Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients.

Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction.

Uphill Accumulation of Ionic Species into a Lipid Vesicle by the Concentration Gradient of Counter Ions.

The "uphill (against the concentration gradient)" accumulation of a hydrophobic cation (rhodamine 6G, R6G+) into the inner phase of a giant unilamellar vesicle (GUV) was realized with the concentration gradient of the counter anion (X- = ClO4-, BF4-, or Br-) in the presence of phosphate buffer (P-, pH = 7) in the inner and outer phase of the GUV and detected as the increase of the R6G+ fluorescence intensity in the inner phase using a confocal laser scanning fluorescence microscope. The addition of X- in the outer phase of the GUV caused the accumulation of R6G+ in the inner phase. The degree and kinetics of the accumulation were dependent on the concentration and type of X-; e.g., the inner concentration of R6G+ reached 2.5 times that in the outer phase of GUV after adding 10 mM ClO4-. The accumulation was theoretically simulated by assuming the distribution of ion pairs (R6G+ and X-, R6G+, and P-) between the aqueous phase and the lipid bilayer membrane (ion pair distribution model) and the transmembrane fluxes of R6G+, X- and P-. The theoretical simulation rationalized the accumulation degree and kinetics of the experimental results. The accumulation of the target cation by the concentration gradient of the counter anion demonstrated in this study can be an effective method for the preparation of liposomal drugs.

Distribution of ion pairs into a bilayer lipid membrane and its effect on the ionic permeability.

This work reports the distribution constant of a target ion and a counter-ion between an aqueous phase and an artificial bilayer lipid membrane (BLM) and its influence to the ionic permeability through a BLM. A theoretical formula for ionic permeability through a BLM based on the distribution of the target ion and the counter-ion is also proposed and validated by analyzing the flux of a fluorescent cation [rhodamine 6G (R6G+)] through the BLM in the presence of counter-ions (X- = Br-, BF4-, and ClO4-). The transmembrane flux was evaluated by simultaneous measurement of the transmembrane current density and the transmembrane fluorescence intensity as a function of the membrane potential. The distribution constant of R6G+ and X- between the aqueous and BLM phases was determined by a liposome-extraction method. The measured ionic permeability exhibited non-linear dependent on the aqueous concentration of R6G+ or X-, but proportional to the concentration of R6G+ and X- inside the BLM evaluated from the distribution constant of R6G+ and X-. The proportionality demonstrates that the distribution of cations and anions between the aqueous and BLM phases dominates the flux of ion transport through the BLM. The proposed formula can express the dependence of the transmembrane current on the membrane potential and the concentrations of R6G+ and X- in the aqueous phase.

Assessment of the accuracy of an intermittent-scanning continuous glucose monitoring device in patients with type 2 diabetes mellitus undergoing hemodialysis (AIDT2H) study.

FreeStyle Libre has been approved for use in patients undergoing hemodialysis (HD) in Japan, unlike Europe and the United States; however, evidence regarding its accuracy in such patients is sparse. Forty-one participants with type 2 diabetes undergoing HD were recruited. The overall mean absolute relative difference and mean absolute difference were 23.4% and 33.9 mg/dL, respectively. Sensor glucose levels and capillary glucose levels were significantly correlated (r = 0.858, P < .01), although the sensor glucose levels were significantly lower than the capillary glucose levels. The accuracy of FreeStyle Libre in patients undergoing HD became deteriorated with the days of usage. The percentage of sensor results in Zones A and B in the consensus error grid analysis and in the Clarke error grid analysis were 99.7% and 99.0%, respectively. Its insufficient accuracy necessitates adjunct usage of FreeStyle Libre with self-monitoring of blood glucose in patients undergoing HD.

A Survey on the Current Status of Ophthalmological Consultations in Patients With Diabetes Undergoing Maintenance Hemodialysis and the Effectiveness of Education on Consultation Behavior -Experience of a Single Hemodialysis Clinic in Japan.

Introduction: It is extremely important for patients with diabetes undergoing maintenance hemodialysis (MHD) to receive regular ophthalmologic examinations. However, even in the field of MHD in Japan, where there are many hemodialysis patients and the survival rate is said to be one of the highest in the world, we often see patients with diabetes who do not receive regular ophthalmologic examinations. In this study, we surveyed the status of ophthalmology consultations and the use of diabetic eye notebook (DEN) among hemodialysis patients with diabetes at hemodialysis clinics to confirm the current situation, with the aim of confirming the effectiveness of education on consultation behavior by medical care staff. Materials and Methods: This study included 38 diabetic hemodialysis patients attending one MHD clinic in Japan for one year from March 2018 to March 2019. In the first fact-finding survey in March 2018, hemodialysis care unit nurses (HCUNs) in the hemodialysis unit asked the diabetic hemodialysis patients whether they had consulted an ophthalmologist and used the DEN. Based on the results, the HCUNs recommended that hemodialysis patients with complications of diabetes be educated about the usefulness of regular ophthalmologic examinations, even during MHD, and that they use the DEN. This was followed by a second fact-finding survey in March 2019 to reconfirm ophthalmology consultations and DEN use. Results: Regarding the presence of ophthalmology consultations, 22 of 38 (58%) patients had regular ophthalmology consultations in March 2018, and 27 of 38 (71%) patients had consultations in the following year after receiving information from an HCUN. Only 1 of 22 patients (5%) who consulted the ophthalmologist in March 2018 used a DEN, but 19 of 27 patients (70%) used it the following year. Conclusion: In the future, the development and utilization of a new DEN that includes more detailed patient information, and the spread of self-care guidance to patients by multidisciplinary health care professionals, will increase the consultation rate of MHD patients in Japan and reduce the incidence and progression of ocular diseases in MHD patients.

Favorable Effect on Blood Volume Control in Hemodialysis Patients with Type 2 Diabetes after Switching from Insulin Therapy to Liraglutide, a Human Glucagon-like Peptide-1 Analog--Results from a Pilot Study in Japan-.

OBJECTIVE: Hemodialysis patients are advised to limit the intake of foods in order to control volume status and body weight (BW). We report the clinical course of five Japanese hemodialysis patients with type 2 diabetes mellitus (T2DM) who were switched from insulin to liraglutide, and the efficacy of the treatment, especially in terms of changes in interdialysis weight gain (IDWG). METHODS: This retrospective pilot study included 5 Japanese hemodialysis patients with T2DM. Insulin and other oral hypoglycemic agents, if any, were discontinued before switching to liraglutide. The initial dose of liraglutide was set at 0.3 mg/day for more than 1 week, increased to 0.6 mg/day for more than 1 week and then, to 0.9 mg/day if needed. RESULTS: At baseline, the mean body mass index (BMI) was 23.2 ± 1.2 kg/m2 and mean IDWG was 2.0 ± 0.4 kg. The required dose of liraglutide ranged from 0.3 to 0.9 mg/day. At the end of 3-month treatment, liraglutide reduced HbA1c level, BMI, and IDWG. A significant decrease in cardiothoracic ratio was confirmed on chest radiography. CONCLUSION: Switching from insulin to liraglutide seems effective in hemodialysis patients with T2DM, especially in those with difficult blood fluid volume control associated with failure of dietary restriction.