Developing a Radiomics Atlas Dataset of normal Abdominal and Pelvic computed Tomography (RADAPT) DOI Creative Commons
Elisavet Kapetanou, Stylianos Malamas, Dimitrios Leventis

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 37(4), P. 1273 - 1281

Published: Feb. 21, 2024

Atlases of normal genomics, transcriptomics, proteomics, and metabolomics have been published in an attempt to understand the biological phenotype health disease set basis comprehensive comparative omics studies. No such atlas exists for radiomics data. The purpose this study was systematically create a dataset abdominal pelvic that can be used model development validation. Young adults without any previously known disease, aged > 17 ≤ 36 years old, were retrospectively included. All patients had undergone CT scanning emergency indications. In case abnormal findings identified, relevant anatomical structures excluded. Deep learning automatically segment majority visible with TotalSegmentator as applied 3DSlicer. Radiomics features including first order, texture, wavelet, Laplacian Gaussian transformed extracted PyRadiomics. A Github repository created host resulting dataset. data from total 531 mean age 26.8 ± 5.19 years, 250 female 281 male patients. maximum 53 segmented subsequent extraction. derived 526 non-contrast 400 contrast-enhanced (portal venous) series. is publicly available validation purposes.

Language: Английский

Mechanisms of kidney fibrosis and routes towards therapy DOI
N. Yamashita, Rafael Kramann

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 35(1), P. 31 - 48

Published: Sept. 28, 2023

Language: Английский

Citations

32
Perspectives on single-nucleus RNA sequencing in different cell types and tissues DOI Creative Commons
Nayoung Kim, Huiram Kang, Areum Jo

et al.

Journal of Pathology and Translational Medicine, Journal Year: 2023, Volume and Issue: 57(1), P. 52 - 59

Published: Jan. 10, 2023

Single-cell RNA sequencing has become a powerful and essential tool for delineating cellular diversity in normal tissues alterations disease states. For certain cell types conditions, there are difficulties isolating intact cells transcriptome profiling due to their fragility, large size, tight interconnections, other factors. Single-nucleus (snRNA-seq) is an alternative or complementary approach that difficult isolate. In this review, we will provide overview of the experimental analysis steps snRNA-seq understand methods characteristics general tissue-specific data. Knowing advantages limitations increase its use improve biological interpretation data generated using technique.

Language: Английский

Citations

29
Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients DOI Creative Commons
Kumar Sharma, Guanshi Zhang, Jens Hansen

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(20)

Published: Aug. 24, 2023

Diabetic kidney disease (DKD) can lead to end-stage (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes the Chronic Renal Insufficiency Cohort (CRIC) study, Singapore Study of Macro-angiopathy Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), American Indian determined whether urine adenine/creatinine ratio (UAdCR) could be a biomarker ESKD. ESKD mortality were associated highest UAdCR tertile CRIC study SMART2D. was patients macroalbuminuria SMART2D, study. Empagliflozin lowered nonmacroalbuminuric participants. Spatial metabolomics localized adenine pathology, single-cell transcriptomics identified ribonucleoprotein biogenesis as top pathway proximal tubules macroalbuminuria, implicating mTOR. Adenine stimulated matrix tubular cells via mTOR mouse kidneys. A specific inhibitor production found reduce hypertrophy injury diabetic mice. We propose that endogenous may causative factor DKD.

Language: Английский

Citations

29
Unbiased Human Kidney Tissue Proteomics Identifies Matrix Metalloproteinase 7 as a Kidney Disease Biomarker DOI
Daigoro Hirohama, Amin Abedini,

Salina Moon

et al.

Journal of the American Society of Nephrology, Journal Year: 2023, Volume and Issue: 34(7), P. 1279 - 1291

Published: April 5, 2023

Significance Statement Although gene expression changes have been characterized in human diabetic kidney disease (DKD), unbiased tissue proteomics information for this condition is lacking. The authors conducted an aptamer-based proteomic analysis of samples from patients with DKD and healthy controls, identifying proteins levels that associate function (eGFR) or fibrosis, after adjusting key covariates. Overall, only modestly correlated protein levels. Kidney RNA matrix metalloproteinase 7 (MMP7) strongly fibrosis eGFR. Single-cell sequencing indicated tubule cells are important source MMP7. Furthermore, plasma MMP7 predicted future decline. These findings identify as a biomarker blood Background Diabetic (DKD) responsible close to half all ESKD cases. extensively samples, protein-level not available. Methods We collected 23 individuals ten gathered associated clinical demographics information, implemented histologic analysis. performed using the SomaScan platform quantified level 1305 analyzed by bulk single-cell (scRNA-seq). validated separate cohort well 11,030 samples. Results Globally, transcript showed modest correlation. Our identified 14 eGFR found 152 interstitial fibrosis. Of proteins, metalloprotease strongest association both correlation between was external datasets. primary validation Findings scRNA-seq pointed proximal tubules, connecting principal likely cellular sources increased expression. but also prospective Conclusions findings, which underscore value analysis, diagnostic marker

Language: Английский

Citations

25
Role of biophysics and mechanobiology in podocyte physiology DOI
Jonathan C. Haydak, Evren U. Azeloglu

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(6), P. 371 - 385

Published: March 5, 2024

Language: Английский

Citations

16
Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease DOI Creative Commons
Michal Polonsky, Louisa M.S. Gerhardt, Jina Yun

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 5, 2024

Language: Английский

Citations

13
Glycolytic lactate in diabetic kidney disease DOI Creative Commons

Manjula Darshi,

Luxcia Kugathasan, Soumya Maity

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(11)

Published: June 9, 2024

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) not well defined. Urine lactate was measured patients with type 2 diabetes (T2D) 3 cohorts (HUNT3, SMART2D, CRIC). and plasma were during euglycemic hyperglycemic clamps participants 1 (T1D). Patients the HUNT3 cohort DKD had elevated urine levels compared age- sex-matched controls. In SMART2D CRIC cohorts, third tertile lactate/creatinine associated more rapid estimated glomerular filtration rate decline, relative to first tertile. T1D demonstrated strong association between glucose both urine. Glucose-stimulated likely derives part from proximal tubular cells, since production attenuated sodium-glucose cotransporter-2 (SGLT2) inhibition sections SGLT2-deficient mice. Several glycolytic genes human tubules. above 2.5 mM potently inhibited oxidative phosphorylation tubule (HK2) cells. We conclude that increased under conditions can contribute dysfunction become feed-forward component pathogenesis.

Language: Английский

Citations

9
The Road to Precision Medicine for Acute Kidney Injury DOI Open Access
Bethany C. Birkelo, Jay L. Koyner, Marlies Ostermann

et al.

Critical Care Medicine, Journal Year: 2024, Volume and Issue: 52(7), P. 1127 - 1137

Published: June 13, 2024

Acute kidney injury (AKI) is a common form of organ dysfunction in the ICU. AKI associated with adverse short- and long-term outcomes, including high mortality rates, which have not measurably improved over past decade. This review summarizes available literature examining evidence need for precision medicine critical illness, highlights current heterogeneity field AKI, discusses progress made advancing provides roadmap studying precision-guided care AKI.

Language: Английский

Citations

9
Mitochondrial Dysfunction in Kidney Tubulopathies DOI Creative Commons
Charlotte A. Hoogstraten, Joost G.J. Hoenderop, Jeroen H. F. de Baaij

et al.

Annual Review of Physiology, Journal Year: 2023, Volume and Issue: 86(1), P. 379 - 403

Published: Nov. 28, 2023

Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water solute reabsorption processes along the nephron. Moreover, mitochondria contribute cellular health by regulation of autophagy, (oxidative) stress responses, apoptosis. Mitochondrial abundance is particularly high cortical segments, including proximal distal convoluted tubules. Dysfunction has been described for tubulopathies such as Fanconi, Gitelman, Bartter-like syndromes renal tubular acidosis. In addition, mitochondrial cytopathies often affect (tubular) tissues, Kearns-Sayre Leigh syndromes. Nevertheless, mechanisms which dysfunction results diseases are only scarcely being explored. This review provides an overview development progression tubulopathies. Furthermore, it emphasizes need further mechanistic investigations identify links between function electrolyte reabsorption.

Language: Английский

Citations

18
Metabolic reprogramming heterogeneity in chronic kidney disease DOI Creative Commons
Verónica Miguel, Rafael Kramann

FEBS Open Bio, Journal Year: 2023, Volume and Issue: 13(7), P. 1154 - 1163

Published: Feb. 1, 2023

Fibrosis driven by excessive accumulation of extracellular matrix (ECM) is the hallmark chronic kidney disease (CKD). Myofibroblasts, which are cells responsible for ECM production, activated cross talk with injured proximal tubule and immune cells. Emerging evidence suggests that alterations in metabolism not only a feature but also play an influential role pathogenesis renal fibrosis. The application omics technologies to cell-tracing animal models follow-up functional data suggest cell-type-specific metabolic shifts have particular roles fibrogenic response. In this review, we cover main reprogramming outcomes fibrosis provide future perspective on field fibrometabolism.

Language: Английский

Citations

17