Language：English   Publishing type：Research paper (scientific journal)  

AIMS: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.

DOI： 10.1016/j.jdiacomp.2022.108312

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC  

Background Standard amino acid solutions have recently been removed from the contraindications for use in dialysis patients in Japan. However, the details of their safety and efficacy in these patients are still not known. In this study, we investigated the safety and efficacy of intradialytic parenteral nutrition (IDPN) using ENEFLUID (R) injection containing standard amino acids, glucose, electrolytes, fats, and water-soluble vitamins in maintenance hemodialysis patients with malnutrition. Methods This clinical trial was designed as a multicenter, prospective, non-randomized, open-label, single-arm, observational pilot study. The participants were patients on maintenance hemodialysis who were in the nutritional high-risk group according to the Nutritional Risk Index for Japanese Hemodialysis Patients. One bag of ENEFLUID (R) injection was administered during every hemodialysis session for 12 weeks. The primary endpoint was change in serum transthyretin levels between before and after the 12-week period. As safety endpoints, we evaluated changes in body fluid volume and blood biochemical tests, including blood urea nitrogen and electrolytes, as well as blood glucose variability using flash glucose monitoring (FGM). Results The mean age and body mass index of the 13 participants were 79.0 +/- 10.7 years and 18.0 +/- 1.7 kg/m(2), respectively. No significant changes were observed in nutritional parameters, including serum transthyretin, between before and after the start of the study. After IDPN initiation, there was no obvious fluid overload or significant changes in blood biochemical tests, including electrolytes, and the treatment could be safely continued for 12 weeks. In the FGM analysis, asymptomatic hypoglycemia during hemodialysis was observed at the beginning of the study, but there was a trend toward improvement after 12 weeks (area over the curve < 70 mg/dl per dialysis session: 747.5 +/- 1333.9 to 21.6 +/- 54.3, P = 0.09). Conclusions IDPN using ENEFLUID (R) injection can be safely continued, although it does not significantly improve markers of nutritional status. It also showed the potential to ameliorate asymptomatic hypoglycemia during hemodialysis sessions. More detailed studies of the improvement in nutritional indicators are needed. Trial registration: This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on May 9, 2021 (registration ID, UMIN000044051).

DOI： 10.1186/s41100-022-00432-5

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC  

Background Dulaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM). However, the efficacy and safety of dulaglutide remain unclear in insulin-treated patients with T2DM on maintenance hemodialysis (HD). Methods Dulaglutide treatment was initiated, and the insulin dose was adjusted according to the needs of individual participants. Primary outcomes were changes in the mean and standard deviation (SD) of blood glucose (BG) levels and mean amplitude of glycemic excursions (MAGE) evaluated by continuous glucose monitoring (CGM) for six days, glycated albumin (GA), glycated hemoglobin (HbA1c), pre-dialysis blood glucose levels, and daily total insulin dose from the baseline over 24 weeks. Secondary outcomes were changes in treatment satisfaction and QOL levels from the baseline, measured by using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Diabetes Therapy-Related Quality of Life questionnaire (DTR-QOL) scores. Results The analysis was performed on the 12 participants who completed the study. The GA level (median - 1.8 [interquartile range - 6.6, - 0.3] %; p = 0.026) and daily total insulin dose (- 15.0 [- 24.5, - 9.4] U/day; p = 0.002) significantly decreased without increasing hypoglycemia (area over the glucose curve < 70 mg/dL: 0.0 [- 0.2, 0.0] mg center dot 24 h/dl; p = 0.917). Four patients successfully withdrew from insulin therapy. The levels of HbA1c, SD of BG, and MAGE showed a decreasing tendency, but no significant improvement. Regarding treatment satisfaction and QOL, the total scores of DTSQ (8.0 [0.3, 12.5]; p = 0.041) and DTR-QOL (15.5 [- 1.8, 42.0]; p = 0.023) significantly improved. Conclusion Dulaglutide may help improve glycemic control, treatment satisfaction, and QOL without increasing hypoglycemia in insulin-treated patients with T2DM on maintenance HD. Trial registration This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on October 11, 2016 (registration ID, UMIN000024283).

DOI： 10.1186/s41100-022-00409-4

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Urinary fatty acid binding protein 1 (FABP1, also known as liver-type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1-deficient mice with liver-specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver-derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT-R) either in a hepatocyte- or in a PTEC-specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver-derived FABP1 through a megalin-mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

DOI： 10.1002/path.5775

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Chronic kidney disease (CKD) impairs the anti-inflammatory effects of high-density lipoprotein (HDL) and increases cardiovascular mortality. Though the potential role of dietary interventions to manage HDL is well studied, the clinical trials aimed to increase HDL levels have failed to reduce cardiovascular risk, rendering HDL function to be explored as a more relevant clinical parameter. This study investigates the effects of rice endosperm protein (REP), a plant-based protein, on the anti-inflammatory properties of HDL and renal injury-driven atherosclerosis in comparison with casein, an animal protein. Ten-week-old apolipoprotein E-deficient hyperlipidemic mice underwent uninephrectomy. The mice (n = 6 each) were pair-fed a normal casein-based diet or a REP-based diet (both with 20.0% protein content) for seven weeks. Atherosclerotic lesions were detected by en face Sudan IV staining of the aorta. The number and sizes of the atherosclerotic lesions were significantly lower in the REP-based diet-fed group than the casein-based diet-fed group (p = 0.038). However, the REP-based diet neither elicited an ameliorative effect on kidney function or histology nor impacted the cholesterol profiles. Furthermore, HDL from the REP-based diet-fed mice significantly suppressed the inflammatory cytokine response of human umbilical vein endothelial cells than that from the casein-based diet-fed mice (MCP-1, p = 0.010; IL-6, p = 0.011; IL-1β, p = 0.028). The REP-based diet has a higher potential to lessen the atherosclerotic lesions accelerated by renal mass reduction than a casein-based diet, which could be associated with the anti-inflammatory effects of HDL.

DOI： 10.1080/07315724.2021.1950584

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Recently, attention has been focused on the effect of glucagon on blood glucose variability. The dynamics of glucagon have attracted attention as a new target in the treatment of diabetes patients. However, the dynamics of glucagon in hemodialysis (HD) patients with type 2 diabetes mellitus (T2DM) remain unclear. OBJECTIVES: The aim of this study was to assess the dynamics of glucagon in HD patients with T2DM. MATERIALS AND METHODS: We measured plasma glucagon in HD patients with T2DM by liquid chromatography-high-resolution mass spectrometry (LC-HRMS), sandwich enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). The glucagon levels measured by each method were compared. We used the glucagon levels determined by our developed LC-HRMS method as the standard in this study. RESULTS: Plasma glucagon levels measured by LC-HRMS before HD were significantly higher than those measured after HD. Plasma glucagon levels measured using sandwich ELISA had a significantly higher correlation with those measured using LC-HRMS compared with RIA. CONCLUSIONS: This was the first study to assess glucagon levels in HD patients with T2DM using LC-HRMS, which is considered a highly accurate method. Sandwich ELISA was shown to measure glucagon levels accurately as well.

DOI： 10.1159/000518027

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER HEIDELBERG  

Introduction: Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known.Methods: This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks.Results: Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were - 0.61% [- 1.14, - 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and - 1.67% [- 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (- 0.2% +/- 0.6% vs. 0.4% +/- 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (- 18.4 +/- 31.4 mg/dL vs. 25.2 +/- 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia.Conclusions: Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD.

DOI： 10.1007/s13300-020-00991-y

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

DOI： 10.1038/s41598-020-80853-6

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: The precise blood glucose (BG) profile of hemodialysis patients is unclear, as is the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors in hemodialysis patients with type 2 diabetes. Here, we used continuous glucose monitoring (CGM) to evaluate BG variability in these patients and to assess the efficacy of DPP-4 inhibitors, particularly during hemodialysis sessions and at nighttime (UMIN000012638). METHODS: We examined BG profiles using CGM in 31 maintenance hemodialysis patients with type 2 diabetes. Differences between patients with and without DPP-4 inhibitors (n = 15 and 16, respectively) were analyzed using a linear mixed-effects model to assess changes in glucose levels in 5-min intervals. RESULTS: The model revealed that DPP-4 inhibitor use was significantly associated with suppression of a rapid drop in glucose levels, both with and without adjustment for BG levels at the start of hemodialysis. Moreover, the model revealed that the two groups differed significantly in the pattern of changes in BG levels from 0:00 to 6:55 am. DPP-4 inhibitors suppressed the tendency for subsequent nocturnal hypoglycemia. CONCLUSIONS: This prospective observational exploratory study showed that DPP-4 inhibitors could suppress BG variability during hemodialysis sessions as well as subsequent nocturnal changes in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, UMIN000012638.

DOI： 10.1007/s13300-020-00928-5

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

DOI： 10.1186/s12885-019-6398-2

PubMed

researchmap

DOI： 10.3390/nu11122919

PubMed

researchmap

DOI： 10.1186/s12882-019-1591-8

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

DOI： 10.1007/s10157-018-1648-1

Web of Science

researchmap

DOI： 10.3109/14397595.2016.1174422

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(公社)日本臨床工学技士会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

In maintenance hemodialysis (MHD) patients, low protein intake is associated with protein-energy wasting, a risk factor that affects outcome. However, increased protein intake may lead to hyperphosphatemia and hyperkalemia, which are also mortality risk factors. Here, we evaluated the safety and effects of purified rice endosperm protein (REP), which contains less phosphorus and potassium than soy and casein proteins, as a supplemental protein source for MHD patients. This randomized, double-blind, placebo-controlled, crossover pilot study of REP supplementation (5 g/day x 4 weeks) was carried out in 50 Japanese adult MHD patients (1 dropped out); the primary outcome was the change in the urea kinetic-based normalized protein catabolic rate (nPCR), an indicator of protein intake in MHD patients. Intention-to-treat analyses of 24 patients in the REP-first group and 25 in the placebo-first group showed that REP supplementation increased nPCR significantly by 0.07 g/kg/day (95% confidence interval, 0.03-0.11), whereas changes in serum phosphorus and potassium concentrations were not different from the placebo. REP supplementation did not show a significant effect on other nutritional or metabolic parameters and no specific complications. In conclusion, purified REP with efficient bioavailability may be safe and useful for dietary supplementation in MHD patients.

DOI： 10.1038/s41598-017-18340-8

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：新潟急性血液浄化研究会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC NEPHROLOGY  

Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin. In the clinical setting, cilastatin has been used safely to suppress dehydropeptidase-I-mediated renal metabolism of imipenem, a carbapenem antimicrobial, and thereby limit tubular injury. Here, we tested the hypothesis that cilastatin also blocks megalin-mediated uptake of vancomycin, cisplatin, colistin, and aminoglycosides, thereby limiting the nephrotoxicity of these drugs. Quartz crystal microbalance analysis showed that megalin also binds vancomycin and cisplatin and that cilastatin competes with megalin for binding to gentamicin, colistin, vancomycin, and cisplatin. In kidney specific mosaic megalin knockout mice treated with colistin, vancomycin, or cisplatin, the megalin-replete proximal tubule epithelial cells exhibited signs of injury, whereas the megalin-deficient cells did not. Furthermore, concomitant cilastatin administration suppressed colistin-induced nephrotoxicity in C57BL/6J mice. Notably, cilastatin did not inhibit the antibacterial activity of gentamicin, colistin, or vancomycin in vitro, just as cilastatin did not affect the anticancer activity of cisplatin in previous studies. In conclusion, megalin blockade with cilastatin efficiently suppresses the nephrotoxicity induced by gentamicin, colistin, vancomycin, or cisplatin. Cilastatin may be a promising agent for inhibiting various forms of drug-induced nephrotoxicity mediated via megalin in the clinical setting.

DOI： 10.1681/ASN.2016060606

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER DIABETES ASSOC  

Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using ELISA, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in patients with type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with T2DM. Cultured immortalized rat proximal tubule cells (IRPTCs) treated with fatty acid-free BSA or advanced glycation end product-modified BSA (AGE-BSA), endocytic ligands of megalin, increased EV excretion, and their C-megalin content. C-megalin excretion from IRPTCs via extracellular vesicles was significantly blocked by an exosome-specific inhibitor, GW4869, indicating that this excretion is mainly exocytosis-mediated. AGE-BSA treatment of IRPTCs caused apparent lysosomal dysfunction, which stimulated multivesicular body formation, resulting in increased exosomal C-megalin excretion. In a high-fat diet-induced, megalin-mediated kidney injury model in mice, urinary C-megalin excretion also increased via UEVs. Collectively, exocytosis-mediated urinary C-megalin excretion is associated with the development and progression of DN in patients with T2DM, particularly due to megalin-mediated lysosomal dysfunction in proximal tubules, and hence it could be a candidate biomarker linked with DN pathogenesis.

DOI： 10.2337/db16-1031

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Objective The administration of glucocorticoids usually causes a mild increase in fasting glucose levels and a greater dose-dependent increase in postprandial values in patients without pre-existing diabetes mellitus. Patients with persistent hyperglycemia due to glucocorticoid therapy sometimes require insulin therapy, which might result in increased weight gain and more episodes of hypoglycemia, some of which are severe. On the other hand, scant evidence is available on the efficacy of oral hypoglycemic agents in treating glucocorticoid-induced diabetes. In this study, we evaluated the efficacy of dipeptidyl peptidase (DPP)-4 inhibitors in patients with glucocorticoid-induced diabetes by continuous glucose monitoring (CGM).
Methods We examined the glycemic profiles using CGM at baseline and 1-4 weeks after initiating DPP-4 inhibitor treatment in patients with newly developed glucocorticoid-induced diabetes.
Results Eleven patients who had been diagnosed with kidney disease or other diseases with renal involvement were recruited for the present retrospective study. After starting DPP-4 inhibitors, the mean and standard deviation (SD) of the glucose level, and the mean amplitude of glycemic excursion (MAGE) were significantly improved in comparison to baseline. Furthermore, the area over the curve (AOC) for the glucose levels &lt;70 mg/dL was not increased in comparison to baseline after the initiation of DPP-4 inhibitor treatment. The results indicate that the treatment of patients with glucocorticoid-induced diabetes using DPP-4 inhibitors can minimize the risk of hypoglycemia and reduce glucose variability.
Conclusion DPP-4 inhibitors are potentially useful for blood glucose control in patients with glucocorticoid-induced diabetes.

DOI： 10.2169/internalmedicine.8296-16

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC NEPHROLOGY  

Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control litter mates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid-rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid-depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.

DOI： 10.1681/ASN.2015020190

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Web of Science

researchmap

Language：Japanese   Publishing type：Doctoral thesis  

CiNii Article

CiNii Books

researchmap

Other Link： http://hdl.handle.net/10191/43838

Language：English   Publishing type：Research paper (scientific journal)   Publisher：CAMBRIDGE UNIV PRESS  

The effect of rice protein (RP) on diabetic nephropathy in non-obese, spontaneous type 2 diabetic Goto-Kakizaki (GK) rats was investigated. GK rats at 7 weeks of age were fed 20% RP or casein (C) in standard or high-sucrose diets for 10 weeks. Plasma total cholesterol, TAG, alkaline phosphatase (ALP), adiponectin, creatinine and urinary albumin excretion (UAE) were measured and renal histology was evaluated. Compared with C, RP lowered plasma TAG and improved plasma adiponectin levels in GK rats fed the standard diet (P&lt;0.05), and also lowered total cholesterol and ALP in high-sucrose-fed GK rats (P&lt;0.05). RP markedly suppressed the sharp increase in UAE when GK rats were fed high-sucrose diets (P&lt;0.05), and prevented glomerular mesangial matrix expansion in the deep renal cortex near the corticomedullary junction (P&lt;0.05). These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.

DOI： 10.1017/S0007114513000354

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

A 31-year-old woman with proteinuria, hypocomplementemia, rheumatoid factor, and high serum polyclonal IgM concentration was admitted to our hospital for renal biopsy. She had a past history of two renal biopsies. When she was 12 years old, she developed proteinuria, microscopic hematuria, and hypocomplementemia. She was diagnosed as having 'IgM nephropathy' based on minor glomerular abnormalities as determined by light microscopy and IgM and C3 deposition in the mesangial region by immunofluorescence microscopy at the first biopsy. Despite corticosteroid treatment, her proteinuria did not improve and she discontinued regular outpatient checkups. When she was 29 years old and pregnant, she developed preeclampsia and, after delivery, a second renal biopsy was implemented. She was diagnosed as having progressed 'IgM nephropathy' with endotheliosis induced by preeclampsia. She was treated with angiotensin II receptor blocker and her proteinuria diminished; however, 1 year after the delivery, she developed proteinuria again, along with microscopic hematuria and hypocomplementemia. A third renal biopsy was conducted at 31 years of age and she was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type I on the basis of diffuse mesangial proliferation, endocapillary hypercellularity with double contour of the capillary wall, and lobular formation in glomeruli, as determined by light microscopy. Immunofluorescence staining demonstrated deposits of C3, C4, C1q, and IgM in the mesangial region and capillary wall. She underwent corticosteroid therapy followed by normalization of urinalysis and serum complement level. Although she had initially been diagnosed with 'IgM nephropathy', she was finally diagnosed with secondary MPGN and was successfully treated by corticosteroid therapy.

DOI： 10.1007/s13730-012-0042-1

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER DIABETES ASSOC  

OBJECTIVE-Megalin, an endocytic receptor in proximal tubule cells, is involved in the mechanisms of albuminuria in diabetic nephropathy (DN). To develop efficient novel biomarkers associated with the pathogenesis of DN, we investigated urinary megalin excretion in type 2 diabetes.
RESEARCH DESIGN AND METHODS-Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH2 (amino [A]-megalin assay) and CO OH (C-megalin assay) termini of megalin to analyze urinary forms of megalin in 68 patients with type 2 diabetes.
RESULTS-The A-megalin assay mainly detected a megalin ectodomain form in the soluble urinary fraction, whereas the C-megalin assay identified a full-length form in both soluble and insoluble fractions. Urinary C-megalin levels were significantly high in patients with normoalbuminuria, were elevated in line with increased albuminuria, and showed a better association with estimated glomerular filtration rate (eGFR) (&lt;60 mL/min/1.73 m(2)) than did urinary albumin. In contrast, urinary A-megalin levels were increased in patients with normo- and microalbuminuria but not in those with macroalbuminuria. Urinary C-megalin levels were also positively associated with plasma inorganic phosphate and negatively with hemoglobin levels in those showing no features of bleeding and not taking vitamin D analogs, phosphate binders, or erythropoiesis-stimulating agents.
CONCLUSIONS-Urinary full-length megalin excretion as measured by the C-megalin assay is well associated with reduced eGFR and linked to the severity of DN, phosphate dysregulation, and anemia, whereas urinary excretion of megalin ectodomain as measured by the A-megalin assay may be associated with distinctive mechanisms of earlier DN in type 2 diabetes.

DOI： 10.2337/dc11-1684

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Expression and function of megalin, an endocytic receptor in proximal tubule cells (PTCs), are reduced in diabetic nephropathy, involved in the development of proteinuria/albuminuria. Lipopolysaccharide (LPS) is chronically increased in diabetic sera, by the mechanism called metabolic endotoxemia. We investigated low-level LPS-mediated signaling that regulates megalin expression in immortalized rat PTCs (IRPTCs). Incubation of the cells with LPS (10 ng/ml) for 48 h suppressed megalin protein expression and its endocytic function. TNF-alpha mRNA expression was increased by LPS treatment, and knockdown of the mRNA with siRNA inhibited LPS-mediated downregulation of megalin mRNA expression at the 24-h time point. Incubation of IRPTCs with exogenous TNF-alpha also suppressed megalin mRNA and protein expression at the 24- and 48-h time points, respectively. MEK1 inhibitor PD98059 competed partially but significantly TNF-alpha-mediated downregulation of megalin mRNA expression. Collectively, low-level LPS-mediated TNF-alpha-ERK1/2 signaling pathway is involved in downregulation of megalin expression in IRPTCs. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2011.02.118

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ENDOCRINE SOC  

Impairment of proximal tubular endocytosis of glomerular-filtered proteins including albumin results in the development of proteinuria/albuminuria in patients with chronic kidney disease. However, the mechanisms regulating the proximal tubular function are largely unknown. This study aimed to investigate the role of angiotensin II type 1A receptor (AT(1A)R)- and insulin-mediated signaling pathways in regulating the expression of megalin, a multiligand endocytic receptor in proximal tubule cells (PTCs). Opossum kidney PTC-derived OK cells that stably express rat AT(1A)R but are deficient in endogenous angiotensin II receptors (AT(1A)R-OK cells) were used for this study. Treatment of the cells with angiotensin II suppressed mRNA and protein expression of megalin at 3- and 24-h incubation time points, respectively. Cellular uptake and degradation of albumin and receptor-associated protein, megalin&apos;s endocytic ligands were suppressed 24 h after angiotensin II treatment. The AT(1A)R-mediated decrease in megalin expression was partially prevented by ERK inhibitors. Insulin competed with the AT(1A)R-mediated ERK activation and decrease in megalin expression. Inhibitors of phosphatidylinositol 3- kinase (PI3K), a major component of insulin signaling, also suppressed megalin expression, and activation of the insulin receptor substrate (IRS)/PI3K system was prevented by angiotensin II. Collectively the AT(1A)R-mediated ERK signaling is involved in suppressing megalin expression in the OK cell line, and insulin competes with this pathway. Conversely, the insulin-IRS/PI3K signaling, with which angiotensin II competes, tends to stimulate megalin expression. In conclusion, there is AT(1A)R- and insulin-mediated competitive signaling cross talk to regulate megalin expression in cultured PTCs. (Endocrinology 150: 871 - 878, 2009)

DOI： 10.1210/en.2008-0886

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(公財)臨床薬理研究振興財団  

軽度〜中等度腎機能障害を有する成人2型糖尿病患者(残存機能ネフロンに過剰代謝負荷がかかっていることが推測される)を対象に、エンパグリフロジンによる腎機能保護作用を検証するとともに尿中メガリン(およびメガリンリガンド分子)の動態を調べ、腎機能保護作用がメガリン機能に関連したものであるか検討した。さらに、尿中メガリンなどの検査がコンパニオン診断として有用であるか、探索的な検討を行った。また、SGLT2阻害薬がメガリンの発現・機能に及ぼす影響についても検討を継続した。臨床試験の被験者51名で、平均年齢は62歳であり、男性が32名であった。2名が有害反応のため脱落したが、6ヵ月後、HbA1cとBMIが減少した。現在、メガリンを含む尿中バイオマーカーの推移について解析を行っている。ダパグリフロジン、エンパグリフロジンを投与されたマウスでは尿中の糖排泄増加を認めたが血糖値に差は認められなかった。免疫組織化学染色では近位尿細管におけるメガリンの染色性が低下していることが確認された。またウエスタンブロット法において、メガリンの蛋白がvehicle群と比較して低下していることが認められた。リアルタイムRT-PCRにおいてもメガリンmRNAがvehicle群と比較して低下していることが確認された。ダパグリフロジンを添加されたIRPTCではメガリン蛋白の低下が認められ、mRNAの低下も認められた。

researchmap

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02946&link_issn=&doc_id=20200528150008&doc_link_id=issn%3D1341-1489%26volume%3D26%26issue%3D6%26spage%3D512&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1341-1489%26volume%3D26%26issue%3D6%26spage%3D512&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02946&link_issn=&doc_id=20200528150009&doc_link_id=%2Fao7tousi%2F2020%2F002606%2F011%2F0514-0516%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao7tousi%2F2020%2F002606%2F011%2F0514-0516%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：医歯薬出版(株)  

これまでに、たんぱく質制限に関してさまざまな無作為化比較試験(RCT)とそのメタ解析が行われてきたが、その結果から、慢性腎臓病(CKD)患者に対するたんぱく質摂取制限は、とくに非糖尿病性腎症や1型糖尿病患者のGFR低下抑制に対して有効で、2型糖尿病患者でも有効な可能性があると考えられる。たんぱく質摂取指示量に関しては、『慢性腎臓病に対する食事療法基準2014年版』を参考に、個々の患者の病態やリスクなどを総合的に判断すべきであるが、すくなくとも0.6g/kg体重/dayを下回らない、0.8g/kg体重/day未満のたんぱく質の制限は、死亡のリスクを増やさずにGFR低下抑制に有効である可能性がある。なお、たんぱく質を制限する場合、低栄養の発症リスクを常に念頭におき、必要なエネルギー(25〜35kcal/kg標準体重/day)を確保することが必要である。たんぱく質制限においてはその遵守率(アドヒアランス)が末期腎不全のリスクに大きな影響を与え、遵守率の改善に多職種連携や低たんぱく質食品が有効であることが示唆されている。(著者抄録)

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00060&link_issn=&doc_id=20200316030004&doc_link_id=%2Faa7ayuma%2F2020%2F027211%2F005%2F1129-1132%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2020%2F027211%2F005%2F1129-1132%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(公社)日本透析医会  

我が国では急速に高齢化が進展しており、加齢に伴い腎機能は低下するため、今後しばらくは、透析導入患者数は減少しないことが予想されている。超高齢社会における透析患者の高齢化も必発であり、その対策が急務である。高齢透析患者では、高齢者特有の生理機能の変化や併存疾患による嚥下機能の低下だけでなく、食欲低下からのエネルギー不足や腎不全特有の様々な要因が加わることで、protein energy wasting(PEW)と呼ばれるたんぱく質やエネルギーの貯蔵が減少している状態を招く。したがって高齢透析患者では栄養状態を適格に評価し、適切なタイミングで栄養介入することが必要である。経口栄養補助(oral nutrition supplement;ONS)は栄養状態の改善に寄与することが期待されているが、ONSでその改善が得られなかった症例や経口摂取が上手くいかない症例にとっては、透析中の静脈栄養(intradialytic parenteral nutrition;IDPN)は合理的な治療選択肢である。多くの問題点はあるが、今後、透析施設での透析中の食事提供、食事摂取についても再検討が必要である。(著者抄録)

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J02822&link_issn=&doc_id=20190807240003&doc_link_id=10.4009%2Fjsdt.52.401&url=https%3A%2F%2Fdoi.org%2F10.4009%2Fjsdt.52.401&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(公社)日本栄養・食糧学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02946&link_issn=&doc_id=20181114070006&doc_link_id=issn%3D1341-1489%26volume%3D24%26issue%3D12%26spage%3D1088&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1341-1489%26volume%3D24%26issue%3D12%26spage%3D1088&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(有)科学評論社  

researchmap

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J05098&link_issn=&doc_id=20180705140009&doc_link_id=issn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D610&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D610&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J05098&link_issn=&doc_id=20180705140008&doc_link_id=issn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D608&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D608&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J05098&link_issn=&doc_id=20180705140007&doc_link_id=issn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D606&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D606&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(一社)日本透析医学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)ライフメディコム  

researchmap

Language：Japanese   Publisher：(株)ジェフコーポレーション  

researchmap

Language：Japanese  

DOI： 10.19020/KB.0000000098

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：(一社)日本老年医学会  

researchmap

Language：Japanese   Publisher：(一社)日本老年医学会  

researchmap

Language：Japanese   Publisher：(一社)日本老年医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：新潟県医師会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

SGLT2阻害薬は近位尿細管における糖の再吸収を抑制することで尿糖排泄を増加し血糖低下をもたらす糖尿病治療薬であり、食事療法が密接にその治療効果へ影響を及ぼすことが予想される。症例は40歳女性。SGLT2阻害薬のイプラグリフロジンを開始と同時に、1400kcal/日にて栄養指導を月1回、継続的に行った。連日の食事記録より、2000kcal/日以上であった摂取エネルギーは平均1700kcal/日程度に減少した。35週間で体重は97.6kgから83.4kgと減少、HbA1cは7.4%から6.0%と改善した。SGLT2阻害薬開始後にエネルギー摂取量が増加する可能性が示唆されている。本症例は指導量よりは過剰であったものの、SGLT2阻害薬開始後に減少を認めており、体重減少および血糖改善につながったと考えられる。SGLT2阻害薬を使用中の患者においては正確な食事内容の把握と継続的な栄養指導が重要である。(著者抄録)

researchmap

Language：Japanese   Publisher：科学評論社  

CiNii Article

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本病態栄養学会  

researchmap

Language：Japanese   Publisher：長岡赤十字病院  

74歳女。食欲不振を主訴とした。左上顎洞癌(T3N2bM0)に対して60Gy放射線療法とセツキシマブによる化学療法が行われたが、施行後にCre 1.89mg/dl、尿中赤血球50-99/HPF、尿蛋白 (3+)を認め、急速進行性糸球体腎炎症候群を呈した。腎生検では尿細管間質障害と管内細胞増殖、細胞性半月体を伴う膜性増殖性糸球体腎炎を示し、セツキシマブ投与後に急速進行性糸球体腎炎を呈したこと、尿細管間質障害を伴うIgA沈着優位の管内細胞増殖、メサンギウム融解、細胞性半月体を伴うメサンギウム増殖性腎炎の像が既報と類似していたことから、セツキシマブに伴う腎障害と考えられた。ステロイドパルス療法を行い、後療法として経口ステロイドを継続したところ、一時的に尿毒症とアシドーシスが進行して血液透析導入となったものの、腎機能は徐々に改善して血液透析から離脱できた。経口ステロイドを漸減し、現在、Cre 1.70mg/dl前後で経過している。

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)ライフ・サイエンス  

2型糖尿病を有する透析施行患者に対するアログリプチンの有効性と安全性について検討した。2型糖尿病を有する透析施行患者7例で、アログリプチンの末期腎不全患者の用法・用量から6.25mgを1日1回投与し、投与前および投与後4週ごとのHbA1cを測定した。エリスロポエチン製剤の試験期間中の投与量には変化はなかった。4週後および8週後、12週後における平均HbA1cは、それぞれ6.2±0.4%および5.9±0.3%、5.6±0.3%と投与前に比較して有意に低下した。全例で良好な血糖低下の推移を認めた。投与開始12週後において有意な変化を認めたのは透析前の拡張期血圧のみであったが、わずかながら脂質の項目に低下がみられた。副作用としての低血糖症状は認めなかった。

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(株)中外医学社  

糖尿病性腎症は慢性腎不全に至る最も重要な原因疾患であり,その早期診断,病態把握,予後推定のため,微量アルブミン尿の測定が推奨されている.さらに微量アルブミン尿は,糖尿病の有無にかかわらず,心血管系イベントの危険因子としても知られている.しかしその機序や意義については未だ不明な点も多い.近年,糖尿病における微量アルブミン尿の機序について,糸球体・血管系と尿細管系の相互的関係をふまえ,ネフロン傷害の全体像を把握する重要性を示す報告が蓄積している.本稿では特に,近位尿細管上皮細胞におけるアルブミンの処理機構の問題,あるいはインスリン抵抗性やgenome-wide association studyなどの新しい知見をふまえて,その動向を紹介する.(著者抄録)

researchmap

Language：Japanese   Publisher：Japanese Proteomics Society (Japan Human Proteome Organisation)  

DOI： 10.14889/jhupo.2011.0.186.0

CiNii Article

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：新潟医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap