Coping with a lack of evidence: living-donor kidney transplantation in the initial phase of the SARS-CoV-2 pandemic.

Due to immunosuppressive therapy, transplant patients are more susceptible to viral and bacterial infections. A potentially deadly new virus haunted us in 2020: SARS-CoV­2, causing coronavirus disease 19 (COVID-19). We analyzed the consequences of this previously unknown risk for our living-donor transplant program in the first year of the pandemic. After the complete lockdown in spring 2020, our transplant center in Linz resumed the living-donor kidney transplantation program from June to September 2020, between the first and second waves of COVID-19 in Austria. We compared the outcomes of these living-donor kidney transplantations with the transplant outcomes of the corresponding periods of the three previous years. From June 4 to September 9, 2020, five living-donor kidney transplantations were performed. All donors and recipients were screened for COVID 19 infection by PCR testing the day before surgery. Kidney transplant recipients remained isolated in single rooms until discharge from hospital. All recipients and donors remained SARS-CoV­2 negative during the follow-up of 10 months and have been fully vaccinated to date. The number of living transplants in the studied period of 2020 was constant compared to the same months of 2017, 2018, and 2019. Living-donor kidney transplantation can be continued using testing for SARS-CoV­2 and meticulous hygienic precautions in epidemiologically favorable phases of the SARS-CoV­2 pandemic. Donors and recipients should be carefully selected and informed about risks and benefits.

Successful kidney transplantation in a patient with pre-existing chronic myeloid leukemia treated with imatinib.

Active malignancy is an absolute contraindication to kidney transplantation. As for chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal into a manageable chronic disease with a close-to-normal life expectancy. To date it is unknown whether kidney transplantation can be safely performed in patients with pre-existing CML. We describe the clinical course of a 57-year-old male patient with chronic kidney disease caused by reflux nephropathy. This patient had undergone first kidney transplantation 20 years earlier and had again been on chronic hemodialysis for 6 years when CML was diagnosed. First-line therapy with 400 mg imatinib daily was well tolerated and induced an optimal cytogenetic and molecular response 3 months after initiation. One and a half years after CML diagnosis, a second kidney transplantation from a deceased donor was performed. Immunosuppression included basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids. Currently, 2 years posttransplant, renal allograft function is stable (serum creatinine 1.09 mg/dL, estimated glomerular filtration rate 75 mL/min per 1.73 m2 ), and CML remains in deep molecular remission with imatinib. Imatinib-treated CML in deep molecular remission could be regarded as inactive malignancy and may therefore not be viewed as an absolute contraindication to kidney transplantation.

Sirolimus in renal transplant recipients with tuberous sclerosis complex: clinical effectiveness and implications for innate immunity.

Tuberous sclerosis complex (TSC) is caused by constitutively activated mammalian target of rapamycin (mTOR) resulting in nonmalignant tumours of several organs and consequently renal failure. Recent reports suggest a possible beneficial role of the mTOR-inhibitor (mTOR-I) sirolimus for TSC; however, safety and efficiency of sirolimus in TSC patients after renal transplantation, both as primary immunosuppressant as well as anti-proliferative agent, are still undefined. Moreover, it is currently unknown whether the TSC mutation affects the primary immune response in these patients. In this article, we report on three TSC patients after renal transplantation who have been converted from a calcineurin-inhibitor (CNI)-based immunosuppression to sirolimus. During 2 years of follow-up, renal allograft function was stable or even improved, and no significant sirolimus-associated side-effects were noted. Beneficial effects of sirolimus against TSC were detected in the skin, along with improved spirometric measurements and an arrest of astrocytoma progression. We show that the inflammatory immune response was significantly altered in TSC patients as compared with controls and sirolimus potently affected both inflammatory cytokine production and vascular endothelial growth factor levels in these patients. Larger studies are warranted to further examine the relationship between clinical parameters and the molecular response to mTOR-inhibition in TSC patients after renal transplantation.