ライフサイエンスコーパス: DKD

1 DKD clinical studies have similarly demonstrated that st

2 DKD is a prototypical disease of gene and environmental

3 DKD is an important contributor to the morbidity of pati

4 DKD is characterized by an accumulation of extracellular

5 DKD risk was assigned in youth with type 1 diabetes (n =

6 DKD samples were significant for their racial diversity

7 DKD usually develops in a genetically susceptible indivi

8 ion in the kidneys of mouse models of type 1 DKD.

9 iabetes, despite excessive AER in Cluster 2, DKD glomerular lesions and podocyte structural parameter

10 ins, was analyzed in kidney biopsies from 40 DKD patients and 10 normal controls using laser microdis

11 on on diabetic mouse models would accelerate DKD.

12 FR decline in persons with early or advanced DKD.

13 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD populat

14 Given the multiple factors affecting DKD and the graded differences in disease severity acros

15 ide levels and that MTP-131 protects against DKD and preserves physiological superoxide levels, possi

16 been implicated in the pathogenesis of AKI, DKD and glomerular disorders.

17 tients with type 1 diabetes and albuminuria (DKD(+)) when compared with diabetic patients with normoa

18 ed weight and glycemic status and alleviated DKD but not DPN.

19 Although DKD is not typically classified as an inflammatory glome

20 (KP6) mimics Klotho function and ameliorates DKD.

21 renal superoxide production and ameliorating DKD.

22 (OR 1.43, 95% CI 1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17-1.51, P < 0.001).

23 e profile between DKD-resistant C57BL/6J and DKD-susceptible DBA/2J (D2) glomeruli and demonstrated a

24 rogression in experimental models of AKI and DKD.

25 tion between rs1564939 in the GLRA3 gene and DKD in T2DM (P = 0.016, odds ratio = 0.54 per allele C).

26 in persons with type 2 diabetes mellitus and DKD (T2DKD).

27 rticipants with type 2 diabetes mellitus and DKD and was associated with an increase in diastolic BP.

28 idence for a causal link between obesity and DKD in type 1 diabetes.

29 Conclusions: In patients with OSA and DKD, the prescription of CPAP did not result in a statis

30 est associations between single variants and DKD.

31 tegy to treat diabetic complications such as DKD.

32 ared the early transcriptome profile between DKD-resistant C57BL/6J and DKD-susceptible DBA/2J (D2) g

33 atistically differentially regulated in both DKD glomeruli and tubuli and was associated with increas

34 ons in a type 2 diabetes mouse model of both DKD and DPN.

35 Here, we compare DKD structural-functional relationships in type 1 and ty

36 ry bulb neurons, the phenotypes of complexin DKD and DKO neurons.

37 Furthermore, the complexin DKD but not the complexin DKO caused a compensatory incr

38 Current DKD treatments have expanded to include renin-angiotensi

39 f early (ACCORD) and advanced (VA NEPHRON-D) DKD.

40 ight glucose control significantly decreases DKD incidence, indicating that hyperglycemia-induced met

41 We find that complexin-deficient DKD and DKO neurons invariably exhibit a ~50% decrease i

42 ycemia enhance the future risk of developing DKD despite subsequent glycemic control.

43 cts bestowed the greatest risk of developing DKD in a multivariable model that included HbA1c and oth

44 e results indicate that, in type 2 diabetes, DKD is associated with reduced renal and cardiac superox

45 -cause and cardiovascular death in diabetes, DKD is a major contributor to the progressively expandin

46 sing CKD, including diabetic kidney disease (DKD) and Alport syndrome, is unknown.

47 Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are two co

48 lobal prevalence of diabetic kidney disease (DKD) and end-stage renal disease (ESRD) are rising year

49 he highest risk for diabetic kidney disease (DKD) and fatty liver, emphasizing the importance of insu

50 Diabetic kidney disease (DKD) and its major clinical manifestation, progressive r

51 e identification of diabetic kidney disease (DKD) are needed as current tests lack sensitivity for de

52 Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mor

53 nts with type 2 diabetes and kidney disease (DKD) conventionally define a surrogate endpoint either a

54 largely persist in diabetic kidney disease (DKD) despite reversing hyperglycemia.

55 on are critical for diabetic kidney disease (DKD) development.

56 dent or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes.

57 Diabetic kidney disease (DKD) is a major complication of diabetes and the leading

58 Diabetic kidney disease (DKD) is a major driver of morbidity and mortality worldw

59 Diabetic kidney disease (DKD) is a microvascular complication that leads to kidne

60 Diabetic kidney disease (DKD) is a serious complication of hyperglycemia.

61 on in patients with diabetic kidney disease (DKD) is associated with increased lipid deposition in gl

62 Diabetic kidney disease (DKD) is associated with oxidative stress and mitochondri

63 apeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting pr

64 Early diabetic kidney disease (DKD) is marked by dramatic metabolic reprogramming due t

65 Diabetic kidney disease (DKD) is now the principal cause of chronic kidney diseas

66 Diabetic kidney disease (DKD) is one of the most common and devastating complicat

67 Diabetic kidney disease (DKD) is one of the most common complications of diabetes

68 Diabetic kidney disease (DKD) is recognized as an important public health challen

69 s with diabetes and diabetic kidney disease (DKD) is responsible for close to half of all chronic kid

70 Diabetic kidney disease (DKD) is responsible for close to half of all ESKD cases.

71 Diabetic kidney disease (DKD) is the leading cause of end stage kidney failure wo

72 Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease.

73 Diabetic kidney disease (DKD) is the leading cause of end-stage renal failure, an

74 Diabetic kidney disease (DKD) is the leading cause of ESRD.

75 Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide an

76 Diabetic kidney disease (DKD) is the leading cause of progressive chronic kidney

77 Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) a

78 Diabetic kidney disease (DKD) is the main cause of chronic kidney disease worldwi

79 Diabetic kidney disease (DKD) is the single leading cause of kidney failure in th

80 Diabetic kidney disease (DKD) is the single most common cause of albuminuria and

81 , the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabe

82 Diabetic kidney disease (DKD) progression is not well understood.

83 ogenetic markers of diabetic kidney disease (DKD) progression to ESRD are lacking.

84 the main drivers of diabetic kidney disease (DKD) progression.

85 tion/progression of diabetic kidney disease (DKD) remain poorly understood.

86 Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney d

87 air for classifying diabetic kidney disease (DKD) severity, whereas the covariate-adjusted TSP method

88 the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.

89 Diabetic kidney disease (DKD) typically presents with a reduced estimated glomeru

90 and progression of diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellit

91 Diabetic kidney disease (DKD), also known as diabetic nephropathy, is the leading

92 disease (MASLD) and diabetic kidney disease (DKD), among others.

93 l neuropathy (DPN), diabetic kidney disease (DKD), and diabetic retinopathy (DR) contribute to signif

94 ent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data

95 the progression of diabetic kidney disease (DKD), but their contribution to organ damage in DKD rema

96 Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney

97 ved in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-s

98 titial fibrosis and diabetic kidney disease (DKD), loss of bicaudal C is associated with cystic kidne

99 racterized in human diabetic kidney disease (DKD), unbiased tissue proteomics information for this co

100 mplications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury assoc

101 and progression of diabetic kidney disease (DKD).

102 y for patients with diabetic kidney disease (DKD).

103 and progression of diabetic kidney disease (DKD).

104 the development of diabetic kidney disease (DKD).

105 ts and therapies in diabetic kidney disease (DKD).

106 li of patients with diabetic kidney disease (DKD).

107 ays a major role in diabetic kidney disease (DKD).

108 CKD, also known as diabetic kidney disease (DKD).

109 r susceptibility to diabetic kidney disease (DKD).

110 the early onset of diabetic kidney disease (DKD).

111 of ETC integrity in diabetic kidney disease (DKD).

112 vascular damage in diabetic kidney disease (DKD).

113 rgan damage such as diabetic kidney disease (DKD).

114 pdx1 also leads to diabetic kidney disease (DKD).

115 ontributes to early diabetic kidney disease (DKD).

116 the pathogenesis of diabetic kidney disease (DKD).

117 amaged podocytes in diabetic kidney disease (DKD).

118 logical mediator of diabetic kidney disease (DKD).

119 as been linked with diabetic kidney disease (DKD).

120 kely to provide therapeutic benefit for DPN, DKD, or DR in T2D.

121 therapy on T2D, and the pathogenesis of DPN, DKD and DR.

122 ver, it is conceptually challenging in early DKD because of non-linear intra-individual eGFR trajecto

123 ssion of human VEGFC was protective in early DKD.

124 ine, and histomorphometric evidence of early DKD as compared to db/db mice.

125 ine, and histomorphometric evidence of early DKD as compared to db/db mice.

126 DKD population (NEPHRON-D) than in the early DKD population (ACCORD).

127 nfirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n

128 t three residues of DesA3 showed that either DKD or LEA gave the best enhancement of stability for th

129 In murine models of streptozotocin-elicited DKD, B-hydroxybutyrate therapy inhibited GSK3B and reinf

130 signaling in vitro and prevents established DKD progression in vivo.

131 rials conducted in patients with established DKD will facilitate further refinement of current guidel

132 e-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection

133 ASOs) targeting CHOP ameliorate experimental DKD.

134 port characterizes clinical and experimental DKD and negatively influences podocyte function.

135 isease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis (FIDELITY),

136 kidney disease and type 2 diabetes (FIDELIO-DKD and FIGARO-DKD) and a trial of heart failure (HF) wi

137 ia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a ba

138 participant-level pooled analysis of FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF (FINE-HEART), cardiovas

139 In the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease P

140 prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD studies, finerenone was found to impr

141 renal and cardiovascular risk in the FIDELIO-DKD and FIGARO-DKD trials.

142 The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Dis

143 with CKD and type 2 diabetes in the FIDELIO-DKD trial.

144 phase 3 randomized clinical trials: FIDELIO-DKD and FIGARO-DKD, conducted between September 2015 and

145 ssion in Diabetic Kidney Disease) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and

146 ooled analysis of the FIDELIO-DKD and FIGARO-DKD studies, finerenone was found to improve cardiorenal

147 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis (FIDELITY), a pooled analys

148 ovascular risk in the FIDELIO-DKD and FIGARO-DKD trials.

149 and type 2 diabetes (FIDELIO-DKD and FIGARO-DKD) and a trial of heart failure (HF) with mildly reduc

150 ized clinical trials: FIDELIO-DKD and FIGARO-DKD, conducted between September 2015 and February 2021.

151 level pooled analysis of FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF (FINE-HEART), cardiovascular outcom

152 the prospective testing of these agents for DKD.

153 m the Chronic Renal Insufficiency Cohort for DKD phenotypes, including glycemic control, albuminuria,

154 is no effective therapeutic intervention for DKD.

155 ing the importance of insulin resistance for DKD and hepatosteatosis in T2D.

156 Individuals at high risk for DKD had persistent elevations in uACR defined by area un

157 and establish PP2A as a potential target for DKD progression.

158 ding RNAs as biomarkers and drug targets for DKD.

159 d in combination with first line therapy for DKD.

160 red human podocytes with sera collected from DKD patients, who displayed elevated TNF levels, and foc

161 idney cortex C1P content and to protect from DKD.

162 vel, poor prognostic indicators of time from DKD to ESRD.

163 lar epithelial cells almost completely halts DKD development.

164 stic role of such epigenetic memory in human DKD and to identify new therapeutic targets, we profiled

165 identify NOX5 as a superior target in human DKD compared with other NOX isoforms such as NOX4, which

166 In human DKD, increased urine 8-oxo-deoxyguanosine was associated

167 bese model that mimics key features in human DKD, to evaluate the effect of RDNx on the progression o

168 icroarray analysis and comparison with human DKD showed common pathways affected in human disease and

169 s, ameliorated glycemic status, and improved DKD, but did not impact percent fat mass and DPN.

170 ieved competitive classification accuracy in DKD to LASSO and random forests, while providing more pa

171 tly contributing to complement activation in DKD is of particular interest.

172 infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease.

173 lure, a major cardiovascular complication in DKD.

174 kidney inflammation as a key contributor in DKD pathogenesis, particularly through macrophages.

175 ), but their contribution to organ damage in DKD remains largely unknown.

176 osamine synthesis were also downregulated in DKD glomeruli, but this alteration remained undetectable

177 contribute to sustained renal dysfunction in DKD.

178 uria, and negatively correlated with eGFR in DKD patients.

179 re, our study shows Complement engagement in DKD progression and lays the groundwork for developing b

180 rging role of epigenetics and epigenomics in DKD and the translational potential of candidate epigene

181 thelial cells representing an early event in DKD progression, and suggest that cross talk between glo

182 tified, and their differential expression in DKD was assessed.

183 in-depth evidence for epigenetic features in DKD and AKI, and in epigenetic memories of AKI-to-CKD tr

184 ce to determine the possible role of FHL2 in DKD and to clarify its association with the Wnt pathway.

185 e prognostic value of histologic findings in DKD for time to ESRD in native kidney specimens from bio

186 ed in glomerular endothelial cells (GECs) in DKD.

187 ion characteristic of sclerotic glomeruli in DKD.

188 dy key human kidney cell types implicated in DKD (podocytes, glomerular endothelial, mesangial and pr

189 rises, this finding predicts an increase in DKD prevalence unless intervention should occur.

190 elated urinary metabolites were increased in DKD, but fumarate levels were uniquely reduced by the NO

191 ponding phenotypic changes of macrophages in DKD remain poorly understood.

192 pro-oxidant enzyme NADPH oxidase 5 (NOX5) in DKD, independent of the previously characterized NOX4 pa

193 arkers of inflammation and renal outcomes in DKD.

194 g a new immunometabolic signaling pathway in DKD.

195 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli, and 330 prob

196 ontributing to TEC injury and progression in DKD remain unclear.

197 dal MRAs have anti-albuminuric properties in DKD.

198 ific enzymes involved in lipid remodeling in DKD have not been elucidated.

199 ATG specifically provides renoprotection in DKD is not known.

200 cular endothelial growth factor signaling in DKD glomeruli.

201 may serve as a future therapeutic target in DKD.

202 of a podocyte-targeted VEGFC gene therapy in DKD.

203 ic lncRNA, as a key candidate upregulated in DKD.

204 Incident DKD (11.9%) was defined as an estimated glomerular filtr

205 ecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D).

206 case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort s

207 global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of k

208 tified 338 genes altered in diabetes-induced DKD glomeruli, and PLK2 exhibited the most dramatic chan

209 ure experiments and a streptozotocin-induced DKD model in FHL2 gene-knockout mice to determine the po

210 , and FinnGen Project data) and T1DM-induced DKD (UK-ROI cohort data from Belfast, UK).

211 tistics from three cohorts with T2DM-induced DKD (Bio Bank Japan data, UK Biobank, and FinnGen Projec

212 ted multiple signaling pathways are involved DKD pathogenesis.

213 nd of mouse neurons with a double knockdown (DKD) of complexin-1 and -2 suggested that complexin main

214 tage and several selective features of later DKD in adult mutants.

215 el gene expression changes between the mouse DKD model and patients, they observed consistent pathway

216 ith diabetic patients with normoalbuminuria (DKD(-)) and similar duration of diabetes and lipid profi

217 95% confidence interval (CI): 33.6, 1105] of DKD compared with noncarriers (P = 3.59 x 10-9).

218 al therapeutic agent for the amelioration of DKD.

219 Incident cases of DKD were identified after ~ 6-year.

220 opagating renal injury in the development of DKD by disrupting mitochondrial agility, thereby establi

221 characteristic change in the development of DKD.

222 nal function, and a more recent diagnosis of DKD.

223 ular hypertrophy as initial establishment of DKD similar to the pdx1-/- larvae.

224 diate the persistent long-term expression of DKD-related genes and phenotypes induced by prior glycae

225 that genes associated with these features of DKD are regulated not only by classical signalling pathw

226 However, the continued high incidence of DKD reinforces the urgent need for additional biomarkers

227 KD and correlated with structural lesions of DKD.

228 sion in diabetic mice and reduced markers of DKD at the early and late stages.

229 ts into the pathophysiological mechanisms of DKD.

230 In either an accelerated model of DKD induced by streptozotocin and advanced oxidation pro

231 erstitial fibrosis in a male murine model of DKD.

232 matrix accumulation in the F1 Akita model of DKD.

233 e streptozotocin (HFD + STZ) mouse models of DKD experienced sudden death and greater arrhythmia indu

234 In preclinical models of DKD, overexpression of NOX5 in Nox4-deficient mice enhan

235 nd podocytes of patients and mouse models of DKD.

236 proteins are involved in the pathogenesis of DKD and its progression to end-stage kidney disease (ESK

237 during tubular injury in the pathogenesis of DKD and suggest d-glucarate as a potential therapeutic a

238 at C1-Ten contributes to the pathogenesis of DKD by inducing podocyte hypertrophy under high glucose

239 ator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes.

240 reatment strongly blocks the pathogenesis of DKD induced by both type 2 and type 1 diabetes.

241 that may play a role in the pathogenesis of DKD or could serve as biomarkers.

242 an improvement of predictive performance of DKD risk between 1.1 and 2.4%; and improved classificati

243 ytes, and mitochondria in the early phase of DKD in mice.

244 present a distinct pathogenetic phenotype of DKD will require a large study with a broad spectrum of

245 med using baseline metabolites predictive of DKD progression in our longitudinal Diabetes Heart Study

246 betes, without a change in the prevalence of DKD among those with diabetes.

247 Prevalence of DKD in the United States increased from 1988 to 2008 in

248 The prevalence of DKD in the US population was 2.2% (95% confidence interv

249 The prevalence of DKD increased in direct proportion to the prevalence of

250 Among persons with diabetes, prevalence of DKD was stable despite increased use of glucose-lowering

251 mpact of preterm birth on the progression of DKD has not been studied.

252 ate the effect of RDNx on the progression of DKD in the early and late stages of diabetic nephropathy

253 on the effect of RDNx on the progression of DKD in type 2 diabetes.

254 nctional loss of SCO2, in the progression of DKD using a murine model of Type II Diabetes Mellitus, d

255 nctional loss of SCO2, in the progression of DKD using a murine model of Type II Diabetes Mellitus, d

256 and intra-individually stable progression of DKD.

257 d prevent inflammation in and progression of DKD.

258 lomerulosclerosis even in a different set of DKD samples.

259 Identification of epigenetic signatures of DKD via epigenome-wide association studies might also in

260 epigenetic events during the early stages of DKD could be valuable for timely diagnosis and prompt tr

261 dx1 mutant as a novel model for the study of DKD, showing signs of the early disease progression alre

262 In the largest WES study of DKD, we identified novel rare variant loci attaining exo

263 ven the large interindividual variability of DKD progression.

264 Its effect on DKD is largely unknown.

265 the effect of apnea-hypopnea suppression on DKD progression is unclear.

266 uminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD.

267 th development of macroalbuminuria, ESRD, or DKD over time.

268 genetic memories of AKI-to-CKD transition or DKD development and progression, followed by translation

269 analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m(2

270 mes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D).

271 results identify novel models of progressive DKD that provide researchers with a facile and reliable

272 oxo-deoxyguanosine was associated with rapid DKD progression, and biopsies from patients with DKD sho

273 AS blockade alone is insufficient to reverse DKD progression.

274 type 2 diabetes in Cluster 1 had more severe DKD lesions and approximately four-fold greater rates of

275 Our studies show that DKD susceptibility was linked to mitochondrial dysfuncti

276 Moreover, the DKD consistently increased spontaneous exocytosis, but t

277 d showed greater AER than predicted by their DKD glomerular lesions based on the model.

278 FHL2 knockout significantly attenuated these DKD-induced changes.

279 a key link connecting metabolic pathways to DKD pathogenesis, and measuring urinary fumarate levels

280 test whether obesity is causally related to DKD using Mendelian randomization, which exploits the ra

281 kk1) also showed increased susceptibility to DKD.

282 esearch efforts will be needed to understand DKD pathogenesis and to identify novel drug targets.

283 While DKD is considered a microvascular complication of diabet

284 Because many genes associate with DKD, multiomics approaches were used to narrow the list

285 defines methylation changes associated with DKD phenotypes, the key role of underlying genetic varia

286 ular transcriptional changes associated with DKD, whereas pairwise bioinformatic analysis was used fo

287 We also demonstrated that humans with DKD have significantly reduced levels of mitochondrion-d

288 rating kidney biopsies from individuals with DKD.

289 vailable, the outlook for people living with DKD should improve in the next few decades.

290 m progression of kidney disease in mice with DKD and Alport syndrome and increases lifespan in Alport

291 characteristic glomerular changes noted with DKD, including glomerular hypertrophy, mesangial matrix

292 progression, and biopsies from patients with DKD showed increased mitochondrial DNA damage associated

293 mmunostaining of biopsies from patients with DKD, we further confirmed a differential expression of s

294 strategy for the treatment of patients with DKD.

295 sses clinical applications for patients with DKD.

296 me association analysis in 500 subjects with DKD from the Chronic Renal Insufficiency Cohort for DKD

297 ort of adults with diabetes, females without DKD had higher serum pyruvate concentrations than did ma

298 oncentrations than did males with or without DKD.

299 Diabetes and eNOS deletion worsened DKD, which improved with RAS treatment.

300 t TEC-specific RTN1A overexpression worsened DKD in mice, evidenced by enhanced tubular injury, tubul