Subthreshold rejection activity in many kidney transplants currently classified as having no rejection.

Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

Remdesivir Reduces Mortality in Hemato-Oncology Patients with COVID-19.

Introduction: Remdesivir is the first agent with proven clinical efficacy against coronavirus disease 2019 (COVID-19); however, its benefit is associated with early use, and its efficacy has been poorly studied in patients with hemato-oncological diseases, who have an increased risk of a severe course of infection. This study aimed to assess the effects of remdesivir on mortality, mechanical ventilation, and the duration of hospitalization in both the general population and in patients with hemato-oncological diseases. Materials and Methods: Longitudinal data for 4287 patients with confirmed COVID-19 were analyzed, including a subset of 200 individuals with hemato-oncological diseases. In total, 1285 (30.0%) patients received remdesivir, while the remaining patients were treated with other methods. Survival statistics for the 14- and 30-day observation time points were calculated using non-parametric and multivariate Cox models. Results: Mortality for the 14- and 30-day observation time points was notably lower among patients receiving remdesivir (7.2% vs 11.6%, p < 0.001 and 12.7% vs 16.0, p = 0.005, respectively); however, in multivariate models adjusted for age, sex, lung involvement, and lactate dehydrogenase and interleukin-6 levels, the administration of remdesivir did not reduce patient mortality at either the 14-day or 30-day time points. Among patients with haemato-oncological disease, significant survival benefit was observed at 14 and 30 days for patients treated with remdesivir (11.3% vs.16.7% and 24.2% vs 26.1%, respectively; p < 0.001). A favorable effect of remdesivir was also noted for the 14-day time point in multivariate survival analysis (HR:4.03 [95% confidence interval:1.37-11.88]; p = 0.01). Conclusion: Remdesivir significantly reduced the early mortality rate in COVID-19 patients with comorbid hemato-oncological disease, which emphasizes the need to administer this agent to immunosuppressed patients.

C/D Ratio in Long-Term Renal Function.

BACKGROUND/AIMS: Tacrolimus is an immunosuppressive drug. Its C0 concentration, commonly used for monitoring, does not always correspond to its pharmacologic effect. Thölking et al developed an indicator, the C/D ratio, that describes the drug's metabolism rate. Our purpose was to determine whether the points dividing the patients into fast, intermediate, and slow metabolizers that were assumed by those authors would be similar for long-term follow-up after renal transplantation (RTx). METHODS: We examined the C/D ratio in 571 patients at their most recent appointments-1 year and more after renal transplantation. The mean time after RTx was 84 months. We studied kidney function both at the most recent appointment and early after RTx. RESULTS: The median C/D ratio for our group was 1.68. Our observations revealed a negative correlation between the C/D ratio and creatinine concentration and a positive correlation between the C/D ratio and eGFR concentration long term after RTx. We formulated a C/D ratio cutoff point between an eGFR < and ≥ 60 mL/min/1.73 m2 and came up with the value of 1.53. It was found that between the < 1.53 and ≥ 1.53 groups, there were significant differences in creatinine and eGFR concentrations at the most recent appointment, as well as differences in how creatinine and eGFR levels varied over time between RTx and the most recent observation. CONCLUSIONS: The C/D ratio is useful for assessing the effect of the tacrolimus metabolism rate on long-term renal function. We propose the C/D ratio value of 1.53 as the cutoff point below which the ratio provides a negative prognosis for long-term renal function.