Characteristics of the investigated TSC patient cohort.

<p>Characteristics of the investigated TSC patient cohort.</p

Best percentage reduction of contrast to noise ratio as well as size of angiomyolipomas in each individual patient reported at any time point.

<p>In all analyzed patients a reduction in CNR could be observed whereas 2 patients did not show a size reduction of AML under everolimus treatment. AML size is given in mm², results are sorted by value.</p

Signal changes in magnetic resonance imaging with selective fat suppression in TSC patients following the initiation of mTOR inhibitor therapy.

<p>Patients were investigated at baseline and after 0–3 months, 3–6 months and 18–24 months of mTOR inhibitor therapy. Additionally, a control collective of TSC patients without mTOR inhibitor therapy was investigated. A pronounced and significant reduction of the mean contrast to noise ratio (CNR) was already observed in the early group within the first three months. In the control group, no reduction of the mean CNR value was observed. Error bars indicate the standard deviation. P-values generated from linear mixed model statistical analysis (* p<0.01, *** p<0.0001); CNR: Contrast to noise ratio.</p

Size changes in magnetic resonance imaging in TSC patients following the initiation of mTOR inhibitor therapy.

<p>Patients were investigated at baseline and after 0–3 months, 3–6 months and 18–24 months of mTOR inhibitor therapy. Additionally, a control collective of TSC patients without mTOR inhibitor therapy was investigated. A significant (p ≤ 0.05) reduction of the size of angiomyolipomas (in mm²) was already observed in the early group within the first three months. In the control group, no reduction of the size was observed. Error bars indicate the standard deviation. P-values generated from linear mixed model statistical analysis (* p<0.01, ** p<0.001, *** p<0.0001).</p

Fatty transformation of angiomyolipoma in TSC patients after initiation of mTOR inhibitor therapy.

<p><b>A</b>: Example of a large AML at the central part of the right kidney in a 33 year-old female TSC patient. <b>A1</b>: At baseline a heterogeneous AML with a mixed-signal on the T2 fat saturated MR sequence (solid arrows) could be visualized. Slow flowing blood in a small vessel (dotted arrows) appears hyperintense on the fat saturated sequence. The unaffected “healthy” kidney tissue is also visualized with a hyperintense signal (*). <b>A2</b>: 2.5 months following the initiation of the mTOR inhibitor therapy a reduction in the overall signal of the AML on the T2 fat saturated sequence can be visualized. The vessel, which was visible at baseline (A1: dotted line) cannot be delineated anymore. Additionally, a reduction of size of the AML can be visualized. This case represents a good example of how difficult it can be to clearly quantify a size reduction in a heterogenous AML following the initiation of mTOR therapy. <b>B</b>: Example of a AML at the caudal part of the right kidney in a 45 year-old male TSC patient. <b>B1</b>: At baseline a heterogeneous relatively bright angiomyolipoma could be visualized on the T2 fat saturated sequence (arrows). The unaffected “healthy” kidney tissue is visualized with a homogenous hyperintense signal on the T2 fat saturated sequence (*). <b>B2</b>: 3 to 6 months following the initiation of the mTOR inhibitor therapy, a clear reduction in the signal on the T2 fat saturated sequence as well as in the size of the angiomyolipoma is visualized. The signal of the healthy kidney tissue does not change following the initiation of the therapy (*). MRI: Magnetic Resonance Imaging. Fatsat: Fat saturated. Scale bar: 1.5 cm.</p

Trough levels and dosing of everolimus.

<p>Trough levels and dosing of everolimus.</p

Data_Sheet_1_The natural history of de novo donor-specific HLA antibodies after kidney transplantation.pdf

BackgroundDe novo donor-specific HLA antibodies (dnDSA) are key factors in the diagnosis of antibody-mediated rejection (ABMR) and related to graft loss.MethodsThis retrospective study was designed to evaluate the natural course of dnDSA in graft function and kidney allograft survival and to assess the impact of mean fluorescence intensity (MFI) evolution as detected by annual Luminex® screening. All 400 kidney transplant recipients with 731 dnDSA against the last graft (01/03/2000-31/05/2021) were included.ResultsDuring 8.3 years of follow-up, ABMR occurred in 24.8% and graft loss in 33.3% of the cases, especially in patients with class I and II dnDSA, and those with multiple dnDSA. We observed frequent changes in MFI with 5-year allograft survivals post-dnDSA of 74.0% in patients with MFI reduction ≥ 50%, 62.4% with fluctuating MFI (MFI reduction ≥ 50% and doubling), and 52.7% with doubling MFI (log-rank p ConclusionIn summary, we provide an in-depth analysis of the natural course of dnDSA after kidney transplantation, first evidence for the impact of MFI evolution on graft outcomes, and describe a relevant number of patients with a stable disappearance of dnDSA, related to better allograft survival.</p

Image_1_Three-Month Follow-Up of Heterologous vs. Homologous Third SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Secondary Analysis of a Randomized Controlled Trial.pdf

Response to SARS-CoV-2-vaccines in kidney-transplant recipients (KTR) is severely reduced. Heterologous3rd vaccination combining mRNA and vector vaccines did not increase seroconversion at 4 weeks after vaccination, but evolution of antibody levels beyond the first month remains unknown. We have recently completed a randomized-controlled trial on heterologous (Ad26COVS1) vs. homologous (BNT162b2 or mRNA-1273) 3rd vaccination in 201 KTR not developing SARS-CoV-2-spike-protein antibodies following two doses of mRNA vaccine (EurdraCT: 2021-002927-39). Here, we report seroconversion at the second follow-up at 3 months after the 3rd vaccination (prespecified secondary endpoint). In addition, higher cut-off levels associated with neutralizing capacity and protective immunity were applied (i.e., > 15, > 100, > 141, and > 264 BAU/ml). A total of 169 patients were available for the 3-month follow-up. Overall, seroconversion at 3 months was similar between both groups (45 vs. 50% for mRNA and the vector group, respectively; p = 0.539). However, when applying higher cut-off levels, a significantly larger number of individuals in the vector group reached antibody levels > 141 and > 264 BAU/ml at the 3-month follow-up (141 BAU/ml: 4 vs. 15%, p = 0.009 and 264 BAU/ml: 1 vs. 10%, p = 0.018 for mRNA vs. the vector vaccine group, respectively). In line, antibody levels in seroconverted patients further increased from month 1 to month 3 in the vector group while remaining unchanged in the mRNA group (median increase: mRNA = 1.35 U/ml and vector = 27.6 U/ml, p = 0.004). Despite a similar overall seroconversion rate at 3 months following 3rd vaccination in KTR, a heterologous 3rd booster vaccination with Ad26COVS1 resulted in significantly higher antibody levels in responders.</p

Time to renal angiomyolipoma progression.

<p>Time to renal angiomyolipoma progression.</p

Median GFR (A) and creatinine (B) over time.

<p>Medians are connected by lines, means are displayed as dots. Boxes are drawn from P25 to P75. Whiskers extend from P10 to P90. # indicates values that lie outside [P10, P90]. *Baseline assessment is the last performed before start of everolimus. Post-baseline laboratory assessments performed at unplanned schedule or more than 28 days after discontinuation of everolimus are not presented. Only results from central laboratory are included. Abbreviations: BL = baseline; GFR = glomerular filtration rate; P = percentile.</p