The role of complement activation in rhabdomyolysis-induced acute kidney injury

The kidney is one of the major organs affected in preeclampsia. There is evidence suggesting a role for excessive complement activation in the pathogenesis of preeclampsia. We describe a case of preeclampsia with severe features, including HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and acute kidney injury (AKI) that developed following caesarian section. The patient required renal replacement therapy. A trial of daily plasma exchange was not effective. The patient received a single dose of eculizumab, a humanised monoclonal IgG antibody that binds to complement protein C5. One week post administration of eculizumab, there was significant improvement in haematologic, hepatic and renal function. Blood pressure had normalised and renal replacement therapy was discontinued. The use of eculizumab may have contributed to recovery of kidney function further supporting the role of complement activation in the pathogenesis of preeclampsia and associated AKI.

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Complement activation fragments are increased in critically ill pediatric patients with severe acute kidney injury

Kidney360 ◽

10.34067/kid.0004542021 ◽

2021 ◽

pp. 10.34067/KID.0004542021

Author(s):

Erin K Stenson ◽

Zhiying You ◽

Ron Reeder ◽

Jesse Norris ◽

Halden F. Scott ◽

...

Keyword(s):

At Risk ◽

Acute Kidney Injury ◽

Critically Ill ◽

Complement Activation ◽

Kidney Injury ◽

Critically Ill Children ◽

High Morbidity ◽

Increased Risk ◽

Severity Scores

Background:Critically ill children with acute kidney injury (AKI) suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and severity of AKI in critically ill children. Methods:A biorepository of critically ill children from a prior multi-site study was leveraged to identify children with stage 3 AKI and matched to patients without AKI based on PELOD-2 (illness severity) scores. Specimens were analyzed for plasma and urine complement activation fragments of factor B, C3a, C4a, and sC5b-9. The primary outcomes were MAKE30 and severe AKI rates. Results:14 patients with stage 3 AKI (5 requiring renal replacement therapy [RRT]) were matched to 14 patients without AKI. Urine factor Ba and plasma C4a levels increased stepwise as severity of AKI increased, from no AKI to stage 3 AKI, to stage 3 AKI with RRT need. Plasma C4a levels were independently associated with increased risk of MAKE30 outcomes (OR 3.2; IQR 1.1-8.9), and urine Ba and plasma Bb, C4a, and C3a were independently associated with risk of severe stage 2-3 AKI on day 3 of admission. Conclusions:Multiple complement fragments increase as magnitude of AKI severity increases. Very high levels of urine Ba or plasma C4a may identify patients at risk for severe AKI, hemodialysis, and MAKE30 outcomes. The fragments may be useful as a functional biomarker of complement activation and may identify those patients to study complement inhibition to treat or prevent AKI in critically ill children. These findings suggest the need for further specific investigations of the role of complement activation in critically ill children at risk of 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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The Role of Renal Functional Reserve in Predicting Acute Kidney Injury

Critical Care Clinics ◽

10.1016/j.ccc.2020.11.008 ◽

2021 ◽

Author(s):

Dana Y. Fuhrman

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Functional Reserve ◽

Renal Functional Reserve

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Role of intraoperative oliguria in risk stratification for postoperative acute kidney injury in patients undergoing colorectal surgery with an enhanced recovery protocol: A propensity score matching analysis

PLoS ONE ◽

10.1371/journal.pone.0231447 ◽

2020 ◽

Vol 15 (4) ◽

pp. e0231447 ◽

Cited By ~ 1

Author(s):

Jung-Woo Shim ◽

Kyoung Rim Kim ◽

Yoonju Jung ◽

Jaesik Park ◽

Hyung Mook Lee ◽

...

Keyword(s):

Acute Kidney Injury ◽

Colorectal Surgery ◽

Propensity Score ◽

Risk Stratification ◽

Propensity Score Matching ◽

Enhanced Recovery ◽

Kidney Injury ◽

Propensity Score Matching Analysis ◽

Enhanced Recovery Protocol

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A zebrafish model of infection-associated acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00328.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. F291-F299 ◽

Cited By ~ 7

Author(s):

Xiaoyan Wen ◽

Liyan Cui ◽

Seth Morrisroe ◽

Donald Maberry ◽

David Emlet ◽

...

Keyword(s):

Acute Kidney Injury ◽

Unmet Need ◽

Kidney Injury ◽

Edwardsiella Tarda ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Pericardial Edema ◽

Kidney Injury Molecule 1 ◽

Dose Dependent

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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