Thioredoxin-1 (Trx-1) is a multifunctional protein ubiquitously found in the human body. Trx-1 plays an important role in various cellular functions such as maintenance of redox homeostasis, proliferation, and DNA synthesis, but also modulation of transcription factors and control of cell death. Thus, Trx-1 is one of the most important proteins for proper cell and organ function. Therefore, modulation of Trx gene expression or modulation of Trx activity by various mechanisms, including post-translational modifications or protein–protein interactions, could cause a transition from the physiological state of cells and organs to various pathologies such as cancer, and neurodegenerative and cardiovascular diseases. In this review, we not only discuss the current knowledge of Trx in health and disease, but also highlight its potential function as a biomarker.

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Background and Aims The impairing effect of chronic kidney disease-associated pruritus (CKD-aP) on the quality of life (QoL) of patients undergoing haemodialysis (HD) is well-established. The aim of this post-hoc analysis was to assess the impact of itch relief on QoL, as measured by the 5-D itch scale, in patients with CKD-aP enrolled in the Phase 3 KALM-1 and -2 clinical trials. This study also aimed to confirm the use of ≥5-point reduction in 5-D itch scale total score as a threshold for clinically meaningful improvement in itch-related QoL, by comparing to notable improvement on the Patients’ Global Impression of Change (PGI-C) scale. Method Data were pooled from 851 patients with moderate-to-severe CKD-aP undergoing HD in the KALM-1 and -2 trials testing difelikefalin vs placebo. Sustained responders were defined as patients who achieved a ≥3-point improvement in the weekly mean 24-hour Worst Itching Intensity Numerical Rating Scale [WI-NRS] score at Week 12 of the study, whereas non-sustained responders were defined as patients that reported a ≥3-point improvement in any week of the study but not at Week 12. Improvements in QoL, as measured by the mean change in 5-D itch scale total score from baseline to Week 12, were compared in sustained responders vs non-sustained responders. Data were analysed by ANCOVA multiple imputation, with a missing-at-random assumption. The mean change in 5-D itch scale total score was analysed in relation to patients’ reporting on the five categories of the PGI-C scale. Results In pooled analysis, 305 patients undergoing HD with CKD-aP qualified as sustained responders, whereas 128 patients were non-responders. Reduction in 5-D itch scale total score over 12 weeks was significantly higher in sustained responders compared with non-sustained responders (least squares [LS] mean ±standard error; –7.1±0.2 vs –4.0±0.3, LS mean difference –3.0±0.3, p<0.001) (Figure 1). Greater reductions in 5-D itch scale total score were observed in patients reporting more substantial improvements in PGI-C. Specifically, patients reporting much, or very much, improvement in PGI-C scored ≥5-point reduction on the 5-D itch scale (mean ±standard error; –5.3±0.2 and –8.2±0.3, respectively) (Figure 2). Conclusion This study observed a greater improvement in QoL, as measured by the 5-D itch scale total score, in patients with CKD-aP who reported a clinically meaningful reduction in itch, as measured by WI-NRS, at Week 12. These results also support the use of ≥5-point reduction in the 5-D itch scale total score as a threshold for clinically meaningful improvement in the QoL of patients with CKD-aP. As only sustained responders exceeded this threshold, these data suggest that continued treatment of itch may be necessary to maximally improve QoL in these patients.

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Nierenersatzverfahren wie die Peritonealdialyse (PD), die als Heimdialyseverfahren durchgeführt werden, haben sich während der SARS-CoV-2-Pandemie (SARS-CoV-2: „severe acute respiratory syndrome coronavirus 2“) zur Einhaltung eines „social distancing“ als vorteilhaft gegenüber der Zentrumsdialyse erwiesen. Dies resultiert in vergleichsweise weniger Infektionen und Hospitalisierungen bei PD-Patienten 1.