Long-Term Outcomes in Patients with Acute Kidney Injury

Noble, Rebecca; Lucas, Bethany; Selby, Nicholas M.

doi:10.2215/cjn.10410919

Cited by 73 publications

(65 citation statements)

References 77 publications

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“…There is no specific treatment for AKI apart from passive support or renal replacement therapy such as volume control or dialysis in clinic (Moore et al, 2018). It is urgent, therefore, to develop specific and effective treatment for AKI to reduce mortality and prevent its progression to chronic kidney disease (Mehta et al, 2015;Noble et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Chen

Zhang

et al. 2020

J Pharmacol Exp Ther

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Caspase-3 siRNA CASP3siRNA, targeting murine caspase-3 mRNA (NCBI CoreNucleotide Accession No. BC038825), were synthesized (Life Technologies, Paisley, UK). The sequences of the CASP3siRNA (Ambion In Vivo, catalogue number: 4457309) were sense 5'-CCUGGUUACUAUUCCUGGAtt-3' and antisense 5'-UCCAGGAAUAGUAACCAGGtg-3'. The negative control siRNA (NCsiRNA) was also provided by Life Technologies (Ambion In Vivo, catalogue number: 4457289), with sequences of sense 5'-UAACGACGCGACGACGUAAtt-3' and antisense 5'-UUACGUCGUCGCGUCGUUAtt-3'. Both CASP3siRNA and NCsiRNA were chemically modified by locked nuclei acid. Renal IR surgery Male C57BL/6 mice, 8-12 weeks, were purchased from the Experimental Animal Center of Yangzhou University, China. All animal experiments were performed according to the guidelines of the Laboratory Animal Monitoring Committee of Jiangsu Province.

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Section: Introductionmentioning

confidence: 99%

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Chen

Zhang

et al. 2020

J Pharmacol Exp Ther

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“…While urinary stones are notorious for causing severe pain and renal colic, morbidity has traditionally been linked to urinary tract obstruction and/or infection (3). Acute kidney injury (AKI) is defined by an abrupt decrease in renal function and has been strongly linked to increases in morbidity and mortality (4)(5)(6)(7). USD-associated AKI is most often attributed to the obstruction of a solitary kidney or both kidneys simultaneously and occurs in 1-2% of adult stone formers (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Acute Kidney Injury Associated With Urinary Stone Disease in Children and Young Adults Presenting to a Pediatric Emergency Department

et al. 2020

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Background: Acute kidney injury (AKI) due to urinary stone disease (USD) is rare in adults; AKI rates in children with USD may be higher, and emerging data links stones to chronic kidney disease (CKD) development in adults.Methods: This study is a retrospective analysis of USD patients at a single pediatric hospital system's emergency department (ED). Patients were initially identified by USD ICD codes; USD was then confirmed by imaging or physician documentation; patients had to have baseline creatinine (Cr) and Cr in the ED for comparison to be included. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO), Acute Kidney Injury Network (AKIN), and Pediatric Risk, Injury, Failure, Loss, End Stage (pRIFLE).Results: Of the 589 total visits, 264/589 (45%) had data to evaluate for AKI, 23% were AKI(+) and 77% were AKI(–). pRIFLE was most common (82%) and 18% were only positive by AKIN/KDIGO. AKI(+) were more likely to be younger (16.7 vs. 17.4 years, p = 0.046) and more likely to present with vomiting {odds ratio [OR] [95% confidence interval (CI)]: 2.4 [1.4–4.3], p = 0.002}; also, the proportion of AKI(+) was significantly higher in <18 vs. ≥18 years [26.9 vs. 15.5%, p = 0.032, OR (95% CI): 2.0 (1.1–3.9)]. Urinary tract infection (UTI) and obstruction rates were similar between groups. AKI(+) patients had a significant OR <1 suggesting less risk of receiving non-steroidal anti-inflammatory drugs (NSAIDs); however, 51% of them did receive NSAIDs during their ED encounter. AKI(+) patients were more likely to require admission to the hospital (53 vs. 32%, p = 0.001).Conclusion: We have demonstrated a novel association between USD-induced renal colic and AKI in a group of young adults and children. AKI(+) patients were younger and were more likely to present with vomiting. AKI(+) patients did not have higher rates of obstruction or UTI, and 51% of AKI(+) received NSAIDs.

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“…There is no speci c treatment for AKI apart from passive support or renal replacement therapy such as volume control or dialysis in clinic (Moore et al, 2018). It is urgent, therefore, to develop speci c and effective treatment for AKI to reduce mortality and prevent its progression to chronic kidney disease (Mehta et al, 2015;Noble et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

Wu¹,

Chen²,

Zhang³

et al. 2020

Preprint

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Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation, (CASP3siRNA) on ischemia/reperfusion (IR)-induced AKI. Utilizing a mouse model with 30-min renal bilateral ischemia and 48-h reperfusion, the renoprotection of CHBP or CASP3siRNA was demonstrated in renal function and structure, active caspase-3 and HMGB1 expression. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, differentially expressed genes (DEGs) were identified with fold change > 1.414 and P < 0.05. In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6, SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). This proof-of-effect study indicated the potent renoprotection of CASP3siRNA upon CHBP at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.

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Long-Term Outcomes in Patients with Acute Kidney Injury

Cited by 73 publications

References 77 publications

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Acute Kidney Injury Associated With Urinary Stone Disease in Children and Young Adults Presenting to a Pediatric Emergency Department

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

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