Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients

Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19–2.14, 1.60 per mg/dL; 1.14–2.23 and 0.82 per 10 pg/mL; 0.68–0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.Doi Y., Hamano T., Ichimaru N., et al. Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients. Scientific Reports 10, 13766 (2020); https://doi.org/10.1038/s41598-020-70709-4

MondoA and AKI and AKI-to-CKD Transition

Maeda S., Sakai S., Takabatake Y., et al. MondoA and AKI and AKI-to-CKD Transition. Journal of the American Society of Nephrology , (2024); https://doi.org/10.1681/ASN.0000000000000414.Key PointsThe expression of MondoA was decreased in the renal tubules of patients with CKD.Genetic ablation of MondoA in proximal tubules inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon.MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the transcription factor EB-peroxisome proliferator-activated receptor-γ coactivator-1α axis.BackgroundElderly individuals and patients with CKD are at a higher risk of AKI. The transcription factor MondoA is downregulated in the kidneys of aged individuals or patients with AKI; however, its roles in AKI development and the AKI-to-CKD transition remain unknown.MethodsWe investigated the expression of MondoA in human kidney biopsy samples, ischemia-reperfusion-injured (IRI) mouse kidneys, and cultured proximal tubular epithelial cells under hypoxia/reoxygenation. The role of MondoA during the initial and recovery phases after IRI was evaluated using proximal tubule-specific MondoA knockout mice and MondoA-deficient proximal tubular epithelial cells. Furthermore, we explored the involvement of Rubicon and transcription factor EB (TFEB), both of which are downstream factors of MondoA.ResultsMONDOA expression was decreased in the renal tubules of patients with CKD. In mouse kidneys, MondoA expression was decreased under ischemia, whereas its expression was increased during reperfusion. Genetic ablation of MondoA in proximal tubular epithelial cells inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon. Ablation of Rubicon in MondoA-deficient IRI kidneys activated autophagy and protected mitochondrial function. MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the TFEB-peroxisome proliferator-activated receptor-γ coactivator-1α axis. Pharmacological upregulation of TFEB contributed to maintaining mitochondrial biogenesis and increased peroxisome proliferator-activated receptor-γ coactivator-1α transcription.ConclusionsOur findings demonstrate that MondoA protected against vulnerability to AKI by maintaining autophagy and subsequently supporting mitochondrial function to prevent progression to CKD

Background Factors Affecting Visual Acuity at Initial Visit in Eyes with Central Retinal Vein Occlusion : Multicenter Study in Japan

Purpose: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. Methods: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients’ baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. Results: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = −0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (β = 0.191, p < 0.001) and the right eye (β = −0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. Conclusions: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results

Delphi Method Consensus-Based Identification of Primary Trauma Care Skills Required for General Surgeons in Japan

Purpose General surgeons at regional hospitals should have the primary trauma care skills necessary to treat critically ill trauma patients to withstand transfer. This study was conducted to identify a consensus on primary trauma care skills for general surgeons. Methods An initial list of acute care surgical skills was compiled, and revised by six trauma experts (acute care surgeons); 33 skills were nominated for inclusion in the Delphi consensus survey. Participants (councilors of the Japanese Society for Acute Care Surgery) were presented with the list of 33 trauma care skills and were asked (using web-based software) to rate how strongly they agreed or disagreed (using a 5-point Likert scale) with the necessity of each skill for a general surgeon. The reliability of consensus was predefined as Cronbach’s α ≥ 0.8, and trauma care skills were considered as primarily required when rated 4 (agree) or 5 (strongly agree) by ≥ 80% participants. Results There were 117 trauma care specialists contacted to participate in the Delphi consensus survey panel. In the 1st round, 85 specialists participated (response rate: 72.6%). In the 2nd round, 66 specialists participated (response rate: 77.6%). Consensus was achieved after two rounds, reliability using Cronbach’s α was 0.94, and 34 items were identified as primary trauma care skills needed by general surgeons. Conclusion A consensus-based list of trauma care skills required by general surgeons was developed. This list can facilitate the development of a new trauma training course which has been optimized for general surgeons

Changes in Outer Retinal Microstructures during Six Month Period in Eyes with Acute Zonal Occult Outer Retinopathy-Complex

application/pdf内容の要旨・審査結果の要旨 / 三重大学大学院医学系研究科 生命医科学専攻 臨床医学系講座 眼科学分

Changes in Outer Retinal Microstructures during Six Month Period in Eyes with Acute Zonal Occult Outer Retinopathy-Complex

application/pdfPurpose: To study the changes in the outer retinal microstructures during a six month period after the onset of acute zonal occult outer retinopathy (AZOOR)-complex by spectral-domain optical coherence tomography (SD-OCT). Methods: Seventeen eyes of 17 patients with the AZOOR-complex were studied. The integrity of the external limiting membrane (ELM), ellipsoid zone (EZ; also called the inner/outer segment junction), and interdigitation zone (IDZ; also called the cone outer segment tips) were evaluated in the SD-OCT images obtained at the initial visit and at six months. The three highly reflective bands were divided into three types; continuous, discontinuous, and absent. The integrity of the outer nuclear layer (ONL) was also assessed. Results: Among the three highly reflective bands, the IDZ was most altered at the initial visit and least recovered at six months. Fifteen of 17 eyes (88%) had a recovery of at least one of the three bands at six months in the retinal area where the ONL was intact, and these areas showed an improvement of visual field. Three eyes (18%) had retinal areas where the ONL was absent at the initial visit, and there was no recovery in both the retinal structures and visual fields in these areas. Conclusions: Our results indicate that more than 85% eyes with AZOOR-complex show some recovery in the microstructures of the outer retina during a six month period if the ONL is intact. We conclude that SD-OCT is a useful method to monitor the changes of the outer retinal microstructure in eyes with the AZOOR-complex.本文 / Department of Ophthalmology, Mie University Graduate School of Medicine8

Oral active vitamin d therapy as a potential chemoprevention against post-transplant malignancy

Post-transplant malignancy (PTM) is a limiting factor for both patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVDs) could reduce the development of PTM in KTRs and evaluated the effects of AVD therapy in a prospective cohort of ambulatory KTRs in a Japanese single center. We used a propensity score (PS) of having received AVDs estimated by 25 clinically relevant factors to adjust for these confounders. Among 218 participants, the mean age was 49.4 (SD, 12.1) years, 63.3% were male, the median time since transplantation was 11.2 (interquartile range [IQR], 5.2–17.1) years, and 42.2% had been treated with AVDs at baseline. The AVDs consisted of calcitriol (58.7%) and alfacalcidol (41.3%), and their median doses were 0.5 (IQR, 0.5–0.5) μg and 0.5 (IQR, 0.25–1.0) μg, respectively. During a median follow-up of 2.9 (IQR, 2.1–3.0) years, PTM was observed to have developed in 5 (5.4%) of 92 AVD users and in 11 (8.7%) of 126 non-users. Cox regression analysis with stratification by the PS tertiles showed that AVDs were significantly associated with a lower risk of PTM (hazard ratio, 0.25 [95% confidence interval, 0.07–0.82], P=0.022). The level of serum 25-hydroxyvitamin D was generally low (median, 16.6 ng/ml), and not significantly associated with PTM. Sensitivity analyses with stratification by PS quartiles, PS matching, or inverse probability weighting yielded similar results. Our results suggest a novel potential strategy to prevent PTM by using a normal dose of AVDs with a well-known safety profile. A randomized controlled trial should be performed to confirm our findings