Extended-release tacrolimus — currently available drug formulations in the light of own clinical experience

Takrolimus o przedłużonym uwalnianiu jest dostępny w Polsce w dwóch postaciach: zarejestrowanego od 2007 roku Advagrafu i niedawno wprowadzonego do obrotu Envarsusu. Przesłankę do stosowania takrolimusu podawanego raz na dobę stanowi próba poprawy stabilności jego działania immunosupresyjnego w ciągu doby oraz polepszenia współpracy pacjenta w tym zakresie. Obie postaci leku różnią się w istotny sposób m.in. w zakresie farmakokinetyki i sposobu dawkowania. W niniejszym artykule przedstawiono najważniejsze korzyści i ograniczenia dotyczące stosowania obu postaci takrolimusu u pacjentów po przeszczepieniu nerki.In Poland, extended-release takrolimus is available in two formulations: Advagraf® once daily, registered in 2007, and newly-released Envarsus®. The invention of once daily tacrolimus formulations was intended to optimize the immunosuppressive effects over whole 24-hour period and to increase the patient’s compliance. Both formulations differ in terms of pharmacokinetics and dosing details. This short review presents the most important clinical and pharmacological aspects of both extended-release formulations of tacrolimus in the kidney transplantation setting

Urologic complications following renal transplantation

Przeszczepianie nerek od ponad 60 lat jest uznaną metodą leczenia schyłkowej niewydolności nerek. Zmieniła się technika chirurgiczna, metody doboru biorcy i dawcy, leki immunosupresyjne. Obecnie roczne przeżycie chorego i przeszczepu wynosi odpowiednio około 93% i 91%, a pięcioletnie odpowiednio 91% i 77%. Z przeszczepianiem nerek związane jest występowanie powikłań chirurgicznych, które mogą doprowadzić do niewydolności graftu i zgonu biorcy. Wśród nich dominują powikłania urologiczne, a częstość kształtuje się na poziomie 2–20%.Wraz z rozwojem nowych technik diagnostycznych i terapeutycznych zmienia się sposób postępowania w przypadku podejrzenia powikłań urologicznych, leczenie operacyjne w większości zostało zastąpione technikami endoskopowymi, a tylko w skrajnych przypadkach konieczne jest usunięcie nerki przeszczepionej.Celem tego artykułu jest analiza i podsumowanie aktualnych doniesień dotyczących powikłań urologicznych po przeszczepieniu nerki (KTx) u dorosłych. Zagadnienie to wydaje się być szczególnie istotne z powodu coraz większej liczby transplantacji nerek w Polsce, przy jednocześnie skąpych doniesieniach w piśmiennictwie polskim na temat nowych standardów diagnostycznych i leczniczych w przypadku wystąpienia powikłań urologicznych po przeszczepieniu nerki.The renal transplantation over 60 years becomes a method of treatment of the end-stage renal failure. The surgical technique has been modified, better methods of donor-recipient matching have been developed, and new immunosuppressive medications have been introduced. Currently, a 1-year survival of a patient and graft is approximately 93% and 91%, whilst a 5-year survival — 91% and 77% respectively.The renal transplantation is, just as any other surgical procedure, inextricably linked with surgical complications which may result in graft failure and even recipient’s death. Urologic complications are the most common type of complications following renal transplantation. Their incidence falls within the range of 2–20% of all transplantations.Together with the development of new methods of diagnosis and treatment the procedure administered in the case of suspicion of urologic complications has also been changing. In most cases surgical treatment has been replaced with endoscopic techniques and only in rare cases it is necessary to remove the implanted graft. The purpose of this article is to analyse and summarise the latest reports on the urologic complications following kidney transplantation (KTx) in adults. This problem seems to be particularly important due to an increasing number of renal transplantations in Poland and scant information in the Polish literature about new diagnostic and therapeutic standards in the case of urologic complications following renal transplantation

Increased EBV DNAemia after Anti-SARS-CoV-2 Vaccination in Solid Organ Transplants

The reactivation of latent viruses during SARS-CoV-2 infection is well recognized, and coinfection with Epstein–Barr virus (EBV) has been associated with severe clinical cases of COVID-19 infection. In transplant patients, EBV infection presents a significant challenge. Assessing the potential impact of SARS-CoV-2 vaccinations on EBV infections in stable kidney and liver transplant recipients was the objective of our study. Ten solid-organ-transplant (SOT) patients (eight kidney and two liver) vaccinated with standard doses of mRNA COVID-19 vaccines were included. EBV DNA viral load measurements were conducted prior to the vaccination and during a follow-up period (at the first month and after six months) after the second vaccine dose. After the second dose, a significant increase in median viremia was observed (p < 0.01) in 9 patients, and in one patient, the reactivation of EBV infection was found. Six months later, the median viremia decreased significantly (p < 0.05). The EBV viral load should be closely monitored as it could lead to the earlier diagnosis and treatment of EBV-related complications. Despite experiencing a decrease in the viral load six months post-vaccination, some patients still had a viral load over the baseline, which increased the risk of potential complications

Lung Ultrasound B-lines Occurrence in Relation to Left Ventricular Function and Hydration Status in Hemodialysis Patients

Background and objective: Reliable assessment of the fluid status in hemodialysis (HD) patients is often difficult. A lung ultrasound with an assessment of the B-lines (“lung comets„ (LCs)) number is a novel hydration status measure. However, the occurrence of left ventricular dysfunction may have a significant effect on pulmonary congestion and further modulate the LC number. The aim of this study was to analyze to what extent left ventricular dysfunction, pulmonary hypertension, and hypervolemia affect the occurrence of LC in a cohort of prevalent HD patients. Material and methods: This cross-sectional study included 108 assessments performed in 54 patients who attended thrice weekly outpatient HD. Each patient’s fluid status was evaluated twice, prior to HD sessions, using echocardiography, LC number assessment, measurement of inferior vena cava (IVC) diameters, and bioelectric impedance analysis (BIA). Patients were stratified into three subgroups according to their LC number. Results: There were 76 separate assessments with mild (<14), 16 with moderate (14⁻30), and 16 with severe (>30) LC occurrence. There was a negative correlation between the LC number and left ventricular ejection fraction (LVEF), and positive correlations between the LC number and mitral gradient, and the left and right atrium area and volume, but not with the BIA-derived relative fluid overload. Multivariate linear regression analysis revealed that the LC number was proportionally related to the mitral gradient (β = 0.407 (0.247⁻0.567), p < 0.001) and IVC max diameter (β = 0.219 (0.060⁻0.378), p < 0.01), and was inversely related to LVEF (β = −0.431 (−0.580 to −0.282), p < 0.001). Conclusions: The number of LCs appears to reflect both overhydration and left ventricular dysfunction in our HD patients cohort. Therefore, heart failure must be considered as an important factor limiting the usefulness of LCs number assessment in this population

Clinical Outcomes of Transplanted Kidneys from Deceased Donors Using Different Generic Preservation Solutions

Background and Objectives: StoreProtect Plus® is a preserving solution for cold organ storage, with a composition identical to Institute Georges Lopez (IGL-1) solution. The aim of this single center study was to compare the clinical performance of StoreProtect Plus with the generic counterpart of University of Wisconsin preservation fluid, named SPS-1®. Materials and Methods: The clinical outcomes of 168 consecutive organs preserved with StoreProtect Plus solution and 167 organs preserved with SPS-1 solution were compared. During an 18-month post-transplant follow-up period, kidney graft function, the frequency of acute rejection, post-transplant diabetes, and infectious complications, as well as patient and graft survival were analyzed. Results: There was significantly more immediate graft function (IGF) (39.3 vs. 24.0%; p < 0.01) and less slow graft function (SGF) (38.7 vs. 51.5%; p < 0.05) in the StoreProtect Plus group in comparison with the SPS-1 group, whereas the occurrence of DGF was similar in both groups. Long-term kidney graft function was comparable. Multivariate regression analysis showed that the use of StoreProtect Plus vs. SPS-1 solution (rpartial = 0.217; p < 0.001) and the amount of residual diuresis (rpartial = 0.147; p < 0.001) independently increased the occurrence of IGF, whereas Scr > 1.5 mg/dL prior to organ procurement (rpartial = −0.198; p < 0.001), longer CIT (rpartial = −0.170; p < 0.01), and CVD donor death (rpartial = −0.214; p < 0.001) were associated with SGF. Conclusions: The higher occurrence of IGF was found in kidney transplant recipients whose organs were preserved using StoreProtect Plus solution as compared with SPS-1 solution. The two groups did not differ in kidney graft function, the frequency of post-transplant complications, as well as patient and graft survival

Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose Reduction?

Background. Observational data suggest that the fixed initial recommended tacrolimus (Tc) dosing (0.2 mg/kg/day) results in supratherapeutic drug levels in some patients during the early posttransplant period. The aim of the study was to analyze a wide panel of patient-related factors and their interactions which increase the risk for first Tc blood level > 15 ng/ml. Materials and Methods. We performed a retrospective analysis of 488 consecutive adult kidney transplant recipients who were initially treated with triple immunosuppressive regimen containing tacrolimus twice daily. The analysis included the first assessment of Tc trough blood levels and several demographic, anthropometric, laboratory, and comedication data. Results. The multiple logistic regression analysis showed that age > 55 years, BMI > 24.6 kg/m2, blood hemoglobin concentration > 9.5 g/dl, and the presence of anti-HCV antibodies independently increased the risk for first Tc level > 15 ng/ml. The relative risk (RR) for first tacrolimus level > 15 ng/ml was 1.88 (95% CI 1.35–2.64, p<0.001) for patients with one risk factor and 2.81 (2.02–3.89, p<0.001) for patients with two risk factors. Conclusions. Initial tacrolimus dose reduction should be considered in older, overweight, or obese kidney transplant recipients and in subjects with anti-HCV antibodies. Moreover, dose reduction of tacrolimus is especially important in patients with coexisting multiple risk factors

The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series

Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4&ndash;7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9&ndash;65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4&ndash;75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7&ndash;91.1) mL/min/1.73m2. Neutropenia &lt; 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial