High urinary glucose is associated with improved renal prognosis in patients with diabetes mellitus.

AIMS/INTRODUCTION: The relationship between renal function and urinary glucose is poorly understood in diabetes patients who are not using sodium-glucose cotransporter 2 inhibitors. This study aimed to investigate the association of urinary glucose excretion with renal function prognosis in such patients. MATERIALS AND METHODS: This retrospective cohort study included 1,172 patients with type 1 or 2 diabetes mellitus. Patients were recruited and data were collected between 1 January 2007 and 31 December 2011; follow-up data were collected until 30 June 2015. The primary outcome was set as a 30% decline in estimated glomerular filtration rate relative to baseline. The relationship between this outcome and urinary glucose was investigated using Cox proportional hazards model. For analysis, patients were categorized into two groups: urinary glucose <5 g/day or ≥5 g/day. Interaction terms were analyzed. RESULTS: Multivariate analysis showed that the prognosis of renal function was significantly better in patients with high urinary glucose (≥5 g/day; adjusted hazard ratio 0.58, 95% confidence interval 0.35-0.96; P = 0.034). Significant interactions were observed between high urinary glucose and male sex (hazard ratio 0.33, 95% confidence interval 0.14-0.74; P = 0.007), and between high urinary glucose and longer duration of diabetes (≥10 years; hazard ratio 0.25, 95% confidence interval 0.11-0.58; P = 0.001). CONCLUSIONS: The present study suggests that high urinary glucose is associated with prognosis in diabetes patients not taking sodium-glucose cotransporter 2 inhibitors. Measurement of 24-h urinary glucose excretion might have clinical utility for predicting renal prognosis.

Removal of Aß Oligomers from the Blood: A Potential Therapeutic System for Alzheimer's Disease.

PURPOSE: Amyloid-ß protein (Aß) is one of the causative proteins of Alzheimer's disease. We have been developing extracorporeal blood Aß-removal systems as a method for enhancing Aß clearance from the brain. We reported previously that medical adsorbents and hemodialyzers removed Aß monomers from peripheral blood, which was associated with influx of Aß monomers from the brain into the bloodstream. Our intent here was to develop a method to promote clearance of Aß oligomers and to provide an estimate of the molecular size of intact Aß oligomers in plasma. METHODS: Two hollow-fiber devices with different pore sizes (Membranes A and B) were evaluated as removers of Aß oligomers with human plasma in vitro. The concomitant removal of Aß oligomers and monomers was investigated by using Membrane B and hexadecyl alkylated cellulose beads or polysulfone hemodialyzers. Double-filtration plasmapheresis with Membrane A was investigated as an approach for the removal of plasma Aß oligomers in humans. RESULTS: Aß oligomers were effectively removed by both Membranes A and B. The increase of Aß oligomers in plasma was observed just after the removal of plasma Aß oligomers in humans. The intact molecular size of major Aß oligomers in the plasma was estimated to be larger than albumin at approximately 60 kDa or more. Additionally, the concomitant removal of Aß monomers and oligomers evoked dissociation of larger Aß oligomers into smaller ones and monomers. CONCLUSION: Aß oligomers were cleared from plasma both in vitro and in human subjects by using hollow-fiber membranes with large pores, indicating that their intact sizes were mostly larger than 60 kDa. Aß oligomers in peripheral circulation were increased after some clearances in human. Further investigation will determine whether the Aß oligomers detected in circulation after clearance were via influx from the brain.

Dipeptidyl peptidase-4 inhibitors-associated bullous pemphigoid: A retrospective study of 168 pemphigoid and 9,304 diabetes mellitus patients.

AIMS/INTRODUCTION: Bullous pemphigoid (BP) might be drug-induced. The present study evaluated the relationship between BP and dipeptidyl peptidase-4 inhibitors (DPP4Is). MATERIALS AND METHODS: We recruited patients diagnosed with BP at Ogaki Municipal Hospital from 1 December 2009 through 31 December 2017. We retrospectively collected data from medical records and divided patients into two groups based on whether they received DPP4Is. Additionally, we determined the incidence of BP in patients who were first prescribed DPP4Is at our hospital during the study period. RESULTS: Of 168 patients diagnosed with BP, 133 (79.1%) were positive for anti-BP180NC16a antibody. A total of 32 (19.0%) patients had been prescribed a DPP4I, 21 of whom (65.6%) were positive for anti-BP180NC16a antibody; this rate was lower than that in patients not receiving a DPP4I (82.3%; P = 0.0360). A total of 16 patients with type 2 diabetes mellitus had not been prescribed a DPP4I; only one (6.3%) was positive for anti-BP180NC16a antibody (P = 0.0339). During the study period, 9,304 patients were prescribed DPP4Is, eight of whom developed BP; six (75.0%) had non-inflammatory BP, and five of the six (83.3%) were negative for anti-BP180NC16a antibody. CONCLUSIONS: The positive rate of anti-BP180NC16a antibody was lower in BP patients with DPP4I than without DPP4I, regardless of type 2 diabetes mellitus. The antibody titer was low in both the overall and type 2 diabetes mellitus populations. The prevalence of BP in 9,304 patients receiving DPP4Is was 0.0859%, which is higher than that in the general population. As DPP4Is are common diabetes treatments, we must be aware of the risk of BP.

Renoprotective effects of topiroxostat for Hyperuricaemic patients with overt diabetic nephropathy study (ETUDE study): A prospective, randomized, multicentre clinical trial.

AIM: We aimed to evaluate the anti-albuminuric effects of topiroxostat in Japanese hyperuricaemic patients with diabetic nephropathy. METHODS: In this 24-week, multicentre, open-label, randomized (1 : 1) trial, we assigned hyperuricaemic patients with diabetic nephropathy (estimated glomerular filtration rate ≥ 20 mL/min per 1.73m2 ) and overt proteinuria (0.3 ≤ urine protein to creatinine ratio (UPCR) <3.5 g/g Cr) to either high dose (160 mg daily) or low dose (40 mg daily) topiroxostat. The primary endpoint was the change in albuminuria indicated by urine albumin-to-creatinine ratio (UACR) from the baseline at the final time point. RESULTS: A total of 80 patients underwent randomization. The changes in UACR after 24 weeks of treatment (or at the final time point if patients failed to reach 24 weeks) relative to the baseline were -122 mg/gCr (95% CI: -5.1 to -240.1, P = 0.041) in patients treated with high dose, while treatment with low dose topiroxostat could not show significant reduction (P = 0.067). In the linear mixed model including baseline albuminuria, eGFR, age, and sex as covariates, the decreases in UACR were still significant from baseline to 12 weeks by 228.7 ± 83.2 mg/gCr (P = 0.0075) in the high dose group. The adverse-event profile during this study was not different between the groups. CONCLUSION: Topiroxostat 160 mg daily reduced albuminuria in patients with diabetic nephropathy. (Funded by Sanwa Kagaku Kenkyusho; Trial registration, UMIN000015403).

Adsorptive filtration systems for effective removal of blood amyloid ß: a potential therapy for Alzheimer's disease.

Accumulation of amyloid-ß protein (Aß) in the brain causes cognitive impairment in Alzheimer's disease. We hypothesized that an extracorporeal system that rapidly removed Aß from the blood may accelerate Aß drainage from the brain. We previously reported that dialyzers remove blood Aßs effectively, mainly by adsorption on the inner surfaces of the hollow fibers, resulting in lower Aß accumulation in the brains of patients undergoing hemodialysis than the controls without hemodialysis. The aim of the present study was to create a more convenient and effective blood Aß removal system using adsorptive filtration, in which the filtrate returned to the body. Filtration from inside to outside of the fibers may enhance the adsorption of plasma Aßs on the surface of micropores inside the hollow fiber walls. Hence, pool solutions of 4 ng/mL synthetic Aß1-40 and Aß1-42 peptides (300 mL) or human plasma (1000 mL of 250-346 pg/mL Aß1-40 and 30-48 pg/mL Aß1-42) were circulated through polysulfone dialyzers at a flow rate of 50 mL/min to evaluate an adsorptive filtration system. The rates of Aß reduction from the pool solutions significantly increased along with the filtration rates. A filtration rate of > 1 mL/min, preferably 5-10 mL/min resulted in an 80-100% reduction of Aßs within 30 min of circulation. The rates of Aßs passing through the membrane walls were maintained around 0% for plasma Aßs during circulation. Thus, our adsorptive filtration systems may be useful for removing blood Aßs for patients with Alzheimer's disease.

Association between 24h Urinary Sodium and Potassium Excretion and Estimated Glomerular Filtration Rate (eGFR) Decline or Death in Patients with Diabetes Mellitus and eGFR More than 30 ml/min/1.73m2.

BACKGROUND: Data regarding the association between 24h urinary sodium and potassium excretion with kidney outcomes in patients with diabetes mellitus is currently scarce. METHODS: We conducted a single-center, retrospective cohort study in which 1230 patients with diabetes who had undergone a 24h urinary sodium and potassium excretion test were analyzed. Patients with incomplete urine collection were excluded based on 24h urinary creatinine excretion. Outcomes were the composite of a 30% decline in eGFR or death. Multivariate cox regression analysis was used to investigate the association between urinary sodium and potassium excretion and outcomes. RESULTS: With a mean follow up period of 5.47 years, 130 patients reached the outcomes (30% decline in eGFR: 124, death: 6). Mean (SD) eGFR and 24h urinary sodium and potassium excretion at baseline were 78.6 (19.5) ml/min/1.73m2, 4.50 (1.64) g/day, and 2.14 (0.77) g/day. Compared with sodium excretion < 3.0 g/day, no significant change in risk of outcomes was observed with increased increments of 1.0 g/day. Compared with potassium excretion of < 1.5 g/day, 2.0-2.5 g/day, and 2.5-3.0 g/day were significantly associated with a lower risk of outcomes (hazard ratio [HR], 0.49 and 0.44; 95% confidence interval [CI], 0.28 to 0.84 and 0.22 to 0.87). CONCLUSIONS: 24h urinary sodium excretion was not significantly associated with a risk of 30% decline in eGFR or death in patients with diabetes. However, an increased risk of 30% decline in eGFR or death was significantly associated with 24h urinary potassium excretion < 1.5 g/day than with 2.0-2.5 g/day and 2.5-3.0 g/day.

Recent analysis of status and outcomes of peritoneal dialysis in the Tokai area of Japan: the second report of the Tokai peritoneal dialysis registry.

BACKGROUND: Early withdrawal within 3 years after starting peritoneal dialysis (PD) and PD-related peritonitis have been major obstacles preventing increases in the population of PD patients. To address these problems, we implemented education programs for medical staff. This study analyzed the recent status and outcomes of PD therapy, focusing on findings such as the incidence and prognosis of peritonitis as of 5 years after our last study. METHODS: We investigated background, laboratory data and status of PD therapy, reasons for withdrawal from PD and incidental statements on peritonitis from 2010 to 2012 (R2), and compared findings with those from our last study of 2005-2007 (R1). RESULTS: Early PD therapy withdrawal in R2 clearly improved to 44.7 %, compared with 50.9 % in R1. Peritonitis incidence improved slightly from once per 42.8 months/patient in R1 to once per 47.3 months/patient in R2. Notably, PD-related peritonitis as a cause of mortality improved markedly in R2, but outcomes of PD-related peritonitis did not change significantly between R1 and R2. In contrast, social problems increased as a reason for withdrawal from PD therapy. CONCLUSION: Our efforts at education might have been useful for improving early withdrawal from PD and deaths attributable to PD-related peritonitis. However, since improvements to incidence of PD-related peritonitis were limited by education, further improvement in PD-related peritonitis incidence requires development of new sterilized connecting systems during PD-bag exchanges to decrease PD-related peritonitis opportunities. Construction of medical support systems to address social problems is required to maintain long-term PD therapy.

Fulminant type 1 diabetes mellitus associated with a reactivation of Epstein-Barr virus that developed in the course of chemotherapy of multiple myeloma.

A 70-year-old woman who was diagnosed with multiple myeloma underwent chemotherapy. Three months after beginning chemotherapy, she was readmitted to the hospital because of fever and hepatopathy. Her elevated Epstein-Barr virus (EBV) antibody levels showed that the hepatopathy was caused by reactivation of EBV. On the 18th hospital day, the levels of fasting plasma glucose (FPG; 451 mg/dL) and pancreatic enzymes were suddenly elevated. Elevation of HbA1c level (6.4%) was slight, as compared with that of the FPG level. Arterial blood gas analysis showed metabolic acidosis and diabetic ketoacidosis was suspected. The serum C-peptide level was below the detectable limit both before and after glucagon load, thereby suggesting an insulin-dependent state. These features were identical to the features for fulminant type 1 diabetes mellitus. The levels of EBV anti-viral capsid antigen immunoglobulin M decreased, and the clinical course was identical to that associated with reactivation of EBV infection. (J Diabetes Invest, doi: 10.1111/j.2040.1124.2010.00061.x, 2010).