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1. Clinical relevance of proteinuria selectivity index and fractional excretion of sodium in patients with nephrotic syndrome

Author

Takashin Nakayama, Tatsuhiko Azegami, Shintaro Yamaguchi, Keita Hirano, Motoaki Komatsu, Kentaro Fujii, Koji Futatsugi, Hidenori Urai, Takahisa Kawaguchi, Tomoaki Itoh, Norifumi Yoshimoto, Aika Hagiwara, Akihito Hishikawa, Hiroto Matsuda, Takashi Ando, Yasuyoshi Yamaji, Marohito Murakami, Akinori Hashiguchi, Yuko Kaneko, Takashi Yokoo, and Kaori Hayashi

Subjects
Nephrotic syndrome, Proteinuria selectivity index, Fractional excretion of sodium, Complete remission, Minimal change disease, Medicine, Science
Abstract

Abstract Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Published
2024
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2. The proteinuria selectivity index value predicts the remission of IgA nephropathy: a retrospective cohort study

Author

Ryunosuke Mitsuno, Takashin Nakayama, Wataru Ito, Tomomi Maruki, Ran Nakamichi, Keika Adachi, Norifumi Yoshimoto, Akihito Hishikawa, Aika Hagiwara, Shintaro Yamaguchi, Toshiaki Monkawa, Jun Yoshino, Akinori Hashiguchi, Tatsuhiko Azegami, and Kaori Hayashi

Subjects
Biomarker, IgA nephropathy, proteinuria, proteinuria selectivity index, Diseases of the genitourinary system. Urology, RC870-923
Abstract

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and leads to end-stage kidney disease. The proteinuria selectivity index (PSI) has been used to assess the prognosis in nephrotic syndrome, but its predictive value in patients with IgAN remains unclear. This single-center retrospective cohort study included patients who diagnosed with IgAN between March 2012 and March 2020. The PSI was calculated at the time of kidney biopsy. Patients were followed up from the time of kidney biopsy to kidney replacement therapy, death, transfer to another facility, or study completion. Ninety-four patients with a median age of 51 years were enrolled and divided according to the cutoff value of PSI determined by the receiver operating characteristic curve analysis into low-PSI (PSI

Published
2024
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3. Efficacy of sucrose and povidone–iodine mixtures in peritoneal dialysis catheter exit-site care

Author

Takashin Nakayama, Kohkichi Morimoto, Kiyotaka Uchiyama, Naoki Washida, Ei Kusahana, Eriko Yoshida Hama, Ryunosuke Mitsuno, Shun Tonomura, Norifumi Yoshimoto, Akihito Hishikawa, Aika Hagiwara, Tatsuhiko Azegami, Jun Yoshino, Toshiaki Monkawa, Tadashi Yoshida, Shintaro Yamaguchi, and Kaori Hayashi

Subjects
Sucrose, Povidone–iodine, Peritoneal dialysis, Exit-site infections, Tunnel infections, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Exit-site infection (ESI) is a common recurring complication in patients undergoing peritoneal dialysis (PD). Sucrose and povidone–iodine (SPI) mixtures, antimicrobial ointments that promote wound healing, have been used for the treatment of ulcers and burns, but their efficacy in exit–site care is still unclear. Methods This single-center retrospective observational study included patients who underwent PD between May 2010 and June 2022 and presented with episodes of ESI. Patients were divided into SPI and non-SPI groups and followed up from initial ESI onset until PD cessation, death, transfer to another facility, or June 2023. Results Among the 82 patients (mean age 62, [54–72] years), 23 were treated with SPI. The median follow-up duration was 39 months (range, 14–64), with an overall ESI incidence of 0.70 episodes per patient-year. Additionally, 43.1% of second and 25.6% of third ESI were caused by the same pathogen as the first. The log-rank test demonstrated significantly better second and third ESI-free survival in the SPI group than that in the non-SPI group (p

Published
2024
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4. The body mass index change is associated with death or hemodialysis transfer in Japanese patients initiating peritoneal dialysis

Author

Daiki Kojima, Naoki Washida, Kiyotaka Uchiyama, Eriko Yoshida Hama, Tomoki Nagasaka, Ei Kusahana, Takashin Nakayama, Kengo Nagashima, Yasunori Sato, Kohkichi Morimoto, Takeshi Kanda, and Hiroshi Itoh

Subjects
Obesity, sarcopenia, frailty, malnutrition, peritonitis, heart failure, Diseases of the genitourinary system. Urology, RC870-923
Abstract

AbstractA decreased body mass index (BMI) over time is associated with a poor prognosis for patients on hemodialysis. We aimed to examine whether this association also applies to patients with peritoneal dialysis (PD). BMI change was defined as the percentage change in the BMI between the time of PD catheter insertion and six months after its insertion. The association between the BMI change and all-cause mortality or PD discontinuation from six months after PD catheter insertion until October 2021 was investigated. This retrospective cohort study included 122 patients (aged 61.1 ± 12.1 years; 90 males) who underwent PD catheter insertion between January 2008 and March 2020. The median follow-up period was 43.1 (21.2–78.8) months. The median six-month percentage change in the BMI was −2.14 (−5.56–1.84)%, and patients were categorized into tertiles based on their BMI changes. The fully-adjusted Cox regression analysis revealed a significantly higher rate of PD discontinuation or all-cause mortality (hazard ratio (HR): 2.48; 95%; confidence interval (CI): 1.41–4.37) in patients with the lowest tertile (T1, BMI change: 0.67%) than those in the T2 group (HR: 1.18; 95% CI: 0.66–2.11). A decreased BMI over time is independently associated with HD transfer or all-cause mortality among patients initiating PD, which highlights the importance of the 6-month BMI change as a novel prognostic marker.

Published
2023
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5. Peritoneal dialysis-related peritonitis with encapsulated ascites due to Mycobacterium abscessus subsp. massilience and subsp. bolletii: a case series and literature review

Author

Tomoki Nagasaka, Kiyotaka Uchiyama, Ryoichi Shirai, Ryunosuke Mitsuno, Tomomi Maruki, Eriko Yoshida Hama, Erina Sugita, Ei Kusahana, Rena Sumura, Takashin Nakayama, Satoshi Kinugasa, Kohkichi Morimoto, Yoshitaka Ishibashi, Naoki Washida, and Hiroshi Itoh

Subjects
Peritoneal dialysis-related peritonitis, Encapsulated ascites, Mycobacterium abscessus, Mycobacterium abscessus subsp. massilience, Mycobacterium abscessus subsp. bolletii, Non-tuberculous mycobacterium, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background As there is no established standard of care for non-tuberculous mycobacterium (NTM) peritoneal dialysis (PD)-related peritonitis, its treatments have to be case-dependent, which is often difficult. Additionally, several reported cases were accompanied by encapsulated ascites, adhesive ileus, and encapsulating peritoneal sclerosis, suggesting treatment difficulties. We report two cases of PD-related peritonitis with encapsulated ascites due to Mycobacterium abscessus subsp. massilience and subsp. bolletii. To the best of our knowledge, this is the first case series to report PD-related peritonitis caused by Mycobacterium abscessus subsp. bolletii. Case presentation The first case is that of a 74-year-old male patient who started PD six years ago for end-stage renal failure due to diabetic nephropathy. In February 2021, he presented with signs of infection at the exit-site and swelling of the tunnel. Mycobacterium abscessus subsp. massilience was detected in the culture of the exit-site exudate; thus, he was diagnosed with tunnel infection (caused by NTM). Subsequently, fever, abdominal pain, and increased cell counts in the PD drainage fluid were observed, and he was judged to have NTM peritonitis. His general condition improved after PD catheter removal in addition to antimicrobial treatment and encapsulated ascites drainage. The second case is that of a 52-year-old man who commenced PD for end-stage renal failure due to nephrosclerosis 12 years ago. In May 2022, he was diagnosed with PD-related peritonitis based on signs of infection at the exit-site, encapsulated ascites on computed tomography, and a cloudy PD drainage fluid. Mycobacterium abscessus subsp. bolletii was detected in the culture of the exit-site exudate, which led to the diagnosis of NTM peritonitis. In addition to antimicrobial treatment, PD catheter removal and encapsulated ascites drainage were performed. The patient also had adhesive bowel obstruction due to peritonitis and required decompression therapy with the insertion of a gastric tube. Conclusions PD catheter removal and encapsulated ascites drainage might have improved inflammation and treatment outcomes. Additionally, Mycobacterium abscessus might be prone to forming encapsulated cavities and/or intestinal adhesions; however, further accumulation of cases clarifying “subspecies” of Mycobacterium abscessus is necessary to confirm this hypothesis.

Published
2023
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6. Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection

Author

Takashin Nakayama, Tatsuhiko Azegami, Maki Kiso, Masaki Imai, Ryuta Uraki, Kaori Hayashi, Akihito Hishikawa, Norifumi Yoshimoto, Ran Nakamichi, Erina Sugita-Nishimura, Eriko Yoshida-Hama, Yoshihiro Kawaoka, and Hiroshi Itoh

Subjects
Medicine, Science
Abstract

Abstract Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global pandemic. Although several vaccines targeting SARS-CoV-2 spike proteins protect against COVID-19 infection, mutations affecting virus transmissibility and immune evasion potential have reduced their efficacy, leading to the need for a more efficient strategy. Available clinical evidence regarding COVID-19 suggests that endothelial dysfunction with thrombosis is a central pathogenesis of progression to systemic disease, in which overexpression of plasminogen activator inhibitor-1 (PAI-1) may be important. Here we developed a novel peptide vaccine against PAI-1 and evaluated its effect on lipopolysaccharide (LPS)-induced sepsis and SARS-CoV-2 infection in mice. Administration of LPS and mouse-adapted SARS-CoV-2 increased serum PAI-1 levels, although the latter showed smaller levels. In an LPS-induced sepsis model, mice immunized with PAI-1 vaccine showed reduced organ damage and microvascular thrombosis and improved survival compared with vehicle-treated mice. In plasma clot lysis assays, vaccination-induced serum IgG antibodies were fibrinolytic. However, in a SARS-CoV-2 infection model, survival and symptom severity (i.e., body weight reduction) did not differ between vaccine- and vehicle-treated groups. These results indicate that although PAI-1 may promote the severity of sepsis by increasing thrombus formation, it might not be a major contributor to COVID-19 exacerbation.

Published
2023
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8. Vaccination against connective tissue growth factor attenuates the development of renal fibrosis

Author

Takashin Nakayama, Tatsuhiko Azegami, Kaori Hayashi, Akihito Hishikawa, Norifumi Yoshimoto, Ran Nakamichi, Erina Sugita, and Hiroshi Itoh

Subjects
Medicine, Science
Abstract

Abstract There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.

Published
2022
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9. Correlation between acylcarnitine/free carnitine ratio and cardiopulmonary exercise test parameters in patients with incident dialysis

Author

Wataru Ito, Kiyotaka Uchiyama, Ryunosuke Mitsuno, Erina Sugita, Takashin Nakayama, Toshinobu Ryuzaki, Rina Takahashi, Yoshinori Katsumata, Kaori Hayashi, Takeshi Kanda, Naoki Washida, Kazuki Sato, and Hiroshi Itoh

Subjects
carnitine, cardiopulmonary exercise test, dialysis, peak oxygen consumption, VE/VCO2 slope, work rate, Physiology, QP1-981
Abstract

Objective: Diminished physical capacity is common and progressive in patients undergoing dialysis, who are also prone to deficiency in carnitine, which plays a pivotal role in maintaining skeletal muscle and cardiac function. The present study aimed to evaluate the association of carnitine profile with exercise parameters in patients with incident dialysis.Design and Methods: This was a single-center cross-sectional study including 87 consecutive patients aged 20–90 years who were initiated on dialysis in Keio University Hospital between December 2019 and December 2022 and fulfilled the eligibility criteria. Exercise parameters were evaluated via cardiopulmonary testing (CPX) using the electronically braked STRENGTH ERGO 8 ergometer, whereas the carnitine profile was assessed by determining serum free carnitine (FC), acylcarnitine (AC) levels and AC/FC ratio.Results: The mean cohort age was 62.1 ± 15.2 years, with male and hemodialysis predominance (70% and 73%, respectively). AC/FC was 0.46 ± 0.15, and CPX revealed peak oxygen consumption (VO2) of 13.9 ± 3.7 (mL/kg/min) with percent-predicted peak VO2 of 53.6% ± 14.7% and minute ventilation (VE)/carbon dioxide output (VCO2) slope of 35.1 ± 8.0. Fully-adjusted multivariate linear regression analysis showed that AC/FC was significantly associated with decreased peak VO2 (β, −5.43 [95% confidence interval (CI), −10.15 to −0.70]) and percent-predicted peak VO2 (β, −19.98 [95% CI, −38.43 to −1.52]) and with increased VE/VCO2 slope (β, 13.76 [95% CI, 3.78–23.75]); FC and AC did not exhibit similar associations with these parameters. Moreover, only AC/FC was associated with a decreased peak work rate (WR), percent-predicted WR, anaerobic threshold, delta VO2/delta WR, and chronotropic index.Conclusion: In patients on incident dialysis, exercise parameters, including those related to both skeletal muscle and cardiac function, were strongly associated with AC/FC, a marker of carnitine deficiency indicating altered fatty acid metabolism. Further studies are warranted to determine whether carnitine supplementation can improve exercise capacity in patients on incident dialysis.

Published
2023
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10. Compared effectiveness of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on hyperkalemia in patients with chronic kidney disease

Author

Takashin Nakayama, Shintaro Yamaguchi, Kaori Hayashi, Kiyotaka Uchiyama, Takaya Tajima, Tatsuhiko Azegami, Kohkichi Morimoto, Tadashi Yoshida, Jun Yoshino, Toshiaki Monkawa, Takeshi Kanda, and Hiroshi Itoh

Subjects
chronic kidney disease, electrolytes, hyperkalemia, calcium polystyrene sulfonate, sodium zirconium cyclosilicate, metabolic acidosis, Medicine (General), R5-920
Abstract

Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.

Published
2023
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11. Case report: Importance of early and continuous tocilizumab therapy in nephrotic syndrome associated with idiopathic multicentric Castleman disease: A case series

Author

Daiki Kojima, Shintaro Yamaguchi, Akinori Hashiguchi, Kaori Hayashi, Kiyotaka Uchiyama, Norifumi Yoshimoto, Keika Adachi, Takashin Nakayama, Ken Nishioka, Takaya Tajima, Kohkichi Morimoto, Jun Yoshino, Tadashi Yoshida, Toshiaki Monkawa, Takeshi Kanda, and Hiroshi Itoh

Subjects
idiopathic multicentric Castleman disease, renal pathology, secondary nephrotic syndrome, IL-6 inhibitor, tocilizumab, acute kidney injury, Medicine (General), R5-920
Abstract

Idiopathic multicentric Castleman disease (iMCD) is a systemic and polyclonal lymphoproliferative disease involving multiple organs, including the kidneys, due to the overproduction of interleukin-6 (IL-6). Recently, several reports have suggested that excessive IL-6 actions in iMCD could have a causal relationship with the development of diverse histopathological renal manifestations that cause nephrotic syndrome. However, the treatment for such cases remains unclear. We report a series of three cases of nephrotic syndrome due to iMCD that helps to delineate the importance of early and continuous therapy with the anti-interleukin-6 receptor antibody tocilizumab. First, treatment was suspended for infectious control, and the patient presented with nephrotic syndrome due to diffuse mesangial and endocapillary hypercellularity without immune deposits complicating acute kidney injury. Second, iMCD was treated with prednisolone alone. The patient suddenly developed nephrotic syndrome due to immune-complex glomerulonephritis, not otherwise specified, complicated with acute kidney injury. In the third case, nephrotic syndrome secondary to membranous glomerulonephritis was diagnosed, with a skin rash and IgE antibodies to tocilizumab, and was therefore treated with prednisolone alone. In contrast to the first two cases, the third progressed to end-stage renal disease on hemodialysis. Taken together, this series suggests that clinicians should maintain clinical vigilance for iMCD as a possible underlying component of nephrotic syndrome, since iMCD presents with a variety of renal pathologies. Prompt initiation and continuous administration of tocilizumab are likely key determinants of renal outcomes in such cases. In particular, when tocilizumab is suspended due to infection or in the perioperative period, consideration of its expeditious resumption should be made, taking into account both the withdrawal period and systemic conditions.

Published
2023
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12. Perimortem changes in clinical parameters in patients undergoing maintenance hemodialysis

Author

Tadashi Yoshida, Kohkichi Morimoto, Takashin Nakayama, Takuto Torimitsu, Shotaro Kosugi, Takuma Oshida, Nobuko Yamaguchi, and Mototsugu Oya

Subjects
Hemodialysis, Forgoing, Withdrawal, Blood pressure, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background End-of-life medical care for patients receiving maintenance hemodialysis (HD) therapy has become an increasingly important issue worldwide. Thus far, no clear indicators and/or biomarkers exist regarding the timing of HD therapy withdrawal. Methods To clarify the perimortem circumstances, we examined temporal changes in multiple clinical parameters during the last 10 serial HD sessions of 65 terminal patients with end-stage renal disease who had undergone maintenance HD and died in our hospital. Results The results showed that, while most of the laboratory data were unaltered, the physical parameters, such as systolic blood pressure and consciousness levels, gradually and significantly deteriorated toward the last HD session prior to death. The frequency of the use of vasopressors and O2 inhalation tended to increase. The accumulation of such severe conditions was observed at the last HD session. Of interest, the accumulation of severe conditions at the last HD session in patients with malignancies was significantly less than those with cardiovascular diseases or infectious diseases. The accumulation of severe conditions at the last HD session did not differ between patients who withdrew HD versus those who continued HD. Conclusion The results of the present study suggest that predicting the timing of maintenance HD therapy withdrawal is likely to be difficult and that the timing of maintenance HD therapy termination may differ among patient groups with distinct comorbid conditions.

Published
2021
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13. Home‐based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial

Author

Kiyotaka Uchiyama, Keika Adachi, Kaori Muraoka, Takashin Nakayama, Takuma Oshida, Marie Yasuda, Akihito Hishikawa, Hitoshi Minakuchi, Kazutoshi Miyashita, Hirobumi Tokuyama, Shu Wakino, and Hiroshi Itoh

Subjects
Home‐based exercise, Chronic kidney disease, Randomized controlled trial, Incremental shuttle walking test, Quality of life, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract

Abstract Background The potential effects of aerobic and resistance training in patients with severe chronic kidney disease (CKD) are not fully elucidated. This study investigated the effects of a home‐based exercise programme on physical functioning and health‐related quality of life (HRQOL) in patients with Stage 4 CKD, equivalent to estimated glomerular filtration rate of 15–30 mL/min/1.73 m2. Methods Forty‐six patients with Stage 4 CKD (median age, 73 years; 33 men) were randomly assigned to exercise (n = 23) and control (n = 23) groups. Exercise group patients performed aerobic exercise at 40–60% peak heart rate thrice weekly and resistance training at 70% of one‐repetition maximum twice weekly at home for 6 months. Control patients received no specific intervention. Primary outcomes were distance in incremental shuttle walking test and HRQOL assessed using the Kidney Disease Quality of Life—Short Form questionnaire. Secondary outcomes included kidney function assessed with combined urea and creatinine clearance, urinary biomarkers, and anthropometric and biochemical parameters associated with CKD. Results Improvement in incremental shuttle walking test was significantly greater in the exercise group compared with controls (39.4 ± 54.6 vs. −21.3 ± 46.1; P

Published
2021
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14. Bullous pemphigoid in patients receiving peritoneal dialysis: a case series and a literature survey

Author

Kohkichi Morimoto, Tadashi Yoshida, Naoki Washida, Kiyotaka Uchiyama, Takashin Nakayama, Hiroshi Itoh, and Mototsugu Oya

Subjects
bullous pemphigoid, peritoneal dialysis, hemodialysis, incidence, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Although several cases of BP in end-stage renal disease patients receiving peritoneal dialysis (PD) or hemodialysis have been reported, the incidence of BP in these patients remains unknown. We recently experienced three PD patients diagnosed with BP. The skin injury was likely to be a trigger of BP in all the three PD patients. Nifedipine and icodextrin exposures were possible factors directly or indirectly affecting the onset of BP, because they were common in the three cases. We also report that the incidence of BP in PD patients was 3/478.3 person-years in a single-center 10-year study. This case series with a literature survey describes that the skin and tissue injuries are potential triggers responsible for the onset of BP in dialysis patients and that the incidence of BP in these patients seems to be much higher than that in the general population.

Published
2021
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16. High body mass index is a risk factor for transition to hemodialysis or hybrid therapy and peritoneal dialysis-related infection in Japanese patients undergoing peritoneal dialysis

Author

Eriko Yoshida Hama, Kiyotaka Uchiyama, Tomoki Nagasaka, Ei Kusahana, Takashin Nakayama, Itaru Yasuda, Kohkichi Morimoto, Naoki Washida, and Hiroshi Itoh

Subjects
Japan, Renal Dialysis, Risk Factors, Nephrology, Urology, Humans, Kidney Failure, Chronic, Obesity, Peritonitis, Peritoneal Dialysis, Body Mass Index, Retrospective Studies
Abstract

Obesity may negatively impact the clinical outcomes of patients undergoing peritoneal dialysis (PD). However, the impact of obesity on PD-related outcomes remains unclear. We herein examined the association of high body mass index (BMI) with complete hemodialysis (HD) transfer, transition to HD and PD/HD hybrid therapy, peritonitis, catheter exit-site and tunnel infection (ESI/TI), and heart failure-related hospitalization.This retrospective cohort study included 120 patients who underwent PD-catheter insertion between January 2008 and June 2018. BMI ≥ 25 kg/mThe follow-up duration was 46.2 (23.3-75.3) months. The time until transfer to HD and hybrid therapy was significantly shorter in the high BMI group than that in the low BMI group, whereas the time until HD transfer was not significantly different between the two groups (P 0.001 and 0.18, respectively). Peritonitis-free and ESI/TI-free survivals were significantly shorter in the high BMI group than those in the low BMI group (P = 0.006 and 0.03, respectively). After adjusting for age, sex, diabetes mellitus, and estimated glomerular filtration rate, high BMI remained a significant risk factor for transferring to HD and hybrid therapy, peritonitis, and ESI/TI (hazard ratio [HR] 2.60, P 0.001; HR 2.08, P = 0.01; HR 2.64, P = 0.02, respectively).BMI ≥ 25 kg/m

Published
2022
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18. Effects of renin-angiotensin system inhibitors on the incidence of unplanned dialysis

Author

Takashin, Nakayama, Kohkichi, Morimoto, Kiyotaka, Uchiyama, Ei, Kusahana, Naoki, Washida, Tatsuhiko, Azegami, Takeshi, Kanda, Tadashi, Yoshida, and Hiroshi, Itoh

Subjects
Male, Renin-Angiotensin System, Renal Dialysis, Physiology, Incidence, Internal Medicine, Humans, Kidney Failure, Chronic, Female, Renal Insufficiency, Chronic, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract

Unplanned dialysis initiation is associated with poor outcomes. It is controversial whether patients with advanced chronic kidney disease (CKD) should receive renin-angiotensin system (RAS) inhibitor therapy. The aim of this study was to evaluate the effect of RAS inhibitor therapy in patients with advanced CKD on the incidence of unplanned dialysis initiation. This single-center, retrospective study included patients who started maintenance dialysis at our hospital between April 2014 and March 2021. Patients who initiated dialysis within 6 months of nephrology referral or after kidney transplant were excluded. Among 334 patients (aged 70.0 [59.0-79.0] years; 28.4% women), 186 (55.7%) and 148 (44.3%) had planned and unplanned dialysis initiation, respectively. Multivariate logistic regression analysis revealed that the use of RAS inhibitors was significantly associated with a lower incidence of unplanned dialysis initiation (odds ratio [OR], 0.36; P 0.01). Female sex (OR, 0.41; P 0.05), use of potassium binders (OR, 0.28; P 0.001), earlier referral to nephrology (OR, 0.39; P 0.01), and earlier discussion of renal replacement therapy (OR, 0.33; P 0.001) were also significantly associated with a lower incidence, whereas older age (OR, 1.28; P 0.05), higher Charlson Comorbidity Index (OR, 1.24; P 0.05), and faster decline in kidney function (OR, 1.29; P 0.01) were associated with a higher risk of unplanned dialysis initiation. RAS inhibitor therapy in patients with advanced CKD is associated with a lower risk of unplanned dialysis initiation.

Published
2022
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21. Home‐based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial

Author

Takashin Nakayama, Kaori Muraoka, Hitoshi Minakuchi, Keika Adachi, Hirobumi Tokuyama, Kazutoshi Miyashita, Kiyotaka Uchiyama, Shu Wakino, Takuma Oshida, Hiroshi Itoh, Akihito Hishikawa, and Marie Yasuda

Subjects
Male, Quality of life, medicine.medical_specialty, Renal function, Diseases of the musculoskeletal system, law.invention, Randomized controlled trial, law, Chronic kidney disease, Physiology (medical), Internal medicine, Heart rate, Humans, Medicine, Aerobic exercise, Orthopedics and Sports Medicine, Renal Insufficiency, Chronic, Incremental shuttle walking test, Exercise, Aerobic capacity, Aged, Home‐based exercise, business.industry, QM1-695, Resistance Training, Original Articles, Anthropometry, medicine.disease, Exercise Therapy, RC925-935, Human anatomy, Original Article, business, Kidney disease
Abstract

Background The potential effects of aerobic and resistance training in patients with severe chronic kidney disease (CKD) are not fully elucidated. This study investigated the effects of a home‐based exercise programme on physical functioning and health‐related quality of life (HRQOL) in patients with Stage 4 CKD, equivalent to estimated glomerular filtration rate of 15–30 mL/min/1.73 m2. Methods Forty‐six patients with Stage 4 CKD (median age, 73 years; 33 men) were randomly assigned to exercise (n = 23) and control (n = 23) groups. Exercise group patients performed aerobic exercise at 40–60% peak heart rate thrice weekly and resistance training at 70% of one‐repetition maximum twice weekly at home for 6 months. Control patients received no specific intervention. Primary outcomes were distance in incremental shuttle walking test and HRQOL assessed using the Kidney Disease Quality of Life—Short Form questionnaire. Secondary outcomes included kidney function assessed with combined urea and creatinine clearance, urinary biomarkers, and anthropometric and biochemical parameters associated with CKD. Results Improvement in incremental shuttle walking test was significantly greater in the exercise group compared with controls (39.4 ± 54.6 vs. −21.3 ± 46.1; P

Published
2021
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22. Eosinophilic Reaction at the Time of Catheter Insertion Predicts Survival in Patients Initiating Peritoneal Dialysis

Author

Naoki Washida, Takashin Nakayama, Hiroshi Itoh, Ei Kusahana, Kiyotaka Uchiyama, and Kohkichi Morimoto

Subjects
Male, medicine.medical_specialty, Catheters, medicine.medical_treatment, Urology, Peritonitis, Renal function, Peritoneal dialysis, Catheters, Indwelling, medicine, Humans, Aged, Retrospective Studies, Catheter insertion, business.industry, Proportional hazards model, Hazard ratio, Retrospective cohort study, Hematology, General Medicine, medicine.disease, Nephrology, Peritoneal Dialysis − Research Article, Heart failure, Kidney Failure, Chronic, business, Peritoneal Dialysis
Abstract

Introduction: Despite excellent biocompatibility, insertion of silicone peritoneal dialysis (PD) catheters can induce minor foreign body reaction, affecting long-term patient outcomes. We evaluated the effect of eosinophilic reaction associated with PD catheter insertion on outcomes of patients initiating PD. Methods: Eosinophilic reaction to PD catheter insertion was defined as the ratio of peripheral blood eosinophil count at 1 week after insertion (E1W) to pre-insertion eosinophil count (E0), and the association of E1W/E0 with technique survival, peritonitis-free survival, and heart failure (HF)-related hospitalization-free survival was analyzed. Results: This retrospective cohort study included 116 patients (89 male patients) who underwent PD catheter insertion between January 2008 and June 2018 (61.3 ± 12.9 years). The follow-up duration was 46.2 (23.8–75.3) months. E1W was significantly higher than E0 (median, 333 vs. 234/μL, p < 0.001), with a median E1W/E0 of 1.54. The log-rank test showed that technique survival, peritonitis-free survival, and HF-related hospitalization-free survival were significantly better in patients with E1W/E0 < 1.54 than in those with E1W/E0 ≥ 1.54 (p = 0.002, p = 0.01; HR 2.19, p < 0.001; HR 2.15, p < 0.001, respectively). Conclusion: Eosinophilic reaction at the time of PD catheter insertion is a novel marker that may predict outcomes in patients initiating PD.

Published
2021
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24. Effect of Tolvaptan in Patients with Chronic Kidney Disease Stage G5, and Impact of Concomitant Use of Thiazide Diuretics: A Retrospective Cohort Study

Author

Kiyotaka Uchiyama, Daiki Kojima, Eriko Yoshida Hama, Tomoki Nagasaka, Takashin Nakayama, Rina Takahashi, Takaya Tajima, Kohkichi Morimoto, Naoki Washida, and Hiroshi Itoh

Subjects
Pharmacology (medical)
Abstract

The diuretic effect of tolvaptan, a vasopressin V2 receptor antagonist, in patients with severe renal dysfunction remains poorly characterized. Thiazide diuretics reduce urinary volume (UV) in patients with nephrogenic diabetes insipidus, which lacks V2 receptor function.This retrospective study investigated the acute urinary effects of tolvaptan in patients with stage G5 chronic kidney disease and congestive heart failure (CHF), and the impact of thiazide diuretics on the urinary effects of tolvaptan.UVs 24 h before and after tolvaptan administration and 30-day dialysis initiation rate were compared between patients with and without thiazide diuretic administration.Thiazide diuretics were used in 26 of the 106 recruited patients (age 73.4 ± 13.0 years; estimated glomerular filtration rate 8.07 ± 3.13 mL/min/1.73 mTolvaptan exhibited significant diuretic effects in patients with CHF, including those with severe renal dysfunction, which were diminished with concomitant thiazide diuretic use.

Published
2022

26. Efficacy of dexmedetomidine on peritoneal dialysis catheter insertion

Author

Ran Nakamichi, Shu Wakino, Takashin Nakayama, Takahiro Kasai, Kiyotaka Uchiyama, Naoki Washida, Hiroshi Itoh, Ei Kusahana, and Kohkichi Morimoto

Subjects
Male, endocrine system, Nausea, Urology, medicine.medical_treatment, 030232 urology & nephrology, Pain, Procedural, 030204 cardiovascular system & hematology, Anesthesia, Spinal, Catheterization, Peritoneal dialysis, 03 medical and health sciences, 0302 clinical medicine, polycyclic compounds, Humans, Hypnotics and Sedatives, Medicine, Dexmedetomidine, Adverse effect, Aged, Retrospective Studies, Catheter insertion, business.industry, Retrospective cohort study, Middle Aged, Treatment Outcome, Nephrology, Anesthesia, Propensity score matching, Female, medicine.symptom, business, Peritoneal Dialysis, Body mass index, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract

Dexmedetomidine (DEX) is a sedative agent with minimal respiratory and hemodynamic effects. The present study aimed to evaluate its effectiveness in peritoneal dialysis (PD) catheter insertion. This single-center retrospective study included patients who underwent PD catheter insertion under spinal anesthesia in our hospital between January 2016 and December 2020. Patients were divided into the DEX and non-DEX groups according the use of DEX. After 1:1 propensity score matching to adjust for age, sex, body mass index, mean blood pressure (BP), and Charlson comorbidity index, we compared operation-related outcomes, including peak numerical rating scale (NRS), occurrence of nausea, vital signs, or operative time between the two groups. Of a total of 44 patients, 9 patients received DEX, and 35 did not. After propensity score matching, each group consisted of 8 patients. Peak NRS was significantly lower (P = 0.003) in the DEX group compared with the non-DEX group. Maximum mean BP during the operation was also significantly lower in the DEX group compared with the non-DEX group (P = 0.020), with no significant differences in minimum mean BP between the two groups (P = 0.831). The DEX group showed a trend of shortened operative time (P = 0.068). There were no significant differences in the occurrence of nausea (P = 1.000). Moreover, there was no clinically important adverse event associated with use of DEX. The use of DEX in PD catheter insertion under spinal anesthesia could safely improve operative analgesia.

Published
2021
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27. Health-Related Quality of Life Sleep Score Predicts Transfer to Hemodialysis among Patients on Peritoneal Dialysis

Author

Tomoki Nagasaka, Naoki Washida, Kiyotaka Uchiyama, Eriko Yoshida Hama, Ei Kusahana, Takashin Nakayama, Itaru Yasuda, Kohkichi Morimoto, and Hiroshi Itoh

Subjects
Health Information Management, Leadership and Management, Health Policy, Health Informatics, peritoneal dialysis, sleep, health-related quality of life, kidney disease quality of life-short form, transfer to hemodialysis
Abstract

Despite the superiority of peritoneal dialysis (PD) over hemodialysis (HD) regarding health-related quality of life (HRQOL), the specific HRQOL domain(s) that predict unplanned HD transfer remains uncertain. In this cohort study, we assessed the HRQOL of 50 outpatients undergoing PD using the Japanese version 1.3 Kidney Disease Quality of Life-Short Form from March 2017 to March 2018 and prospectively analyzed the association of each HRQOL component with HD transfer until June 2021. During the follow-up (41.5 (13.0–50.1) months), 21 patients were transferred to HD. In a multivariate Cox proportional hazards model adjusted for age, sex, PD vintage, urine output, Charlson comorbidity index, and incremental shuttle walking test, a higher sleep score was significantly associated with lower HD transfer rates (HR 0.70 per 10, p = 0.01). An adjusted subdistribution hazard model where elected transition to HD, death, and transplantation were considered competing events of unintended HD transfer that showed sleep score as an exclusive predictor of HD transfer (HR 0.70 per 10, p = 0.002). Our results suggest that sleep score among the HRQOL subscales is instrumental in predicting HD transfer in patients undergoing PD.

Published
2022

28. Exercise Parameters Predict Technique Survival in Patients on Peritoneal Dialysis

Author

Takashin Nakayama, Keika Adachi, Kaori Muraoka, Takahiro Kasai, Kazutoshi Miyashita, Kiyotaka Uchiyama, Shu Wakino, Kohkichi Morimoto, Naoki Washida, and Hiroshi Itoh

Subjects
Male, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, Peritonitis, Peritoneal dialysis, Internal medicine, Clinical endpoint, Humans, Medicine, In patient, Exercise, Survival rate, Aerobic capacity, Aged, Aged, 80 and over, Exercise Tolerance, Hand Strength, business.industry, Hematology, General Medicine, Middle Aged, Prognosis, Survival Analysis, Survival Rate, Nephrology, Female, Hemodialysis, business, Peritoneal Dialysis, Follow-Up Studies, Cohort study
Abstract

Objective: The incremental shuttle walking test (ISWT) is an important marker of aerobic capacity in patients on peritoneal dialysis (PD). This study aimed to evaluate its predictive value for PD-related outcomes. Methods: This single-center cohort study recruited outpatients on maintenance PD from our hospital between March 2017 and March 2018. Exercise capacity was assessed using measurement of ISWT and handgrip and quadriceps strength. Patients were divided into 2 groups according to the median of exercise capacity and prospectively followed up until cessation of PD, death, or the study end (October 2019). The primary end point of this study was technique survival rate, and secondary outcomes were rates of peritonitis-free survival and PD-related hospitalization-free survival. Results: Among the 50 participants, age and PD vintage were [median (IQR)] 62.5 (58.3–70) and 3.5 (1.3–6.5) years, respectively. At the end of the study, 3 of the 28 participants (11%) in the long-ISWT group and 13 of the 22 participants (59%) in the short-ISWT group were transferred to hemodialysis. The short-ISWT group showed lower technique survival rate (p < 0.001), peritonitis-free survival rate (p = 0.01), and PD-related hospitalization-free survival rate (p < 0.01) than the long-ISWT group, whereas those survival rates did not differ when participants were divided by handgrip or quadriceps strength. Multivariate analysis revealed lower ISWT to be independently associated with technique failure (p = 0.002). Conclusion: The ISWT is an important predictor of technique survival for patients on PD. Monitoring and enhancing ISWT as a marker of aerobic capacity might improve PD-related outcomes.

Published
2020
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29. Effects of exercise on residual renal function in patients undergoing peritoneal dialysis: A post‐hoc analysis of a randomized controlled trial

Author

Kaori Muraoka, Takashin Nakayama, Kazutoshi Miyashita, Takahiro Kasai, Hiroshi Itoh, Keika Adachi, Shu Wakino, Kiyotaka Uchiyama, Kohkichi Morimoto, and Naoki Washida

Subjects
Male, medicine.medical_specialty, Urinary system, medicine.medical_treatment, 030232 urology & nephrology, Urology, Renal function, 030204 cardiovascular system & hematology, Fatty Acid-Binding Proteins, Kidney Function Tests, Peritoneal dialysis, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Post-hoc analysis, Humans, Medicine, In patient, business.industry, Hematology, Middle Aged, Physical Functional Performance, Home Care Services, Exercise Therapy, Renal Elimination, Outcome and Process Assessment, Health Care, Nephrology, Creatinine, Kidney Failure, Chronic, Female, Anuria, medicine.symptom, business, Peritoneal Dialysis, Usual care group, Biomarkers
Abstract

We aimed to investigate the effects of exercise on renal outcomes in patients undergoing peritoneal dialysis (PD). In a post-hoc analysis of a randomized controlled trial of a 12-week home-based exercise program involving 47 patients undergoing PD, we excluded 18 patients with anuria and analyzed 13 and 16 patients in the usual care and exercise groups, respectively. The primary outcomes were weekly renal creatinine clearance (CCr) and urinary biomarkers: liver-type fatty acid-binding protein (L-FABP) and the microalbumin-to-creatinine ratio (ACR). Although the maintenance of weekly renal CCr in the exercise group was not significantly different compared with that in the usual care group (P = .09), urinary L-FABP levels (P = .02) and ACR (P = .04) were significantly decreased in the exercise group. To the best of our knowledge, this is the first study to demonstrate the beneficial effects of exercise on renal outcomes in patients undergoing PD.

Published
2020
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30. Serum thymus and activation-regulated chemokine level is associated with the severity of chronic kidney disease-associated pruritus in patients undergoing peritoneal dialysis

Author

Takashin Nakayama, Kohkichi Morimoto, Kiyotaka Uchiyama, Ei Kusahana, Naoki Washida, Tatsuhiko Azegami, Takeshi Kanda, Tadashi Yoshida, and Hiroshi Itoh

Subjects
Cross-Sectional Studies, Nephrology, Pruritus, Quality of Life, Humans, General Medicine, Chemokine CCL17, Middle Aged, Renal Insufficiency, Chronic, Peritoneal Dialysis, Severity of Illness Index, Biomarkers, Aged
Abstract

Background: Thymus and activation-regulated chemokine (TARC), which induces a Th2-dominated inflammation, is a well-known biomarker that reflects the severity of atopic dermatitis. The present study aimed to evaluate TARC as a Th2-associated marker with chronic kidney disease-associated pruritus (CKD-aP) in patients with peritoneal dialysis (PD). Methods: This single-centre cross-sectional study included patients who underwent PD in our hospital between August 2020 and July 2021. The severity and impaired quality of life (QOL) of CKD-aP were assessed using the visual analogue scale (VAS) and Japanese version of the 5-D itch scale (5D-J), respectively. Results: A total of 48 patients with PD were included in the present study. Age and dialysis vintage were (mean ± SD) 64.8 ± 12.0 year and (median (IQR)) 38.5 (11.5–91.5) month, respectively. VAS and 5D-J scores were 3.3 ± 2.0 and 10.5 (9.0–12.0), respectively. Serum TARC level was 481.5 (278.9–603.4) pg/mL (upper limits of normal 450 pg/mL) and significantly correlated with VAS ( r = 0.39, p = 0.006) and 5D-J score ( r = 0.37, p = 0.009). Multivariate linear analysis revealed that higher serum TARC level was significantly associated with VAS ( p < 0.001) and 5D-J score ( p < 0.001). Furthermore, the serum brain natriuretic peptide level tended to be associated with VAS ( p = 0.060) and 5D-J score ( p = 0.029). Conclusion: Serum TARC level is an independent predictor of the severity and impaired QOL of CKD-aP in patients with PD, and TARC might be involved in the pathogenesis of CKD-aP.

Published
2022

31. Self-assessment sheet submission rate predicts technique survival in patients initiating peritoneal dialysis

Author

Ei Kusahana, Kiyotaka Uchiyama, Nobuko Yamaguchi, Maiko Hirashima, Tomoko Togashi, Yuriko Yamamoto, Michiyo Imai, Mayumi Ashida, Keiko Yamamura, Takashin Nakayama, Itaru Yasuda, Kohkichi Morimoto, Naoki Washida, and Hiroshi Itoh

Subjects
Male, Survival Rate, Self-Assessment, Nephrology, Humans, Kidney Failure, Chronic, Female, General Medicine, Peritonitis, Peritoneal Dialysis, Aged, Retrospective Studies
Abstract

Patients play a crucial role in preventing peritoneal dialysis (PD)-related events, including peritonitis and fluid overload, as PD procedures are mainly carried out at home. We asked patients to submit a PD self-assessment sheet at each outpatient visit in our daily clinical practice and evaluated its usefulness for outcomes in patients initiating PD.This retrospective cohort study included patients who underwent PD catheter insertion between January 2008 and October 2018. The submission rate of a PD self-assessment sheet was calculated from medical records until PD cessation or study completion (October 2020). The association between the submission rate and technique survival was analysed.Among the 105 recruited patients (78 men, 60.4 ± 12.2 years), 44 discontinued PD and transferred to haemodialysis during the study period. The follow-up was 52.3 (28.7-79.3) months, and the median submission rate was 78%. The log-rank test showed that technique survival was significantly better in patients with a submission rate ≥ 78% than those with a submission rate 78% (p = .006). The submission rate remained significantly associated with less technique failure (hazard ratio 0.88 per 10%, p = .002) by the Cox regression analysis adjusted for age, sex, Charlson comorbidity index, estimated glomerular filtration rate and geriatric nutritional risk index.The submission rate of a PD self-assessment sheet is useful as a predictor of technique survival in patients initiating PD. Instruction that increases submission may improve technique survival in PD patients.

Published
2022

40. Fibronectin Glomerulopathy Confused with Glomerular Endothelial Injury in a Patient with Takotsubo Cardiomyopathy

Author

Tatsuhiko Azegami, Akinori Hashiguchi, Takashin Nakayama, Kaori Hayashi, Takeshi Kanda, and Hiroshi Itoh

Subjects
Nephrotic Syndrome, Glomerulonephritis, Membranoproliferative, Takotsubo Cardiomyopathy, Kidney Glomerulus, Internal Medicine, Humans, Female, General Medicine, Middle Aged, Confusion
Abstract

A 46-year-old woman developed takotsubo cardiomyopathy and nephrotic syndrome. The first kidney biopsy suggested non-immune-complex-mediated membranoproliferative glomerulonephritis (MPGN), and she was diagnosed with glomerular endothelial injury associated with takotsubo cardiomyopathy. A second biopsy was performed two years later because of persistent proteinuria despite renin-angiotensin system inhibition. This biopsy indicated non-immune-complex-mediated MPGN, but a mesangial and subendothelial substance of a higher electron density than that in the first biopsy was detected, suggesting the possibility of glomerular disease with non-immune deposits rather than endothelial injury. Finally, she was diagnosed with fibronectin nephropathy. Although rare, fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN.

Published
2021

42. Effects of a remote patient monitoring system for patients on automated peritoneal dialysis: a randomized crossover controlled trial

Author

Kiyotaka Uchiyama, Kohkichi Morimoto, Naoki Washida, Ei Kusahana, Takashin Nakayama, Tomoaki Itoh, Takahiro Kasai, Shu Wakino, and Hiroshi Itoh

Subjects
Male, Nephrology, Patient Satisfaction, Urology, Quality of Life, Humans, Kidney Failure, Chronic, Prospective Studies, Peritoneal Dialysis, Aged, Monitoring, Physiologic
Abstract

Remote patient monitoring (RPM) has contributed to improved patient-centered outcomes and prognosis in patients with end-stage renal disease on automated peritoneal dialysis (APD). However, evidence from prospective trials is lacking.The participants (n = 15; median age: 65 years; males: 10; peritoneal dialysis vintage: 6.4 ± 3.5 years) randomly received APD therapy using the Kaguya® APD system either with or without the connective use of the cloud-based RPM software Sharesource® for 12 weeks. The primary outcome was patient satisfaction assessed using a modified nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) questionnaire. The secondary outcomes were healthcare resource consumption, the health-related quality of life (HRQOL) subscales assessed with the Kidney Disease Quality of Life-Short Form questionnaire, and clinical laboratory parameters.Significant improvements were observed in the TSQM-9 subscales of Effectiveness (64.4 ± 18.8 vs. 57.8 ± 18.8; P = 0.006) and Convenience (76.3 ± 15.4 vs. 63.3 ± 17.3; P 0.001) in patients on Sharesource®. Moreover, Sharesource® reduced the total amount of healthcare resource consumption (0.80 ± 1.32 vs. 1.87 ± 2.39 times/12 weeks; P = 0.02) and consultation time during regular monthly visits (813 ± 269 vs. 1024 ± 292 s; P 0.001). A significant increase in ultrafiltration volume was found associated with more frequent modification of APD prescription in patients with Sharesource®. Sharesource® also improved the HRQOL subscale of General Health and Vitality.Sharesource® can improve patient-centered outcomes in patients on APD while reducing the treatment burden for both patients and medical staff.The study was registered in the Japan Registry of Clinical Trials (jRCT Number: jRCTs032190005).

Published
2021

43. Seasonal variation and predictors of intradialytic blood pressure decline: a retrospective cohort study

Author

Kiyotaka Uchiyama, Naoki Washida, Keigo Shibagaki, Takashin Nakayama, Akane Yanai, Hiroshi Itoh, Ei Kusahana, and Kohkichi Morimoto

Subjects
medicine.medical_specialty, Physiology, medicine.drug_class, medicine.medical_treatment, Blood Pressure, Calcium channel blocker, Cohort Studies, Chronic kidney disease-mineral and bone disorder, Renal Dialysis, Internal medicine, Internal Medicine, medicine, Humans, Prospective Studies, Dialysis, Retrospective Studies, business.industry, Retrospective cohort study, Seasonality, medicine.disease, Confidence interval, Blood pressure, Cardiology, Kidney Failure, Chronic, Hemodialysis, Seasons, Hypotension, Cardiology and Cardiovascular Medicine, business
Abstract

The risk factors for intradialytic systolic blood pressure decline remain poorly understood. We aimed to identify clinical and laboratory predictors of the intradialytic systolic blood pressure decline, considering its seasonal variation. In a retrospective cohort of 47,219 hemodialysis sessions of 307 patients undergoing hemodialysis over one year in three dialysis clinics, the seasonal variation and the predictors of intradialytic systolic blood pressure decline (predialysis systolic blood pressure--nadir intradialytic systolic blood pressure) were assessed using cosinor analysis and linear mixed models adjusted for baseline or monthly hemodialysis-related variables, respectively. The intradialytic systolic blood pressure decline was greatest and least in the winter and summer, respectively, showing a clear seasonal pattern. In both models adjusted for baseline and monthly hemodialysis-related parameters, calcium channel blocker use was associated with a smaller decline (-4.58 [95% confidence interval (CI), -5.84 to -3.33], P < 0.001; -3.66 [95% CI, -5.69 to -1.64], P < 0.001) and α blocker use, with a greater decline (3.25 [95% CI, 1.53-4.97], P < 0.001; 3.57 [95% CI, 1.08-6.06], P = 0.005). Baseline and monthly serum phosphorus levels were positively correlated with the decline (1.55 [95% CI, 0.30-2.80], P = 0.02; 0.59 [95% CI, 0.16-1.00], P = 0.007), and baseline and monthly normalized protein catabolic rates were inversely correlated (respectively, -22.41 [95% CI, -33.53 to -11.28], P < 0.001; 9.65 [95% CI, 4.60-14.70], P < 0.001). In conclusion, calcium channel blocker use, α blocker avoidance, and serum phosphorus-lowering therapy may attenuate the intradialytic systolic blood pressure decline and should be investigated in prospective trials.

Published
2021

45. Vaccination Against Receptor for Advanced Glycation End Products Attenuates the Progression of Diabetic Kidney Disease

Author

Takashin Nakayama, Akihito Hishikawa, Ran Nakamichi, Kaori Hayashi, Norifumi Yoshimoto, Hiroshi Itoh, and Tatsuhiko Azegami

Subjects
Male, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Receptor for Advanced Glycation End Products, Type 2 diabetes, RAGE (receptor), Diabetes Mellitus, Experimental, Mice, Glycation, Internal Medicine, medicine, Animals, Diabetic Nephropathies, Type 1 diabetes, biology, business.industry, Glomerular basement membrane, Vaccination, Antibody titer, medicine.disease, medicine.anatomical_structure, Immunology, biology.protein, Disease Progression, Antibody, business
Abstract

Effective treatment of diabetic kidney disease (DKD) remains a large unmet medical need. Within the disease’s complicated pathogenic mechanism, activation of the advanced glycation end-products (AGEs)–receptor for AGEs (RAGE) axis plays a pivotal role in the development and progression of DKD. To provide a new therapeutic strategy against DKD progression, we developed a vaccine against RAGE. Three rounds of immunization of mice with the RAGE vaccine successfully induced antigen-specific serum IgG antibody titers, and elevated antibody titers were sustained for at least 38 weeks. In addition, RAGE vaccination significantly attenuated the increase in urinary albumin excretion in streptozotocin-induced diabetic mice (type 1 diabetes model) and leptin-receptor–deficient db/db mice (type 2 diabetes model). In microscopic analyses, RAGE vaccination suppressed glomerular hypertrophy and mesangial expansion in both diabetic models and significantly reduced glomerular basement membrane thickness in streptozotocin-induced diabetic mice. Results of an in vitro study indicated that the serum IgG antibody elicited by RAGE vaccination suppressed the expression of AGE-induced vascular cell adhesion molecule 1 and intracellular adhesion molecule 1 in endothelial cells. Thus, our newly developed RAGE vaccine attenuated the progression of DKD in mice and is a promising potential therapeutic strategy for patients with DKD.

Published
2020

46. Difficulty in managing nephrotic syndrome-associated cerebral venous thrombosis

Author

Hirobumi Tokuyama, Norifumi Yoshimoto, Takashin Nakayama, Takuto Torimitsu, Hiroshi Itoh, Takeshi Kanda, Shu Wakino, and Ryunosuke Mitsuno

Subjects
Adult, medicine.medical_specialty, Nephrotic Syndrome, Deep vein, Prednisolone, 030232 urology & nephrology, Case Report, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Glucocorticoids, Venous Thrombosis, business.industry, Renal vein thrombosis, General Medicine, Heparin, medicine.disease, Thrombosis, Cerebral Veins, Magnetic Resonance Imaging, Venous thrombosis, Catheter, medicine.anatomical_structure, Treatment Outcome, Cardiology, Female, business, Nephrotic syndrome, medicine.drug
Abstract

Thromboembolism is one of the most serious complications of nephrotic syndrome (NS). Although the occurrence of renal vein thrombosis or deep vein thrombosis is well recognized in NS patients, they rarely develop cerebral venous thrombosis (CVT). The mortality rate of CVT patients is still approximately 10%, and 6-10% of patients who survive have a severe and permanent disability. Herein, we report the case of a 26-year-old woman with multiple thrombotic risk factors, including the presence of NS, use of oral contraceptives, smoking, and alcohol consumption who developed wide-range CVT. Undetermined fraction heparin, albumin and AT-III transfusion, and direct mechanical catheter thrombectomy were insufficient for the improvement of CVT. However, CVT eventually improved along with the remission of NS by prednisolone administration. This process indicates that in the management of CVT associated with NS, it is crucial to control the activity of NS. Currently, knowledge on the treatment for NS associated with CVT is limited, and this is a subject of urgent investigation.

Published
2020

47. Calcified cerebral embolism due to aortic valve calcification

Author

Takashin Nakayama, Shu Wakino, and Hiroshi Itoh

Subjects
Nephrology, Male, medicine.medical_specialty, Physiology, medicine.medical_treatment, MEDLINE, Cerebral embolism, Physiology (medical), Internal medicine, medicine, Humans, Diabetic Nephropathies, Aged, business.industry, Calcinosis, Aortic Valve Stenosis, Intracranial Embolism, Echocardiography, Aortic Valve, Cardiology, Kidney Failure, Chronic, Hemodialysis, Aortic valve calcification, business, Tomography, X-Ray Computed
Published
2020

49. Undifferentiated high-grade pleomorphic sarcoma of the mediastinum

Author

Keita Hirano, Takashin Nakayama, Yohei Numasawa, and Kohei Hashimoto

Subjects
Undifferentiated High Grade Pleomorphic Sarcoma, Pathology, medicine.medical_specialty, Infectious Diseases, medicine.anatomical_structure, business.industry, Clinical Image, Medicine, Mediastinum, Parasitology, business, Microbiology
Published
2019

50. Syndrome of inappropriate secretion of antidiuretic hormone associated with angiotensin-converting enzyme inhibitor therapy in the perioperative period

Author

Takashin Nakayama, Ruri Kawauchi, Satoru Komatsumoto, Kazuo Isozumi, Kyohei Ogawa, Ayaka Mitsui, Shintaro Hirai, Hiroto Fujisaki, Keita Hirano, and Takayuki Takahashi

Subjects
medicine.medical_specialty, Medicine (General), hyponatremia, Angiotensin-Converting Enzyme Inhibitors, Case Report, 030204 cardiovascular system & hematology, Pharmacology, Inappropriate ADH Syndrome, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, R5-920, Internal medicine, Internal Medicine, Medicine, Humans, 030212 general & internal medicine, perioperative, Perioperative Period, Aged, chemistry.chemical_classification, business.industry, Inappropriate secretion, lisinopril, Lisinopril, Angiotensin converting enzyme inhibitor therapy, Perioperative, medicine.disease, Enzyme, chemistry, angiotensin-converting enzyme inhibitor, Disease Progression, Female, Syndrome of inappropriate secretion of antidiuretic hormone, business, Hyponatremia, medicine.drug, Antidiuretic, Hormone
Abstract

Introduction: Angiotensin-converting enzyme (ACE) inhibitors are one of the most commonly used medications for hypertension. Rarely, ACE inhibitors have the potential to cause a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Case presentation: A 70-year-old woman with > 10 years ACE inhibitor therapy with normonatremia suddenly developed severe SIADH when she took a liquid diet in the uneventful perioperative period, with hemodynamic stability and no surgical complications. She promptly recovered from SIADH subsequent to discontinuing the ACE inhibitor therapy and changing her diet. Therefore, it was assumed that excess antidiuretic hormone secretion due to an ACE inhibitor and free water load from the liquid diet contributed to hyponatremia in our patient. Conclusion: Patients treated with an ACE inhibitor can latently experience inappropriate secretion of antidiuretic hormone, and rapidly develop severe hyponatremia together with additional factors affecting water or salt homeostasis regardless of the length of the administration duration. Clinicians should monitor serum sodium levels in such patients not only just after the initiation of ACE inhibitors but also upon the appearance of those factors.

Published
2019

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