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Background/Objectives: Anemia is a frequent multifactorial co-morbidity in end-stage kidney disease (ESKD) associated with morbidity and poor QoL. Apart from insufficient erythropoietin formation, iron deficiency (ID) contributes to anemia development. Identifying patients in need of iron supplementation with current ID definitions is difficult since no good biomarker is available to detect actual iron needs. Therefore, new diagnostic tools to guide therapy are needed. Methods: We performed a prospective cohort study analyzing tissue iron content with MRI-based R2*-relaxometry in 20 anemic ESKD patients and linked it with iron biomarkers in comparison to 20 otherwise healthy individuals. Results: ESKD patients had significantly higher liver (90.1 s−1 vs. 36.1 s−1, p < 0.001) and spleen R2* values (119.8 s−1 vs. 19.3 s−1, p < 0.001) compared to otherwise healthy individuals, while their pancreas and heart R2* values did not significantly differ. Out of the 20 ESKD patients, 17 had elevated spleen and 12 had elevated liver R2* values. KDIGO guidelines (focusing on serum iron parameters) would recommend iron supplementation in seven patients with elevated spleen and four patients with elevated liver R2* values. Conclusions: These findings highlight that liver and especially spleen iron concentrations are significantly higher in ESKD patients compared to controls. Tissue iron overload diverged from classical iron parameters suggesting need of iron supplementation. Measurement of MRI-guided tissue iron distribution might help guide treatment of anemic ESKD patients. [ABSTRACT FROM AUTHOR]

Fibrinogen-like 2 (FGL2) was recently found to be associated with fibrosis in a mouse model of kidney damage and was proposed as a potential therapeutic target in chronic kidney disease (CKD). We assessed the association of renal FGL2 mRNA expression with the disease outcome in two independent CKD cohorts (NEPTUNE and Innsbruck CKD cohort) using Kaplan Meier survival analysis. The regulation of FGL2 in kidney biopsies of CKD patients as compared to healthy controls was further assessed in 13 human CKD transcriptomics datasets. The FGL2 protein expression in human renal tissue sections was determined via immunohistochemistry. The regulators of FGL2 mRNA expression in renal tissue were identified in the co-expression and upstream regulator analysis of FGL2-positive renal cells via the use of single-cell RNA sequencing data from the kidney precision medicine project (KPMP). Higher renal FGL2 mRNA expression was positively associated with kidney fibrosis and negatively associated with eGFR. Renal FGL2 mRNA expression was upregulated in CKD as compared with healthy controls and associated with CKD progression in the Innsbruck CKD cohort (p-value = 0.0036) and NEPTUNE cohort (p-value = 0.0048). The highest abundance of FGL2 protein in renal tissue was detected in the thick ascending limb of the loop of Henle and macula densa, proximal tubular cells, as well as in glomerular endothelial cells. The upstream regulator analysis identified TNF, IL1B, IFNG, NFKB1, and SP1 as factors potentially inducing FGL2-co-expressed genes, whereas factors counterbalancing FGL2-co-expressed genes included GLI1, HNF1B, or PPARGC1A. In conclusion, renal FGL2 mRNA expression is elevated in human CKD, and higher FGL2 levels are associated with fibrosis and worse outcomes. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

Introduction: Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and investigate the potential occurrence of peripheral edema., Methods: A total of 4 clinical visits were performed before, during, and after a 6-day bicycle ride in 13 ultracyclists (5 female, 8 male) including serial laboratory analyses of blood and urine, bioelectrical impedance, and echocardiography. Throughout the ride, participants continuously tracked fluid intake, measured extremity circumferences daily, and self-tested urinary electrolytes using a point-of-care testing device. Portrait photos were judged by 20 physicians for occurrence of facial and eyelid edema., Results: Participants covered a mean distance of 1205 km and 19,417 vertical meters. From baseline to day 6, body weight remained stable ( P  = 0.479); however, body composition changed with increasing total body water (TBW) (+1.98 l ± 1.37, P  = 0.003) and plasma volume (+18.86 % ± 10.7, P  < 0.001). A significant increase in N-terminal pro brain natriuretic peptide (NT-proBNP) (+297.99 ng/l ± 190.42, P  < 0.001) until day 6 indicates concomitant cardiac volume overload. Swelling of face and eyelids peaked on day 5 (both P  ≤ 0.033). On recovery, changes partly resolved. Although urinary sodium concentration showed a nadir on day 4 (-32.18 mmol/l ± 23.88, P  = 0.022), plasma osmolality (+5.69 mmosmol/kg ± 5.88, P  = 0.004) and copeptin (+38.28 pg/ml ± 18.90, P  < 0.001) increased steadily until day 6., Conclusion: Ultracycling over multiple days induces extracellular volume expansion, peripheral edema, and cardiac volume overload. Renal sodium and water retention is likely contributing to this condition., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Background and Objectives: Renal transplantation is the preferred form of renal replacement therapy for the majority of patients with end stage renal disease (ESRD). The Internet is a key tool for people seeking healthcare-related information. This current work explored the interest in kidney transplantation based on Internet search queries using Google Trends TM ., Design, Setting, Participants, and Measurements: We performed a Google Trends TM search with the search term "kidney transplantation" between 2004 (year of inception) and 2018. We retrieved and analyzed data on the worldwide trend as well as data from the United Network for Organ Sharing (UNOS), the Organización Nacional de Trasplantes (ONT), the Eurotransplant area, and the National Health Service (NHS) Transplant Register. Google Trends TM indices were investigated and compared to the numbers of performed kidney transplants, which were extracted from the respective official websites of UNOS, ONT, Eurotransplant, and the NHS., Results: During an investigational period of 15 years, there was a significant decrease of the worldwide Google Trends TM index from 76.3 to 25.4, corresponding to an absolute reduction of -50.9% and a relative reduction by -66.7%. The trend was even more pronounced for the UNOS area (-75.2%), while in the same time period the number of transplanted kidneys in the UNOS area increased by 21.9%. Events of public interest had an impact on the search queries in the year of occurrence, as shown by an increase in the Google Trends TM index by 39.2% in the year 2005 in Austria when a person of public interest received his second live donor kidney transplant., Conclusions: This study indicates a decreased public interest in kidney transplantation. There is a clear need to raise public awareness, since transplantation represents the best form of renal replacement therapy for patients with ESRD. Information should be provided on social media, with a special focus on readability and equitable access, as well as on web pages., Competing Interests: The authors declare no conflicts of interest.