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Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.

INTRODUCTION: Von Willebrand disease (VWD) is the second most common inherited coagulation disorder, and appropriate perioperative management is necessary when considering major surgery. There are few reports of patients with VWD who have undergone hepatectomy, especially minimally invasive hepatectomy. To our knowledge, this is the first reported case of a patient with VWD who successfully underwent robotic hepatectomy with von Willebrand factor (VWF) and factor VIII (FVIII) supplementation.CASE PRESENTATION: A 75-year-old female was referred to our hospital because of a liver tumor that was diagnosed during follow-up after hepatitis C treatment. She had also been diagnosed with VWD in her 30s. CT and MRI showed a 24-mm mass in segment 8 of the liver, bordered by the middle hepatic vein (MHV). To ensure safe perioperative management, replacement therapy with a VWF- or FVIII-containing concentrate was administered from preoperative day 1 to POD 14. Robotic extended segmentectomy (segment 8) was performed, with resection of the MHV. Liver parenchyma was dissected using the crush and clamp technique under the Pringle maneuver. Estimated intraoperative blood loss was 160 mL, and total operative time was 601 min. The patient needed 2 units of fresh frozen plasma on POD 1; however, no other transfusions, including red blood cells, were required. Although the patient presented with postoperative ascites and was treated with diuretics, she was discharged on POD 20 without any bleeding event. The final pathological finding was intrahepatic cholangiocarcinoma.CONCLUSIONS: We encountered a patient with intrahepatic cholangiocarcinoma and VWD who was successfully treated with anatomical hepatectomy by robotic-assisted laparoscopic surgery under perioperative replacement therapy with a VWF- or FVIII-containing concentrate. With appropriate perioperative management, major hepatectomy can be applied for VWD patients despite their high risk of postoperative hemorrhagic complications.

Evaluating the formation of clusters in finite and infinite nuclear systems is a fundamental problem in nuclear physics, and the variation in clustering in the isotope chain up to the neutron drip-line is one such intriguing phenomenon. Recently, experiments performed using the (p, pα) reactions have revealed a negative correlation between α-cluster formation and neutron number in Sn isotopes, showing a trend opposite to that theoretically predicted for Be and B isotopes. Although the observed charge radii of the Be and B isotopes suggest the formation of clusters as the neutron drip-line is approached, these radii themselves are not a physical quantity that can directly probe the cluster structure. Here, we directly investigate the cluster formation in Be and B isotopes to elucidate the possibility of clustering as the neutron drip-line is approached. It has been shown that the sum of the S-factors (i.e., S(α), S(6He), and S(8He)) increases as the neutron drip-line approaches, in agreement with those of previous studies. The results indicate that the excess neutrons contribute to the formation of 6He and 8He clusters as well as α clusters. Thus, S(α) is not sufficient to estimate the enhancement of clustering in Be and B isotopes.

Aims/Introduction We evaluated the efficacy of multifactorial intensive treatment (IT) on renal outcomes in patients with type 2 diabetes and advanced‐stage diabetic kidney disease (DKD). Materials and Methods The Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan) is a multicenter, open‐label, randomized controlled trial with a 5‐year follow‐up period. We randomly assigned 164 patients with advanced‐stage diabetic kidney disease (urinary albumin‐to‐creatinine ratio ≥300 mg/g creatinine, serum creatinine level 1.2–2.5 mg/dL in men and 1.0–2.5 mg/dL in women) to receive either IT or conventional treatment. The primary composite outcome was end‐stage kidney failure, doubling of serum creatinine or death from any cause, which was assessed in the intention‐to‐treat population. Results The IT tended to reduce the risk of primary end‐points as compared with conventional treatment, but the difference between treatment groups did not reach the statistically significant level (hazard ratio 0.69, 95% confidence interval 0.43–1.11; P = 0.13). Meanwhile, the decrease in serum low‐density lipoprotein cholesterol level and the use of statin were significantly associated with the decrease in primary outcome (hazard ratio 1.14; 95% confidence interval 1.05–1.23, P < 0.001 and hazard ratio 0.53, 95% confidence interval 0.28–0.998, P < 0.05, respectively). The incidence of adverse events was not different between treatment groups. Conclusions The risk of kidney events tended to decrease by IT, although it was not statistically significant. Lipid control using statin was associated with a lower risk of adverse kidney events. Further follow‐up study might show the effect of IT in patients with advanced diabetic kidney disease. The Diabetic Nephropathy Remission and Regression Team Trial in Japan was designed to clarify the beneficial effects of multifactorial intensified intervention by the team approach with medical staffs at each institution. There was an overall trend toward a lower risk on the development of kidney events in the intensive treatment group than in the conventional treatment group in this trial, but the benefit of intensive treatment could not be confirmed statistically. Lipid control by statin was associated with lower risk of kidney events in addition to strict control of blood glucose and blood pressure.

The Joint Committee on Diabetic Nephropathy has revised its Classification of Diabetic Nephropathy (Classification of Diabetic Nephropathy 2014) in line with the widespread use of key concepts, such as the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). In revising the Classification, the Committee carefully evaluated, as relevant to current revision, the report of a study conducted by the Research Group of Diabetic Nephropathy, Ministry of Health, Labor and Welfare of Japan. Major revisions to the Classification are summarized as follows: (i) eGFR is substituted for GFR in the Classification; (ii) the subdivisions A and B in stage 3 (overt nephropathy) have been reintegrated; (iii) stage 4 (kidney failure) has been redefined as a GFR <30 mL/min/1.73 m2, regardless of the extent of albuminuria; and (iv) stress has been placed on the differential diagnosis of diabetic nephropathy versus non‐diabetic kidney disease as being crucial in all stages of diabetic nephropathy.

According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed. In the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline. Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease.

Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD). The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin. We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/Cr and higher C-megalin/Cr groups were − 0.904 and −0.749 ml/min/1.73 m2/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was −1.888 ml/min/1.73 m2/year steeper in the group with both higher A- and higher C-megalin/Cr than in the other group. These results remained significant when adjusted for known urinary biomarkers (albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-d-glucosaminidase). Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers. •Megalin, a proximal tubular endocytic receptor, is excreted in urine in two forms.•The forms are A-megalin, an ectodomain form, and C-megalin, a full-length form.•Each form was found to be a marker of rapid progression of diabetic kidney disease.•The combination of both markers predicts more rapid progression of the disease.•These results are independent of other known urinary markers.

Background The number of patients suffering from diabetic nephropathy resulting in end-stage kidney disease is increasing worldwide. In clinical settings, there are limited data regarding the impact of the urinary albumin-to-creatinine ratio (UACR) and reduced estimated glomerular filtration rate (eGFR) on renal and cardiovascular outcomes and all-cause mortality. Methods We performed a historical cohort study of 4328 Japanese participants with type 2 diabetes from 10 centers. Risks for renal events (requirement for dialysis or transplantation, or half reduction in eGFR), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), and all-cause mortality were assessed according to UACR and eGFR levels. Results During follow-up (median 7.0 years, interquartile range 3.0–8.0 years), 419 renal events, 605 cardiovascular events and 236 deaths occurred. The UACR levels increased the risk and the adjusted hazard ratios for these three events. In addition to the effects of UACR levels, eGFR stages significantly increased the adjusted hazard ratios for renal events and all-cause mortality, especially in patients with macroalbuminuria. Diabetic nephropathy score, based on the prognostic factors, well predicted incidence rates per 1000 patient/year for each event. Conclusions Increased UACR levels were closely related to the increase in risks for renal, cardiovascular events and all-cause mortality in Japanese patients with type 2 diabetes, whereas the association between high levels of UACR and reduced eGFR was a strong predictor for renal events.

This multicenter cohort study retrospectively assessed the association between polar vasculosis and the progression of diabetic kidney disease (DKD) in type 2 diabetes. We enrolled 811 patients with type 2 diabetes, biopsy-proven DKD, and proteinuria (≥0.15 g/g creatinine [g/day]). The association between polar vasculosis and other kidney lesions was explored. The outcome was DKD progression defined as a composite of renal replacement therapy initiation or 50% decline in estimated glomerular filtration rate (eGFR) from baseline. Of the 811 cases, 677 (83.5%) had polar vasculosis. In multivariate logistic regression analysis, subendothelial widening of the glomerular basement membrane, glomerulomegaly, glomerular class in the Renal Pathology Society classification ≥IIb, vascular lesions, age, eGFR, and hemoglobin A1c were positively associated with polar vasculosis, whereas interstitial fibrosis and tubular atrophy (IFTA) was negatively associated with polar vasculosis. During a median follow-up of 5.2 years, progression of DKD occurred in 322 of 677 (7.4 events/100 person-years) and 79 of 134 (11.4 events/100 person-years) cases with and without polar vasculosis, respectively. Kaplan-Meier analysis showed that polar vasculosis was associated with lower cumulative incidences of DKD progression. Multivariate Cox regression analyses showed that polar vasculosis was associated with a lower risk of DKD progression, regardless of eGFR or proteinuria subgroups. These associations between polar vasculosis and better kidney outcome were unchanged considering all-cause mortality before DKD progression as a competing event. This study showed that polar vasculosis of DKD was associated with less advanced IFTA and a better kidney outcome in type 2 diabetes with proteinuria.

Background Dietary acid load has been suggested to mediate the progression of chronic kidney disease (CKD). However, it is unclear what kinds of foods are actually associated with dietary acid load in patients with CKD. The self-administered diet history questionnaire (DHQ), which semi-quantitatively assesses the dietary habits of Japanese individuals through 150 question items, can estimate average daily intake of various foods and nutrients during the previous month. Using the DHQ, we investigated the association of dietary acid load with CKD progression. We also analyzed the kinds of food that significantly affect dietary acid load. Methods Subjects were 96 outpatients with CKD (average estimated glomerular filtration rate [eGFR], 53.0 ± 18.1 ml/min/1.73 m 2 ) at Niigata University Hospital, who had completed the DHQ in 2011. We calculated net endogenous acid production (NEAP) from potassium and protein intake evaluated by the DHQ in order to assess dietary acid load. CKD progression was assessed by comparing eGFR between 2008 and 2014. Results NEAP was not correlated with protein intake ( r  = 0.088, p  = 0.398), but was negatively correlated with potassium intake ( r  = − 0.748, p  < 0.001). Reduction in eGFR from 2008 to 2014 was estimated to be significantly greater in patients with higher NEAP (NEAP > 50.1 mEq/day, n  = 45) than in those with lower NEAP (NEAP ≤50.1 mEq/day, n  = 50) by 5.9 (95% confidence interval [95%CI], 0.1 to 11.6) ml/min/1.73 m 2 . According to multiple logistic regression analysis, higher NEAP was significantly associated with lower intake of fruits (odds ratio [OR], 6.454; 95%CI, 2.19 to 19.00), green and yellow vegetables (OR, 5.18; 95%CI, 1.83 to14.66), and other vegetables (OR, 3.87; 95%CI, 1.29 to 11.62). Conclusions Elevated NEAP could be a risk factor for CKD progression. Low intake of fruits and vegetables would increase dietary acid load and might affect the progression of renal dysfunction in Japanese CKD patients.