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Background Osteocrin (OSTN), a bone-derived humoral factor, was reported to act on heart and bone by potentiating the natriuretic peptide (NP) system. Ostn gene polymorphisms have been associated with renal function decline, but its pathophysiological role in the kidney remains unclear. Methods The role of endogenous OSTN was investigated using systemic Ostn -knockout (KO) mice. As a model for OSTN administration, liver-specific Ostn -overexpressing mice crossed with KO (KO-Tg) were generated. These mice were subjected to unilateral ischemia–reperfusion injury (IRI) and renal lesions after 21 days of insult were evaluated. A comprehensive analysis of the Wnt/β-catenin pathway was performed using a polymerase chain reaction (PCR) array. Reporter plasmid-transfected proximal tubular cells (NRK52E) were used to investigate the mechanism by which OSTN affects the pathway. Results After injury, KO mice showed marginal worsening of renal fibrosis compared with wild-type mice, with comparable renal atrophy. KO-Tg mice showed significantly ameliorated renal atrophy, fibrosis and tubular injury, together with reduced expressions of fibrosis- and inflammation-related genes. The PCR array showed that the activation of the Wnt/β-catenin pathway was attenuated in KO-Tg mice. The downstream targets Mmp7, Myc and Axin2 showed similar results. MMP7 and Wnt2 were induced in corticomedullary proximal tubules after injury, but not in KO-Tg. In NRK52E, OSTN significantly potentiated the inhibitory effects of NP on transforming growth factor β1–induced activation of the Wnt/β-catenin pathway, which was reproduced by a cyclic guanosine monophosphate analog. Conclusions Ectopic Ostn overexpression ameliorated subsequent renal injury following ischemia–reperfusion. OSTN could represent possible renoprotection in acute to chronic kidney disease transition, thus serving as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Aim: Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin‐induced nephrotoxicity. We compared the cisplatin‐induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non‐small cell lung cancer. Methods: Patients with advanced non‐small cell lung cancer suitable to receive cisplatin‐containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle. Results: The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P =.66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression‐free survival and overall survival. Conclusion: The preventive effect of the two forced diuretics on cisplatin‐induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations. [ABSTRACT FROM AUTHOR]

The article discusses that increasing research has been conducted about patients' preferences for their role in treatment decision making. It mentions that decision making shared between patients and healthcare providers could result in various benefits, including the improvement of patient satisfaction and clinical outcomes; and also mentions that anxiety and depression status could affect patients' perception of their roles in decision making.

The co-occurrence of subacute thyroiditis (SAT) and Graves' disease (GD) is rare. A 62-year-old Japanese man presented with shifting neck pain and elevated thyroid hormone level. The patient tested positive for thyroid-stimulating hormone receptor antibodies. Additionally, thyroid hormone levels did not decrease during treatment with prednisolone for SAT. Consequently, concurrent GD was suspected, and diagnostic assistance was obtained by confirming increased uptake on 99m Technetium thyroid scintigraphy. A genetic analysis of human leukocyte antigen (HLA) revealed genotypes associated with susceptibility to SAT (HLA-B*35:01) and GD (HLA-DPB1*05:01). Furthermore, the possibility of coronavirus disease 2019 as a related environmental factor cannot be ruled out in this case.

In an integrated swine farm with 135 sows in Nagasaki Prefecture, premature births and stillbirths were observed in six sows in June and July 2023, and their etiology was investigated. Leptospiral flaB gene was detected in the kidney of one stillborn fetus and the placenta of its sow by nested PCR. Multilocus sequence typing revealed that the infecting strain was Leptospira interrogans ST118. In addition, leptospiral antigens were detected in lesions of the above tissues by immunohistochemical staining. The examined sow and several other sows in the farm had antibodies against serogroup Hebdomadis. These results suggested that L. interrogans serogroup Hebdomadis ST118 was the causative agent of premature births and stillbirths that occurred in this farm.

Acute kidney injury (AKI) is a life-threatening condition and often progresses to chronic kidney disease or the development of other organ dysfunction even after recovery. Despite the increased recognition and high prevalence of AKI worldwide, there has been no established treatment so far. The aim of this study was to investigate the renoprotective effect of Kyoto University substance 121 (KUS121), a novel valosin-containing protein modulator, on AKI. In in vitro experiments, we evaluated cell viability and ATP levels of proximal tubular cells with or without KUS121 under endoplasmic reticulum (ER) stress conditions. In in vivo experiments, the effects of KUS121 were examined in mice with AKI caused by ischemia-reperfusion injury. ER-associated degradation (ERAD)-processing capacity was evaluated by quantification of the ERAD substrate CD3delta-YFP. KUS121 protected proximal tubular cells from cell death under ER stress. The apoptotic response was mitigated as indicated by the suppression of C/EBP homologous protein expression and caspase-3 cleavage, with maintained intracellular ATP levels by KUS121 administration. KUS121 treatment suppressed the elevation of serum creatinine and neutrophil gelatinase-associated lipocalin levels and attenuated renal tubular damage after ischemia-reperfusion. The expression of inflammatory cytokines in the kidney was also suppressed in the KUS121-treated group. Valosin-containing protein expression levels were not altered by KUS121 both in vitro and in vivo. KUS121 treatment restored ERAD-processing capacity associated with potentiation of its upstream pathway, phosphorylated inositol-requiring enzyme-1α, and spliced X box-binding protein-1. In conclusion, these findings indicate that KUS121 can protect renal tubular cells from ER stress-induced injury, suggesting that KUS121 could be a novel and promising therapeutic compound for ischemia-associated AKI. NEW & NOTEWORTHY Novel findings of this study are as follows: 1 ) Kyoto University substance 121 (KUS121), a novel valosin-containing protein (VCP) modulator, can reduce ATP consumption of VCP; 2 ) KUS121 reduced endoplasmic reticulum (ER) stress and improved cell viability in proximal tubular cells; 3 ) KUS121 exerted renoprotective effects against ischemia-reperfusion injury; and 4 ) KUS121 may prevent ischemic acute kidney injury with ATP retention and restoring ER-associated degradation capacity.

Aim: Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin-induced nephrotoxicity. We compared the cisplatin-induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non-small cell lung cancer., Methods: Patients with advanced non-small cell lung cancer suitable to receive cisplatin-containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle., Results: The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P = .66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression-free survival and overall survival., Conclusion: The preventive effect of the two forced diuretics on cisplatin-induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations., (© 2020 John Wiley & Sons Australia, Ltd.)

Pemetrexedis a key drug in the first and second -line therapy for non-small-cell lung cancer. It exhibits an increased area under the plasma drug concentration-time curve, and it has a prolonged half -life when administered to patients with reduced renal function, resulting in a high frequency of neutropenia. Accordingly, pemetrexed is administered to these patients with caution. Herein, we retrospectively investigated the background characteristics of patients with a creatinine clearance rate (Ccr) of<45 mL/min, who experienced severe adverse events due to pemetrexed. Thirty-eight patients with a Ccr of <45 mL/min were administered pemetrexed. Of these patients, 13 (34%) developed severe adverse events (≥Grade 3) such as neutropenia, thrombocytopenia, and nausea. Multiple logistic regression analysis revealed that a Ccr of <30 mL/min (p= 0.033) and the concomitant use of non-steroidal anti-inflammatory drugs (p=0.012) were significant risk factors for adverse events. Therefore, whenever possible, pemetrexed administration should be avoided in patients with a Ccr of <30 mL/ min and in those receiving concomitant non-steroidal anti-inflammatory drugs.