Tacrolimus (TAC) has a narrow therapeutic window and patient-specific pharmacokinetic variability. In our study, we analyzed the association between TAC exposure, metabolism, and kidney graft outcomes (function, rejection, and histological lesions). TAC trough (C0), coefficient of variation (TAC CV), concentration/dose ratio (C/D), and biomarkers related to kidney injury molecule-1 (KIM-1) and neutrophil gelatinase lipocalin (NGAL) were analyzed. We examined 174 patients who were subjected to a triple immunosuppressive regimen and underwent kidney transplantation between 2017 and 2022. Surveillance biopsies were performed at the time of kidney implantation and at three and twelve months after transplantation. We classified patients based on their Tac C/D ratios, classifying them as fast (C/D ratio < 1.05 ng/mL × 1/mg) or slow (C/D ratio ≥ 1.05 ng/mL × 1/mg) metabolizers. TAC exposure/metabolism did not significantly correlate with interstitial fibrosis/tubular atrophy (IF/TA) progression during the first year after kidney transplantation. TAC CV third tertile was associated with a higher chronicity score at one-year biopsy. TAC C/D ratio at three months and Tac C0 at six months were associated with rejection during the first year after transplantation. A fast TAC metabolism at six months was associated with reduced kidney graft function one year (OR: 2.141, 95% CI: 1.044–4.389, p = 0.038) and two years after transplantation (OR: 4.654, 95% CI: 1.197–18.097, p = 0.026), and TAC CV was associated with reduced eGFR at three years. uNGAL correlated with IF/TA and chronicity scores at three months and negatively correlated with TAC C0 and C/D at three months and one year. Conclusion: Calculating the C/D ratio at three and six months after transplantation may help to identify patients at risk of suffering acute rejection and deterioration of graft function.
With an increasing number of marginal donors, additional methods for the evaluation of cadaveric kidney quality are required. This study aimed to evaluate pretransplant deceased donor serum (s) and urine (u) biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18, and C-X-C motif chemokine 10 (CXCL10) for predicting early and late graft function. In total, 43 deceased kidney donors and 76 corresponding recipients were enrolled. Delayed graft function (DGF) occurred in 27.6% of cases. sIL-18, sKIM-1, uNGAL, and uKIM-1 were predictors of DGF. A model incorporating sIL-18, uKIM-1, and clinical factors was developed to predict DGF (AUROC 0.863). Univariate analysis showed a negative association between uKIM and graft eGFR at 6, 12, 24, and 36 months, but this was not confirmed in the multivariate analysis. In conclusion, we report a superior performance of donor biomarkers for predicting DGF and later graft function over serum creatinine. Higher levels of donor sIL-18 and uKIM in conjunction with expanded-criteria donors and longer cold ischemia times predicted DGF. With no renal tubular damage in zero-time donor biopsies, higher pretransplant urine and serum NGAL levels were associated with better allograft function one year after transplantation, and sNGAL with graft function three years after transplantation.
Immunotherapy treatment with checkpoint inhibitors (ICIs) has led to a breakthrough in the treatment of oncological diseases. Despite its clinical effectiveness, this treatment differs from others, such as cytotoxic chemotherapy, in that it causes immune-related adverse events. This type of toxicity can affect any organ or organ system of the body. We present a literature review and a rare clinical case from our clinical practice, in which a patient with metastatic clear cell renal carcinoma was treated with a single dose of dual checkpoint blockade (cytotoxic T-lymphocyte-4 (CTLA-4) and programmed death-1 (PD-1)) and simultaneously diagnosed with colitis, hepatitis, and nephritis. After early immunosuppressive treatment with the glucocorticoids, complete organ function recovery was achieved. The follow-up revealed a sustained complete response lasting more than a year.
Background and Objectives: Non-invasive imaging biomarkers for the early detection of chronic kidney allograft injury are needed to improve long-term transplant outcomes. T1 mapping by magnetic resonance imaging (MRI) has emerged as a promising method to assess renal structure and function. This study aimed to determine the potential of MRI as a diagnostic tool for evaluating graft function and structural changes in kidney grafts 1 year after transplantation. Materials and Methods: Thirty-four kidney transplant recipients were prospectively recruited, with 27 completing the follow-up at one year. Renal MRI at 3T was performed to acquire T1, T2, and apparent diffusion coefficient (ADC) maps. Clinical parameters, including estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio (PCR), and histological IF/TA scores, were collected. MRI parameters were compared across the groups stratified by clinical and histological markers. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. Results: At 1 year, T1 corticomedullary differentiation (CMD) values were significantly higher in patients with elevated ACR (≥3 mg/mmol), PCR (≥15 mg/mmol), and mild to moderate or severe IF/TA, reflecting a reduction in the corticomedullary gradient. T1 CMD demonstrated moderate-to-good diagnostic performance in detecting ACR (AUC 0.791), PCR (AUC 0.730), and IF/TA (AUC 0.839). No significant differences were observed in T2 or ADC values across these groups. T1 CMD also showed a significant positive correlation with ACR but not with eGFR, suggesting a closer association with structural rather than functional deterioration. Conclusions: T1 mapping, particularly T1 CMD, shows promise as a non-invasive imaging biomarker for detecting chronic allograft injury and monitoring renal function 1 year after kidney transplantation.
Background and Objectives: The safety and effectiveness of vaccines are among the key priorities in COVID-19 pandemic management. Moreover, evidence-based data regarding vaccine safety and immunogenicity can play an important role in building the trust of the community regarding vaccination. The aim of this study was to investigate the safety and immunogenicity of Pfizer-BioNTech vaccine among healthcare workers in one hospital, 21 days after first dose. Materials and Methods: This study was conducted in the Hospital of the Lithuanian University of Health Sciences between February and March 2021. Hospital employees who arrived to receive the second dose of the Pfizer-BioNTech vaccine 21 days after the first one were invited to participate in the study: they were asked to complete an anonymous adverse events questionnaire and were offered a SARS-CoV-2 IgG/IgM rapid test. The study was performed at a single point, 21 days after the first dose of the vaccine. Results: Data of 4181 vaccine recipients were analysed. The first vaccine dose was associated with a 53.6% incidence of adverse events, mainly local reactions. Adverse events occurred more frequently in younger participants and women. Moderate adverse events were experienced by 1.4% of the vaccine recipients; 6.2% were incapacitated. Of the 3439 participants who performed a rapid IgG test, 94.5% were positive for IgG antibodies after the first vaccine dose. Seroconversion rates were lower in participants older than 47 years. Conclusions: Despite 1.4% moderate adverse events, no safety concerns or anaphylaxis were identified. The Pfizer-BioNTech vaccine induced an immune response in the overwhelming majority of recipients after a single dose. Younger participants experienced adverse events and were positive for IgG antibodies more frequently than older counterparts. It is important to mention that this study specifically considered short-term safety and reactions following vaccination and that long-term adverse effects were not investigated in the study. Thus, future research into both long-term adverse reactions and immune system programming is essential.
Background/Objectives: Kidney transplantation (kTx) is the preferred treatment for end-stage kidney disease. Limited evaluation of structural changes in transplanted kidneys hinders the timely prediction of disease progression and the implementation of treatment modifications. Protocol biopsies provide valuable insights but are invasive and carry risks of biopsy-related complications. This study investigates whether multiparametric magnetic resonance imaging (MRI), including T1 and T2 mapping and diffusion-weighted imaging (DWI), can predict kidney function and the progression of interstitial fibrosis and tubular atrophy (IF/TA) in the early post-transplant period. Methods: A prospective study was conducted at The Hospital of Lithuanian University of Health Sciences Kauno Klinikos from May 2022 to March 2024. Thirty-four patients receiving kidney transplants from deceased donors underwent baseline biopsies and post-transplant MRI scans. Follow-up assessments included kidney function evaluation, biopsies, and MRI scans at three months post-transplant. Results: Significant correlations were observed between MRI parameters and kidney function: T1 and apparent diffusion coefficient (ADC) corticomedullary differentiation (CMD) correlated with eGFR at discharge (r = −0.338, p = 0.05; r = 0.392, p = 0.022, respectively). Linear and logistic regression models demonstrated that post-transplant T1 and ADC CMD values significantly predicted kidney function at discharge. Furthermore, T1 CMD values measured 10–15 days post-transplant predicted IF/TA progression at three months post-kTx, with an area under the curve of 0.802 (95% CI: 0.616–0.987, p = 0.001) and an optimal cut-off value of −149.71 ms. The sensitivity and specificity were 0.818 and 0.273, respectively (Youden’s index = 0.545). T2 mapping was not predictive. Conclusions: This study highlights the potential immediate clinical utility of MRI-derived biomarkers, particularly ADC and T1 CMD, in centers equipped with advanced imaging capabilities as tools for assessing kidney function in the early post-transplant period. With an AUROC of 0.802, T1 CMD demonstrates strong discriminatory power for predicting IF/TA progression early in the post-transplant period.