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.

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.

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.

Histopathological examination of removed kidney allografts: Is it useful? A retrospective cohort study.

The incidence and relevance of histological findings in removed allografts is unknown. In this study, we investigated the outcome of routine histopathological examination of removed allografts. We performed a retrospective cohort study in patients with kidney graft failure ≥3 months after transplantation. In this cohort, 244 allograft nephrectomies were performed. We routinely sent removed grafts for histopathological examination. In 197 cases, a pathology report was available for analysis. In 21 of the 197 grafts, gross necrosis precluded adequate interpretation. Signs of rejection were reported in 163 of the remaining 176 allografts. Recurrences of the original disease were found in 13 cases. These were all known from prior biopsies. Relevant secondary findings were present in eight cases: renal cell carcinoma (n = 2), urothelial cell carcinoma, candida pyelonephritis (n = 2), post-transplant lymphoproliferative disease, polyomavirus inclusions, and membranous nephropathy. All conditions were diagnosed before graft nephrectomy, except for one case of papillary renal cell carcinoma of 0.8 cm. As expected, signs of acute and/or chronic rejection are the main histopathological finding in grafts that are removed after late graft failure. Unexpected secondary findings are very rare. Therefore, it is justifiable to restrict histopathological examination of removed kidney allografts to specific cases.

Review: Management of patients with kidney allograft failure.

Late 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.

Graft nephrectomy is recommended in case of early graft failure. When the graft fails more than 3-6 months after transplantation, it is current practice to follow a wait-and-see policy. A common indication for graft removal is the graft intolerance syndrome. We aimed to create a risk prediction model for the occurrence of graft intolerance resulting in graft nephrectomy. We collected data of kidney transplantations performed in our center between 1980 and 2010 that failed at least 6 months after transplantation. We evaluated the association between baseline characteristics and the occurrence of graft nephrectomy because of graft intolerance using a competing risk regression model. Prognostic factors were included in a multivariate prediction model. In- and exclusion criteria were met in 288 cases. In 48 patients, the graft was removed because of graft intolerance. Donor age, the number of rejections, and shorter graft survival were predictive factors for graft nephrectomy because of the graft intolerance syndrome. These factors were included in a prediction rule. Using donor age, graft survival, and the number of rejections, clinicians can predict the need for graft nephrectomy with a reasonable accuracy.