MO469POSSIBLE MECHANISMS OF THE SARS-COV-2-INDUCED AKI PROGRESSION TO CKD: A FORWARD-LOOKING PERSPECTIVE

Abstract Background and Aims Coronavirus disease 2019 (COVID 19) was identified in December 2020 and is still growing in most parts of the world. The wide range of affected organs is likely based on the shared expression of the main severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry-receptor angiotensin-converting enzyme 2 (ACE2). Therefore, broad distribution of ACE2 receptors in various tissues play a key role in the multi-organ dysfunction and death due to COVID-19. Method International databases including PubMed, Embase, Web of Science, Scopus, and Cochrane Library Databases were used for search of articles by 30 December 2020. Keywords were nephropathy, COVID-19, coronavirus, renal injury, acute kidney injury, chronic kidney injury, and SARS-CoV-2 or a combination of them in the titles/abstracts. After the collection of related studies, Mendeley software was used to categorize and eliminate the duplicate titles. Then, studies with inappropriate purposes were removed. The selected studies were done on humans and published in English. Results Due to high prevalence of acute kidney injury (AKI) in patients with COVID-19, we summarize the molecular insights into viral infection mechanisms and implications for AKI. Moreover, mechanisms of the AKI to chronic kidney disease (CKD) transition such as relative contribution of immune cell response, fibroblasts activation, endothelial dysfunction and subsequent hypoxia may contribute to association of AKI with worse outcomes during this virus pandemic. Conclusion We highlight the state of the knowledge on SARS-CoV-2-dependent mechanisms for AKI and list the potential management options for prevention of AKI worsening and the imminent possibility of CKD. Finally, we aim to provide a better understanding of why Coronavirus induce AKI and, subsequently, progression to CKD in the coming years and further discuss the acute as well as long-term renal consequences. MO469 Figure: Potential interrelationship between endothelial dysfunction, tubular epithelial injury, interstitial inflammation, and fibrosis are likely to create a vicious cycle that can lead to the progression of acute kidney injury to chronic kidney disease (AKI to CKD) during COVID-19.

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Emerging roles for lymphatics in acute kidney injury: Beneficial or maleficent?

Experimental Biology and Medicine ◽

10.1177/1535370220983235 ◽

2021 ◽

pp. 153537022098323

Author(s):

Heidi A Creed ◽

Joseph M Rutkowski

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Immune Cell ◽

Lymphatic Vessels ◽

Kidney Injury ◽

Systemic Infection ◽

Post Injury ◽

Drug Induced ◽

Increased Risk

Acute kidney injury, a sudden decline in renal filtration, is a surprisingly common pathology resulting from ischemic events, local or systemic infection, or drug-induced toxicity in the kidney. Unchecked, acute kidney injury can progress to renal failure and even recovered acute kidney injury patients are at an increased risk for developing future chronic kidney disease. The initial extent of inflammation, the specific immune response, and how well inflammation resolves are likely determinants in acute kidney injury-to-chronic kidney disease progression. Lymphatic vessels and their roles in fluid, solute, antigen, and immune cell transport make them likely to have a role in the acute kidney injury response. Lymphatics have proven to be an attractive target in regulating inflammation and immunomodulation in other pathologies: might these strategies be employed in acute kidney injury? Acute kidney injury studies have identified elevated levels of lymphangiogenic ligands following acute kidney injury, with an expansion of the lymphatics in several models post-injury. Manipulating the lymphatics in acute kidney injury, by augmenting or inhibiting their growth or through targeting lymphatic-immune interactions, has met with a range of positive, negative, and sometimes inconclusive results. This minireview briefly summarizes the findings of lymphatic changes and lymphatic roles in the inflammatory response in the kidney following acute kidney injury to discuss whether renal lymphatics are a beneficial, maleficent, or a passive contributor to acute kidney injury recovery.

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N-Acetylcysteine for Preventing of Acute Kidney Injury in Chronic Kidney Disease Patients Undergoing Cardiac Surgery: A Metaanalysis

The Heart Surgery Forum ◽

10.1532/hsf.2193 ◽

2018 ◽

Vol 21 (6) ◽

pp. E513-E521 ◽

Cited By ~ 4

Author(s):

Guiyuan He ◽

Qi Li ◽

Wenxin Li ◽

Li Wang ◽

Jun Yang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Kidney Disease ◽

Intravenous Infusion ◽

Kidney Injury ◽

Cochrane Library ◽

Cardiac Events ◽

Primary Analysis ◽

Clinical Trial Registry

Objective: The aim of this study was to determine whether N-acetylcysteine (NAC) has an effect on acute kidney injury (AKI) in chronic kidney disease patients undergoing cardiac surgery. Methods: We reviewed literature through PubMed, Medline through PubMed and OVID, The Cochrane Library, Wan Fang Database, China Biology Medicine Database, Chinese Periodical Database, China Knowledge Resource Integrated Database, and Chinese Clinical Trial Registry (1980 to July 10, 2018). Two investigators independently collected the data and assessed the quality of each study. RevMan 5.3 was used for the present metaanalysis. Results: A total of 5 RCTs (N = 678 participants) were included in the primary analysis. Pooled analysis showed that intravenous infusion of NAC significantly reduced the incidence of AKI (RR = 0.77, 95% = 0.63 to 0.94, P < .01) and that NAC could decrease the adverse cardiac events (RR = 0.83, 95% = 0.70 to 0.97, P < .05), but that it may increase the length of stay in the ICU (mean difference [MD] = 2.1, 95% CI = 1.61 to 2.60, P < .01). There were no statistically significant differences between the 2 groups in the requirement for renal replacement therapy(RRT) (RR = 1.33, 95% = 0.63 to 2.81, P = .45) and all-cause mortality (RR = 0.51, 95% = 0.25 to 1.06, P = .07). Conclusion: Our study shows that intravenous infusion of NAC could prevent postoperative AKI in preexisting-renal-failure patients undergoing cardiac surgery.

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The Involvement of Chronic Kidney Disease and Acute Kidney Injury in Disease Severity and Mortality in Patients with COVID-19: A Meta-Analysis

Kidney & Blood Pressure Research ◽

10.1159/000512211 ◽

2020 ◽

pp. 1-14

Author(s):

Bin Wang ◽

Qing Luo ◽

Weiguang Zhang ◽

Shuai Yu ◽

Xiaowei Cheng ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Disease Severity ◽

Meta Analysis ◽

Kidney Injury ◽

Research Network ◽

Cochrane Library ◽

Severe Condition ◽

Increased Risk

Background: A meta-analysis was performed to evaluate the association of chronic kidney disease (CKD) and acute kidney injury (AKI) with the clinical prognosis of patients with coronavirus disease 2019 (COVID-19). Methods: The PubMed, EMBASE, Cochrane Library, medRxiv, Social Science Research Network, and Research Square databases (from December 1, 2019 to May 15, 2020) were searched to identify studies that reported the associations of CKD/AKI and disease severity/mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and meta-regression was performed. Results: In total, 42 studies enrolling 8,932 participants were included in this meta-analysis. The quality of most included studies was moderate to high. Compared with patients without previously diagnosed CKD, those with CKD had a significantly increased risk of progressing to a severe condition (OR 2.31, 95% CI 1.64–3.24) or death (OR 5.11, 95% CI 3.36–7.77). Similarly, compared with patients without AKI, those with AKI had a significantly increased risk of progressing to a severe condition (OR 11.88, 95% CI 9.29–15.19) or death (OR 30.46, 95% CI 18.33–50.59). Compared with patients with previously diagnosed CKD, those with AKI were more likely to progress to a severe condition (pgroup < 0.001, I2 = 98.3%) and even to death (pgroup < 0.001, I2 = 96.5%). Age had a significant impact on the association between CKD and disease severity (p = 0.001) but had no impact on the associations between AKI and disease severity (p = 0.80), between CKD and mortality (p = 0.51), or between AKI and mortality (p = 0.86). Four important complications (cardiac injury, shock, acute respiratory distress syndrome, and liver injury) did not significantly affect the associations between CKD/AKI and disease severity/mortality, indicating that CKD/AKI may be independent clinical prognostic indicators for patients with COVID-19. Conclusions: In COVID-19 patients, CKD/AKI was associated with worse outcomes compared with those without CKD/AKI. AKI was associated with higher risks of severity and mortality than CKD.

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NLRP3 associated with chronic kidney disease progression after ischemia/reperfusion-induced acute kidney injury

Cell Death Discovery ◽

10.1038/s41420-021-00719-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Zhihuang Zheng ◽

Kexin Xu ◽

Chuanlei Li ◽

Chenyang Qi ◽

Yili Fang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Immune Cell ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Chronic Phase ◽

Kidney Injury ◽

Receptor Protein ◽

Tubular Damage

AbstractNod-like receptor protein 3 (NLRP3), as an inflammatory regulator, has been implicated in acute kidney injury (AKI). Failed recovery after AKI can lead to chronic kidney disease (CKD). However, the role of NLRP3 in the AKI-CKD transition is still unknown. A mild or severe AKI mouse model was performed by using ischemia-reperfusion injury (IRI). We evaluated the renal NLRP3 expression in acute and chronic phases of ischemic AKI, respectively. Although serum creatinine (Cr) and blood urea nitrogen (BUN) levels in AKI chronic phase were equivalent to normal baseline, histological analysis and fibrotic markers revealed that severe AKI-induced maladaptive tubular repair with immune cell infiltration and fibrosis. Tubular damage was restored completely in mild AKI rather than in severe AKI. Of note, persistent overexpression of NLRP3 was also found in severe AKI but not in mild AKI. In the severe AKI-induced chronic phase, there was a long-term high level of NLRP3 in serum or urine. Overt NLRP3 was mainly distributed in the abnormal tubules surrounded by inflammatory infiltrates and fibrosis, which indicated the maladaptive repair. Renal Nlrp3 overexpression was correlated with infiltrating macrophages and fibrosis. Renal NLRP3 signaling-associated genes were upregulated after severe AKI by RNA-sequencing. Furthermore, NLRP3 was found increased in renal tubular epitheliums from CKD biopsies. Together, persistent NLRP3 overexpression was associated with chronic pathological changes following AKI, which might be a new biomarker for evaluating the possibility of AKI-CKD transition.

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Subclinical kidney injury induced by repeated cisplatin administration results in progressive chronic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00636.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. F161-F172 ◽

Cited By ~ 14

Author(s):

Cierra N. Sharp ◽

Mark A. Doll ◽

Judit Megyesi ◽

Gabrielle B. Oropilla ◽

Levi J. Beverly ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Endothelial Dysfunction ◽

Kidney Disease ◽

Mouse Model ◽

Chronic Inflammation ◽

Interstitial Fibrosis ◽

Kidney Injury ◽

Dosing Regimen ◽

Repeated Dosing

Cisplatin is used to treat many solid cancers, but its dose-limiting side effect is nephrotoxicity, causing acute kidney injury in 30% of patients. Previously, we have developed a mouse model that better recapitulates the cisplatin dosing regimen humans receive and found that repeated dosing of cisplatin induces interstitial renal fibrosis. Chronic kidney disease is progressive and is characterized by chronic inflammation, worsening interstitial fibrosis, development of glomerulosclerosis, and endothelial dysfunction. To determine if damage caused by repeated cisplatin dosing results in bona fide chronic kidney disease, mice were treated with our repeated dosing regimen and then aged for 6 mo. These mice had progressive, chronic inflammation and worsened interstitial fibrosis compared with mice euthanized after day 24. Mice aged for 6 mo developed glomerular pathologies, and endothelial dysfunction was persistent. Mice treated with only two doses of cisplatin had little inflammation or kidney damage. Thus repeated dosing of cisplatin causes long-term effects that are characteristic of chronic kidney disease. This translational mouse model of cisplatin injury may better represent the 70% of patients that do not develop clinical acute kidney injury and can be used to identify both biomarkers for early injury, as well as novel therapeutic targets for the prevention of cisplatin-induced chronic kidney disease.

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Comparative Efficacy of Statins for Prevention of Contrast-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease: A Network Meta-Analysis

Angiology ◽

10.1177/0003319718801246 ◽

2018 ◽

Vol 70 (4) ◽

pp. 305-316 ◽

Cited By ~ 8

Author(s):

Xinbin Zhou ◽

Jin Dai ◽

Xiaoming Xu ◽

Zhijun Wang ◽

Haibin Xu ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Cardiac Catheterization ◽

Meta Analysis ◽

Kidney Injury ◽

Cochrane Library ◽

High Dose ◽

Iodinated Contrast ◽

Reduced Risk

Contrast-induced acute kidney injury (CI-AKI) is a common complication of iodinated contrast medium administration during cardiac catheterization. Statin treatment has been shown to be associated with reduced risk of CI-AKI; however, the results are inconsistent, especially for patients with chronic kidney disease (CKD). Thus, we conducted a network meta-analysis to evaluate the effects of statins in the prevention of CI-AKI. We systematically searched several databases (including, Embase, PubMed, the Cochrane Library, and ClinicalTrials.gov ) from inception to January 31, 2018. The primary outcome was occurrence of CI-AKI in patients with CKD undergoing cardiac catheterization. Both pairwise and network meta-analysis were performed. Finally, 21 randomized controlled trials with a total of 6385 patients were included. Results showed that statin loading before contrast administration was associated with a significantly reduced risk of CI-AKI in patients with CKD undergoing cardiac catheterization (odds ratio: 0.46; P < .05). Atorvastatin and rosuvastatin administered at high dose may be the most effective treatments to reduce incidence of CI-AKI, with no difference between these 2 agents.

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