ABSTRACT
Structure-function relationships of supported metal nanoparticle catalysts in the CO-assisted oxidation of ethane to ethanol were investigated. A rutile TiO2-supported Pt nanoparticle catalyst exhibited the highest ethanol production rate and selectivity. During the reaction, sequential changes in the geometric/electronic states and the particle size of the Pt nanoparticles were observed. The comparison of the catalytic performances of model catalysts with controlled metal-support interactions revealed that Pt0 nanoparticles of 2-3 nm with a high fraction of the surface Ptδ+ species are highly active for the oxidation of ethane to ethanol. The coadded CO plays a pivotal role not only in tuning the oxidation state of the surface Pt but also in producing H2O2, which is the true oxidant for the reaction. The supported Pt nanoparticle uses in situ-generated H2O2 to activate ethane, where the C2H5OOH intermediate is formed through a nonradical mechanism and subsequently converted to C2H5OH. This reaction occurs even at 50 °C with an apparent activation energy of 32 kJ mol-1. The present study sheds light on the usefulness of surface-engineered Pt nanoparticles for the low-temperature oxidation of ethane to ethanol.
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Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture. The resulting human kidney organoids show extensive endothelialization with a cellular identity most closely related to human kidney endothelia. Endothelialized kidney organoids also show increased maturation of nephron structures, an associated fenestrated endothelium with de novo formation of glomerular and venous subtypes, and the emergence of drug-responsive renin expressing cells. The creation of an engineered vascular niche capable of improving kidney organoid maturation and cell type complexity is a significant step forward in the path to clinical translation. Thus, incorporation of an engineered endothelial niche into a previously published kidney organoid protocol allowed the orthogonal differentiation of endothelial and parenchymal cell types, demonstrating the potential for applicability to other basic and translational organoid studies.
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We have found an efficient adsorption feature provided by an NaCaA-85 zeolite for N2O even at 298 K and at lower pressures: N2O adsorption capacities of 1.33 mmol g-1 and 4.69 mmol g-1 under respective pressures of 0.3 and at 100 Torr, respectively, indicating the best performance among adsorbent materials so far reported. These adsorption peculiarities will pave a new way for developing excellent materials working for adsorption/separation processes of N2O.
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SIGNIFICANCE STATEMENT: In this study, we demonstrate that a common, low-cost compound known as octanedioic acid (DC 8 ) can protect mice from kidney damage typically caused by ischemia-reperfusion injury or the chemotherapy drug cisplatin. This compound seems to enhance peroxisomal activity, which is responsible for breaking down fats, without adversely affecting mitochondrial function. DC 8 is not only affordable and easy to administer but also effective. These encouraging findings suggest that DC 8 could potentially be used to assist patients who are at risk of experiencing this type of kidney damage. BACKGROUND: Proximal tubules are rich in peroxisomes, which are damaged during AKI. Previous studies demonstrated that increasing peroxisomal fatty acid oxidation (FAO) is renoprotective, but no therapy has emerged to leverage this mechanism. METHODS: Mice were fed with either a control diet or a diet enriched with dicarboxylic acids, which are peroxisome-specific FAO substrates, then subjected to either ischemia-reperfusion injury-AKI or cisplatin-AKI models. Biochemical, histologic, genetic, and proteomic analyses were performed. RESULTS: Both octanedioic acid (DC 8 ) and dodecanedioic acid (DC 12 ) prevented the rise of AKI markers in mice that were exposed to renal injury. Proteomics analysis demonstrated that DC 8 preserved the peroxisomal and mitochondrial proteomes while inducing extensive remodeling of the lysine succinylome. This latter finding indicates that DC 8 is chain shortened to the anaplerotic substrate succinate and that peroxisomal FAO was increased by DC 8 . CONCLUSIONS: DC 8 supplementation protects kidney mitochondria and peroxisomes and increases peroxisomal FAO, thereby protecting against AKI.
Subject(s)
Acute Kidney Injury , Dicarboxylic Acids , Dietary Supplements , Reperfusion Injury , Animals , Humans , Mice , Acute Kidney Injury/prevention & control , Acute Kidney Injury/pathology , Cisplatin , Dicarboxylic Acids/administration & dosage , Fatty Acids , Proteomics , Reperfusion Injury/prevention & control , Reperfusion Injury/pathologyABSTRACT
We present a partially-oxidised bimetallic Mo-Pt subnanoparticle (Mo4Pt8Ox) enabling thermally-driven CO2 hydrogenation to CO at room temperature and atmospheric pressure. A mechanistic study explained the full catalytic cycle of the reaction from CO2 activation to catalyst reactivation. DFT calculations revealed that alloying with Mo lowers the activation barrier by weakening the CO adsorption. This finding could be a first step for low-energy CO2 conversion.
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BACKGROUND: Mean corpuscular volume (MCV) and red cell distribution width (RDW), as well hemoglobin, are reported to be associated with mortality in various populations. However, associations between such hematological parameters and adverse outcomes in patients with CKD have not been sufficiently elucidated. METHODS: A total of 1,320 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between hematological parameters of anemia (MCV and RDW) and adverse outcomes, such as ESKD, all-cause death, and cardiovascular events, in patients with non-dialysis-dependent CKD. Baseline hematological parameters were grouped as follows: hemoglobin into 3 categories (< 11.0 g/dL, 11.0 ≤ - < 13.0 g/dL [reference], and ≥ 13.0 g/dL); MCV into 5 categories (< 90 fL, ≥ 90 - < 94 fL [reference], ≥ 94 - < 98 fL, ≥ 98 - < 102 fL, and ≥ 102 fL); and RDW into 2 categories (< 13.6% [reference] vs ≥ 13.6%). RESULTS: During the median observational period of 4.7 years, 120 patients developed ESKD, 160 developed cardiovascular events, and 122 died. Hemoglobin < 11 g/dL (hazard ratio [HR] 1.56, 95% confidence interval [CI], 1.00-2.42), MCV < 90 fL (HR 2.01, 95% CI 1.14-3.54), and RDW ≥ 13.6% (HR 1.57, 95% CI 1.01-2.42) were significantly associated with higher risks of ESKD. Hemoglobin < 11 g/dL, MCV ≥ 98 fL, and RDW ≥ 13.6% were significantly associated with higher risks of all-cause death. No significant associations between hematological parameters and risk of cardiovascular events were confirmed. CONCLUSION: In patients with non-dialysis-dependent CKD, MCV, RDW, and hemoglobin were associated with increased risks of ESKD and all-cause mortality.
Subject(s)
Anemia , Cardiovascular Diseases , Renal Insufficiency, Chronic , Humans , Cohort Studies , Anemia/diagnosis , Anemia/epidemiology , Erythrocyte Indices , Hemoglobins/analysis , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Prognosis , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiologyABSTRACT
The cholesterol-conjugated heteroduplex oligonucleotide (Chol-HDO) is a double-stranded complex; it comprises an antisense oligonucleotide (ASO) and its complementary strand with a cholesterol ligand. Chol-HDO is a powerful tool for achieving target RNA knockdown in the brains of mice after systemic injection. Here, a quantitative model analysis was conducted to characterize the relationship between the pharmacokinetics (PK) and pharmacodynamics (PD), non-coding RNA metastasis-associated lung adenocarcinoma 1 (Malat1) RNA, of Chol-HDO, in a time-dependent manner. The established PK model could describe regional differences in the observed brain concentration-time profiles. Incorporating the PD model enabled the unique knockdown profiles in the brain to be explained in terms of the time delay after single dosing and enhancement following repeated dosing. Moreover, sensitivity analysis of PK exposure/persistency, target RNA turnover, and knockdown potency identified key factors for the efficient and sustained target RNA knockdown in the brain. The simulation of an adequate dosing regimen quantitatively supported the benefit of Chol-HDO in terms of achieving a suitable dosing interval. This was achieved via sufficient and sustained brain exposure and subsequent strong and sustained target RNA knockdown in the brain, even after systemic injection. The present study provides new insights into drug discoveries and development strategies for HDO in patients with neurogenic disorders. SIGNIFICANCE STATEMENT: The quantitative model analysis presented here characterized the PK/PD relationship of Chol-HDO, enabled its simulation under various conditions or assumptions, and identified key factors for efficient and sustained RNA knockdown, such as PK exposure and persistency. Chol-HDO appears to be an efficient drug delivery system for the systemic administration of desired drugs to brain targets.
Subject(s)
Oligonucleotides , RNA , Mice , Animals , Blood-Brain Barrier , Cholesterol , DNAABSTRACT
Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease characterised by autoantibodies targeting insulin receptors. TBIR is often complicated by systemic lupus erythematosus (SLE). We describe the case of a 59-year-old Japanese man with TBIR complicated with lupus nephritis (LN), who presented with nephrotic syndrome and severe hypoglycaemia. Treatment with prednisolone (PSL), mycophenolate mofetil (MMF), and tacrolimus (TAC) resulted in improved SLE activity and glucose intolerance with the reduction of anti-insulin receptor autoantibodies. To the best of our knowledge, this is the first reported case of TBIR complicated with LN that was successfully treated using multitarget therapy with PSL, MMF, and TAC.
Subject(s)
Insulin Resistance , Lupus Nephritis , Humans , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/drug therapy , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Prednisolone/therapeutic use , Tacrolimus/therapeutic use , Treatment OutcomeABSTRACT
Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.
Subject(s)
Cardiovascular Diseases , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cohort Studies , Disease Progression , Humans , Kidney Failure, Chronic/epidemiology , Phosphorus , Renal Insufficiency, Chronic/epidemiology , Risk FactorsABSTRACT
BACKGROUND AND OBJECTIVE: Polypharmacy is common in patients with CKD and reportedly associated with adverse outcomes. However, its effect on kidney outcomes among patients with CKD has not been adequately elucidated. Hence, this investigation was aimed at exploring the association between polypharmacy and kidney failure requiring KRT. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively examined 1117 participants (median age, 66 years; 56% male; median eGFR, 48 ml/min per 1.73 m2) enrolled in the Fukushima CKD Cohort Study to investigate the association between the number of prescribed medications and adverse outcomes such as kidney failure, all-cause mortality, and cardiovascular events in Japanese patients with nondialysis-dependent CKD. Polypharmacy and hyperpolypharmacy were defined as the regular use of 5-9 and ≥10 medications per day, respectively. RESULTS: The median number of medications was eight; the prevalence of polypharmacy and hyperpolypharmacy was each 38%. During the observation period (median, 4.8 years), 120 developed kidney failure, 153 developed cardiovascular events, and 109 died. Compared with the use of fewer than five medications, adjusted hazard ratios (95% confidence intervals) associated with polypharmacy and hyperpolypharmacy were 2.28 (1.00 to 5.21) and 2.83 (1.21 to 6.66) for kidney failure, 1.60 (0.85 to 3.04) and 3.02 (1.59 to 5.74) for cardiovascular events, and 1.25 (0.62 to 2.53) and 2.80 (1.41 to 5.54) for all-cause mortality. CONCLUSIONS: The use of a high number of medications was associated with a high risk of kidney failure, cardiovascular events, and all-cause mortality in Japanese patients with nondialysis-dependent CKD under nephrology care.
Subject(s)
Polypharmacy , Renal Insufficiency, Chronic/therapy , Renal Replacement Therapy , Aged , Cohort Studies , Disease Progression , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: In this study, we identified a novel glycophorin variant (GP.MOT) in a Mia -positive Japanese blood donor. The proband with this glycophorin variant was discovered by antigen screening of samples from 475,493 Japanese blood donors using monoclonal anti-Mia . STUDY DESIGN AND METHODS: Standard serological techniques and flow cytometry were performed. GP.MOT RBCs were examined by immunoblotting using anti-GPA, anti-MUT or anti-Mur. Genome DNA was extracted from whole blood, and the GYPA/GYPB was analyzed by polymerase chain reactions and Sanger sequencing. RESULTS: The MNS blood group of the proband was M + N + w S-s + with the presence of other low-frequency antigens including Mia , Mur, MUT, and KIPP. A 43-kDa molecule, which is almost equivalent in size to glycophorin A (GPA), was identified by immunoblotting using monoclonal anti-MUT and anti-Mur. Sanger sequencing clearly indicated that the proband had two different GYPA*M alleles at SNP rs62334651 (GYPA*M232 + 55A and GYPA*M232 + 55G), as well as a GYP(B-A) hybrid allele (GYP*MOT) with breakpoints located on pseudoexon 3 of GYPB from c.210 to c.219. DISCUSSION: We identified a hybrid glycophorin GP.MOT with the deduced unique amino acid sequence GPB (20-45)-GPΨB (46-70)-GPA (71-149), which has not been previously reported.
Subject(s)
Glycophorins/genetics , Alleles , Amino Acid Sequence , Base Sequence , Blood Donors , Genetic Variation , Humans , Japan , MNSs Blood-Group System/genetics , Sequence Analysis, DNAABSTRACT
As previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19-2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26-0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.
Subject(s)
Enzyme Inhibitors/administration & dosage , Hypertension/drug therapy , Xanthine Oxidase/antagonists & inhibitors , Aged , Female , Follow-Up Studies , Humans , Hypertension/enzymology , Hypertension/epidemiology , Japan/epidemiology , Male , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: Serum potassium disorders, commonly observed in chronic kidney disease (CKD), are reportedly associated with higher mortality, but their impact on renal outcomes is still controversial. METHODS: The present study used the longitudinal data of the Fukushima CKD cohort study to investigate the relationships between hypokalemia and hyperkalemia and adverse outcomes such as renal outcomes and all-cause mortality in Japanese patients with non-dialysis-dependent CKD. The study involved 1330 CKD patients followed-up for 2.8 years. The primary endpoint of the present study was a kidney event, defined as a combination of doubling of baseline serum creatinine and end-stage kidney disease. RESULTS: Hyperkalemia (≥ 5.0 mmol/L) was noted in 10.6% and hypokalemia (< 4.0 mmol/L) in 16.4% of the study population. Significant U-shaped associations were observed between potassium levels and both kidney events and all-cause mortality on univariate Cox regression analyses. After adjustment for covariates, both hypokalemia and hyperkalemia were significantly associated with an increased risk of kidney events, with the lowest risk at a serum potassium of 4.0-4.4 mmol/L. Compared with a reference level of 4.0-4.4 mmol/L, the adjusted hazard ratio for kidney events was 2.49 (1.33-4.66) for serum potassium < 4.0 mmol/L, 1.72 (1.00-2.96) for 4.5-4.9 mmol/L, and 2.16 (1.15-4.06) for ≥ 5.0 mmol/L. There was no significant association between serum potassium levels and mortality after multivariate adjustment. CONCLUSION: Hypokalemia and hyperkalemia were associated with an increased risk of CKD progression, but not with mortality in Japanese patients with non-dialysis-dependent CKD.
Subject(s)
Hyperkalemia/epidemiology , Hypokalemia/epidemiology , Potassium/blood , Renal Insufficiency, Chronic/epidemiology , Aged , Biomarkers/blood , Cause of Death , Disease Progression , Female , Humans , Hyperkalemia/blood , Hyperkalemia/diagnosis , Hyperkalemia/mortality , Hypokalemia/blood , Hypokalemia/diagnosis , Hypokalemia/mortality , Incidence , Japan , Longitudinal Studies , Male , Middle Aged , Prognosis , Prospective Studies , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Risk Assessment , Risk Factors , Time FactorsABSTRACT
BACKGROUND: Serial management of renal anemia using continuous erythropoietin receptor activator (CERA) throughout the peritoneal dialysis initiation period has rarely been reported. We investigated the efficacy and dosage of CERA treatment from pre- to post-peritoneal dialysis initiation for anemia management in patients with end-stage renal disease. METHODS: Twenty-six patients (13 men; mean age 60.9 years) who started peritoneal dialysis between April 2012 and April 2018 were investigated. Serial changes in hemoglobin levels, transferrin saturation and ferritin levels, CERA dosage, and the erythropoietin resistance index (ERI) over a 48 week period were retrospectively examined. RESULTS: Mean hemoglobin levels increased significantly from 10.5 g/dL at 24 weeks prior to the peritoneal dialysis initiation to 11.5 g/dL at 4 weeks post-initiation. The proportion of patients with hemoglobin levels ≥ 11 g/dL increased significantly after peritoneal dialysis initiation. The mean CERA dosage was 57.0 µg/month at 24 weeks prior to dialysis initiation, 86.5 µg/month at initiation, and 72.0 µg/month at 4 weeks post-initiation. Thus, the dosage tended to increase immediately before peritoneal dialysis initiation and then decreased thereafter. Hemoglobin levels were significantly lower, while the CERA dosage for maintaining hemoglobin levels and ERI tended to be higher at dialysis initiation in patients with diabetes than in those without diabetes. CONCLUSION: Treatment with CERA prior to and during the peritoneal dialysis initiation achieved fairly good anemia management in patients with and without diabetes. The CERA dosage could be reduced in patients without diabetes after dialysis initiation.
Subject(s)
Anemia/drug therapy , Erythropoietin/therapeutic use , Kidney Failure, Chronic/complications , Peritoneal Dialysis , Polyethylene Glycols/therapeutic use , Adult , Aged , Female , Hemoglobins/analysis , Humans , Kidney Failure, Chronic/therapy , Male , Middle AgedABSTRACT
Isolation of the atomic O radical anion bound to a metal ion (metal-oxyl) on solid surfaces is highly desirable for an understanding of how we should design the surface structure for using oxyl as the reactive site. Owing to the analytical difficulty of oxyl, however, even identification of oxyl remains scarce. Herein, we report isovalent ZnII-oxyl and GaIII-oxyl bonds isolated in the zeolite matrix. Close similarities in reactivity, spectroscopic property, and bonding nature were observed between them, but their site requirements were entirely different; the former is generated at the monovalent ion-exchangeable site, whereas the latter at the divalent ion-exchangeable site. This study strongly suggests that tuning the polarization of the metal-oxygen bond using the charge-controlled lattice oxygens is a useful way to constrain surface metal-oxyl bonds.
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BACKGROUND: In patients with chronic kidney disease (CKD), dysbiosis in the gastrointestinal microbiome is thought to be associated with increased production of uremic toxins, such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Sucroferric oxyhydroxide (SFO), an iron-based phosphate binder, may affect the gastrointestinal microbiome and the production of uremic toxins. We aimed to examine whether SFO administration affected distribution of gastrointestinal microbiome and serum uremic toxin levels in CKD patients undergoing hemodialysis. METHODS: In this single-center, open-label, interventional study, 18 maintenance hemodialysis patients with hyperphosphatemia were prescribed with SFO. We collected serum samples before and after 3 months of administration, and serum levels of IS and PCS were measured. A control group of 20 hemodialysis patients without SFO was evaluated. We evaluated gastrointestinal microbiome of patients pre- and post-SFO administration by 16S rDNA sequencing and bioinformatics analysis. RESULTS: Serum IS and PCS levels were significantly elevated after administration of SFO (IS before 2.52 ± 1.60 mg/dl vs. after 3.13 ± 1.51 mg/dl, P = 0.008; PCS before 2.32 ± 2.44 mg/dl vs. after 3.45 ± 2.11 mg/dl, P = 0.002), while serum IS and PCS levels did not change in the control group. Microbiome analysis in the SFO group showed no significant change in diversity and major components in phylum, class, order, family, gene, and species. CONCLUSION: Administration of SFO increased the serum levels of IS and PCS with no change of major components of gastrointestinal microbiome.
Subject(s)
Dysbiosis/drug therapy , Ferric Compounds/therapeutic use , Gastrointestinal Microbiome/drug effects , Renal Insufficiency, Chronic/microbiology , Sucrose/therapeutic use , Aged , Aged, 80 and over , Case-Control Studies , Cresols/blood , Drug Combinations , Dysbiosis/etiology , Feces/microbiology , Ferric Compounds/pharmacology , Humans , Indican/blood , Middle Aged , Renal Dialysis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Sucrose/pharmacology , Sulfuric Acid Esters/bloodABSTRACT
BACKGROUND: Inadequate blood pressure control is one of the important causes of chronic kidney disease (CKD), but only a limited number of reports have examined blood pressure control in Japanese patients with pre-dialysis CKD. Differences in blood pressure control due to underlying renal disease in pre-dialysis patients with CKD were investigated in the present study using the baseline data of the Fukushima CKD cohort study. METHODS: The study involved 1351 CKD patients, classified by underlying disease of primary renal disease, hypertensive nephropathy, diabetic nephropathy, other nephropathies, or unknown. Target blood pressure of CKD patients was defined as < 130/80 mmHg in patients under 75 years old with diabetes and/or proteinuria, and < 140/90 mmHg in other patients. RESULTS: The achievement rate of target systolic blood pressure was lower in the diabetic and hypertensive nephropathy groups than in the primary renal disease group (33.3%, 46.0% vs. 68.1%, p < 0.001). However, the number of antihypertensive medications increased in the diabetic and hypertensive nephropathy groups compared to the primary renal disease group (2.16, 2.04 vs. 1.55, p < 0.001). Inadequate blood pressure control was independently related to the underlying renal disease, with a significant difference between diabetic nephropathy and primary renal disease (odds ratio 3.19; 95% confidence interval, 2.16-4.69; p < 0.001). CONCLUSION: This study showed that blood pressure control differs by the underlying renal disease. Blood pressure control was poor especially in diabetic nephropathy despite multidrug combination antihypertensive treatment. It is necessary to verify whether strict blood pressure control improves patients' prognosis in diabetic nephropathy.
Subject(s)
Blood Pressure , Diabetic Nephropathies/physiopathology , Hypertension, Renal/physiopathology , Hypertension/physiopathology , Nephritis/physiopathology , Renal Insufficiency, Chronic/physiopathology , Aged , Antihypertensive Agents/therapeutic use , Cross-Sectional Studies , Diabetic Nephropathies/complications , Female , Glomerulonephritis/complications , Glomerulonephritis/physiopathology , Humans , Hypertension/drug therapy , Hypertension, Renal/complications , Japan , Male , Middle Aged , Nephritis/complications , Prospective Studies , Renal Insufficiency, Chronic/etiology , SystoleABSTRACT
TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) is thought of as an atypical type of idiopathic multicentric Castleman's disease. Interleukin-6, vascular endothelial growth factor (VEGF), and other cytokines are considered etiological factors. A 45-year-old woman was admitted to hospital with unknown fever and abdominal pain. She had thrombocytopenia, anasarca, proteinuria/hematuria, and slight hepatosplenomegaly. Based on her clinical course and laboratory data, she was diagnosed as having TAFRO syndrome. Kidney biopsy showed a membranoproliferative glomerulonephritis (MPGN)-like lesion containing lobulations of glomeruli, endothelial cell swelling, double contours of the glomerular basement membrane, and mesangiolysis. She was treated with methylprednisolone pulse (500 mg/day) and oral prednisolone (60 mg/day) therapy. The pleural effusion and ascites disappeared, and renal function normalized. Cyclosporine was added to prevent relapse. She went home, with no relapse 8 months after hospitalization. MPGN-like lesions were found frequently in patients with TAFRO syndrome in recent reports. However, there are few reports of pathologically confirmed cases of progressive renal involvement in TAFRO syndrome. The relationship between VEGF expression in renal tissue and the pathogenesis of renal injury in TAFRO syndrome was investigated in the present case.
Subject(s)
Castleman Disease/blood , Castleman Disease/drug therapy , Castleman Disease/pathology , Kidney/pathology , Vascular Endothelial Growth Factor A/metabolism , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Castleman Disease/diagnosis , Cyclosporine/administration & dosage , Cyclosporine/therapeutic use , Female , Fever/diagnosis , Fever/etiology , Glomerulonephritis, Membranoproliferative/pathology , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Kidney/blood supply , Kidney Glomerulus/pathology , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Thrombocytopenia/diagnosis , Thrombocytopenia/etiology , Treatment OutcomeABSTRACT
BACKGROUND: Anti-KANNO, a broadly reactive RBC alloantibody, is found among some Japanese pregnant women, but the genetic basis of the corresponding antigen remains unclear. STUDY DESIGN AND METHODS: We integrated a statistical approach to identify the coding gene for KANNO antigen by conducting a genome-wide association study (GWAS) on four KANNO-negative individuals and 415 healthy Japanese. We also applied whole-exome sequencing to them and performed a replication study to confirm the identified genome variation using independent 14 KANNO-negative individuals. A monoclonal antibody-specific immobilization of erythrocyte antigens (MAIEA) assay was used to locate KANNO antigen on RBC-specific membrane protein. In vivo and in vitro binding assays of anti-KANNO were further applied to the cells expressing a candidate protein. RESULTS: The GWAS revealed a genome-wide significant association of chromosome 20p13 locus (p = 2.76E-08; odds ratio > 1000 [95% confidence interval = 48-23,674]). The identified single-nucleotide polymorphism located in an intronic region of the prion protein (PRNP) gene. Whole-exome sequencing revealed a missense variant in the PRNP gene (rs1800014, E219K), which is in linkage disequilibrium with the single-nucleotide polymorphism identified in the GWAS. All 18 KANNO-negative individuals possessed the homozygous genotype of the missense variant. The MAIEA assay using anti-KANNO and mouse antihuman prion protein showed a clear difference between KANNO-positive and KANNO-negative RBCs. Anti-KANNO showed direct binding to CHO-K1 cells expressing wild-type PRNP but not to those expressing E219K PRNP. CONCLUSION: We first identified the coding gene of the high-frequency antigen KANNO located in PRNP and the missense variation (E219K) that affects the seropositivity of the KANNO antigen, which were confirmed by PRNP overexpressed cells.
Subject(s)
Blood Group Antigens/genetics , Chromosomes, Human, Pair 20/genetics , Gene Frequency , Genome, Human , Glycoproteins/genetics , Polymorphism, Single Nucleotide , Prion Proteins/genetics , Genome-Wide Association Study , HumansABSTRACT
The dominant oxidation state of cadmium is +ii. Although extensive investigations into the +ii oxidation state have been carried out, the chemistry of CdI is still largely underdeveloped. Here, we report a new functionality of cadmium created by the zeolite lattice: room temperature O transfer from N2O to CO mediated by the nearest monovalent cadmium ions in MFI zeolite. Thermal activation of CdII ion-exchanged MFI zeolite in vacuo affords the diamagnetic [CdI-CdI]2+ species with a short CdI-CdI σ bond (2.67 Å). This species generates two CdIË sites under UV irradiation through homolytic cleavage of the CdI-CdI σ bond, and the thus-formed nearest CdIË sites abstract an O atom from N2O to generate the [CdII-Ob-CdII]2+ core, where Ob means bridged oxygen. This bridging atomic oxygen species is transferred to CO at room temperature, through which CO oxidation and regeneration of the CdI-CdI σ bond then proceed. This is the first example pertaining to the reversible redox reactivity of the nearest monovalent cadmium ions toward stable small molecules. In situ spectroscopic characterization captured all the intermediates in the reaction processes, and these data allowed us to calibrate the density-functional-theory cluster calculations, by means of which we were able to show that the charge compensation requirement at the nearest two Al sites arrayed circumferentially in the 10-membered ring of MFI zeolite creates such novel functionalities of cadmium. The unprecedented reactivity of CdI and its origin are discussed.