Diabetic Kidney Disease

Alicic, Radica Z.; Rooney, Michelle Nayahamui; Tuttle, Katherine R.

doi:10.2215/cjn.11491116

Cited by 1,859 publications

(971 citation statements)

References 75 publications

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“…Podocytes decreased in frequency by >10-fold in diabetic mice (to 12 out of 14,837 total cells, 0.08%), consistent with previous reports that podocytes are one of the earliest cell types to be damaged and lost in DKD ( Fig. 3C) [39][40][41] . HyPRseq also detected an increase in thick ascending limb/distal convoluted tubule (TAL/DCT) cells and a decrease in endothelial cells, in agreement with early changes observed in DKD ( Fig.…”

Section: Measuring Cell Type Frequencies and Low-abundance Genes In Tsupporting

confidence: 91%

HyPR-seq: Single-cell quantification of chosen RNAs via hybridization and sequencing of DNA probes

Marshall

Doughty

Subramanian

et al. 2020

Preprint

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Single-cell quantification of RNAs is important for understanding cellular heterogeneity and gene regulation, yet current approaches suffer from low sensitivity for individual transcripts, limiting their utility for many applications. Here we present Hybridization of Probes to RNA for sequencing (HyPR-seq), a method to sensitively quantify the expression of up to 100 chosen genes in single cells. HyPR-seq involves hybridizing DNA probes to RNA, distributing cells into nanoliter droplets, amplifying the probes with PCR, and sequencing the amplicons to quantify the expression of chosen genes. HyPR-seq achieves high sensitivity for individual transcripts, detects nonpolyadenylated and low-abundance transcripts, and can profile more than 100,000 single cells. We demonstrate how HyPR-seq can profile the effects of CRISPR perturbations in pooled screens, detect time-resolved changes in gene expression via measurements of gene introns, and detect rare transcripts and quantify cell type frequencies in tissue using low-abundance marker genes. By directing sequencing power to genes of interest and sensitively quantifying individual transcripts, HyPR-seq reduces costs by up to 100-fold compared to whole-transcriptome scRNA-seq, making HyPR-seq a powerful method for targeted RNA profiling in single cells.

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Section: Measuring Cell Type Frequencies and Low-abundance Genes In Tsupporting

confidence: 91%

HyPR-seq: Single-cell quantification of chosen RNAs via hybridization and sequencing of DNA probes

Marshall

Doughty

Subramanian

et al. 2020

Preprint

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“…1 Metabolic alterations associated with diabetes lead to renal pathologic changes including tubulointerstitial inflammation and fibrosis, glomerular hypertrophy, and glomerulosclerosis. 1 However, because only less than 10% of patients with diabetes ultimately reach end-stage renal disease, there must be something missing in our understanding of the pathophysiology of DKD. Genetic studies have not identified a major genetic contribution, 2,3 although it is likely that there are important genetic determinants.…”

mentioning

confidence: 99%

The Warburg Effect in Diabetic Kidney Disease

Zhang

Darshi

Sharma

2018

Seminars in Nephrology

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Summary Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in diabetic patients. Defining risk factors for DKD using a reductionist approach has proven challenging. Integrative omics-based systems biology tools have shed new insights in our understanding of DKD and have provided several key breakthroughs for identifying novel predictive and diagnostic biomarkers. In this review, we highlight the role of the Warburg effect in DKD and potential regulating factors such as sphingomyelin, fumarate, and pyruvate kinase muscle isozyme M2 in shifting glucose flux from complete oxidation in mitochondria to the glycolytic pathway and its principal branches. With the development of highly sensitive instruments and more advanced automatic bioinformatics tools, we believe that omics analyses and imaging techniques will focus more on singular-cell-level studies, which will allow in-depth understanding of DKD and pave the path for personalized kidney precision medicine.

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“…These risk factors can be classified as those relating to susceptibility, initiation, and progression. The following factors are considered to influence progression: ethnicity; systemic conditions, including control of hyperglycemia, overweight, and hypertension; factors leading to acute kidney injury (AKI); and high protein intake (15). However, these risk factors cannot completely explain the rapid progression of DKD in the current study cohort.…”

Section: Discussionmentioning

confidence: 92%

Implications of a Family History of Diabetes and Rapid eGFR Decline in Patients With Type 2 Diabetes and Biopsy-Proven Diabetic Kidney Disease

et al. 2019

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Objective: This study aimed to identify the risk factors for a rapid decline in the estimated glomerular filtration rate (eGFR) in Chinese patients with type 2 diabetes and biopsy-proven diabetic kidney disease (DKD). Method:This was a retrospective cohort study. Patients with biopsy-proven DKD who had been followed-up for at least 1 year were enrolled. Baseline clinicopathological data and serum creatinine levels that had been measured at least three times during follow-up in our hospital were collected. Patients were allocated to two groups of rapid decliners and slow decliners according to the median eGFR slope. The associations between potential risk factors and rapid eGFR decline were analyzed using logistic regression.Results: A total of 128 eligible patients were enrolled and they had a mean age of 51.5 ± 10.7 years. During a median follow-up of 2 years, the median eGFR slope was −8.1 ± 14.4 mL/min/1.73 m 2 /year. The eGFR decline was significantly faster in patients with a family history of diabetes in first-degree relatives, nephrotic-range proteinuria, higher grades of glomerular pathology, and interstitial inflammation. No differences in the rate of the eGFR decline were observed in subgroups created according to sex, age, hypertension, glycosylated hemoglobin, diabetic retinopathy, interstitial fibrosis, and tubular atrophy. Logistic regression indicated that a family history of diabetes was independently associated with a rapid decline in eGFR, even after adjustment for factors including baseline eGFR and proteinuria. Conclusion:A family history of diabetes in first-degree relatives is independently associated with a rapid decline in eGFR in the current relatively young studied patients. Our findings suggested that early diagnosis and treatment is important for these patients.

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Diabetic Kidney Disease

Abstract: Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide.

Cited by 1,859 publications

References 75 publications

HyPR-seq: Single-cell quantification of chosen RNAs via hybridization and sequencing of DNA probes

HyPR-seq: Single-cell quantification of chosen RNAs via hybridization and sequencing of DNA probes

The Warburg Effect in Diabetic Kidney Disease

Implications of a Family History of Diabetes and Rapid eGFR Decline in Patients With Type 2 Diabetes and Biopsy-Proven Diabetic Kidney Disease

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