Inhibition of COX-1 attenuates the formation of thromboxane A2 and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

2015 ◽  
Vol 309 (4) ◽  
pp. F332-F340 ◽  
Author(s):  
Katharina Mederle ◽  
Manuel Meurer ◽  
Hayo Castrop ◽  
Klaus Höcherl

Thromboxane (Tx) A2 has been suggested to be involved in the development of sepsis-induced acute kidney injury (AKI). Therefore, we investigated the impact of cyclooxygenase (COX)-1 and COX-2 activity on lipopolysaccharide (LPS)-induced renal TxA2 formation, and on endotoxemia-induced AKI in mice. Injection of LPS (3 mg/kg ip) decreased glomerular filtration rate (GFR) and the amount of thrombocytes to ∼50% of basal values after 4 h. Plasma and renocortical tissue levels of TxB2 were increased ∼10- and 1.7-fold in response to LPS, respectively. The COX-1 inhibitor SC-560 attenuated the LPS-induced fall in GFR and in platelet count to ∼75% of basal levels. Furthermore, SC-560 abolished the increase in plasma and renocortical tissue levels of TxB2 in response to LPS. The COX-2 inhibitor SC-236 further enhanced the LPS-induced decrease in GFR to ∼40% of basal values. SC-236 did not alter thrombocyte levels nor the LPS-induced increase in plasma and renocortical tissue levels of TxB2. Pretreatment with clopidogrel inhibited the LPS-induced drop in thrombocyte count, but did not attenuate the LPS-induced decrease in GFR and the increase in plasma TxB2 levels. This study demonstrates that endotoxemia-induced TxA2 formation depends on the activity of COX-1. Our study further indicates that the COX-1 inhibitor SC-560 has a protective effect on the decrease in renal function in response to endotoxin. Therefore, our data support a role for TxA2 in the development of AKI in response to LPS.

2011 ◽  
Vol 6 (9) ◽  
pp. 2150-2156 ◽  
Author(s):  
Christine A. White ◽  
Andrew D. Rule ◽  
Christine P. Collier ◽  
Ayub Akbari ◽  
John C. Lieske ◽  
...  

2020 ◽  
Vol 20 (4) ◽  
pp. e312-317
Author(s):  
Folake M. Afolayan ◽  
Olanrewaju T. Adedoyin ◽  
Mohammed B. Abdulkadir ◽  
Olayinka R. Ibrahim ◽  
Sikiru A. Biliaminu ◽  
...  

Objectives: Serum creatinine levels are often used to diagnose acute kidney injury (AKI), but may not necessarily accurately reflect changes in glomerular filtration rate (GFR). This study aimed to compare the prevalence of AKI in children with severe malaria using diagnostic criteria based on creatinine values in contrast to cystatin C. Methods: This prospective cross-sectional study was performed between June 2016 and May 2017 at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. A total of 170 children aged 0.5–14 years old with severe malaria were included. Serum cystatin C levels were determined using a particle-enhanced immunoturbidmetric assay method, while creatinine levels were measured using the Jaffe reaction. Renal function assessed using cystatin C-derived estimated GFR (eGFR) was compared to that measured using three sets of criteria based on creatinine values including the Kidney Disease: Improved Global Outcomes (KDIGO) and World Health Organization (WHO) criteria as well as an absolute creatinine cut-off value of >1.5 mg/dL. Results: Mean serum cystatin C and creatinine levels were 1.77 ± 1.37 mg/L and 1.23 ± 1.80 mg/dL, respectively (P = 0.002). According to the KDIGO, WHO and absolute creatinine criteria, the frequency of AKI was 32.4%, 7.6% and 16.5%, respectively. In contrast, the incidence of AKI based on cystatin C-derived eGFR was 51.8%. Overall, the rate of detection of AKI was significantly higher using cystatin C compared to the KDIGO, WHO and absolute creatinine criteria (P = 0.003, <0.001 and <0.001, respectively). Conclusion: Diagnostic criteria for AKI based on creatinine values may not indicate the actual burden of disease in children with severe malaria. Keywords: Biomarkers; Acute Kidney Injury; Renal Failure; Glomerular Filtration Rate; Cystatin C; Creatinine; Malaria; Nigeria.


2018 ◽  
Vol 25 (6) ◽  
pp. 73-77 ◽  
Author(s):  
V. V. Elagin ◽  
D. A. Kostina ◽  
O. I. Bratchikov ◽  
M. V. Pokrovsky ◽  
T. G. Pokrovskaya

Aim.The research was designed to study the renoprotective properties of erythropoietin derivatives on the kidney ischemiareperfusion experimental model.Materials and methods.The renoprotective properties of asialo erythropoietin (0.4 μg/kg and 2.4 μg/kg 30 minutes before the induction of ischemia) and carbamylated darbepoetin (50 μg/kg 24 hours before the ischemic stimulus) were studied in comparison with erythropoietin and darbepoetin in a series of experiments on male Wistar rats on a 40-minute bilateral model of renal ischemia-reperfusion. The renoprotective properties were evaluated by the results of biochemical markers of acute kidney injury, the dynamics of glomerular filtration rate and fractional sodium excretion, as well as the severity of microcirculatory disorders.Results.It was found that the prophylactic use of asialo erythropoietin (dose-dependent) and carbamylated darbepoetin leads to a decrease in the serum concentration of markers of acute renal damage, an increase in the glomerular filtration rate, a decrease in fractional sodium excretion, and a decrease in microcirculatory disorders.Conclusion.Asialo erythropoietin and carbamylated darbepoetin have the pronounced renoprotective properties and are the promising agents for the prevention and treatment of acute kidney injury.


2021 ◽  
Author(s):  
Mônica Rika Nakamura ◽  
Lúcio R. Requião-Moura ◽  
Roberto Mayer Gallo ◽  
Camila Botelho ◽  
Júlia Taddeo ◽  
...  

Abstract Due to the high costs, the strategy to reduce the impact of cytomegalovirus (CMV) after kidney transplant (KT) involves preemptive treatment in low and middle-income countries. Thus, this retrospective cohort study compared the performance of antigenemia transitioned to quantitative nucleic acid amplification testing, RT-PCR, in KT recipients receiving preemptive treatment as a strategy to prevent CMV infection. Between 2016 and 2018, 363 patients were enrolled and received preemptive treatment based on antigenemia (n=177) or RT-PCR (n=186). The primary outcome was CMV infection or disease. There were no differences in one-year cumulative incidence of CMV-related events (50.8% vs. 44.1%, P=0.20), neither in time to diagnosis (47.0 vs. 47.0 days) among patients conducted by antigenemia vs. RT-PCR, respectively. The length of CMV first treatment was longer with RT-PCR (20.0 vs. 27.5 days, P<0.001), while the rate of retreatment was not different (14.7% vs. 11.8%, P=0.48). In the Cox regression, the variables associated with CMV-related events were acute rejection within 30 days (HR=2.05, p=0.01) and 30-day glomerular filtration rate (HR=0.98, p<0.001). In conclusion, acute rejection and glomerular filtration rate are risk factors for CMV infection and disease, showing comparable performance in the impact of CMV-related events between antigenemia and RT-PCR for preemptive treatment.


2017 ◽  
Author(s):  
Jayme E. Locke ◽  
John T Killian Jr

This updated review on the renal system provides a concise overview of the topics most important to the general surgeon. Anatomic topics have been expanded to also include variant anatomy and surgical approaches. There is a new focus on the accuracy and utility of equations for estimating the glomerular filtration rate, as well as supplementation and pharmacology for the general surgeon with discussions of vitamin D and erythropoietin. Acute kidney injury is defined; its pathophysiology is discussed; and its management is outlined, highlighting evidence-based practice. Finally, urologic surgery is addressed with a focus on donor nephrectomy and its consequences, as well as the management of iatrogenic ureteral injuries. Key words: acute kidney injury; contrast nephropathy; erythropoiesis-stimulating agents; estimated glomerular filtration rate; iatrogenic ureteral injury; laparoscopic donor nephrectomy; renal surgical anatomy; vitamin D supplementation


2021 ◽  
Vol 25 (4) ◽  
pp. 64-70
Author(s):  
V. N. Mineev ◽  
T. S. Vasilieva ◽  
A. V. Smirnov ◽  
O. V. Galkina ◽  
V. I. Trofi mov

INTRODUCTION. Previously, we postulated the common pathogenetic mechanisms in bronchial asthma (BA) and chronic kidney disease (CKD). The kidney injury molecule-1 (KIM-1) is considered as an early biomarker of the proximal renal tubules damage. In the available literature, there is only one clinical study of KIM-1 in children BA.THE AIM of the study is to  assess KIM-1 levels in different variants of BA.PATIENTS AND METHODS. The 24 BA patients were examined. Glomerular filtration rate (eGFR) by CKD-EPI was calculated. The concentration of the kidney injury molecule -1 (KIM-1) in urine was determined by enzyme immunoassay. Urinary albumin was determined by the immunoturbidimetric method. VEGF-A in serum was determined by enzyme immunoassay (sandwich variant).RESULTS. In the urine of BA patients, KIM-1 was detected, and its level in patients with a non-allergic variant is significantly higher than in patients with an allergic variant of the disease. Factor analysis was carried out, the following was revealed: the KIM-1 component with a high positive factor load is associated with a key characteristic of BA such as the severity of the disease course, as well as with a high negative factor load – with a component of the glomerular filtration rate; the KIM-1 component with a high positive factor load is associated with the presence of drug intolerance in BA patients; the microalbuminuria component is negatively associated with the severity of BA disease course, as well as with the components KIM-1, VEGF-A, which seems to be associated with the use of systemic glucocorticoids in severe BA disease course; the KIM-1 component is positively associated with the VEGF-A component, which may indicate possible KIM-1 involvement in hypoxic kidney injury in BA. CONCLUSION. The obtained data suggest that in BA, first of all, in a non-allergic variant of the disease and in a severe course of BA, kidney injure is formed, detected using kidney injure molecule-1 KIM-1.


2017 ◽  
Author(s):  
Jayme E. Locke ◽  
John T Killian Jr

This updated review on the renal system provides a concise overview of the topics most important to the general surgeon. Anatomic topics have been expanded to also include variant anatomy and surgical approaches. There is a new focus on the accuracy and utility of equations for estimating the glomerular filtration rate, as well as supplementation and pharmacology for the general surgeon with discussions of vitamin D and erythropoietin. Acute kidney injury is defined; its pathophysiology is discussed; and its management is outlined, highlighting evidence-based practice. Finally, urologic surgery is addressed with a focus on donor nephrectomy and its consequences, as well as the management of iatrogenic ureteral injuries. Key words: acute kidney injury; contrast nephropathy; erythropoiesis-stimulating agents; estimated glomerular filtration rate; iatrogenic ureteral injury; laparoscopic donor nephrectomy; renal surgical anatomy; vitamin D supplementation


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