Plasma creatinine below limit of quantification in a patient with acute kidney injury

Abstract Background Vancomycin and piperacillin–tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic AKI occurs, only that serum creatinine increases with VAN+TZP. Previous preclinical work demonstrated that novel urinary biomarkers and histopathologic scores were not increased in the VAN+TZP group compared with VAN alone. The purpose of this study was to assess changes in urinary output and plasma creatinine between VAN, TZP, and VAN+TZP treatments. Methods Male Sprague–Dawley rats (n = 32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1,400 mg/kg/day intraperitoneally, or VAN+TZP for 3 days. Animals were placed in metabolic cages pre-study and on drug dosing days 1–3. Urinary output, plasma creatinine, urinary biomarkers were compared daily and kidney histopathology was compared at the end of therapy between the groups. Mixed-effects, repeated-measures models were employed to assess differences between the groups. Results In the VAN-treated rats, urinary output was increased on days 1, 2 and 3 compared with baseline and saline (P < 0.01 for all), whereas it increased later for VAN+TZP (i.e., day 2 and 3 compared with saline, P < 0.001). No changes in urinary output were observed with saline and TZP alone. Plasma creatinine rose for VAN on days 1, 2, and 3 from baseline and VAN+TZP on day 3 (P < 0.02 for all), but no treatment group was different from saline. In the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared with controls (P < 0.001). Elevations were seen only after 3 days of treatment with VAN+TZP (P < 0.001 KIM-1, P < 0.05 clusterin). No changes in urinary biomarkers output were observed with saline and TZP alone. Histopathology was only elevated in the VAN group compared with saline (P < 0.002). No histopathology changes were noted with VAN+TZP. Conclusion All groups with VAN demonstrated kidney injury; however, VAN+TZP did not cause more kidney injury than VAN alone in a rat model of VIKI when using plasma creatinine, urinary output, or urinary biomarkers as outcomes. Histopathology data suggest that adding TZP did not worsen VAN-induced AKI and may even be protective. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.

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P0544INHIBITION OF 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE (15-PGDH) PROTECTS MICE AGAINST CONTRAST-INDUCED ACUTE KIDNEY INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0544 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Byeong Woo KIm ◽

Sun hee Kim ◽

Ki beom Bae

Keyword(s):

Acute Kidney Injury ◽

Blood Flow ◽

Protective Effect ◽

Renal Blood Flow ◽

Smooth Muscle Actin ◽

Kidney Injury ◽

Plasma Creatinine ◽

Histological Evaluation ◽

Vehicle Group ◽

Before And After

Abstract Background and Aims Although the mechanism of contrast-induced acute kidney injury (CI-AKI) is not fully known, the imbalance of vasoconstrictive and vasodilative mediators plays a major role. Prostaglandin E2 (PGE2) is one of the vasodilators involved in this process. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) causes elevation of PGE2 level in tissue by delaying the rapid degradation of PGE2 by the enzyme. We tested the hypothesis that the 15-PGE2 inhibitor would protect against CI-AKI in a mouse model and attempted to elucidate the mechanism involved. Method 10-week aged male C57/BL6 Mice were injected with 10gI/kg of iodixanol by tail vein. Renal blood flow measurement, right nephrectomy, and blood sampling were taken at 48 hours after iodixanol injection. The 15-PGDH inhibitor was injected before and after iodixanol administration. Plasma creatinine, NGAL, KIM-1 were measured as biomarkers for renal function. Histological evaluation was analyzed by the necrosis scoring system and TUNEL assay. Arteriolar area of outer medulla was analyzed by α-smooth muscle actin stain. Renal blood flow was measured by the non-invasive laser doppler. Results Plasma creatinine (1.94±0.75 vs 1.11±0.44 mg/dL, p=0.005), NGAL (299.7±115.87 vs 140.4±76.56 ng/mL, p=0.004), and KIM-1 (2.09±2.34 vs 0.43±0.89 ng/mL, p=0.024) levels were significantly lower when the 15-PGDH inhibitor was injected before and after iodixanol administration than the vehicle group. But no significant renal protective effect was shown when the 15-PGDH inhibitor was injected before or after iodixanol administration. The 15-PGDH inhibitor administration before and after iodixanol injection showed a significantly wider renal arteriolar area (683.63±248.46 vs 1132.97±357.46 μm2, p=0.039) and larger renal blood flow (360.0±49.72 vs 635.1±27.20, p=0.011) than vehicle administration. Conclusion The 15-PGDH inhibitor has a renal protective effect against CI-AKI in mice by increasing renal blood flow when injected intravenously before and after iodine contrast media administration.

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Monitoring of plasma creatinine and urinary γ-glutamyl transpeptidase improves detection of acute kidney injury by more than 20%*

Critical Care Medicine ◽

10.1097/ccm.0b013e3181fa431a ◽

2011 ◽

Vol 39 (1) ◽

pp. 52-56 ◽

Cited By ~ 8

Author(s):

Valéry Blasco ◽

Sandrine Wiramus ◽

Julien Textoris ◽

François Antonini ◽

Carole Bechis ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Plasma Creatinine ◽

Glutamyl Transpeptidase

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Point of care measurement of plasma creatinine in critically ill patients with acute kidney injury

Anaesthesia ◽

10.1111/j.1365-2044.2008.05818.x ◽

2009 ◽

Vol 64 (4) ◽

pp. 403-407 ◽

Cited By ~ 28

Author(s):

A. Udy ◽

S. O’Donoghue ◽

V. D’Intini ◽

H. Healy ◽

J. Lipman

Keyword(s):

Acute Kidney Injury ◽

Critically Ill ◽

Critically Ill Patients ◽

Point Of Care ◽

Kidney Injury ◽

Plasma Creatinine

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Early Diabetes Aggravates Renal Ischemia/reperfusion-induced Acute Kidney Injury

10.21203/rs.3.rs-145880/v1 ◽

2021 ◽

Author(s):

Mariana de Ponte ◽

Vanessa Cardoso ◽

Juliana Costa-Pessoa ◽

Maria Oliveira-Souza

Keyword(s):

Acute Kidney Injury ◽

Risk Factor ◽

Mrna Expression ◽

Ischemia Reperfusion ◽

Kidney Tissue ◽

Kidney Injury ◽

Plasma Creatinine ◽

Ki 67 ◽

Early Diabetes ◽

The Impact

Abstract Acute kidney injury (AKI) due to ischemia and reperfusion (IR) can be associated with the progression of chronic kidney injury. In addition, studies suggest that chronic diabetes is an independent risk factor for AKI; however, the impact of early diabetes on the severity of AKI remains unknown. We investigated the effects of early diabetes on the pathophysiology of renal IR-induced AKI. C57BL/6J mice were randomly assigned into the following groups: 1) sham-operated; 2) renal IR; 3) streptozotocin (STZ - 55 mg/kg/day) and sham-operated; and 4) STZ and renal IR. On the 12th day after treatments, the animals were subjected to bilateral IR for 30 minutes followed by reperfusion for 48 hours, and the mice were euthanized by exsanguination. Renal function was assessed by analyzing the plasma creatinine and urea concentrations with biochemical methods. Proteinuria was evaluated using a commercial kit. Kidney tissue was used to evaluate the morphology, gene expression by qPCR, and protein expression by Western blotting. Compared to the sham operated, renal IR resulted in increased plasma creatinine and urea levels, decreased nephrin mRNA expression, increased tubular cast formation, and Kim-1, Ki-67, pro-inflammatory and pro-fibrotic factor mRNA expression. Compared with the sham treatment, STZ treatment resulted in hyperglycemia, but did not induce changes in kidney function or pro-inflammatory or pro-fibrotic factors. However, STZ treatment aggravated renal IR-induced AKI by exacerbating glomerular and tubular injury, inflammation, and the profibrotic response. Early diabetes constitutes a relevant risk factor for renal IR-induced AKI.

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A Simple Method to Detect Recovery of Glomerular Filtration Rate following Acute Kidney Injury

BioMed Research International ◽

10.1155/2014/542069 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

John W. Pickering ◽

John Mellas

Keyword(s):

Acute Kidney Injury ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Kidney Injury ◽

Plasma Creatinine ◽

Creatinine Concentration ◽

Simple Method ◽

Creatinine Excretion ◽

Excretion Rates

In acute kidney injury (AKI), elevated plasma creatinine is diagnostic of an earlier loss of glomerular filtration rate (GFR) but not of the concomitant GFR. Only subsequent creatinine changes will inform if GFR had already recovered or not. We hypothesized that the creatinine excretion rate to production rate ratio would provide this information. A retrospective analysis of 482 critically ill patients from two intensive care units (ICU) is shown. Plasma creatinine was measured on ICU entry and 12 hours later. Four-hour creatinine excretion rates (E) were measured on entry. Creatinine production rates were estimated (eG). The ability of the ratioE/eGto predict a decrease in plasma creatinine concentration, identify recovered AKI (≥0.3 mg/dL decrease), and predict AKI (≥0.3 mg/dL increase) was assessed by the area under the receiver operator characteristic curves (AUC). There was a linear relationship between reduced creatinine concentration andE/eG(r2=0.15;P<0.0001).E/eGpredicted a decrease in creatinine (AUC 0.70 (0.65 to 0.74)), identified recovered AKI (0.75 (0.67 to 0.84)), and predicted AKI (0.80 (0.73 to 0.86)). A ratio of the rates of creatinine excretion to estimated production much less than 1 indicated a concomitant GFR below baseline, whereas a ratio much more than 1 indicated a recovering or recovered GFR.

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Urinary Mitochondrial DNA Identifies Renal Dysfunction and Mitochondrial Damage in Sepsis-Induced Acute Kidney Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/8074936 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 16

Author(s):

Qiongyuan Hu ◽

Jianan Ren ◽

Huajian Ren ◽

Jie Wu ◽

Xiuwen Wu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Mitochondrial Dna ◽

Mitochondrial Dysfunction ◽

Renal Dysfunction ◽

Renal Injury ◽

Cecal Ligation ◽

Surrogate Marker ◽

Kidney Injury ◽

Plasma Creatinine ◽

Acute Renal Dysfunction

Background. Recent animal studies have shown that mitochondrial dysfunction initiates and accelerates renal injury in sepsis, but its role in sepsis remains unknown. Mitochondrial stress or dying cells can lead to fragmentation of the mitochondrial genome, which is considered a surrogate marker of mitochondrial dysfunction. Therefore, we evaluated the efficiency of urinary mitochondrial DNA (UmtDNA) as a marker of renal dysfunction during sepsis-induced acute kidney injury (AKI). Methods. We isolated DNA from plasma and urine of patients. mtDNA levels were quantified by quantitative PCR. Sepsis patients were divided into no AKI, mild AKI, and severe AKI groups according to RIFLE criteria. Additionally, cecal ligation and puncture (CLP) was established in rats to evaluate the association between UmtDNA and mitochondrial function. Results. A total of 52 (49.5%) developed AKI among enrolled sepsis patients. Increased systemic mtDNA did not correlate with systemic inflammation or acute renal dysfunction in sepsis patients, while AKI did not have an additional effect on circulating mtDNA levels. In contrast, UmtDNA was significantly enriched in severe AKI patients compared with that in the mild AKI or no AKI group, positively correlated with plasma creatinine, urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1, and inversely with the estimated glomerular filtration rate. Additionally, UmtDNA increased in rats following CLP-induced sepsis. UmtDNA was predictive of AKI development and correlated with plasma creatinine and blood urea nitrogen in the rat sepsis model. Finally, the UmtDNA level was inversely correlated with the cortical mtDNA copy number and relative expression of mitochondrial gene in the kidney. Conclusion. An elevated UmtDNA level correlates with mitochondrial dysfunction and renal injury in sepsis patients, indicating renal mitochondrial injury induced by sepsis. Therefore, UmtDNA may be regarded as a valuable biomarker for the occurrence of AKI and the development of mitochondria-targeted therapies following sepsis-induced AKI.

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Gene knockout of the Na+-glucose cotransporter SGLT2 in a murine model of acute kidney injury induced by ischemia-reperfusion

AJP Renal Physiology ◽

10.1152/ajprenal.00607.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. F1100-F1112 ◽

Cited By ~ 1

Author(s):

Josselin Nespoux ◽

Rohit Patel ◽

Haiyan Zhang ◽

Winnie Huang ◽

Brent Freeman ◽

...

Keyword(s):

Acute Kidney Injury ◽

Mrna Expression ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Urine Osmolality ◽

Plasma Creatinine ◽

Thick Ascending Limb ◽

Wild Type ◽

Urinary Glucose ◽

Kidney Injury Molecule 1

In the early proximal tubule, Na+-glucose cotransporter 2 (SGLT2) mediates the bulk of renal glucose reabsorption. Gene deletion in mice ( Sglt2−/−) was used to determine the role of SGLT2 in acute kidney injury induced by bilateral ischemia-reperfusion (IR). In Sglt2−/− and littermate wild-type mice, plasma creatinine increased similarly on day 1 after IR. This was associated with an equal increase in both genotypes in the urinary kidney injury molecule-1-to-creatinine ratio, a tubular injury marker, and similarly reduced urine osmolality and increased plasma osmolality, indicating impaired urine concentration. In both IR groups, FITC-sinistrin glomerular filtration rate was equally reduced on day 14, and plasma creatinine was similarly and incompletely restored on day 23. In Sglt2−/− mice subjected to IR, fractional urinary glucose excretion was increased on day 1 but reduced and associated with normal renal Na+-glucose cotransporter 1 (Sglt1) mRNA expression on day 23, suggesting temporary SGLT1 suppression. In wild-type mice subjected to IR, renal Sglt1 mRNA was likewise normal on day 23, whereas Sglt2 mRNA was reduced by 57%. In both genotypes, IR equally reduced urine osmolality and renal mRNA expression of the Na+-K+-2Cl− cotransporter and renin on day 23, suggesting thick ascending limb dysfunction, and similarly increased renal mRNA expression of markers of injury, inflammation, oxidative stress, and fibrosis (kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, transforming growth factor-β1, NADPH oxidase-2, and collagen type 1). This was associated with equal increases in kidney histological damage scores and similar degree of capillary loss in both genotypes. The data indicate that genetic deletion of SGLT2 did not protect the kidneys in the initial injury phase or the subsequent recovery phase in a mouse model of IR-induced acute kidney injury.

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Role of intratubular pressure during the ischemic phase in acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00527.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. F1158-F1165 ◽

Cited By ~ 8

Author(s):

Jin Wei ◽

Jiangping Song ◽

Shan Jiang ◽

Gensheng Zhang ◽

Donald Wheeler ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Artery ◽

Kidney Injury ◽

Renal Ischemia ◽

Plasma Creatinine ◽

Renal Veins ◽

Artery Pressure ◽

Intratubular Pressure ◽

Proximal Tubular

Acute kidney injury (AKI) induced by clamping of renal vein or pedicle is more severe than clamping of artery, but the mechanism has not been clarified. In the present study, we tested our hypothesis that increased proximal tubular pressure (Pt) during the ischemic phase exacerbates kidney injury and promotes the development of AKI. We induced AKI by bilateral clamping of renal arteries, pedicles, or veins for 18 min at 37°C, respectively. Pt during the ischemic phase was measured with micropuncture. We found that higher Pt was associated with more severe AKI. To determine the role of Pt during the ischemic phase on the development of AKI, we adjusted the Pt by altering renal artery pressure. We induced AKI by bilateral clamping of renal veins, and the Pt was changed by adjusting the renal artery pressure during the ischemic phase by constriction of aorta and mesenteric artery. When we decreased renal artery pressure from 85 ± 5 to 65 ± 8 mmHg, Pt decreased from 53.3 ± 2.7 to 44.7 ± 2.0 mmHg. Plasma creatinine decreased from 2.48 ± 0.23 to 1.91 ± 0.21 mg/dl at 24 h after renal ischemia. When we raised renal artery pressure to 103 ± 7 mmHg, Pt increased to 67.2 ± 5.1 mmHg. Plasma creatinine elevated to 3.17 ± 0.14 mg·dl·24 h after renal ischemia. Changes in KIM-1, NGAL, and histology were in the similar pattern as plasma creatinine. In summary, we found that higher Pt during the ischemic phase promoted the development of AKI, while lower Pt protected from kidney injury. Pt may be a potential target for treatment of AKI.

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Sepsis-associated acute kidney injury

EMERGENCY MEDICINE ◽

10.22141/2224-0586.17.6.2021.242326 ◽

2021 ◽

Vol 17 (6) ◽

pp. 44-50

Author(s):

L.A. Maltseva ◽

L.V. Novytska-Usenko ◽

V.V. Nykonov ◽

T.V. Kanchura

Keyword(s):

Acute Kidney Injury ◽

Intensive Care ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Creatinine Level ◽

Kidney Injury ◽

Plasma Creatinine ◽

Advantages And Disadvantages ◽

Plasma Creatinine Level

Acute kidney injury (AKI) is a condition that develops as a result of a rapid decrease in the glomerular filtration rate, which leads to the accumulation of nitrogenous, including urea and creatinine, and non-nitrogenous metabolic products with electrolytic disorders, impairment of the acid-base balance, and the volume of fluid excreted by the kidneys. Objective: to provide a review of the literature concerning sepsis-associated acute kidney injury. We presented the problems of diagnosis, risk factors, the pathogenesis of sepsis-associated acute kidney injury, as well as to outline terminologically the clinical form of sepsis-associated acute kidney injury: the paradigm shifts from ischemia and vasoconstriction to hyperemia and vasodilation, from acute tubular necrosis to acute tubular apoptosis. Sepsis contributes significantly to the development of AKI: in sepsis, it occurs in 19 % of patients; nevertheless, it is much more frequent in septic shock (45 % of cases), the mortality of individuals with AKI is especially high in non-septic and septic conditions (45 and 73 %, respectively). To effectively diagnose the functional state of the kidneys and conduct nephroprotective therapy, stratification scales for assessing the severity of acute kidney damage are applied, which are based on the determination of plasma creatinine level and urine output: RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure), AKIN (Acute Kidney Injury Network), KDIGO (Kidney Disease Improving Global Outcomes); the experts considered KDIGO scale more modern and perfect. It has been found that plasma creatinine is not an early biomarker of AKI that indicates the advisability of using other integral indicators. AKI biomarkers are substances that either participate in the pathological process or witness it allowing diagnose AKI even before an increase in plasma creatinine level. The characteristics of the structure, role of functions of such biomarkers as neutrophil gelatinase-associated lipocalin, cystatin C, interleukin-18, kidney injury molecule-1 and others are given. Intensive care for sepsis-associated acute kidney injury includes the standard therapy corresponding to 2016 Surviving Sepsis Campaign and KDIGO guidelines. Also, the paper focuses on renal replacement therapy (RRT): renal and extrarenal indications for the initiation, factors affecting the initiation of RRT, the timing of initiation, ways of optimization, the timing of RRT discontinuation, recommendations for the dose of RRT, the dose of renal replacement therapy in sepsis-associated AKI, choice of method, advantages and disadvantages of continuous RRT and intermittent hemodialysis, medication support for continuous therapy, the role of hemodialysis machine in the intensive care unit.

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