A zebrafish model of infection-associated acute kidney injury

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

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Role of Urinary Beta 2 Microglobulin and Kidney Injury Molecule-1 in Predicting Kidney Function at One Year Following Acute Kidney Injury

International Journal of Nephrology and Renovascular Disease ◽

10.2147/ijnrd.s319933 ◽

2021 ◽

Vol Volume 14 ◽

pp. 225-234

Author(s):

Dhanin Puthiyottil ◽

PS Priyamvada ◽

Mattewada Naveen Kumar ◽

Anand Chellappan ◽

Bobby Zachariah ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Function ◽

Kidney Injury ◽

Beta 2 ◽

One Year ◽

Beta 2 Microglobulin ◽

Kidney Injury Molecule 1

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The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity

International Journal of Molecular Sciences ◽

10.3390/ijms20205238 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5238 ◽

Cited By ~ 12

Author(s):

Daniela Maria Tanase ◽

Evelina Maria Gosav ◽

Smaranda Radu ◽

Claudia Florida Costea ◽

Manuela Ciocoiu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

In Vivo Studies ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Induced Apoptosis ◽

Kidney Injury Molecule 1

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

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Acute kidney injury in term infants with asphyxia and the role of ACE, AGT2R1, eNOS genes polymorphisms in its development

SOVREMENNAYA PEDIATRIYA ◽

10.15574/sp.2016.76.109 ◽

2016 ◽

Vol 76 (4) ◽

pp. 109-112

Author(s):

O. Korobka ◽

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Term Infants

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Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity

Scientific Reports ◽

10.1038/s41598-020-80853-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masashi Arita ◽

Satoshi Watanabe ◽

Nobumasa Aoki ◽

Shoji Kuwahara ◽

Ryo Suzuki ◽

...

Keyword(s):

Anticancer Agents ◽

Cell Injury ◽

Kidney Injury ◽

Antitumor Effects ◽

Cisplatin Nephrotoxicity ◽

Proximal Tubular ◽

Nephrotoxic Drugs ◽

Kidney Injury Molecule 1 ◽

Dose Dependent

AbstractCisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

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Are Tubular Injury Markers NGAL and KIM-1 Useful in Pediatric Neurogenic Bladder?

Journal of Clinical Medicine ◽

10.3390/jcm10112353 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2353

Author(s):

Joanna Bagińska ◽

Agata Korzeniecka-Kozerska

Keyword(s):

Neurogenic Bladder ◽

Kidney Injury ◽

Healthy Children ◽

Tubular Injury ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Activity Assessment ◽

Kidney Injury Molecule 1 ◽

Tract Infections ◽

Neutrophil Gelatinase

The lack of early biomarkers of renal damage in children with neurogenic bladder (NB) prompts us to investigate the role of promising proteins: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). This prospective analysis was conducted on 58 children with NB and 25 healthy children. We assessed urinary levels of NGAL and KIM-1 in both groups. Age, sex, anthropometric measurements, activity assessment, renal function, and urodynamics parameters were analyzed. The differences between the median uNGAL and uKIM-1 in the NB group compared to control were recorded. However, only uNGAL levels were statistically significantly higher. Statistically significant correlation was found between gender, recurrent urinary tract infections, bladder trabeculation, its compliance, activity assessment, and uNGAL. To conclude, elevated levels of uNGAL may be considered a biomarker of tubular injury in children with NB due to MMC in contrast to uKIM-1.

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