A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients

A high intrapatient variability (IPV) in tacrolimus exposure is a risk factor for poor long-term outcomes after kidney transplantation. The main objective of this trial was to investigate whether tacrolimus IPV decreases after switching patients from immediate-release (IR)-tacrolimus to either extended-release (ER)-tacrolimus or LifeCyclePharma (LCP)-tacrolimus. In this randomized, prospective, open-label, cross-over trial, adult kidney transplant recipients on a stable immunosuppressive regimen, including IR-tacrolimus, were randomized for conversion to ER-tacrolimus or LCP-tacrolimus, and for the order in which IR-tacrolimus and the once-daily formulations were taken. Patients were followed 6 months for each formulation, with monthly tacrolimus predose concentration assessments to calculate the IPV. The IPV was defined as the coefficient of variation (%) of dose corrected predose concentrations. Ninety-two patients were included for analysis of the primary outcome. No significant differences between the IPV of IR-tacrolimus (16.6%) and the combined once-daily formulations (18.3%) were observed (% difference +1.7%, 95% confidence interval [CI] -1.1% to -4.5%, p = 0.24). The IPV of LCP-tacrolimus (20.1%) was not significantly different from the IPV of ER-tacrolimus (16.5%, % difference +3.6%, 95% CI -0.1% to 7.3%, p = 0.06). In conclusion, the IPV did not decrease after switching from IR-tacrolimus to either ER-tacrolimus or LCP-tacrolimus. These results provide no arguments to switch kidney transplant recipients from twice-daily (IR) tacrolimus formulations to once-daily (modified-release) tacrolimus formulations when the aim is to lower the IPV.Personalised Therapeutic

Review: Management of patients with kidney allograft failure

Item does not contain fulltextLate allograft loss in kidney transplant recipients remains a common problem and is associated with high mortality and morbidity. The management of patients with a failed kidney allograft includes a few major dilemmas: when to start dialysis, what is the optimal management regarding immunosuppression, and should an allograft nephrectomy be performed. In suitable candidates for a repeated transplantation there are additional matters to take in consideration. In this review we will discuss these dilemmas by providing an overview of current evidence and gaps in our knowledge. As many of these issues are incompletely resolved, we conclude that more studies are needed to improve the management of patients with a failed kidney allograft

Graft intolerance syndrome requiring graft nephrectomy after late kidney graft failure: can it be predicted? A retrospective cohort study

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A rare tongue ulcer in a renal transplant recipient

Contains fulltext : 225247.pdf (publisher's version ) (Open Access

Monoclonal gammopathy of renal significance presenting with cryoglobulinaemia type I associated severe thrombotic microangiopathy

We report a 53-year-old man who presented with acute renal failure. His medical history revealed a spondyloarthropathy, for which secukinumab was started recently, and a monoclonal gammopathy of unknown significance. Kidney function deteriorated despite the withdrawal of secukinumab and dialysis was started. In the serum, type 1 cryoglobulins were present and a kidney biopsy showed ischaemic glomeruli, with thrombosis of the larger interlobular arteries. Other causes of thrombotic microangiopathy were excluded. Bone marrow immunophenotyping showed 1% monoclonal plasma cells. A diagnosis of monoclonal gammopathy of renal significance was made. Haematological treatment resulted in haematological and renal response

Can We Predict Graft Intolerance Syndrome After Kidney Transplant Failure? External Validation of a Previously Developed Model.

Previously we established a prediction model for graft intolerance syndrome requiring graft nephrectomy in patients with late kidney graft failure. The aim of this study is to determine generalizability of this model in an independent cohort. The validation cohort included patients with late kidney graft failure between 2008 and 2018. Primary outcome is the prognostic performance of our model, expressed as the area under the receiver operating characteristic curve (ROC-AUC), in the validation cohort. In 63 of 580 patients (10.9%) a graft nephrectomy was performed because of graft intolerance. The original model, which included donor age, graft survival and number of acute rejections, performed poorly in the validation cohort (ROC-AUC 0.61). After retraining of the model using recipient age at graft failure instead of donor age, the model had an average ROC-AUC of 0.70 in the original cohort and of 0.69 in the validation cohort. Our original model did not accurately predict the graft intolerance syndrome in a validation cohort. However, a retrained model including recipient age at graft failure instead of donor age performed moderately well in both the development and validation cohort enabling identification of patients with the highest and lowest risk of graft intolerance syndrome