Molecular determinants of acute kidney injury

Husi, Holger; Human, Christin

doi:10.5249/jivr.v7i2.615

Cited by 8 publications

(12 citation statements)

References 105 publications

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“…AKI is related to the mechanisms of inflammation, oxidative stress, and apoptosis in cellular and molecular pathways [37, 38]. TIMP-2 and IGFBP7 can participate in these mechanisms and reflect early damage of the kidney [35].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis

et al. 2017

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BackgroundTissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), inducers of G1 cell cycle arrest, are two recently discovered good biomarkers for early diagnosis of acute kidney injury (AKI). To obtain a more robust performance measurement, the present meta-analysis was performed, pooling existing studies.MethodsLiterature in the MEDLINE (via PubMed), Ovid, Embase, and Cochrane Library databases was systematically searched from inception to 12 October 2016. Studies that met the set inclusion and exclusion criteria were identified by two independent investigators. The diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was evaluated by pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses. The causes of heterogeneity were explored by sensitivity and subgroup analyses.ResultsA total of nine published and eligible studies assessing 1886 cases were included in this meta-analysis. Early diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was assessed using a random-effects model. Pooled sensitivity and specificity with corresponding 95% CIs were 0.83 (95% CI 0.79–0.87, heterogeneity I 2 = 68.8%) and 0.55 (95% CI 0.52–0.57, I 2 = 92.9%), respectively. Pooled positive LR, negative LR, and DOR were 2.37 (95% CI 1.87–2.99, I 2 = 82.6%), 0.30 (95% CI 0.21–0.41, I 2 = 43.4%), and 9.92 (95% CI 6.09–16.18, I 2 = 38.5%), respectively. The AUC estimated by SROC was 0.846 (SE 0.027) with a Q* value of 0.777 (SE 0.026). Sensitivity analysis indicated that one study significantly affected the stability of pooled results. Subgroup analysis showed that population setting and AKI threshold were the key factors causing heterogeneity in pooled sensitivity and specificity.ConclusionsOn the basis of recent evidence, urinary [TIMP-2] × [IGFBP7] is an effective predictive factor of AKI.Trial registrationPROSPERO registration number: CRD42016051186. Registered on 10 November 2016.

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Section: Discussionmentioning

confidence: 99%

Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis

et al. 2017

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Section: Discussionmentioning

confidence: 99%

“…AKI is a common condition in patients who are hospitalized for major surgery or are critically ill, and is associated with increased mortality ( 27 ). Previous reports on the molecular mechanisms underlying this disease have been conflicting ( 27 , 28 ). Increasingly, evidence has suggested that apoptosis is the major mechanism underlying early tubule cell death in contemporary clinical AKI ( 29 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

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Aldosterone induces NRK-52E cell apoptosis in acute kidney injury via rno-miR-203 hypermethylation and Kim-1 upregulation

Xiao

Tang

Zhou

et al. 2016

Experimental and Therapeutic Medicine

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Acute kidney injury (AKI) is characterized by an acute reduction in kidney function as identified by an increase in serum creatinine levels and reduction in urine output. Kidney injury molecule-1 (Kim-1) is a hallmark of kidney diseases, since it is typically non-detectable in the non-injured kidney, but upregulated and excreted in the urine during AKI. Aldosterone (Aldo) is a mediator of the renin-angiotensin-Aldo system with a pivotal role in the regulation of salt and extracellular fluid metabolism. In the present study, mice subjected to renal ischemia/reperfusion-induced AKI were investigated. The mice exhibited elevated levels of Aldo and angiotensin II, together with increased Kim-1 expression levels in renal tissue. Treatment of the mice with the Aldo receptor antagonist spironolactone decreased Kim-1 expression levels. These results suggest that Aldo may be associated with the expression of Kim-1 during AKI. However, the molecular mechanism underlying the role of Aldo in Kim-1 expression is unclear, and thus was investigated using NRK-52E cells. Aldo was found to induce the apoptosis of NRK-52E cells via the hypermethylation of rno-microRNA (miR)-203 and upregulation of Kim-1. In addition, luciferase reporter assays demonstrated that Kim-1 was a target gene of rno-miR-203 in NRK-52E cells. Furthermore, Aldo-induced NRK-52E cell apoptosis was reduced by treatment with pre-miR-203 and spironolactone to a greater extent when compared with either alone. The results may provide a promising diagnostic marker or novel therapeutic target for AKI.

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“…These findings would suggest that physical activity exerts its positive effects also through the vitamin D pathway. Summing up, (i) physical activity is shown to increase the circulating levels of vitamin D [43][44][45][46]; (ii) vitamin D is also shown to exert its anti-inflammatory effects through the NKκB inhibition [49]; and (iii) NGAL is shown to be upregulated by induction of the NF-kB pathway [50,51]. The question remains: Does AMTE have any effect on NGAL expression?…”

Section: Introductionmentioning

confidence: 99%

Adapted Moderate Training Exercise Decreases the Expression of Ngal in the Rat Kidney: An Immunohistochemical Study

et al. 2019

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Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of several injuries and is upregulated in inflammatory conditions. Vitamin D was shown to have anti-inflammatory effects and to increase after physical activity. This work aimed to assess, through immunohistochemistry, the effects of an adapted moderate training exercise (AMTE) on the expression of NGAL and vitamin D receptor (VDR) in the kidney and heart of rats. Sixteen rats were distributed into two groups: the sedentary control group and the experimental group, subjected to AMTE on the treadmill for 12 weeks. The results showed the basal expression of NGAL and VDR in both the heart and the kidney in sedentary rats; no differences in the expression of both NGAL and VDR in the heart; and a decreased NGAL and an increased VDR expression in the kidney of rats subjected to AMTE. These results suggest a possible protective role of AMTE on NGAL-associated injuries in the kidney, probably through the vitamin D signaling pathway. Our results represent an interesting preliminary data that may open new horizons in the management of NGAL-associated kidney injuries. However, further studies are needed to confirm these results and to comprehend the specific interaction between NGAL and VDR pathways in the kidney.

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Molecular determinants of acute kidney injury

Cited by 8 publications

References 105 publications

Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis

Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis

Aldosterone induces NRK-52E cell apoptosis in acute kidney injury via rno-miR-203 hypermethylation and Kim-1 upregulation

Adapted Moderate Training Exercise Decreases the Expression of Ngal in the Rat Kidney: An Immunohistochemical Study

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