daily tacrolimus in de novo kidney transplantation is increasingly common. Therefore, we were interested in bioavailability aspects of novel once‐daily tacrolimus (LCPT, Envarsus) and once‐daily tacrolimus extended‐release formulation (ER‐Tac, Advagraf) compared with twice‐daily immediate‐release tacrolimus (IR‐Tac, Prograf). Furthe...

The Eurotransplant Senior Program has been implemented to utilize kidneys from elderly donors for age-matched recipients, but concerns have been raised about the longterm outcome. We investigated the outcomes of all elderly patients in our center. All candidates for kidney transplantation ≥ 65 years were identified. Patients entering the waitlist f...

Objective: Ovarian cysts are a common finding in reproductive-aged females. Most of them are functional cysts that typically resolve spontaneously and require no treatment. However, ovarian cysts may also be adverse events associated with inhibitors of the mammalian target of rapamycin (mTOR). Both approved mTOR inhibitors everolimus and sirolimus...

Objectives: Mycophenolic acid (MPA) is an immunosuppressive agent which is commonly used in a fixed dose regime in solid organ transplantation. For clinical trials and therapeutic drug monitoring measuring plasma concentrations is necessary. Also, stability issues have to be addressed. Methods: We describe an isocratic, RP-based HPLC-UV method f...

The lack of donors is favoring living kidney donor (LKD) transplantation worldwide, quite often beyond the classic age-matching rules. We analysed renal function (RF) at 1 and 5 years in all donor and recipients as well as death-censored graft and patient survival. LKD recipients were divided into 4 subgroups: young recipients-young donors (YR-YD;...

AimsMycophenolic acid (MPA) suppresses lymphocyte proliferation through inosine monophosphate dehydrogenase (IMPDH) inhibition. Two formulations are approved: Mycophenolate mofetil (MMF) and Enteric-Coated Mycophenolate Sodium (EC-MPS)). Pantoprazole (PAN) inhibits gastric acid secretion which may alter MPA exposure. Data from healthy volunteers su...

Background: It is unclear if the severity or the timing of acute cellular rejection (ACR) defined by Banff classification 2009 is associated with graft survival. Methods: Borderline changes, TCMR I (interstitial rejection), and TCMR II/III (vascular rejection) were defined as low, moderate, and high ACR severity, respectively. Approximately 270...

Purpose: This study aimed to assess the safety, pharmacokinetic and activity profiles of the human-mouse chimeric monoclonal anti-disialoganglioside GD2 antibody ch14.18 produced in Chinese hamster ovary (CHO) cells (ch14.18/CHO). Methods: Sixteen children with recurrent/refractory neuroblastoma (median age 7.6 y) were enrolled in this Phase 1 d...

In a 6-month prospective, openlabel, multicenter study, 128 de novo kidney transplant patients receiving cyclosporine (CsA) and steroids were randomized to an intensified regimen of enteric-coated mycophenolate sodium (EC-MPS) or to a standard EC-MPS regimen to Week 6 posttransplant, after which the regimen was identical. In a follow-up study to Mo...

Virtual Panel Reactive Antibodies (vPRA) has been implemented to gauge sensitization worldwide. It is unclear how it associates with long-term outcomes, and its correlation with peak (pPRA) or actual (aPRA) has not been studied. We retrospectively reviewed data from 18-65 year-old kidney-only transplant patients during 1.1.1996-31.7.2011 in our cen...

Mycophenolic acid (MPA) is an immunosuppressive agent that acts as a selective, non-reversible inhibitor of the enzyme inosine-5'-monophosphate dehydrogenase (IMPDH). Malformations have been described in children after maternal exposure to mycophenolate. However, the causal link is unclear in most cases because women had been treated with a combina...

Evaluation of vascular variants is crucial for donor assessment prior to living kidney transplantation. Both contrast-enhanced (CE) magnetic resonance angiography (MRA) and multislice computed tomography (MSCT) are currently used for imaging living kidney donors. Aim of this study was the comparison of the accuracy of MSCT angiography and CE-MRA fo...

Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus ther...

Since many drug targets and metabolizing enzymes are developmentally regulated, we investigated a potential comparable regulation of inosine 5'-monophosphate dehydrogenase (IMPDH) activity that has recently been advocated as a pharmacodynamic biomarker of mycophenolic acid (MPA) effects in the paediatric population. Since the field of pharmacodynam...

Inosine 5'monophosphate dehydrogenase (IMPDH) is the rate limiting enzyme in the de novo synthesis of guanine nucleotides. The direct determination of target enzyme activity as a biomarker of mycophenolic acid (MPA) may help to estimate better the individual response to the immunosuppressant. However, the assessment of the clinical utility of this...

An important goal in transplantation is to tailor immunosuppression to the individual needs of the patient, avoiding both rejection and over-immunosuppression. Opportunistic infections and malignancies remain a significant cause of death after transplantation and are obvious consequences of over-immunosuppression. Currently, monitoring of immunosup...

INTRODUCTION AND AIMS: Impaired glucose metabolism manifest as new onset diabetes after transplantation (NODAT) and impaired glucose intolerance (IGT) is a common and important unwanted outcomes with potential impacts on cardiovascular risks, infections and long-term patient and graft outcomes. Autosomal dominant polycystic kidney disease (ADPKD) h...

In the course of the influenza A H1N1 pandemic, transplanted patients were recommended to receive vaccination. In the present study, we evaluated the immune response to an adjuvanted influenza A H1N1 vaccine (Pandemrix®) in renal allograft recipients. Sixty patients and 22 healthy controls participated in a prospective observational study and recei...

We investigated the pharmacokinetic and pharmacogenetic implications of conversion from a twice-daily (P-Tac) to a once-daily (A-Tac) tacrolimus (Tac) formulation. We analyzed Tac levels in a cohort of 41 renal transplant patients with a stable graft function over a period of 1 year before and after conversion. After conversion, the patients had, o...

Efficacy and safety of an intensified dosing (ID) regimen of enteric-coated mycophenolate sodium (EC-MPS), which achieves higher mycophenolic acid exposure early posttransplantation, were evaluated in comparison with a standard dosing (SD) regimen. In total, 128 de novo kidney transplant recipients treated with basiliximab induction, cyclosporine A...

The prevalence of acute renal allograft rejection has decreased substantially in past decades due to new and more specific immunosuppressive compounds but improvements in long-term graft function have not been achieved. There is a large need for new immunosuppressive agents that lack toxicity of current agents such as calcineurin inhibitors but sho...

Rejection still has a fundamental impact on patient and graft survivals after renal transplantation. Published studies vary widely in their reporting of biopsy-proven acute rejection (BPAR) and non-BPAR rates. We undertook a systematic search of existing publications for reasons explaining this difference. Additionally, we analyzed our own populati...

Mycophenolic acid (MPA) therapy is a fundamental component of most post-transplant immunosuppressive regimens. Side effects, however, are common and frequently necessitate dose reductions or discontinuations. Enteric-coated mycophenolate sodium (EC-MPS) is designed to improve the gastrointestinal (GI) tolerability of MPA. This review assesses the p...

Patients with blood group O have disadvantages in the allocation of deceased donor organs in the Eurotransplant Kidney Allocation System and fewer ABO-compatible living donors. In order to investigate the consequences of this dilemma, we analysed the outcome of patients with blood group O in our transplantation programme. A single-centre analysis o...

Pharmacokinetic drug monitoring has been used for many years to relate immunosuppressant dose to drug exposure in vivo. However, this conventional therapeutic drug monitoring of blood immunosuppressant levels may not necessarily predict the pharmacologic effects on immune cells. The direct determination of target enzyme activity (eg, calcineurin ac...

Background and objective: The clinical manifestation of angioedema ranges from minor facial edema up to life-threatening swelling of mouth and throat. Hereditary defects, drugs, and food allergies may play a role in the development of angioedema. We systematically investigated the incidence of angioedema in renal allograft recipients treated with m...

Pharmacokinetic (PK) and pharmacodynamic (PD) monitoring strategies and clinical outcome were evaluated in enteric-coated mycophenolate sodium (EC-MPS)-treated renal allograft recipients. PK [mycophenolic acid (MPA)] and PD [inosine monophosphate dehydrogenase (IMPDH) activity] data were analysed in 66 EC-MPS and ciclosporin A (CsA)-treated renal a...

Adequate early mycophenolic acid (MPA) exposure is an important determinant for effective rejection prophylaxis. This pharmacokinetic study investigated whether an intensified dosing regimen of enteric-coated mycophenolate sodium (EC-MPS) could achieve higher mycophenolic acid (MPA) exposure early after transplantation versus a standard dosing regi...

The active metabolite of mycophenolate mofetil (MMF), mycophenolic acid, inhibits the activity of the target enzyme inosine monophosphate dehydrogenase (IMPDH). The aim of this study was to correlate eight different single nucleotide polymorphisms of the IMPDH type II gene to the activity of the IMPDH enzyme to explain between-patient differences i...

Previous studies predicted that limited sampling strategies (LSS) for estimation of mycophenolic acid (MPA) area-under-the-curve (AUC(0-12)) after ingestion of enteric-coated mycophenolate sodium (EC-MPS) using a clinically feasible sampling scheme may have poor predictive performance. Failure of LSS was thought to be due to the slow absorption of...

Background: In recent years, in renal transplantation the so called blood group 0 problem has emerged. This is presumably due to disadvantages of these patients in the allocation of deceased donor organs as well as to the lack of an AB0-compatible living donor. In order to assess the importance of this problem we have analysed data of our transplan...

The effect of mycophenolate mofetil (MMF) on T cell function has not been evaluated in patients undergoing kidney transplantation. The aim of this study was to assess the effect of 1g of MMF on T cell function, that is, intralymphocyte cytokine expression, T cell activation (CD25 and CD71), and T cell proliferation, as well as inosine monophosphate...

Mycophenolic acid (MPA) inhibits the enzyme inosine 5'-monophosphate dehydrogenase (IMPDH). Thus, the measurement of IMPDH activity could serve as a specific pharmacodynamic (PD) tool for monitoring MPA therapy. At present, however, monitoring of pharmacokinetic parameters is preferred over that of PD parameters because, in general, PD assays are l...

Background: Transplant patients are prescribed a variety of medications with multiple dosing schemes at different time points. Pill burden is a potential contributing factor to medication nonadherence in solid organ transplant recipients. Methods: In this cohort-study a self-designed not validated self-reporting questionnaire was applied in our out...

Objective: This study aimed to examine efficacy, safety and tolerability during the first 6 months post transplantation of an initially intensified-dosing regimen of enteric-coated mycophenolate sodium (ECMPS). Methods: 128 de-novo kidney transplant patients (pts) were treated with basiliximab, steroids and standard CsA doses and randomized either...

Objective: The pharmacokinetics of mycophenolic acid (MPA) were compared in renal transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). Methods: MPA concentration-time profiles were included from EC-MPS- (n = 208) and MMF-treated (n = 184) patients 4-257 months after renal transplantati...

Renal transplantation is the method of choice for treatment of end stage-renal disease. A successful transplantation requires a detailed knowledge about donor selection, the evaluation and the perioperative management of recipients. Similarly important is a profound knowledge on effectiveness, side effects and application of immunosuppressive drugs...

The combination of synergistic drugs is the main strategy to prevent early acute rejection and to provide long-term effective rejection prophylaxis. Evaluation of drug concentrations to guide drug dosing is routinely established for calcineurin-inhibitors CNIs and mTOR inhibitors. Arguments in favour of therapeutic drug-monitoring TDM are the large...

The pharmacokinetics of mycophenolic acid (MPA) were compared in renal transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). MPA concentration-time profiles were included from EC-MPS- (n = 208) and MMF-treated (n = 184) patients 4-257 months after renal transplantation. Population pharmaco...