scholarly journals Glomerular function and urinary biomarker changes between vancomycin and vancomycin plus piperacillin-tazobactam in a translational rat model.

Author(s):  
Jack Chang ◽  
Gwendolyn Pais ◽  
Kimberly Valdez ◽  
Sylwia Marianski ◽  
Erin F. Barreto ◽  
...  

Clinical studies have reported additive nephrotoxicity associated with the combination of vancomycin (VAN) and piperacillin-tazobactam (TZP). This study assessed differences in glomerular filtration rate (GFR) and urinary biomarkers between rats receiving VAN and those receiving VAN+TZP. Male Sprague-Dawley rats (n=26) were randomized to receive 96 hours of intravenous VAN at 150mg/kg/day, intraperitoneal TZP at 1400 mg/kg/day, or VAN+TZP. Kidney function was evaluated using fluorescein-isothiocyanate sinistrin and a transdermal sensor to estimate real-time glomerular filtration rate (GFR). Kidney injury was evaluated via urinary biomarkers including kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to a saline control, only rats in the VAN group showed significant declines in GFR by day 4 (-0.39 mL/min/100 g body weight, 95% CI: -0.68 to -0.10, p=0.008). When the VAN+TZP and VAN alone treatment groups were compared, significantly higher urinary KIM-1 was observed in the VAN alone group on day 1 (18.4 ng, 95% CI: 1.4 to 35.3, p=0.03), day 2 (27.4 ng, 95% CI: 10.4 to 44.3, p=0.002), day 3 (18.8 ng, 95% CI: 1.9 to 35.8, p=0.03), and day 4 (23.2 ng, 95% CI: 6.3 to 40.2, p=0.007). KIM-1 was the urinary biomarker that most correlated with decreasing GFR on day 3 (Spearman’s rho: -0.45, p = 0.022) and day 4 (Spearman’s rho: -0.41, p = 0.036). Kidney function decline and increased KIM-1 were observed among rats that received VAN only, but not TZP or VAN+TZP. Addition of TZP to VAN does not worsen kidney function or injury in our translational rat model.

2021 ◽  
Author(s):  
Jack Chang ◽  
Gwendolyn Pais ◽  
Kimberly Valdez ◽  
Sylwia Marianski ◽  
Erin F Barreto ◽  
...  

Clinical studies have reported additive nephrotoxicity associated with the combination of vancomycin (VAN) and piperacillin-tazobactam (TZP). This study assessed differences in glomerular filtration rate (GFR) and urinary biomarkers between rats receiving VAN and those receiving VAN+TZP. Male Sprague-Dawley rats (n=26) were randomized to receive 96 hours of intravenous VAN at 150mg/kg/day, intraperitoneal TZP at 1400 mg/kg/day, or VAN+TZP. Kidney function was evaluated using fluorescein-isothiocyanate sinistrin and a transdermal sensor to estimate real-time glomerular filtration rate (GFR). Kidney injury was evaluated via urinary biomarkers including kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to a saline control, only rats in the VAN group showed significant declines in GFR by day 4 (-0.39 mL/min/100 g body weight, 95% CI: -0.68 to -0.10, p=0.008). When the VAN+TZP and VAN alone treatment groups were compared, significantly higher urinary KIM-1 was observed in the VAN alone group on day 1 (18.4 ng, 95% CI: 1.4 to 35.3, p=0.03), day 2 (27.4 ng, 95% CI: 10.4 to 44.3, p=0.002), day 3 (18.8 ng, 95% CI: 1.9 to 35.8, p=0.03), and day 4 (23.2 ng, 95% CI: 6.3 to 40.2, p=0.007). KIM-1 was the urinary biomarker that most correlated with decreasing GFR on day 3 (Spearman’s rho: -0.45, p = 0.022) and day 4 (Spearman’s rho: -0.41, p = 0.036). Kidney function decline and increased KIM-1 were observed among rats that received VAN only, but not TZP or VAN+TZP. Addition of TZP to VAN does not worsen kidney function or injury in a validated translational rat model.


Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 655-661
Author(s):  
Mina Khorashadi ◽  
Remi Beunders ◽  
Peter Pickkers ◽  
Matthieu Legrand

Assessment of kidney function is primarily based on urine output and Creatinine (Cr)-based methods to estimate glomerular filtration rate (GFR). The latter is confounded as Cr is not exclusively filtered by the kidney and rises relatively late after the onset of acute kidney injury (AKI). This leads to delays in recognition of reduced kidney function and diagnosis of AKI, particularly in critically ill patients where kidney function can change rapidly. The gold standard methods of GFR determination, such as inulin or iohexol clearance, are labor intensive and unfeasible in acute clinical settings. Proenkephalin A 119–159 (PENK) has been intensively studied as a novel biomarker of kidney function. PENK belongs to the enkephalin peptide family and is freely filtrated in the glomerulus. Plasma PENK concentration appears to correlate strongly with GFR. Moreover, increased plasma PENK concentrations are found to be associated with long-term kidney outcomes and mortality. In this review, we summarize the role of PENK in assessment of kidney function and its capacity to predict various clinical outcomes.


2019 ◽  
Vol 3 (1) ◽  
pp. 28-37
Author(s):  
Annisa Wimaulia Azlin ◽  
Rachmat Hidayat ◽  
Kemas Ya'kub Rahadiyanto

Acute kidney injury (AKI) is a sudden decrease of kidney function. The incidence of AKI is increasing every year. One of the causes of AKI is the lack of blood supply to the kidneys (prerenal). At the present time, there are not many studies that report unilateral ischemic-reperfusion (UIR) duration which can cause kidney damage especially glomerulus. The aim of this study is to determine the effect of UIR duration to glomerular microscopic appearance, GFR and cystatin C produced in Wistar white rats. This study was performed in vivo by using Post-test Only Control Group Design. Unilateral Ischemic-Reperfusion was administered on the rat’s left kidney and recovery was done according to specified time. After recovery time, rat’s blood was taken, the rat was euthanized, and its kidneys were taken and stained with Picrosirius Red coloring. The kidneys were observed by using OptiLED and the photos were analyzed with ImageJ software. Blood samples were tested by ELISA to measure the cystatin C levels and the levels were converted into Larrson formula to obtain Glomerular Filtration Rate. The level of cystatin C increased along with the longer duration of UIR and compared inversely proportional to GFR which decreased along with the rise of UIR duration. Cystatin C and GFR had a significant mean difference (p<0.05) with all groups, except for the duration of the UIR group <60 minutes. The percentage of collagen obtained fluctuated but the whole group which was carried out by UIR had a significantly different collagen amount (p <0.05) with the sham-operated group. The average glomerular picture showed the addition of collagen, Bowman's capsule thickening and vascular retraction. The longer duration of UIR will worsen the kidney function.   Keywords: Unilateral Ischemic-Reperfusion, Cystatin C. Glomerular Filtration Rate, Collagen Area Fraction, Glomerulus


2018 ◽  
Vol 6 (25) ◽  
pp. 26-30
Author(s):  
Praveen Ratanasrimetha ◽  
Miguel Quirich ◽  
Sorot Phisitkul

Serum creatinine and glomerular filtration rate (GFR) are the current standard tests tomeasure kidney function. The baseline GFR does not reflect full function of the kidney sincehuman kidneys do not always work at full capacity. Similarly, serum creatinine is not a sensitivemeasure for kidney function or injury. In healthy individuals the GFR physiologically increasesin response to certain stresses or stimuli, such as protein loading.Renal functional reserve (RFR) is defined as the difference between the maximalglomerular filtration rate (generally determined after oral or intravenous protein loading) and thebaseline glomerular filtration rate. The absence of a normal RFR can help identify patients whoare more susceptible to kidney injury. The RFR is also important in patients who develop acutekidney injury and chronic kidney disease. Even though the GFR might return to a baselinelevel, there may be some loss of RFR which can make the patient more susceptible to anotherepisode of kidney injury.Acute kidney injury and chronic kidney disease are considered interconnected syndromes;each is a risk factor for the other. There are no current recommendations regarding theperformance of routine determinations of RFR. Physicians should focus on clinical history andphysical examination in patients with a history of prior episodes of acute kidney injury, monitorrenal function, and avoid nephrotoxic insults.


2015 ◽  
Vol 42 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Carmen A. Peralta ◽  
Paul Muntner ◽  
Rebecca Scherzer ◽  
Suzanne Judd ◽  
Mary Cushman ◽  
...  

Background/Aims: Persons with occult-reduced estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2 detected by serum cystatin C but missed by creatinine) have high risk for complications. Among persons with preserved kidney function by creatinine-based eGFR (eGFRcreat >60 ml/min/1.73 m2), tools to guide cystatin C testing are needed. Methods: We developed a risk score to estimate an individual's probability of reduced eGFR by cystatin C (eGFRcys <60 ml/min/1.73 m2) in The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and externally validated in the Third National Health and Nutrition Examination Survey (NHANES III). We used logistic regression with Bayesian model averaging and variables available in practice. We assessed performance characteristics using calibration and discrimination measures. Results: Among 24,877 adults with preserved kidney function by creatinine, 13.5% had reduced eGFRcys. Older and Black participants, current smokers and those with higher body mass index, lower eGFRcreat, diabetes, hypertension and history of cardiovascular disease were more likely to have occult-reduced eGFR (p < 0.001). The final risk function had a c-statistic of 0.87 in REGARDS and 0.84 in NHANES. By risk score, 72% of occult-reduced eGFR cases were detected by screening only 22% of participants. Conclusions: A risk score using characteristics readily accessible in clinical practice can identify the majority of persons with reduced eGFRcys, which is missed by creatinine.


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.


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