Human CD36 overexpression in renal tubules accelerates the progression of renal diseases in a mouse model of folic acid-induced acute kidney injury

Background Renal diseases represent a major public health problem. The demonstration that maladaptive repair of acute kidney injury (AKI) can lead to the development of chronic kidney disease (CKD) and end-stage renal disease has generated interest in studying the pathophysiological pathways involved. Animal models of AKI–CKD transition represent important tools to study this pathology. We hypothesized that the administration of multiple doses of folic acid (FA) would lead to a progressive loss of renal function that could be characterized through biochemical parameters, histological classification and nuclear magnetic resonance (NMR) profiling. Methods Wistar rats were divided into groups: the control group received a daily intraperitoneal (I.P.) injection of double-distilled water, the experimental group received a daily I.P. injection of FA (250 mg kg body weight−1). Disease was classified according to blood urea nitrogen level: mild (40–80 mg dL−1), moderate (100–200 mg dL−1) and severe (>200 mg dL−1). We analyzed through biochemical parameters, histological classification and NMR profiling. Results Biochemical markers, pro-inflammatory cytokines and kidney injury biomarkers differed significantly (P < 0.05) between control and experimental groups. Histology revealed that as damage progressed, the degree of tubular injury increased, and the inflammatory infiltrate was more evident. NMR metabolomics and chemometrics revealed differences in urinary metabolites associated with CKD progression. The main physiological pathways affected were those involved in energy production and amino-acid metabolism, together with organic osmolytes. These data suggest that multiple administrations of FA induce a reproducible model of the induction of CKD. This model could help to evaluate new strategies for nephroprotection that could be applied in the clinic.

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Tanshinone IIA Attenuates Renal Fibrosis after Acute Kidney Injury in a Mouse Model through Inhibition of Fibrocytes Recruitment

BioMed Research International ◽

10.1155/2015/867140 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Chunming Jiang ◽

Qiuyuan Shao ◽

Bo Jin ◽

Rujun Gong ◽

Miao Zhang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Folic Acid ◽

Mouse Model ◽

Renal Fibrosis ◽

Kidney Injury ◽

Tanshinone Iia ◽

Novel Therapy ◽

Beneficial Effects ◽

Effective Interventions ◽

Increased Risk

Acute kidney injury (AKI) is associated with an increased risk of developing advanced chronic kidney disease (CKD). Yet, effective interventions to prevent this conversion are unavailable for clinical practice. In this study, we examined the beneficial effects of Tanshinone IIA on renal fibrosis in a mouse model of folic acid induced AKI. We found that Tanshinone IIA treatment significantly attenuated the folic acid elicited kidney dysfunction on days 3, 14, and 28. This effect was concomitant with a much lessened accumulation of fibronectin and collagen in tubulointerstitium 28 days after folic acid injury, denoting an ameliorated renal fibrosis. The kidney protective and antifibrotic effect of Tanshinone IIA was likely attributable to an early inhibition of renal recruitment of fibrocytes positive for both CD45 and collagen I. Mechanistically, Tanshinone IIA treatment not only markedly diminished renal expression of chemoattractants for fibrocytes such as TGFβ1 and MCP-1, but also significantly reduced circulating fibrocytes at the acute phase of kidney injury. These data suggested that Tanshinone IIA might be a novel therapy for preventing progression of CKD after AKI.

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Faculty Opinions recommendation of Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13870977.15308080 ◽

2012 ◽

Author(s):

Antonio Seguro

Keyword(s):

Acute Kidney Injury ◽

Mouse Model ◽

Kidney Injury ◽

Tubular Epithelium ◽

Renal Microcirculation

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Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: a nested case–control study

BMJ Open ◽

10.1136/bmjopen-2020-041543 ◽

2021 ◽

Vol 11 (2) ◽

pp. e041543

Author(s):

Keiko Ikuta ◽

Shunsaku Nakagawa ◽

Kenji Momo ◽

Atsushi Yonezawa ◽

Kotaro Itohara ◽

...

Keyword(s):

Acute Kidney Injury ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Case Control Study ◽

Kidney Injury ◽

Case Control ◽

Renal Diseases ◽

Increased Risk ◽

Nested Case Control ◽

Control Study

ObjectivesThis study aimed to assess whether the combined use of proton pump inhibitors (PPIs) with non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics (penicillins, macrolides, cephalosporins or fluoroquinolones) was associated with an increased risk of acute kidney injury (AKI).DesignA nested case–control study.SettingA health insurance claims database constructed by the Japan Medical Data Center.ParticipantsPatients were eligible if they were prescribed a PPI, NSAID and antibiotic at least once between January 2005 and June 2017. The patients who were new PPI users and did not have any history of renal diseases before cohort entry were included (n=219 082). The mean age was 45 and 44% were women.InterventionsCurrent use of PPIs, NSAIDs, or antibiotics.Primary outcome measuresAcute kidney injury.ResultsDuring a mean follow-up of 2.4 (SD, 1.7) years, 317 cases of AKI were identified (incidence rate of 6.1/10 000 person-years). The current use of PPIs was associated with a higher risk of AKI compared with past PPI use (unadjusted OR, 4.09; 95% CI, 3.09 to 5.44). The unadjusted ORs of AKI for the current use of PPIs with NSAIDs, cephalosporins and fluoroquinolones, compared with the current use of PPIs alone, were 3.92 (95% CI, 2.40 to 6.52), 2.57 (1.43 to 4.62) and 3.08 (1.50 to 6.38), respectively. The effects of concurrent use of PPIs with NSAIDs, cephalosporins or fluoroquinolones remain significant in the adjusted model. The analyses on absolute risk of AKI confirmed the results from the nested case–control study.ConclusionsConcomitant use of NSAIDs with PPIs significantly increased the risk for AKI. Moreover, the results suggested that concomitant use of cephalosporins or fluoroquinolones with PPIs was associated with increased risk of incident AKI.

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Potent efficacy of Stachybotrys microspora triprenyl phenol-7, a small molecule having anti-inflammatory and antioxidant activities, in a mouse model of acute kidney injury

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.174496 ◽

2021 ◽

Vol 910 ◽

pp. 174496

Author(s):

Keita Shibata ◽

Terumasa Hashimoto ◽

Keiji Hasumi ◽

Koji Nobe

Keyword(s):

Acute Kidney Injury ◽

Mouse Model ◽

Small Molecule ◽

Antioxidant Activities ◽

Kidney Injury ◽

Stachybotrys Microspora ◽

Anti Inflammatory

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Tanshinone IIA Protects Against Folic Acid-Induced Acute Kidney Injury

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500403 ◽

2016 ◽

Vol 44 (04) ◽

pp. 737-753 ◽

Cited By ~ 13

Author(s):

Chunming Jiang ◽

Wei Zhu ◽

Qiuyuan Shao ◽

Xiang Yan ◽

Bo Jin ◽

...

Keyword(s):

Acute Kidney Injury ◽

Folic Acid ◽

Salvia Miltiorrhiza ◽

Kidney Injury ◽

Inflammatory Cells ◽

Tanshinone Iia ◽

Nuclear Antigen ◽

Local Inflammatory Response ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Injured Kidney

Tanshinone IIA is a diterpene extracted from Salvia miltiorrhiza, a popular and safe herb medicine that has been widely used in China and other Asian countries. Previous studies have demonstrated the pleiotropic effects of Tanshinone IIA on many disease treatments via its antitoxicity, anti-inflammation, anti-oxidative stress, as well as antifibrosis activities. However, its effect on acute kidney injury (AKI) has not been fully investigated. Here, we show for the first time that systemic administration of Tanshinone IIA can lead to improved kidney function in folic acid-induced kidney injury mice. In the acute phase of AKI, Tanshinone IIA attenuated renal tubular epithelial injury, as determined by histologic changes and the detection of Neutrophil gelatinase-associated lipocalin (NGAL) in the kidney and urine. Additionally, Tanshinone IIA treatment resulted in elevated proliferating cell nuclear antigen (PCNA) expression and decreased inflammatory cells infiltration as well as chemokine expression, suggesting that Tanshinone IIA promoted renal repair following AKI and inhibited local inflammatory response in the injured kidney. This led to decreased long-term fibrosis in the injured kidney, characterized by less accumulation of fibronectin and collagen I in tubulointerstitium. Taken together, these results suggest that Tanshinone IIA may represent a potential approach for AKI treatment.

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Single Cell Profiling of Acute Kidney Injury Reveals Novel Transcriptional Signatures, Mixed Identities and Epithelial-to-Stromal Crosstalk

10.1101/2019.12.30.890905 ◽

2019 ◽

Author(s):

Valeria Rudman-Melnick ◽

Mike Adam ◽

Andrew Potter ◽

Saagar M. Chokshi ◽

Qing Ma ◽

...

Keyword(s):

Acute Kidney Injury ◽

Single Cell ◽

Stromal Cells ◽

Gene Activation ◽

Kidney Injury ◽

Rapid Decline ◽

Renal Tubules ◽

Developmental Gene ◽

Single Cell Profiling

SummaryAcute kidney injury (AKI) is a rapid decline of renal function, with an incidence of up to 67% of intensive care unit patients. Current treatments are merely supportive, emphasizing the need for deeper understanding that could lead to improved therapies. We used single cell RNA sequencing, in situ hybridization and protein expression analyses to create comprehensive renal cell specific transcriptional profiles of multiple AKI stages. We revealed that AKI induces marked dedifferentiation, renal developmental gene activation and mixed identities in injured renal tubules. Moreover, we identified potential pathologic crosstalk between epithelial and stromal cells, and several novel genes involved in AKI. We also demonstrated the definitive effects of age on AKI outcome, and showed that renal developmental genes hold a potential as novel AKI markers. Moreover, our study provides the resource power which will aid in unraveling the molecular genetics of AKI.

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Untargeted Metabolomics Reveals the Protective Effect of a Traditional Chinese Herbal Decoction on Cisplatin-Induced Acute Kidney Injury

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8524132 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Yuyan Li ◽

Xinhui Liu ◽

Siqi Liu ◽

Jiandong Lu ◽

Jianping Chen ◽

...

Keyword(s):

Acute Kidney Injury ◽

Mouse Model ◽

High Performance ◽

Kidney Injury ◽

Underlying Mechanism ◽

Lysine Biosynthesis ◽

Chinese Herbal ◽

Flight Mass Spectrometry ◽

Herbal Decoction ◽

Group A

Our previous studies have demonstrated that Jian-Pi-Yi-Shen formula (JPYSF), a traditional Chinese herbal decoction, has a renoprotective effect in 5/6 nephrectomy-induced chronic kidney injury. However, the role and potential mechanisms of JPYSF in the treatment of acute kidney injury (AKI) remain unknown. This study was designed to test the beneficial effect of JPYSF in an AKI mouse model and to investigate the underlying mechanism by using metabolomics analysis. The AKI mouse model was induced by a single intraperitoneal injection of cisplatin at a dose of 20 mg/kg. The mice in the treatment group were pretreated orally with JPYSF (18.35 g/kg/d) for 5 days before cisplatin injection. Seventy-two hours after cisplatin injection, serum and kidney samples were collected for biochemical and histological examination. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-ﬂight mass spectrometry (UHPLC-QTOF/MS) was applied to analyze metabolic profiling variations in the kidney. The results showed that pretreatment with JPYSF obviously reduced the levels of serum creatinine and blood urea nitrogen and alleviated renal pathological injury in AKI mice. Orthogonal partial least-squares discriminant analysis (OPLS-DA) score plot revealed a clear separation between the AKI and AKI + JPYSF group. A total of 68 and 87 significantly differentially expressed metabolites were identified in the kidney of AKI mice responding to JPYSF treatment in negative and positive ion mode, respectively. The pivotal pathways affected by JPYSF included vitamin B6 metabolism, alanine, aspartate and glutamate metabolism, lysine biosynthesis, and butanoate metabolism. In conclusion, JPYSF can protect the kidney from cisplatin-induced AKI, which may be associated with regulating renal metabolic disorders.

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Super-resolution ultrasound imaging for in vivo microvasculature assessment in acute kidney injury mouse model

The Journal of the Acoustical Society of America ◽

10.1121/1.5101711 ◽

2019 ◽

Vol 145 (3) ◽

pp. 1859-1859

Author(s):

Qiyang Chen ◽

Brittney M. Rush ◽

Jaesok Yu ◽

Roderick Tan ◽

Kang Kim

Keyword(s):

Acute Kidney Injury ◽

Mouse Model ◽

Ultrasound Imaging ◽

Kidney Injury ◽

Super Resolution

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Renal diseases and emergencies

10.1093/med/9780199565979.003.00011 ◽

2016 ◽

Author(s):

Dr Andrew Davenport

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Urinary Tract Infection ◽

Urinary Tract ◽

Renal Transplant ◽

Urinary Tract Obstruction ◽

Kidney Injury ◽

Renal Diseases ◽

Transplant Patients

Chapter 11 discusses diseases and emergencies involving renal medicine, including investigation of the renal tract, acute kidney injury (AKI), haematuria and proteinuria, urinary tract infection (UTI), urinary tract obstruction, tumours of the renal tract, chronic kidney disease (CKD), and renal transplant patients.

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