MDPI AGActa Medica Okayama2075-44181662026Seasonal Variations in the Risk of Outpatient Acute Kidney Injury in Patients with Chronic Kidney Disease845ENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroHaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Acute kidney injury (AKI) frequently occurs in the outpatient setting and is associated with adverse renal and survival outcomes. However, there is no established definition of outpatient AKI, and the risk factors, especially seasonal variation, remain limited. This study aimed to investigate seasonal variation in the risk of outpatient AKI. Methods: This retrospective observational study used routinely collected clinical laboratory data from a single hospital in Japan between 2007 and 2022. Outpatient AKI was defined as ≥35% relative decline in estimated glomerular filtration rate (eGFR) compared with a preceding outpatient measurement obtained within 14–90 days. Monthly and seasonal variations in outpatient AKI risk in patients with chronic kidney disease (CKD) were evaluated using logistic regression models. Subgroup analyses were performed according to AKI stage, age group, and CKD stage. Results: A total of 203,853 outpatient records were analyzed. The incidence of outpatient AKI was highest in August and lowest in November. Analyses demonstrated significantly increased odds ratios of outpatient AKI in January, February, July, and August. Seasonally, the risk was significantly higher during the summer. Stage-specific analyses showed that AKI stage 1 was more frequent in the summer, whereas AKI stage 2 tended to increase during the winter. Conclusions: Outpatient AKI exhibits distinct seasonal patterns, with increased risk during both summer and winter and differential associations according to AKI severity and baseline kidney function. Recognition of these patterns may help identify vulnerable populations and inform targeted preventive strategies for outpatient AKI.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-44181642026Recent Advances in Kidney Disease Diagnosis and Treatment: Bridging Molecular Insights and Clinical Practice549ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025Exacerbation of Proteinuria in a Patient with Behçet’s Disease and IgA Nephropathy Following Colchicine Discontinuation457461ENTomohikoAsakawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYuKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoshimasaSakurabuDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyoshiKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRikaTakemotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/69849This case involves a 23-year-old male who was diagnosed with Behçet’s disease 5 years ago and managed with colchicine. Two months ago, he underwent renal biopsy due to abnormal urinalysis and kidney dysfunction, leading to a diagnosis of IgA nephropathy. He subsequently underwent tonsillectomy followed by glucocorticoid pulse therapy. However, after the tonsillectomy, discontinuing colchicine led to increased proteinuria, despite the glucocorticoid pulse therapy. Upon reintroducing colchicine, urinary protein excretion decreased, achieving incomplete remission. These findings suggest that colchicine may be effective in decreasing proteinuria in patients with Behçet’s disease complicated by IgA nephropathy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Elucidation of puberulic acid–induced nephrotoxicity using stem cell-based kidney organoids42195ENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesSoichiroHaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesRecent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2’-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1320-53583052025A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Featurese70057ENMiyuKanazawaOkayama University Medical SchoolKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoyaAokiOkayama University Medical SchoolMihiroSueDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromasaMiyakeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-172915112025Kidney Organoids: Current Advances and Applications1680ENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroHaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation of organoids that exhibit nephron-like structures, including glomerular and tubular structures. Kidney organoids have been widely applied in several directions, including disease modeling and therapeutic screening, drug nephrotoxicity evaluation, and regenerative medicine. In particular, kidney organoids offer a promising platform for studying genetic kidney diseases, such as polycystic kidney disease and congenital anomalies of the kidney and urinary tract (CAKUT), by allowing patient-specific modeling for the analysis of pathophysiology and therapeutic screening. Despite several current limitations, such as incomplete maturation, lack of full nephron segmentation, and variability between protocols and cell conditions, further technological innovations such as microfluidics and bioengineering may refine kidney organoid systems. This review highlights recent advances in kidney organoid research, outlines major applications, and discusses future directions to enhance their physiological relevance, functional maturity, and translational integration into preclinical and clinical nephrology.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863232024Successful Treatment for Life Threatening Recurrent Non-traumatic Rectus Sheath Hematoma in a Case with Microscopic Polyangiitis with Rapidly Progressive Glomerulonephritis32433248ENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShihoMorimotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYuyaTerajimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShugoOkamotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakayukiKatsuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriMatsumotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorinagaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMayuUkaDepartment of Radiology, Okayama University HospitalKojiTomitaDepartment of Radiology, Okayama University HospitalHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesA 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1744-99792932025Text mining for case report articles on “peritoneal dialysis” from PubMed database459470ENKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoichiroHaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: The number of published medical articles on peritoneal dialysis (PD) has been increasing, and efficiently selecting information from numerous articles can be difficult. In this study, we examined whether artificial intelligence (AI) text mining can be a good support for efficiently collecting PD information.<br>
Methods: We performed text mining and analyzed all the abstracts of case reports on PD in the PubMed database. In total, 3137 case reports with abstracts related to “peritoneal dialysis” published from 1970 to 2021 were identified.<br>
Results: A total of 280 347 relevant words were extracted from all the abstracts. Word frequency analysis, word dependency analysis, and word frequency transition analysis showed that peritonitis, encapsulating peritoneal sclerosis, and child have been important keywords. Theseanalyses not only reflected historical background but also anticipated future trends of PD study.<br>
Conclusion: These suggest that text mining can be a good support for efficiently collecting PD information.No potential conflict of interest relevant to this article was reported.S. Karger AGActa Medica Okayama0250-80952025Supplement-induced acute kidney injury reproduced in kidney organoidsENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesSoichiroHaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: Acute kidney injury associated with the consumption of Beni-koji CholesteHelp supplements, which contain red yeast rice (Beni-Koji), has become a significant public health concern in Japan. While renal biopsy findings from several case reports have suggested tubular damage, no definitive causal relationship has been established, and the underlying mechanisms of kidney injury remain poorly understood. The complexity of identifying toxic substances in supplements containing various bioactive compounds makes conventional investigative approaches both time-consuming and challenging. This highlights an urgent need to establish a reliable platform for assessing organ-specific toxicity in such supplements. In this study, we utilized a kidney organoid model derived from adult rat kidney stem cells (KS cells) to assess the potential tubular toxicity of these supplements. Methods: KS cell clusters were cultured in three-dimensional system supplemented with growth factors to promote kidney organoids. The organoids were subsequently exposed to Beni-koji CholesteHelp supplements or cisplatin, followed by histological and molecular analyses to evaluate structural impacts. Results: Established organoids had the kidney-like structures including tubular-like structures and glomerulus-like structures at the tips of multiple tubules. Treatment with Beni-koji CholesteHelp supplements induced significant tubular damage in the organoids, characterized by epithelial cell thinning, structural disruption, and increase in cleaved-caspase 3-positive apoptotic tubular cells, similar to the organoids treated with cisplatin. Conclusion: These findings provide the first evidence suggesting that certain toxicants in specific batches of Beni-koji CholesteHelp supplements cause direct renal tubular injury. This KS cell-based organoid system represents a cost-effective, reproducible, and technically simple platform for nephrotoxicity screening.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44181512024The Gut-Kidney Axis in Chronic Kidney Diseases21ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroHaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818416102024Presumed Choroidopathy of IgG4-Related Disease Discovered During 16-Year Follow-Up of a Patient With Polycystic Kidney Diseasee70865ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaPathology, Okayama University HospitalKenjiTsujiNephrology, Okayama University HospitalImmunoglobulin G4 (IgG4)-related disease is characterized by infiltration with IgG4-producing plasma cells in different organs and the elevation of serum IgG4. We present a patient with polycystic kidney disease in long-term follow-up who developed bilateral lacrimal gland enlargement and presumed IgG4-related choroidopathy at different time points. A 45-year-old woman developed bilateral upper eyelid swelling. Head MRI showed bilateral lacrimal gland enlargement, and the resection on both sides revealed foci of infiltration with lymphocytes and plasma cells in bilateral lacrimal glands. The IgG4-immunostaining did not satisfy the diagnostic criteria. She had been taking oral valsartan 40 mg daily for hypertension with polycystic kidney disease.<br>
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The patient was well until the age of 49 years, when she noticed yellowish vision in the right eye compared to the left eye. The right eye showed multiple yellowish spotty lesions in the deep retina to choroid with a mildly hyperemic optic disc, while the left eye showed the normal fundus. No inflammation was noted in the anterior segments of both eyes. Fundus angiography demonstrated early-phase no-filling with late-phase leakage by fluorescein dye and both early-phase and late-phase no-filling by indocyanine green dye, leading to the diagnosis of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). She began to have oral prednisolone tapered from 30 mg daily and discontinued in a year. At the age of 52 years, she switched to candesartan 8 mg daily and began to have tolvaptan (a selective competitive vasopressin receptor 2 (V2) antagonist) 90 mg daily for polycystic kidney disease with liver cysts. At that time, the lesions in the right eye had mild degeneration.<br>
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The patient was followed once a year ophthalmologically to maintain good vision. At 57 years, serum IgG4, which was measured for the first time on suspicion of IgG4-related disease, was elevated to 269.6 mg/dL. In the following four years to the latest visit at 61 years, she kept stable but high levels of serum IgG4 around 300 mg/dL. Serum IgG4 measurement is helpful to make a clinical diagnosis and, hence, a clinical decision since the spectrum of IgG4-related disease remains obscure.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2192-44491412024A case of membranous nephropathy complicated by Cronkhite–Canada syndrome successfully treated with mizoribine7280ENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShihoMorimotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCronkhite–Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy, hyperpigmentation, and diarrhea. While the relationship between CCS and nephritis remains unclear, seven cases of nephritis complicated by CCS have been reported to date, all of which were membranous nephropathy (MN). A 57-year-old man presented with taste disturbance, hair loss, nail plate atrophy, skin pigmentation, and frequent diarrhea. Endoscopic findings showed multiple polyposis of the stomach and large intestine. Given the above, he was diagnosed with CCS. The symptoms gradually improved with prednisolone treatment, although urinary protein and hypoproteinemia appeared during the tapering of prednisolone. He was diagnosed with MN using a renal biopsy, and immunofluorescence microscopy with IgG subclass staining showed predominantly diffuse granular capillary wall staining of IgG4. The cause of secondary MN was not found, including malignant tumors. Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2590-05955122023Kidney Veno-Muscular Characteristics and Kidney Disease Progression: A Native Kidney-Biopsy Study100733ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKensakuTakahashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakafumiMoritaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRationale & Objective: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants.<br>
Study Design: Retrospective cohort study.<br>
Setting & Participants: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled.<br>
Predictors: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score.<br>
Outcomes: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy.<br>
Analytical Approach: Cox proportional hazards model.<br>
Results: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91).<br>
Limitations: Single-center study and small sample size.<br>
Conclusions: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-441813182023MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury2893ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAcute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-441813192023Role of Semaphorin 3A in Kidney Development and Diseases3038ENYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases.No potential conflict of interest relevant to this article was reported.The Japanese Society of Internal MedicineActa Medica Okayama0918-291862152023Co-occurrence of Three Systemic Diseases: ANCA-associated Vasculitis, Sjogren's syndrome and Sarcoidosis22152221ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesYukaOkuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesYosukeAsanoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesKimitomoYamaokaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Sjogren's syndrome (SjS), and sarcoidosis are systemic diseases targeting multiple organs. While a careful differential diagnosis of these dis-eases is often required, their co-occurrence in the same patient has been previously reported. We herein report a 58-year-old Japanese man diagnosed with the co-occurrence of three systemic diseases (AAV, SjS, and sar-coidosis) in addition to monoclonal gammopathy of undetermined significance (MGUS), which emphasizes the importance of considering the possible co-occurrence of these diseases as well as their differentiation.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44261342023The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study582ENYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYoheiMaeshimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYukaOkuyamaJapanese Red Cross Society Himeji HospitalNozomuOtakaKagawa Prefectural Central HospitalHaruyoUjikeKagawa Prefectural Central HospitalKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasashiKitagawaNational Hospital Organization Okayama Medical CenterKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorinagaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasaruKinomuraOkayama Saiseikai General HospitalShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKosukeOtaNational Hospital Organization Okayama Medical CenterKeisukeMaruyamaOkayama Saiseikai General HospitalMakotoHiramatsuOkayama Saiseikai General Hospital,YoshiyukiOshiroKawasaki Medical School General Medical CenterShigeruMoriokaOkayama Central HospitalKeiichiTakiueOkayama City HospitalKazuyoshiOmoriShigei Medical Research HospitalMasakiFukushimaShigei Medical Research HospitalNaoyukiGamouJapanese Red Cross Okayama HospitalHiroshiHirataAkebono ClinicRyosukeSatoSato ClinicHirofumiMakinoOkayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 +/- 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44181342023Association between Urinary Creatinine Excretion and Hypothyroidism in Patients with Chronic Kidney Disease669ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensakuTakahashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A. A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesWhile hypothyroidism increases serum creatinine (Cr) levels, it is uncertain whether the elevation is mediated via a decline in the glomerular filtration rate (GFR) or the reflection of enhanced Cr production from the muscles or both. In the present study, we explored an association between urinary Cr excretion rate (CER) and hypothyroidism. A total of 553 patients with chronic kidney disease were enrolled in a cross-sectional study. Multiple linear regression analysis was performed to explore the association between hypothyroidism and urinary CER. The mean urinary CER was 1.01 +/- 0.38 g/day and 121 patients (22%) had hypothyroidism. The multiple linear regression analysis revealed explanatory variables with urinary CER, including age, sex, body mass index, 24 h Cr clearance (24hrCcr), and albumin while hypothyroidism was not considered an independent explanatory variable. In addition, scatter plot analysis with regression fit line representing the association between estimated GFR calculated using s-Cr (eGFRcre) and 24hrCcr revealed that eGFRcre and 24hrCcr had strong correlations with each other in hypothyroid patients as well as euthyroid patients. Collectively, hypothyroidism was not considered an independent explanatory variable for urinary CER in the present study and eGFRcre is a useful marker to evaluate kidney function regardless of the presence of hypothyroidism.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-2392132022Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism1048863ENNatsumiUchiyama-MatsuokaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Academic field of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesYoshihikoItohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesYukiNishiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesEisakuMorimotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesSatoshiFujisawaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesTomohiroTerasakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesTakayukiHaraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesKanakoOgura-OchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesIntroduction<br>While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism.<br><br>
Methods<br>
Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders. <br><br>
Results<br>
Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average Delta eGFR of -41.1 mL/min/1.73 m(2)) and an increase in eGFR in hypothyroidism (an average Delta eGFR of 7.1 mL/min/1.73 m(2)). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for Delta eGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of "masked" CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of "reversible" CKD status in hypothyroidism. <br><br>
Conclusions<br>
We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022The association between hypothyroidism and proteinuria in patients with chronic kidney disease: a cross-sectional study14999ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensakuTakahashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHypothyroidism is known to be correlated with kidney function and nephrotic range proteinuria. However, it is uncertain whether non-nephrotic proteinuria is associated with hypothyroidism. This study aimed to evaluate the association of proteinuria and hypothyroidism in chronic kidney disease (CKD) patients. We conducted a cross-sectional study composed of 421 CKD patients in a single hospital with measurements of 24-h urine protein excretion (UP) and thyroid function tests. Spearman correlation analysis revealed that 24-h Cr clearance (24hrCcr) was positively (r = 0.273, p < 0.001) and UP was negatively (r = - 0.207, p < 0.001) correlated with free triiodothyronine. Frequency distribution analysis stratified by CKD stage and UP for hypothyroidism revealed that the prevalence of hypothyroidism was higher among participants with higher CKD stage and nephrotic range proteinuria. Multivariate logistic regression analysis revealed that 24hrCcr and UP were significantly correlated with hypothyroidism (24hrCcr/10 mL/min decrease: odds ratio [OR], 1.29; 95% confidence interval [CI], 1.18-1.41; UP/1 g increase: OR, 1.10; 95% CI, 1.03-1.17). In addition, nephrotic range proteinuria, but not moderate UP (UP: 1.5-3.49 g/day), was significantly correlated with hypothyroidism compared to UP < 0.5 g/day. In summary, decreased kidney function and nephrotic range proteinuria, not non-nephrotic proteinuria, are independently associated with the hypothyroidism.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1320-53582792022Simulation for ultrasound‐guided renal biopsy using boiled egg753757ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama JapanShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama JapanHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama JapanJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama JapanReal-time ultrasound-guided renal biopsy is generally applied to diagnose multiple kidney diseases. A practical simulation model is desired since it is an invasive technique with higher risks of complications such as bleeding. We developed a simple simulation tool for ultrasound-guided renal biopsy using boiled eggs. Boiled chicken eggs were embedded in the agar, and a biopsy simulation was performed using a real-time ultrasound-guided technique as the renal biopsy simulator by trainees and biopsyproficient nephrologists, and the feedback from the participants was obtained. The ultrasonographic evaluation revealed a clear contrast between egg yolk and white, which clearly mimicked the kidney cortex and medulla region. In addition, we observed the needle entering the egg white under needle penetration, and we obtained the biopsy core consisting of egg white. As for the simulations, all the participants succeeded in obtaining the appropriate samples. A total of 92% of the trainees agreed that the simulation could reduce their fears of performing renal biopsies in patients. In addition, all the trainees and biopsy-proficient nephrologists recommend using the simulator for trainees before conducting renal biopsies on patients. The total cost of the simulator was low (< USD 1/simulator). Collectively, our simulation tool using boiled eggs may be a good candidate for practical simulation models of renal biopsy.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2296-634X102022Potential Strategies for Kidney Regeneration With Stem Cells: An Overview892356ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKidney diseases are a major health problem worldwide. Despite advances in drug therapies, they are only capable of slowing the progression of kidney diseases. Accordingly, potential kidney regeneration strategies with stem cells have begun to be explored. There are two different directions for regenerative strategies, de novo whole kidney fabrication with stem cells, and stem cell therapy. De novo whole kidney strategies include: 1) decellularized scaffold technology, 2) 3D bioprinting based on engineering technology, 3) kidney organoid fabrication, 4) blastocyst complementation with chimeric technology, and 5) the organogenic niche method. Meanwhile, stem cell therapy strategies include 1) injection of stem cells, including mesenchymal stem cells, nephron progenitor cells, adult kidney stem cells and multi-lineage differentiating stress enduring cells, and 2) injection of protective factors secreted from these stem cells, including growth factors, chemokines, and extracellular vesicles containing microRNAs, mRNAs and proteins. Over the past few decades, there have been remarkable step-by-step developments in these strategies. Here, we review the current advances in the potential strategies for kidney regeneration using stem cells, along with their challenges for possible clinical use in the future.No potential conflict of interest relevant to this article was reported.Lippincott Williams & WilkinsActa Medica Okayama0025-797410172022Silica-associated systemic lupus erythematosus with lupus nephritis and lupus pneumonitis A case report and a systematic review of the literaturee28872ENKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasukoFuchimotoDepartment of Respiratory Medicine, Okayama Rosai HospitalTomoyoMifuneDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMayuWatanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaruKinomuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeMiyamotoDepartment of Respiratory Medicine, Okayama Rosai HospitalSaeWadaDepartment of Respiratory Medicine, Okayama Rosai HospitalTaisakuKoyanagiDepartment of Respiratory Medicine, Okayama Rosai HospitalHitoshiSugiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakumiKishimotoDepartment of Respiratory Medicine, Okayama Rosai HospitalJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction Several epidemiological studies have shown that silica exposure triggers the onset of systemic lupus erythematosus (SLE); however, the clinical characteristics of silica-associated SLE have not been well studied. Patient concerns A 67-year-old man with silicosis visited a primary hospital because of a fever and cough. His respiratory condition worsened, regardless of antibiotic medication, and he was referred to our hospital. Diagnosis The patient showed leukopenia, lymphopenia, serum creatinine elevation with proteinuria and hematuria, decreased serum C3 level, and was positive for anti-double stranded DNA antibody, anti-nuclear antibody, and direct Coombs test. He was diagnosed with SLE. Renal biopsy was performed, and the patient was diagnosed with lupus nephritis (class IV-G(A/C) + V defined by the International Society of Nephrology/Renal Pathology Society classification). Computed tomography revealed acute interstitial pneumonitis, bronchoalveolar lavage fluid showed elevation of the lymphocyte fraction, and he was diagnosed with lupus pneumonitis. Interventions Prednisolone (50 mg/day) with intravenous cyclophosphamide (500 mg/body) were initiated. Outcomes The patient showed a favorable response to these therapies. He was discharged from our hospital and received outpatient care with prednisolone slowly tapered off. He had cytomegalovirus and herpes zoster virus infections during treatment, which healed with antiviral therapy. Review: We searched for the literature on sSLE, and selected 11 case reports and 2 population-based studies. The prevalence of SLE manifestations in sSLE patients were comparative to that of general SLE, particularly that of elderly-onset SLE. Our renal biopsy report and previous reports indicate that lupus nephritis of sSLE patients show as various histological patterns as those of general SLE patients. Among the twenty sSLE patients reported in the case articles, three patients developed lupus pneumonitis and two of them died of it. Moreover, two patients died of bacterial pneumonia, one developed aspergillus abscesses, one got pulmonary tuberculosis, and one developed lung cancer. Conclusion Close attention is needed, particularly for respiratory system events and infectious diseases, when treating patients with silica-associated SLE using immunosuppressive therapies.No potential conflict of interest relevant to this article was reported.Hindawi Ltd.Acta Medica Okayama2314-674520222022The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study3157841ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical SciencesShugoOkamotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyoshiKatayamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesMarikoTsuchida-NishiwakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesHidemiTakeuchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesRikaTakemotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesYoshikoHadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesRyokoUmebayashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesNaokoKurookaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesJunEguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesHirofumiNakajimaNakashima HospitalKenichiShikataCenter for Innovative Clinical Medicine, Okayama University HospitalJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical SciencesObjective. We examined whether or not day-to-day variations in lipid profiles, especially triglyceride (TG) variability, were associated with the exacerbation of diabetic kidney disease. Methods. We conducted a retrospective and observational study. First, 527 patients with type 2 diabetes mellitus (DM) who had had their estimated glomerular filtration rate (eGFR) checked every 6 months since 2012 for over 5 years were registered. Variability in postprandial TG was determined using the standard deviation (SD), SD adjusted (Adj-SD) for the number of measurements, and maximum minus minimum difference (MMD) during the first three years of follow-up. The endpoint was a & GE;40% decline from baseline in the eGFR, initiation of dialysis or death. Next, 181 patients who had no micro- or macroalbuminuria in February 2013 were selected from among the 527 patients for an analysis. The endpoint was the incidence of microalbuminuria, initiation of dialysis, or death. Results. Among the 527 participants, 110 reached a & GE;40% decline from baseline in the eGFR or death. The renal survival was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p=0.0073, 0.0059, and 0.0195, respectively). A lower SD, lower Adj-SD, and lower MMD were significantly associated with the renal survival in the adjusted model (hazard ratio, 1.62, 1.66, 1.59; 95% confidence intervals, 1.05-2.53, 1.08-2.58, 1.04-2.47, respectively). Next, among 181 participants, 108 developed microalbuminuria or death. The nonincidence of microalbuminuria was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p=0.0241, 0.0352, and 0.0474, respectively). Conclusions. Postprandial TG variability is a novel risk factor for eGFR decline and the incidence of microalbuminuria in patients with type 2 DM.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-00672212020MicroRNAs as Biomarkers for Nephrotic Syndrome88ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNephrotic syndrome represents the clinical situation characterized by presence of massive proteinuria and low serum protein caused by a variety of diseases, including minimal change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephropathy. Differentiating between diagnoses requires invasive renal biopsies in general. Even with the biopsy, we encounter difficulties to differentiate MCNS and FSGS in some cases. There is no other better option currently available for the diagnosis other than renal biopsy. MicroRNAs (miRNAs) are no-coding RNAs of approximately 20 nucleotides in length, which regulate target genes in the post-transcriptional processes and have essential roles in many diseases. MiRNAs in serum and urine have been shown as non-invasive biomarkers in multiple diseases, including renal diseases. In this article, we summarize the current knowledge of miRNAs as the promising biomarkers for nephrotic syndrome.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1873-5061462020Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors101865ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAdult kidney stem cells are known to have important roles in renal regeneration after acute kidney injury. Although trophic factors from tissue stem cells have been reported to promote the regeneration of other organs, there is limited number of evidence of this phenomenon in the kidneys. Here, we explored the effects of secreted factors from kidney stem cells. We intraperitoneally administered culture supernatant obtained from adult rat kidney stem/progenitor cells into rat kidney ischemia/reperfusion injury models, and the treatment significantly ameliorated renal tubulointerstitial injury, suppressed tubular cell apoptosis, diminished inflammation and promoted the proliferation of both residual renal cells and immature cells. In vitro, treatment with culture supernatant from kidney stem cells significantly promoted cell proliferation and suppressed cisplatin-induced cell apoptosis in both normal rat kidney cells and kidney stem cells. In addition, treatment with culture supernatant increased the expression of nestin in normal rat kidney cells, suggesting the dedifferentiation of tubular cells into stem-like cells. Analysis of the culture supernatant revealed that it contained a variety of growth factors. Taken together, the results suggest that these factors together lead to renal regeneration. In conclusion, adult kidney stem cells contribute to renal regeneration indirectly through the secretion of regenerative factors.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24680249592020Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells15761580ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokiTakahashiDepartment of Nephrology, Faculty of Medical Science, University of FukuiMasayukiIwanoDepartment of Nephrology, Faculty of Medical Science, University of FukuiJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44181072020Deep Learning Could Diagnose Diabetic Nephropathy with Renal Pathological Immunofluorescent Images466ENShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensakuTakahashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesArtificial Intelligence (AI) imaging diagnosis is developing, making enormous steps forward in medical fields. Regarding diabetic nephropathy (DN), medical doctors diagnose them with clinical course, clinical laboratory data and renal pathology, mainly evaluate with light microscopy images rather than immunofluorescent images because there are no characteristic findings in immunofluorescent images for DN diagnosis. Here, we examined the possibility of whether AI could diagnose DN from immunofluorescent images. We collected renal immunofluorescent images from 885 renal biopsy patients in our hospital, and we created a dataset that contains six types of immunofluorescent images of IgG, IgA, IgM, C3, C1q and Fibrinogen for each patient. Using the dataset, 39 programs worked without errors (Area under the curve (AUC): 0.93). Five programs diagnosed DN completely with immunofluorescent images (AUC: 1.00). By analyzing with Local interpretable model-agnostic explanations (Lime), the AI focused on the peripheral lesion of DN glomeruli. On the other hand, the nephrologist diagnostic ratio (AUC: 0.75833) was slightly inferior to AI diagnosis. These findings suggest that DN could be diagnosed only by immunofluorescent images by deep learning. AI could diagnose DN and identify classified unknown parts with the immunofluorescent images that nephrologists usually do not use for DN diagnosis.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006721112020Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury4099ENYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkikoInoue-ToriiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006721112020Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice4054ENKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i-HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1471-2369212020Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report113ENNatsumiMatsuokaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesEikiIchiharaDepartment of Hematology, Oncology, Allergy and Respiratory Medicine,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiHaraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKishioTomaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground</br>
The advent of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with advanced malignancies. On the other hand, these drugs might cause immune-related adverse events (irAEs) including endocrinopathies and nephropathies. Thyroid dysfunction is one of the most common irAEs. For ICIs-induced nephropathies, most cases are due to tubulointerstitial nephritis, which might require steroid treatment. Here, we report a patient with non-small cell lung cancer treated with ICI who developed increased serum creatinine (s-Cr) levels due to ICIs-induced hypothyroidism.</br>
Case presentation</br>
A 57-year-old Asian man with refractory non-small cell lung cancer under ICIs therapy (pembrolizumab, an anti-programmed cell death-1 monoclonal antibody) developed increased s-Cr levels 5 months after the pembrolizumab initiation. His laboratory data, renal biopsy, and Gallium-67 scintigraphy findings denied pembrolizumab-induced tubulointerstitial nephritis. His renal function was correlated with thyroid function. Despite the increase of s-Cr levels, serum cystatin C levels were normal, which could be explained by the hypothyroidism. Levothyroxine treatment improved renal function as well as thyroid function. Then pembrolizumab was resumed, and both his thyroid and renal function remained normal level. Ultimately, we concluded that the increased s-Cr levels were caused by pembrolizumab-induced hypothyroidism.</br>
Conclusion</br>
All clinicians involved in ICI treatment need to recognize the possible increase in s-Cr levels caused by ICIs-induced hypothyroidism, and we propose monitoring serum cystatin C levels to differentiate ICIs-induced hypothyroidism from tubulointerstitial nephritis before invasive renal biopsies or steroid treatment, which are recommended by the prescribing information for pembrolizumab, are performed.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-00672132020Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases756ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMesenchymal stem cells (MSCs) have immunomodulatory and regenerative effects in many organs, including the kidney. Emerging evidence has shown that the trophic effects from MSCs are mainly mediated by the paracrine mechanism rather than the direct differentiation of MSCs into injured tissues. These secretomes from MSCs include cytokines, growth factors, chemokines and extracellular vesicles (EVs) containing microRNAs, mRNAs, and proteins. Many research studies have revealed that secretomes from MSCs have potential to ameliorate renal injury in renal disease models, including acute kidney injury and chronic kidney disease through a variety of mechanisms. These trophic mechanisms include immunomodulatory and regenerative effects. In addition, accumulating evidence has uncovered the specific factors and therapeutic mechanisms in MSC-derived EVs. In this article, we summarize the recent advances of immunomodulatory and regenerative effects of EVs from MSCs, especially focusing on the microRNAs.No potential conflict of interest relevant to this article was reported.