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Abstract Background TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. Case presentation An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. Conclusions Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

Abstract Background Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD) and could be related to oxidative stress. Vascular calcification (VC) has been established as a critical risk factor for accelerated CVD. In CKD, phosphorus (Pi), iron (Fe) and Nrf2 are modulators of VC and important agonists and antagonists of oxidative stress. The aim of this study was to determine whether Fe administration, which is commonly used to treat renal anemia, affects aortic Fe overload and VC, and whether Nrf2 and its related genes, ferritin H and HIF-1α, are involved in the development of VC. Methods A CKD model was created in rats by administering adenine and simultaneously feeding a high-Pi diet. In addition to control and CKD rats without Fe administration (No-Fe group), Fe was administered orally (PO-Fe group) or intraperitoneally (IP-Fe group) to CKD animals to clarify the effects of Fe administration on the aortic Fe and calcium (Ca) contents and the involvement of Nrf2 and its induced antioxidative proteins, ferritin H and HIF-1α, in VC. Results The aortic Fe content increased significantly in the IP-Fe group, which was closely correlated with liver HAMP (hepcidin) expression in all animals. Fe administration had no significant effect on the aortic Ca and Pi contents regardless of the route of Fe administration. The aortic mRNA level of Nrf2 was significantly increased in the IP-Fe group and correlated with serum Pi levels and aortic Fe contents, which could respond to oxidative stress. Notably, the mRNA level of Nrf2 was also significantly correlated with the mRNA levels of ferritin H and HIF-1α. Since we could not measure Nrf2 protein levels in this study, we confirmed the upregulation of HMOX1 and NQO1 mRNA expression in parallel with Nrf2 mRNA. Conclusion Parenteral Fe administration increased aortic Fe in parallel with the liver HAMP mRNA level but did not affect VC. Aortic Nrf2 mRNA levels correlated significantly with aortic Fe and serum Pi levels and with aortic mRNA levels of ferritin H and HIF-1α as well as HMOX1 and NQO1.

Abstract Although the association between non-alcoholic fatty liver disease and chronic kidney disease (CKD) has been well known, it is unclear whether Fibrosis-4 (FIB-4) score is a predictor of CKD development. We performed this retrospective cohort study, with a longitudinal analysis of 5-year follow-up data from Japanese annual health check-ups. Participants with CKD (estimated glomerular filtration rate [eGFR]

Abstract Background In order to facilitate the safe and long-term delivery of peritoneal dialysis (PD), it is necessary to improve the biocompatibility of peritoneal dialysis fluids (PDFs). The novel bicarbonate/lactate-buffered neutral PDFs (B/L-PDFs) are expected to be improved biocompatible. This study evaluated the biocompatibility of B/L-PDFs by analysis on the profile of angiogenesis-related proteins in drained dialysate of patients undergoing PD. Methods Concentrations of 20 angiogenesis-related proteins in the dialysate were semi-quantitatively determined using a RayBio® Human Angiogenesis Antibody Array and were compared between B/L-PDFs and conventional lactate-buffered neutral PDFs (L-PDFs). Results The expression of growth-related oncogene (GRO α/β/γ), which belongs to the CXC chemokine family, decreased significantly after use of the B/L-PDFs compared to the L-PDFs (P = 0.03). The number of the proteins with lower level in the B/L-PDFs compared with L-PDFs was significantly negatively correlated with the PD duration (Spearman ρ = − 0.81, P = 0.004). Conclusion This study suggested that B/L-PDFs are more biocompatible than conventional PDFs.

Abstract Background Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. Methods Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. Results Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. Conclusions Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.

Introduction Serum uric acid (SUA) levels have a linear relationship with the estimated glomerular filtration rate (eGFR). It is unclear whether further changes, subsequent to normal level of SUA can attenuate eGFR decline in a healthy population, so we aimed to determine the normal level of SUA that can contribute to preventing kidney dysfunction. Methods In this retrospective cohort study from Japan, annual health checkup data from 2009 to 2014 was collected. After propensity score matching (1:1), data from 2,634 individuals with basal SUA ≤7.0 mg/dL (normal; mean age, 39 y; mean eGFR, 80.8 mL/min/1.73 m2) and 1,642 individuals with basal SUA >7.0 mg/dL (elevated; mean age, 42 y; mean eGFR, 75.0 mL/min/1.73 m2) were collected to determine the relationship between followed-up SUA level and the rate of change in eGFR. Results In individuals with normal level SUA at baseline, the elevation of SUA (>7.0 mg/dL) accelerated eGFR decline compared to those with normal SUA levels at 5-year follow-up (−4.1 ± 9.6% vs −9.9 ± 9.0%, p 7.0 mg/dL (standardized coefficient; −0.3348, p

BackgroundOur previous study found that acupuncture with low frequency electrical stimulation (Acu/LFES) prevents muscle atrophy by attenuation of protein degradation in mice. The current study examines the impact of Acu/LFES on protein synthesis.MethodC57/BL6 mice received Acu/LFES treatment on hindlimb for 30 min once. Acu/LFES points were selected by WHO Standard Acupuncture Nomenclature and electric stimulation applied using an SDZ-II Electronic acupuncture instrument. Muscle protein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and concentration and size of the collected exosomes were measured using a NanoSight instrument. The mature microRNA library in serum exosomes was validated using a High Sensitivity DNA chip.ResultsProtein synthesis was enhanced in the both hindlimb and forelimb muscles. Blocking exosome secretion with GW4869 decreased the Acu/LFES-induced increases in protein synthesis. MicroRNA-deep sequencing demonstrated that four members of the Let-7 miRNA family were significantly decreased in serum exosomes. Real time qPCR further verified Acu/LFES-mediated decreases of let-7c-5p in serum exosomes and skeletal muscles. In cultured C2C12 myotubes, inhibition of let-7c not only increased protein synthesis, but also enhanced protein abundance of Igf1 and Igf1 receptors. Using a luciferase reporter assay, we demonstrated that let-7 directly inhibits Igf1.ConclusionAcu/LFES on hindlimb decreases let-7-5p leading to upregulation of the Igf1 signaling and increasing protein synthesis in both hindlimb and forelimb skeletal muscles. This provides a new understanding of how the electrical acupuncture treatment can positively influence muscle health.

The prevalence of chronic kidney disease (CKD) increased by 88% from 1990 to 2016. Age of onset of lifestyle-related diseases (such as hypertension, diabetes mellitus, obesity, dyslipidemia, and hyperuricemia), which are risk factors for incident CKD, is lower now compared with the past. Thus, we aimed to evaluate the risk factors for the incidence and progression of CKD in the young and middle-aged population. There are differences in the risk for CKD among the young, middle-aged, and elderly populations. We aimed to assess obesity (which is basic component of metabolic syndrome), waist circumference, and abdominal adiposity, which are predictive factors of CKD in the younger population. Furthermore, we described the management and clinical evidence of hypertension, diabetes mellitus, dyslipidemia, and hyperuricemia for young and middle-aged patients, along with diet management and nutrients associated with kidney function. Kidney function in the young and middle-aged population is mostly normal, and they are considered a low-risk group for incident CKD. Thus, we expect this review to be useful in reducing the prevalence of CKD.

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and α-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN.

Renal fibrosis is a major contributor to the development and progression of chronic kidney disease. A low-protein diet can reduce the progression of chronic kidney disease and reduce the development of renal fibrosis, although the mechanism is not well understood. Urea reabsorption into the inner medulla is regulated by inner medullary urea transporter (UT)-A1 and UT-A3. Inhibition or knockout of UT-A1/A3 will reduce interstitial urea accumulation, which may be beneficial in reducing renal fibrosis. To test this hypothesis, the effect of unilateral ureteral obstruction (UUO) was compared in wild-type (WT) and UT-A1/A3 knockout mice. UUO causes increased extracellular matrix associated with increases in transforming growth factor-β, vimentin, and α-smooth muscle actin (α-SMA). In WT mice, UUO increased the abundance of three markers of fibrosis: transforming growth factor-β, vimentin, and α-SMA. In contrast, in UT-A1/A3 knockout mice, the increase following UUO was significantly reduced. Consistent with the Western blot results, immunohistochemical staining showed that the levels of vimentin and α-SMA were increased in WT mice with UUO and that the increase was reduced in UT-A1/A3 knockout mice with UUO. Masson’s trichrome staining showed increased collagen in WT mice with UUO, which was reduced in UT-A1/A3 knockout mice with UUO. We conclude that reduced UT activity reduces the severity of renal fibrosis following UUO. [ABSTRACT FROM AUTHOR]

The therapeutic values of contact with nature have been increasingly recognized. A growing body of evidence suggests that a unique subcategory of “contemplative landscapes” is particularly therapeutic. Previous studies predominantly focused on observational designs in non-clinical populations. It is not known if these effects can be extrapolated to populations suffering from depression, and experimental designs need to be utilized to establish causality. We examined the effects of in-situ passive exposure to three urban spaces on brain activity, namely a Therapeutic Garden with high Contemplative Landscape scores (TG), Residential Green (RG) and Busy Downtown (BD), and self-reported momentary mood in adults aged 21–74 (n = 92), including 24 clinically depressed and 68 healthy participants. Portable, multimodal electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) systems were used to record brain activity, and a Profile of Mood States (POMS) questionnaire was used to record mood before and after exposure. We tested the interactions between the site, time and group for the mood, and between site and group for the neuroelectric oscillations and brain hemodynamics. Self-reported pre- post-mood was significant only at the TG (p = 0.032) in both groups. The lowest Total Mood Disturbance (TMD) was reported at TG and the highest in BD (p = 0.026). Results from fNIRS indicated marginally significant lower oxy-Hb in the frontal region at TG as compared to BD (p = 0.054) across both groups. The marginally significant effect of site and group was also observed (p = 0.062), with the Clinical group showing much lower oxy-Hb at TG than Healthy. The opposite pattern was observed at BD. EEG results showed differences between Healthy and Clinical groups in the Frontal Alpha Asymmetry (FAA) pattern across the sites (p = 0.04), with more frontal alpha right in the Clinical sample and more left lateralization in the Healthy sample at TG. Temporal Beta Asymmetry (TBA) analyses suggested that patients displayed lower bottom-up attention than Healthy participants across all sites (p = 0.039). The results suggest that both healthy and depressed adults benefitted from exposure to TG, with possibly different pathways of mood improvement. Visiting therapeutic nature with contemplative features may provide valuable support for the treatment of depression in clinical populations and a self-care intervention in non-clinical populations.