Exploring the significance of interleukin-33/ST2 axis in minimal change disease.

Minimal change disease (MCD), a common cause of idiopathic nephrotic syndrome, has been postulated to exhibit an association with allergic conditions. Recent studies revealed the crucial role of interleukin (IL)-33 in type 2 innate immunity. We hypothesized that development of MCD involves an IL-33-related immune response. We examined 49 patients with biopsy-proven MCD, 6 healthy volunteers, and 29 patients in remission. In addition to clinical features, serum and urinary levels of IL-33 and soluble suppression of tumorigenicity 2 protein (sST2), a secreted form of the receptor of IL-33, were analyzed. Although IL-33 was barely detectable in either MCD or control samples, sST2 levels at diagnosis were elevated in MCD patients. Serum sST2 levels of MCD patients were correlated with serum total protein level (r = - 0.36, p = 0.010) and serum creatinine level (r = 0.34, p = 0.016). Furthermore, the elevated sST2 levels were observed to decrease following remission. Immunofluorescence revealed IL-33 expression in the podocytes among MCD patients, with a significant increase compared with controls. In vitro, mouse podocyte cells incubated with serum from a MCD patient at disease onset showed increased IL-33 secretion. These results suggest an IL-33-related immune response plays a role in MCD.

α-Blocker Use in Hemodialysis: The Japan Dialysis Outcomes and Practice Patterns Study.

Rationale & Objective: Despite α-blockers' use for hypertension as add-on therapy in patients treated with hemodialysis, scant information is available on their association, particularly with safety, in these patients. Study Design: Prospective cohort study. Setting & Participants: patients treated with hemodialysis and receiving antihypertensive agents in the Japan Dialysis Outcomes and Practice Patterns Study, phases 4-6, were analyzed. Exposure: Primary exposure was the prescription of α-blocking antihypertensive agents at baseline. Outcomes: Incident fractures, falls, and all-cause mortality. Analytical Approach: Multivariable Cox and modified Poisson regression analysis. Results: Of 5,149 patients treated with hemodialysis (mean age, 65 years; 68% men) receiving antihypertensive drugs, 717 (14%) received α-blocking agents. During a mean follow-up period of 2.0 years, 247 fractures, 525 falls, and 498 deaths occurred. Multivariable analysis showed no significant association of α-blocker use and increased risk of fractures (hazard ratio [HR], 0.92 [95% confidence interval {CI}, 0.61-1.38]), falls (HR, 0.94 [95% CI, 0.74-1.20]), or all-cause deaths (HR, 0.87 [95% CI, 0.64-1.20]) compared with α-blocker nonuse. α-Blocker use was, however, significantly associated with a decreased risk of all-cause mortality in the subgroup analysis, for example, patients who were older (HR, 0.71 [95% CI, 0.51-0.99]), were women (HR, 0.68 [95% CI, 0.48-0.95]), or reported a history of cardiovascular disease (HR, 0.67 [95% CI, 0.48-0.95]) or a predialysis blood pressure of ≥140 mm Hg (HR, 0.69 [95% CI, 0.49-0.98]). Limitations: Selection bias cannot be ruled out given the prevalent user analysis. Conclusions: No significant association between α-blocker use and the risk of worse safety-related outcomes was seen, indicating that clinicians may safely prescribe α-blockers to patients receiving hemodialysis who require blood pressure lowering. Plain-Language Summary: α-Blockers have been generally reserved for use as add-on therapy for resistant or refractory hypertension. However, little is known about the safety of α-blockers in patients treated by hemodialysis. We analyzed 5,149 patients receiving hemodialysis in Japan who were receiving antihypertensive drugs from the Japan Dialysis Outcomes and Practice Patterns Study. The results showed no significant increase in the risk of fractures, falls, or deaths for patients using α-blockers compared with those who did not, suggesting that α-blockers may be safely prescribed for patients receiving hemodialysis who need to lower their blood pressure.

Effects of evocalcet on parathyroid calcium-sensing receptor and vitamin D receptor expression in uremic rats.

Little is known about the effect of the recently developed calcimimetic evocalcet (Evo) on parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) expression. We examined the effects of Evo and cinacalcet (Cina) on CaSR and VDR expression in 5/6 nephrectomized Sprague-Dawley rats fed a high-phosphorus diet for 4 weeks to develop secondary hyperparathyroidism (SHPT). These uremic rats were divided into 4 groups-baseline control (Nx4W) and groups with additional treatment with either the Vehicle, Evo, or Cina for 2 weeks; normal rats were used as normal controls (NC). Blood parameters and parathyroid tissue were analyzed. CaSR and VDR expression levels were determined using immunohistochemistry. The degree of kidney injury and hyperphosphatemia was similar in the uremic groups (Nx4W, Vehicle, Cina, and Evo). Serum parathyroid hormone levels were significantly higher in the Nx4W and Vehicle groups than in the NC group. This increase was significantly suppressed in the Cina and Evo groups compared with that in the Vehicle group. Serum calcium levels were significantly and equally lower in the Cina and Evo groups relative to those in the Vehicle group. CaSR expression was significantly lower in the Nx4W and Vehicle groups than in the NC group. This downregulation was of an equally lesser magnitude in the Cina and Evo groups. A similar trend was observed for VDR expression. These results indicate that Evo and Cina treatment can increase parathyroid CaSR and VDR expression in uremic rats with SHPT, which could provide better control of mineral and bone disorder markers.

Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition on Podocytes in Mouse Nephrotic Syndrome.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to play a crucial role in dyslipidemia, and an increase in serum PCSK9 levels has also been reported in patients with nephrotic syndrome (NS). However, the specific effects of PCSK9 in kidney disease and the therapeutic potential of targeting PCSK9 in NS remain elusive. We thus investigated the effects of evolocumab (EVO) in mice with adriamycin (ADR)-induced NS. Male BALB/c mice were divided into the following 4 groups: Control, N = 11; EVO (monoclonal antibody for PCSK9), N = 11; ADR, N = 11; and ADR+EVO, N = 11. We also performed in vitro experiments using immortalized murine podocyte cells to validate the direct effects of PCSK9 on podocytes. EVO decreased urinary albumin levels and ameliorated podocytopathy in mice with ADR nephropathy. Further, EVO suppressed the Nod-like receptor protein 3 (NLRP3) inflammasome pathway in podocytes. PCSK9 expression upregulated CD36, a scavenger receptor of oxidized low-density lipoprotein (Ox-LDL), which in turn stimulated the absorption of Ox-LDL in vitro. EVO downregulated CD36 expression in podocytes both in vitro and in vivo. Immunofluorescence staining analysis reveals that CD36 and PCSK9 colocalized in the glomerular tufts of mice with ADR nephropathy. In the patients with focal segmental glomerulosclerosis, the CD36+ area in glomerular tufts increased compared with those diagnosed with minor glomerular abnormalities. This study revealed that EVO ameliorated mouse ADR nephropathy through the regulation of CD36 and NLRP3 inflammasome signaling. EVO treatment represents a potential therapeutic strategy for human NS.

Long-Term Effect of Denosumab on Bone Disease in Patients with CKD.

BACKGROUND: The effect of long-term denosumab therapy and of denosumab discontinuation on the cortical bone of the hip regions in dialysis patients has not been studied. METHODS: This retrospective study investigated the cortical and trabecular compartments and estimated strength indices of the hip region, obtained using 3D-SHAPER software, after a maximum of 5 years of denosumab therapy in 124 dialysis patients. A Wilcoxon signed-rank test was used to identify the differences in each parameter before and after denosumab initiation. Similarly, we investigated the changes in these parameters after denosumab discontinuation in 11 dialysis patients. RESULTS: Integral and trabecular volumetric bone mineral densities (BMD) were significantly lower at the start of denosumab therapy than those in 1 year before denosumab initiation. After starting denosumab, areal BMD (median change +7.7% [interquartile range (IQR), +4.6 to +10.6]), cortical volumetric BMD (median change +3.4% [IQR, +1.0 to +4.7]), cortical surface BMD (median change +7.1% [IQR, +3.4 to +9.4]), and cortical thickness (median change +3.2% [IQR, +1.8 to +4.9]) showed a significantly higher trend for 3.5 years, which then stabilized at a higher value compared with baseline. A similar trend in the trabecular volumetric BMD (median change +9.8% [IQR, +3.8 to +15.7]) was observed over 2.5 years, with a higher value maintained thereafter. The whole area of the hip region improved after denosumab therapy. Similar trajectories were also found in the estimated strength indices. Conversely, at 1 year after denosumab discontinuation, these 3D parameters and estimated strength indices tended to largely worsen. The lateral aspect of the greater trochanter was the most pronounced location showing volumetric BMD loss. CONCLUSIONS: The BMD of both cortical and trabecular components in the hip region was significantly higher after starting denosumab therapy. However, these measurements exhibited a trend of declining substantially after the discontinuation of denosumab.

Outcomes of discontinuing renin-angiotensin system inhibitors: a study protocol for conducting systematic review and meta-analysis.

INTRODUCTION: Renin-angiotensin system (RAS) plays a key role in various types of cardiovascular disease and many kinds of RAS inhibitors have been developed. The effect of discontinuation of RAS inhibitors on clinical outcomes is still controversial. This study aims to evaluate the effects of discontinuing RAS inhibitor medication on the clinical outcomes of patients continuously taking these agents. METHODS AND ANALYSIS: This article presents a systematic review protocol described in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will include randomised controlled trials in which the effects of RAS inhibitor withdrawal were evaluated. Initially, four authors will search for eligible studies in MEDLINE, EMBASE, the Cochrane Database Trial Register, European trial registry and ClinicalTrials.gov. Abstracts and full-text screenings will be performed by the four authors with data extraction performed by each author independently. We will include patients taking RAS inhibitors-including ACE inhibitor, angiotensin receptor blocker and angiotensin receptor neprilysin inhibitor and exclude the patients undergoing renal replacement therapy (RRT), adolescents (under 18 years of age) and patients with acute infectious diseases. Our search will be performed on 1 May 2023. Studies in which the patients discontinued RAS inhibitors due to any reason will be included. Patients who continuously took RAS inhibitors under conditions in which the intervention group discontinued these agents will be considered eligible as the comparison group. Death (any cause), Death (cardiovascular disease (CVD)) and CVD events will be set as primary outcomes. Secondary outcomes will be set as RRT, acute kidney injury, renal function (analysis of the change in estimated glomerular filtration rate), hyperkalaemia, proteinuria and blood pressure. ETHICS AND DISSEMINATION: Research ethics approval was not required in this study due to it being a systematic review, and any data belonging to individuals cannot be identified. The results of this study will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: PROSPERO CRD42022300777.

Efficacy and safety of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan (RESCUE-2): A randomized, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Despite optimal treatment, a residual inflammatory risk often remains in patients with atherosclerotic cardiovascular disease. In a US-based phase 2 trial, ziltivekimab, a fully human monoclonal antibody targeting the interleukin-6 ligand, significantly reduced biomarkers of inflammation compared with placebo in patients at high atherosclerotic risk. Here, we report the efficacy and safety of ziltivekimab in Japanese patients. METHODS: RESCUE-2 was a randomized, double-blind, 12-week, phase 2 trial. Participants aged ≥20 years with stage 3-5 non-dialysis-dependent chronic kidney disease and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L were randomized to receive placebo (n = 13) or subcutaneous ziltivekimab 15 mg (n = 11) or 30 mg (n = 12) at Weeks 0, 4, and 8. The primary endpoint was percentage change in hsCRP levels from baseline to end of treatment (EOT; mean of Week 10 and Week 12 values). RESULTS: At EOT, median hsCRP levels were reduced by 96.2 % in the 15 mg group (p < 0.0001 versus placebo), by 93.4 % in the 30 mg group (p = 0.002 versus placebo), and by 27.0 % in the placebo group. Serum amyloid A and fibrinogen levels were also reduced significantly. Ziltivekimab was well tolerated and did not affect total cholesterol to high-density lipoprotein cholesterol ratios. There was a small, but statistically significant increase in triglyceride levels with ziltivekimab 15 mg and 30 mg compared with placebo. CONCLUSIONS: The efficacy and safety results support the development of ziltivekimab for secondary prevention and the treatment of patients at high atherosclerotic risk. CLINICALTRIALS: gov identifier, NCT04626505.

Risk factors for blood vessel rupture during vascular access intervention therapy for hemodialysis patients.

Blood vessel rupture is a major complication associated with vascular access intervention therapy (VAIVT). However, information regarding the risk factors for ruptures related to VAIVT is limited. The purpose of this study was to investigate the risk factors for rupture during VAIVT. This was a single-center, retrospective observational study. Demographic, clinical, anatomical, and VAIVT procedure variables were reviewed and analyzed using multivariate logistic regression. The 211 patients included in the study underwent 628 VAIVT procedures from November 2019 to December 2021, and 20 blood vessel ruptures occurred. Patients with ruptures had significantly lower BMI (p = 0.043), shorter access vintage(p = 0.017), underwent VAIVT for the first time (p = 0.006), and had lower blood flow quantity (p = 0.005), lower brachial artery flow volume (p = 0.018), and higher resistance index (p = 0.011). The multivariate logistic regression revealed that receiving VAIVT for the first time (OR 5.95, 95%CI 1.01-34.84; p = 0.048) and high resistance index (OR 1.86, 95%CI 1.01-3.16; p = 0.02) were significantly associated with a high risk for rupture. Furthermore, receiver operating characteristic curve analysis to assess the sensitivity-specificity profiles of the resistance index for ruptures showed that the optimal threshold was 0.70 (sensitivity/specificity, 0.69/0.70). Heightened surveillance during vascular access intervention therapy is warranted, especially in patients undergoing VAIVT for the first time or patients with a high resistance index (> 0.70).

Fibroblast Growth Factor 23 Exacerbates Cardiac Fibrosis in Deoxycorticosterone Acetate-Salt Mice With Hypertension.

Fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease; however, the mechanisms underlying the effect of FGF23 on cardiac function remain to be investigated. Herein, we studied the effect of continuous intravenous (CIV) FGF23 loading in a deoxycorticosterone acetate (DOCA)-salt mouse model with mild chronic kidney disease and hypertension as well as heart failure with a preserved ejection fraction. Wild-type male mice were randomly allocated to 4 groups: normal control, vehicle-treated DOCA-salt mice, FGF23-treated DOCA-salt mice, and FGF23- and calcitriol-treated DOCA-salt mice. The DOCA-salt mice received the agents via the CIV route for 10 days using an infusion minipump. DOCA-salt mice that received FGF23 showed a marked increase in the serum FGF23 level, and echocardiography in these mice revealed heart failure with a preserved ejection fraction. These mice also showed exacerbation of myocardial fibrosis, concomitant with an inverse and significant correlation with Cyp27b1 expression. Calcitriol treatment attenuated FGF23-induced cardiac fibrosis and improved diastolic function via inhibition of transforming growth factor-ß signaling. This effect was independent of the systemic and local levels of FGF23. These results suggest that CIV FGF23 loading exacerbates cardiac fibrosis and that locally abnormal vitamin D metabolism is involved in this mechanism. Calcitriol attenuates this exacerbation by mediating transforming growth factor-ß signaling independently of the FGF23 levels.

Changes of biomarkers for erythropoiesis, iron metabolism, and FGF23 by supplementation with roxadustat in patients on hemodialysis.

This study aimed to confirm changes in biomarkers of erythropoiesis and iron metabolism and serum fibroblast growth factor 23 (FGF-23) during darbepoetin-α treatment and then switching to the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat. A total of 28 patients on hemodialysis who received weekly doses of darbepoetin-α were switched to roxadustat. Biomarkers for erythropoiesis and iron metabolism and intact and C-terminal FGF-23 were measured in blood samples collected before the HD session on days - 7 (darbepoetin-α injection), - 4, and - 2, and days 0 (switch to roxadustat treatment, three times weekly), 3, 5, 7, 14, 21, and 28. Erythropoietin and erythroferrone levels were elevated on day - 4 by darbepoetin-α injection and decreased to baseline levels at day 0. Levels of erythropoietin were not significantly increased by roxadustat supplementation, but erythroferrone levels were continuously elevated, similar to darbepoetin-α treatment. Hepcidin-25 and total iron binding capacity were significantly decreased or increased in patients treated with roxadustat compared with darbepoetin-α. Changes of intact and C-terminal FGF-23 levels were parallel to changes of phosphate levels during roxadustat treatment. However, the actual and percentage changes of intact FGF-23 and C-terminal FGF-23 in patients with low ferritin levels were greater than those in patients with high ferritin levels. Roxadustat might stimulate erythropoiesis by increasing iron usage through hepcidin-25, which was suppressed by erythroferrone in the physiological erythropoietin condition. Changes of intact FGF-23 and C-terminal FGF-23 levels might be affected by roxadustat in patients on hemodialysis, especially those with a low-iron condition.

Not baseline but time-dependent erythropoiesis-stimulating agent responsiveness predicts cardiovascular disease in hemodialysis patients receiving epoetin beta pegol: A multicenter prospective PARAMOUNT-HD Study.

BACKGROUND: Responsiveness to erythropoiesis-stimulating agents (ESAs) has been reported to be associated with increased cardiovascular disease (CVD) and mortality in patients undergoing hemodialysis (HD). However, the association between hyporesponsiveness to the long-acting ESA, epoetin beta pegol (CERA), and CVD remains unknown. METHODS: This multicenter prospective study included 4034 patients undergoing maintenance HD. After shifting from prior ESA to CERA, we studied the association between erythropoietin resistance index (ERI) at six months and outcomes, including cardiac events, major adverse cardiovascular events (MACE), and all-cause mortality, using Cox proportional hazards models (Landmark analyses) and marginal structural models to adjust for time-dependent confounding factors, including iron-containing medications and hemodiafiltration (HDF). RESULTS: The median dialysis vintage and the observational period were 5.0 years and 22.1 months, respectively. The landmark analyses revealed that the highest tertile of baseline ERI (T3) was associated with a significantly higher all-cause mortality than the lowest tertile (T1) (hazard ratio [HR]: 1.48, 95% CI: 1.03-2.13). Furthermore, marginal structural models revealed that time-dependent ERI T3 was significantly associated with increased cardiac events (HR: 1.59, 95% CI: 1.14-2.23), MACE (HR: 1.60, 95% CI: 1.19-2.15), all-cause mortality (HR: 1.97, 95% CI: 1.40-2.77), and heart failure (HF) (HR: 2.05, 95% CI: 1.23-3.40) compared to T1. A linear mixed effects model showed that iron-containing medications and HDF are negatively associated with time-dependent ERI. CONCLUSIONS: Baseline ERI at six months predicted only all-cause mortality; however, time-dependent ERI was a predictor of cardiac events, all-cause mortality, MACE, and HF. The widespread use of iron-containing medications and HDF would ameliorate ESA hyporesponsiveness.

One-Year Romosozumab Treatment Followed by One-Year Denosumab Treatment for Osteoporosis in Patients on Hemodialysis: An Observational Study.

There is limited evidence on the use of romosozumab (ROMO) in the treatment of osteoporosis in patients on hemodialysis (HD); thus, we aimed to investigate this topic. This prospective, observational, single-center cohort study included 13 prior osteoporosis treatment-naïve patients on HD with osteoporosis. They first received ROMO once monthly for 12 months (210 mg; subcutaneously once every month). Thereafter, they received denosumab (DENO) for an additional 12 months (60 mg; subcutaneously once every 6 months). We examined the incidence of new fractures; treatment safety; and temporal changes in the bone mineral density (BMD), bone metabolism markers, and vascular calcification. No new cases of fractures were noted. The median one-year percentage changes (from the baseline) in the BMDs at the lumbar spine (LS), total hip (TH), and femoral neck (FN) were + 9.0%, + 2.5%, and + 4.7%, respectively. These changes were maintained for 24 months. The corresponding relative changes from the baseline to 24 months thereafter were + 14.9%, + 5.4%, and + 6.5%, respectively. The percentage changes in TH BMD and FN BMD were negatively correlated with baseline BMD. Coronary artery and thoracic aorta calcification scores increased slightly from baseline to 12 months thereafter. However, fatal events (cardiovascular disease-associated and all-cause deaths) did not occur during ROMO treatment. Effectiveness of ROMO was better in patients who had severe osteoporosis with low TH BMD, low FN BMD, and high tartrate-resistant acid phosphatase 5b level at ROMO initiation.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography for patients with Roux-en-Y gastric bypass anatomy: technical overview.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastric bypass anatomy is a well-documented challenge. Traditionally, this problem has been overcome with adjunctive techniques, such as device-assisted ERCP, including double-balloon or single-balloon enteroscopy and laparoscopy-assisted transgastric ERCP. Endoscopic ultrasound-directed transgastric ERCP (EDGE) is a novel technique that enables access to the ampulla using a duodenoscope without surgical intervention and has shown high clinical and technical success rates in recent studies. However, this approach is technically demanding, necessitating a thorough understanding of the gastrointestinal anatomy as well as high operator experience. In this review, we provide a technical overview of EDGE in parallel with our personal experience at our center and propose a simple algorithm to select patients for its appropriate application. In conjunction, the outcomes of EDGE compared with those of device-assisted and laparoscopy-assisted transgastric ERCP will be discussed.

Serum Uromodulin Levels Reflect Severity of Clinicopathological Findings in Early Stage IgA Nephropathy.

INTRODUCTION: Uromodulin (UMOD), also known as Tamm-Horsfall protein, is a kidney-specific protein. Recently, low levels of urinary UMOD (uUMOD) have been reported as a risk factor for renal function decline in IgA nephropathy (IgAN). However, the clinical significance of serum UMOD (sUMOD) is not clear. In this study, we clarified the clinical significance of sUMOD in IgAN. METHODS: One hundred eight biopsy-proven IgAN patients were included in this study. The relationships between sUMOD levels and various clinicopathological findings were evaluated. RESULTS: sUMOD was positively correlated with estimated glomerular filtration rate (eGFR) (p < 0.001, r = 0.5) and negatively correlated with creatinine (Cr) (p < 0.0001, r = -0.51) and urinary protein (UP) (p = 0.005, r = -0.33). In the low sUMOD group (<145 ng/mL), Cr was significantly higher (p < 0.0001) and histopathological changes were severe. The cumulative incidence of a 30% decline in eGFR was 25.6% overall, 0% in histological grade (H-G) I, 33.3% in H-G II, 59.6% in H-G III, and 66.7% in H-G IV. In univariate analyses, prognostic factors for a 30% decline in eGFR were male, high UP, low albumin, low eGFR, and low sUMOD. When comparing the severe histopathological classes (H-G II-IV) and H-G I, low sUMOD was a risk factor for severe histopathological changes. Furthermore, in patients with eGFR > 60 (n = 74), multivariate analyses revealed that low sUMOD independently predicted a 30% decline in eGFR and having severe histopathological changes. CONCLUSION: In IgAN, sUMOD levels were associated with renal function. Low sUMOD levels may be a risk factor for worsening renal function, especially in the early stage of IgAN.

Romosozumab successfully regulated progressive osteoporosis in a patient with autosomal dominant polycystic kidney disease undergoing hemodialysis.

Osteoporosis is a crucial complication in patients with chronic kidney disease (CKD), similar to that in the general population. Although romosozumab, a monoclonal antibody targeting sclerostin, has been administered for patients with CKD, its clinical effectiveness in these patients, especially in patients on hemodialysis (HD), remains to be studied. Herein, we report the case of a 42-year-old man on HD who developed severe osteoporosis. Serum calcium levels were extremely high, bone metabolic markers were abnormal, and the patient had pathological fractures. The bone biopsy indicated a bone metabolism disorder and high bone turnover. We administered romosozumab once a month as an intervention for bone alteration. Through the 10-month usage, bone metabolic markers improved, and the decrease in bone mineral density was ameliorated. We hypothesized that romosozumab could be a therapeutic option for osteoporosis in patients undergoing HD, especially in those with bone mineralization disorders.

Posterior decentering of the humeral head in patients with arthroscopic rotator cuff repair.

BACKGROUND: In some patients with rotator cuff tear (RCT), the axial view of magnetic resonance imaging (MRI) shows subtle posterior decentering (PD) of the humeral head from the glenoid fossa. This is considered to result from a loss of centralization that is typically produced by rotator cuff function. There are few reports on PD in RCT despite the common occurrence of posterior subluxation in degenerative joint disease. In this study, we investigated the effect of PD in arthroscopic rotator cuff repair (ARCR). METHODS: We conducted a retrospective study of consecutive patients who underwent ARCR at our institute and were followed-up for at least 1 year. PD was identified as a 2-mm posterior shift of the humeral head relative to the glenoid fossa in the axial MRI view preoperatively. The tear size and fatty degeneration (FD, Goutallier classification) were also evaluated using preoperative MRI. Retears were evaluated through MRI at 1 year postoperatively. RESULTS: We included 135 shoulders in this study. Ten instances of PD (including seven retears) were observed preoperatively. Fifteen retears (three and 12 retears in the small/medium and large/massive tear groups, respectively) were observed postoperatively. PD was significantly correlated with tear size, FD, and retear occurrence (p<0.01 each). The odds ratio for PD in retears was 34.1, which was greater than that for tear size ≥3 cm and FD grade ≥3. CONCLUSIONS: We concluded that large tear size and FD contribute to the occurrence of PD. Furthermore, PD could be a predictor of retear after ARCR.

Total iron binding capacity is a predictor for muscle loss in maintenance hemodialysis patients.

BACKGROUND: Protein-energy wasting in hemodialysis (HD) patients is characterized by decreased skeletal muscle mass and plasma protein. Some previous studies reported relationships between skeletal muscle dysfunction and iron deficiency. Dialysis patients with malnutrition may have a functional iron deficiency (FID) because of inflammation. Serum total iron binding capacity (TIBC), correlated with transferrin, is a nutritional status marker in HD patients and a biomarker of iron status. The relationship between muscle loss and iron status is unknown. The aim of the present study was to assess the relationship between iron status and change in skeletal muscle mass. METHODS: A prospective cohort of 267 HD patients was examined for 12 months. Blood samples were obtained at baseline to measure TIBC, ferritin, transferrin saturation (TSAT), and hepcidin-25. Nutritional status and changes in muscle mass were assessed by subjective global assessment, albumin, creatinine index, and percentage creatinine generation rate. RESULTS: At baseline, lower tertiles of TIBC were significantly related to lower muscle mass and albumin levels; they were also significantly correlated with high ferritin, hepcidin-25, and TSAT levels, as well as a higher proportion of use of erythropoiesis-stimulating agents. Multiple regression analysis adjusted with confounders showed TIBC was an independent biomarker for decreased muscle mass and albumin. Change in muscle mass remained significantly decreased in the lower tertile of TIBC and in malnourished patients. CONCLUSIONS: The present study demonstrated relationships between FID and muscle loss. TIBC was an independent biomarker of muscle loss in HD patients, considering iron status, inflammation, oxidative stress, and malnutrition.

Bilateral renal subcapsular hematoma caused by polyarteritis nodosa: a case report.

Polyarteritis nodosa, which is a systemic vasculitis of small- and medium-sized arteries, can cause arterial aneurysms in various organs, sometimes resulting in aneurysm rupture and hemorrhage. A kidney is one of the major targets of polyarteritis nodosa. Here, we report a 73-year-old woman who presented with sudden-onset high fever, diarrhea, and renal injury with bilateral renal subcapsular hematoma shown on contrast-enhanced computed tomography scan. She did not have trauma and significant medical history other than breast cancer in remission. Serological and immunological tests except for anti-Sjögren's syndrome-A and anti-Sjögren's syndrome-B were all negative. Digital subtraction angiography revealed bilateral intrarenal micro aneurysms, which allowed us to diagnose the patient with polyarteritis nodosa. As continuous monitoring of bilateral intrarenal hematoma by ultrasonography and computed tomography scan did not detect progression of intrarenal hemorrhage and extra renal hematoma, transcatheter arterial embolization and nephrectomy were not performed. Although hemodialysis therapy was required temporarily for acute kidney injury with anuria, her general condition and kidney function remarkably improved after receiving systemic immunosuppressive therapy with corticosteroids and cyclophosphamide. In conclusion, this is a rare case of polyarteritis nodosa manifesting as spontaneous bilateral subcapsular renal hemorrhage with deteriorated renal function, which was successfully treated with immunosuppressive therapy.