scholarly journals Comparing population pharmacokinetics and acute kidney injury of polymyxin B in Chinese patients with and without renal insufficiency

2020 ◽  
Author(s):  
Peile Wang ◽  
Qilen Zhang ◽  
Zhenfeng Zhu ◽  
Hui Pei ◽  
Min Feng ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Creatinine Clearance ◽  
Normal Renal Function ◽  
Kidney Injury ◽  
Polymyxin B ◽  
Bactericidal Effect ◽  
Chinese Patients ◽  
Population Pharmacokinetic

Despite excellent bactericidal effect, dosing adjustment of polymyxin B for patients with renal insufficiency and polymyxin B-related nephrotoxicity is still a major concern to clinicians. The aim of this study was to compare the population pharmacokinetic (PK) properties of polymyxin B in Chinese patients with different renal function and to investigate the relationship between PK parameters and polymyxin B related-acute kidney injury (AKI). A total of 37 patients with normal renal function (creatinine clearance ≥ 80 mL/min) and 33 with renal insufficiency (creatinine clearance < 80 mL/min) were included. In the two-compartment population PK models, the Cl (2.19 L/h vs 1.58 L/h; P < 0.001) and Q (13.83 L/h vs 10.28 L/h; P < 0.001) values were significantly different between the two groups. The simulated AUCss,24h values for patients with normal renal function were higher than those for patients with renal insufficiency. However, the renal dosing adjustment of polymyxin B seemed not to be necessary. Besides, during the treatment, AKI occurred in 23 (32.86%) patients. The polymyxin B AUCss,24h in patients with AKI was significantly higher than that in patients without AKI (108.66 ± 70.10 mg⋅h/L vs 66.18 ± 34.79 mg⋅h/L; P = 0.001). Both the ROC curve and Logistic regression analysis showed AUCss,24h > 100 mg⋅h/L was a good predictor for the probability of nephrotoxicity.

scholarly journals A reappraisal of polymyxin B dosing based on population pharmacokinetic model in patient with renal insufficiency

2020 ◽  
Author(s):  
Xuben Yu ◽  
Chunhong Zhang ◽  
Jingye Pan ◽  
Ying Dai ◽  
Ziye Zhou ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Renal Function ◽  
Steady State ◽  
Renal Insufficiency ◽  
Creatinine Clearance ◽  
Polymyxin B ◽  
Adult Patients ◽  
Population Pharmacokinetic ◽  
Population Pk ◽  
Dosing Strategy

AbstractBackgroundCurrent FDA-approved label recommends polymyxin B dosing should be adjusted according to renal function, despite several studies proved poor correlation between polymyxin B PK and creatinine clearance. The study aims to assess the impact of renal function on polymyxin B metabolism and identify an alternate dosing strategy by population analysis.MethodsBlood samples from adult patients were collected at steady state during routine therapeutic drug monitoring. Nonlinear mixed effects modeling was employed to build a population PK model of polymyxin B. Monte Carlo simulations were performed to design polymyxin B dosing regimens across various renal function.ResultsPharmacokinetic analyses included 112 polymyxin B concentrations at steady state from 32 adult patients aged 37-93 received intravenous polymyxin B (100-200 mg/d). The creatinine clearance in patients was 5.91-244 mL/min. In the final population PK model, CrCL was the significant covariate on CL (typical value, 1.59 L/hr; between-subject variability, 13%). Mean (SD) individual empirical Bayesian estimates of CL was 1.75 (0.43) L/hr. A new dosing strategy combining the PK/PD targets and Monte Carlo simulation indicated that polymyxin B dose reductions improved the probability of achieving optimal exposures in simulated patients with renal insufficiency. For severe infections caused by organisms with MIC of ≥ 2 mg/L, though a high daily dose (e.g. 200mg/day) would possible for bacterial eradication, the risk of nephrotoxicity is significantly increased.ConclusionA population PK model was established to develop individualized polymyxin B dosage regimens that the dose of polymyxin B should be adjusted according to CrCL.

scholarly journals Contrast-Induced Acute Kidney Injury: Definition, Epidemiology, and Outcome

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Felix G. Meinel ◽  
Carlo N. De Cecco ◽  
U. Joseph Schoepf ◽  
Richard Katzberg
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Time Window ◽  
Contrast Material ◽  
Kidney Injury ◽  
Preventive Strategy ◽  
Iodinated Contrast ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced

Contrast-induced acute kidney injury (CI-AKI) is commonly defined as a decline in kidney function occurring in a narrow time window after administration of iodinated contrast material. The incidence of AKI after contrast material administration greatly depends on the specific definition and cutoff values used. Although self-limiting in most cases, postcontrast AKI carries a risk of more permanent renal insufficiency, dialysis, and death. The risk of AKI from contrast material, in particular when administered intravenously for contrast-enhanced CT, has been exaggerated by older, noncontrolled studies due to background fluctuations in renal function. More recent evidence from controlled studies suggests that the risk is likely nonexistent in patients with normal renal function, but there may be a risk in patients with renal insufficiency. However, even in this patient population, the risk of CI-AKI is probably much smaller than traditionally assumed. Since volume expansion is the only preventive strategy with a convincing evidence base, liberal hydration should be encouraged to further minimize the risk. The benefits of the diagnostic information gained from contrast-enhanced examinations will still need to be balanced with the potential risk of CI-AKI for the individual patient and clinical scenario.

Impact of polymyxin-B-associated acute kidney injury in 1-year mortality and renal function recovery

2018 ◽  
Vol 52 (1) ◽  
pp. 86-89 ◽  
Author(s):  
Eduardo C. Gomes ◽  
Diego R. Falci ◽  
Pedro Bergo ◽  
Alexandre P. Zavascki ◽  
Maria Helena Rigatto
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Injury ◽  
Polymyxin B ◽  
Renal Function Recovery ◽  
Function Recovery

scholarly journals Dosing and Pharmacokinetics of Polymyxin B in Patients with Renal Insufficiency

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Visanu Thamlikitkul ◽  
Yanina Dubrovskaya ◽  
Pooja Manchandani ◽  
Thundon Ngamprasertchai ◽  
Adhiratha Boonyasiri ◽  
...  
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Steady State ◽  
Renal Insufficiency ◽  
Actual Body ◽  
Normal Renal Function ◽  
Polymyxin B ◽  
Poor Correlation ◽  
Actual Body Weight ◽  
Significant Difference

ABSTRACT Polymyxin B remains the last-line treatment option for multidrug-resistant Gram-negative bacterial infections. Current U.S. Food and Drug Administration-approved prescribing information recommends that polymyxin B dosing should be adjusted according to the patient's renal function, despite studies that have shown poor correlation between creatinine and polymyxin B clearance. The objective of the present study was to determine whether steady-state polymyxin B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous polymyxin B (1.5 to 2.5 mg/kg [actual body weight] daily) were included. To measure polymyxin B concentrations, serial blood samples were obtained from each patient after receiving polymyxin B for at least 48 h. The primary outcome was polymyxin B exposure at steady state, as reflected by the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CLCR] ≥ 80 ml/min) at baseline, whereas 14 had renal insufficiency (CLCR < 80 ml/min). The mean AUC of polymyxin B ± the standard deviation in the normal renal function cohort was 63.5 ± 16.6 mg·h/liter compared to 56.0 ± 17.5 mg·h/liter in the renal insufficiency cohort (P = 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual body weight) did not result in a significant difference (28.6 ± 7.0 mg·h/liter versus 29.7 ± 11.2 mg·h/liter, P = 0.80). Polymyxin B exposures in patients with normal and impaired renal function after receiving standard dosing of polymyxin B were comparable. Polymyxin B dosing adjustment in patients with renal insufficiency should be reexamined.

scholarly journals PROGNOSIS SIGNIFICANCE OF CONTRAST-INDUCED ACUTE KIDNEY INJURY IN PATIENTS WITH PREVIOUSLY NORMAL RENAL FUNCTION (UP TO 2 YEARS FOLLOW UP)

2014 ◽  
Vol 63 (12) ◽  
pp. A1853
Author(s):  
Ester Canovas Rodriguez ◽  
Lorenzo Hernando Marrupe ◽  
Alfonso Freites Esteves ◽  
Adriana De La Rosa Riestra ◽  
Javier Alonso Bello ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Normal Renal Function ◽  
Kidney Injury

scholarly journals Continued monitoring of acute kidney injury survivors might not be necessary in those regaining an estimated glomerular filtration rate >60 mL/min at 1 year

2017 ◽  
Vol 32 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Sokratis Stoumpos ◽  
Patrick B. Mark ◽  
Emily P. McQuarrie ◽  
Jamie P. Traynor ◽  
Colin C. Geddes
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Normal Renal Function ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Kidney Injury ◽  
Risk Of Progression

Background. Severe acute kidney injury (AKI) among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who recover to normal renal function. The aim of this study was to determine the long-term renal outcome of patients experiencing AKI requiring dialysis secondary to hypoperfusion injury and/or sepsis who recovered to apparently normal renal function. Methods. All adult patients with AKI requiring dialysis in our centre between 1 January 1980 and 31 December 2010 were identified. We included patients who had estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 12 months or later after the episode of AKI. Patients were followed up until 3 March 2015. The primary outcome was time to chronic kidney disease (CKD) (defined as eGFR persistently <60 mL/min/1.73 m2) from first dialysis for AKI. Results. Among 2922 patients with a single episode of dialysis-requiring AKI, 396 patients met the study inclusion criteria. The mean age was 49.8 (standard deviation 16.5) years and median follow-up was 7.9 [interquartile range (IQR) 4.8–12.7] years. Thirty-five (8.8%) of the patients ultimately developed CKD after a median of 5.3 (IQR 2.8–8.0) years from first dialysis for AKI giving an incidence rate of 1 per 100 person-years. Increasing age, diabetes and vascular disease were associated with higher risk of progression to CKD [adjusted hazard ratios (95% confidence interval): 1.06 (1.03, 1.09), 3.05 (1.41, 6.57) and 3.56 (1.80, 7.03), respectively]. Conclusions. Recovery from AKI necessitating in-hospital dialysis was associated with a very low risk of progression to CKD. Most of the patients who progressed to CKD had concurrent medical conditions meriting monitoring of renal function. Therefore, it seems unlikely that regular follow-up of renal function is beneficial in patients who recover to eGFR >60 mL/min/1.73 m2 by 12 months after an episode of AKI.

scholarly journals MORPHOFUNCTIONAL CHANGES IN KIDNEYS OF RATS WITH GENTAMICIN-INDUCED ACUTE KIDNEY INJURY AND USE OF MELATONIN

2018 ◽  
Vol 24 (1) ◽  
pp. 5-10
Author(s):  
Ye.A. Dudka ◽  
I.I. Zamorskii ◽  
A.Ye. Petriuk ◽  
T.S. Shchudrova
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Creatinine Clearance ◽  
Potassium Level ◽  
Kidney Injury ◽  
Plasma Potassium ◽  
Male Rats ◽  
Histopathological Changes ◽  
Urine Protein ◽  
Plasma Potassium Level

Aminoglycosides are effective antibiotics, but their accumulation in kidney cortex causes nephrotoxic effects in 20-30% of patients, which significantly limits their use. For this reason, search for the new therapies aimed at prevention of gentamicin-induced acute kidney injury (AKI) is highly relevant. Thus, the objective of our research was to study the functional and histopathological changes in kidneys of rats with gentamicin-induced AKI, and estimate the renoprotective potential of pineal hormone melatonin, which possesses antioxidant, anti-inflammatory and immunomodulatory effects. The study was conducted on 24 non-linear male rats. Gentamicin-induced AKI was modeled by daily administration of 4% gentamicin sulphate (80 mg/kg) for 6 days. Melatonin (Sigma Aldrich, USA) was injected daily at a dose of 5 mg/kg. Functional state of kidneys was assessed by diuresis, creatinine clearance, urine protein excretion, fractional excretion of sodium, and plasma potassium level. Documentation of the pathological processes was performed by the computer morphometry of objects in histological preparations. Statistical analysis of the data was performed using SPSS 17.0 software. Administration of gentamicin resulted in a significant impairment of renal function of experimental animals. A decrease in creatinine clearance by 3.1 times along with a reduction of diuresis by 1.9 times, and an increase in plasma creatinine concentration by 2.6 times was observed. There also was an increase in urine protein level by 5.2 times, an elevation of fractional sodium excretion and a reduction of plasma potassium level. Use of melatonin caused a significant improvement of renal function comparing to model pathology group. Functional disturbances were accompanied with the significant histopathological changes in kidney tissue: necrosis of the 27±5.2% epithelial cells of proximal tubules with the signs of hydropic vacuolization (7±2.1%) or reversible hydropic swelling (76±1.5%) in the rest of cells; swelling or deformation of some glomeruli. In the medulla tubular lumen were dilated and partially filled with hyaline casts, tubular cells had signs of dystrophy. Use of melatonin contributed to the restraint of the histopathological changes, confirmed by the decrease of the prevalence and severity of tubular necrosis (1.2%), dystrophy (64±2.3%), and injury of glomeruli. Obtained results verify the significant nephroprotective effect of pineal hormone melatonin, providing a background for the further in-depth study of its renal effects as well as its prospects as a nephroprotector.

Acute kidney injury associated with ingestion of star fruit: Acute oxalate nephropathy: a report of two cases

2019 ◽  
Vol 8 (2) ◽  
pp. 47-51
Author(s):  
Mahmud Javed Hasan ◽  
Nitai Chandra Ray ◽  
Shaikh Shariful Islam ◽  
Shakil Azam Nahid ◽  
Tumpa Shom ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Normal Renal Function ◽  
Herbal Remedy ◽  
Case Reports ◽  
Kidney Injury ◽  
Young Male ◽  
Empty Stomach ◽  
Star Fruit ◽  
History Of

There are few case reports regarding star fruit's nephrotoxicity and neurotoxicity in chronic kidney disease patients. Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit. The first patient is a 52 year-old male diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once for remedy of diabetes. The second patient, a 27 years old young male who developed acute kidney injury following star fruit ingestion in empty stomach. One case needed 4 sessions of hemodialysis another case recovered over 2 weeks without the need for haemodialysis. Consumption of star fruit, especially on an empty stomach or in a state of dehydration may precipitate acute kidney injury. A history of star fruit ingestion must be actively looked for in patients presenting with unexplained acute kidney injury. The use of star fruit as a therapy for diabetes should be discouraged. CBMJ 2019 July: Vol. 08 No. 02 P: 47-51

scholarly journals Acute Kidney Injury Following Star Fruit (Averrhoa carambola) Ingestion in a Previously Healthy Young Man

2017 ◽  
Vol 19 (1) ◽  
pp. 63-65 ◽  
Author(s):  
Abdul Mumith Ruhan ◽  
Parash Ullah ◽  
Md Moyeen Uddin ◽  
MM Jahangir Alam ◽  
Md Shafiqul Bari ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Kidney Injury ◽  
Averrhoa Carambola ◽  
Star Fruit ◽  
Patient’S History ◽  
Oxalate Nephropathy

Star fruit (Averrhoa carambola) is a commonly available and popular fruit in many tropical and subtropical countries. Although star fruit induced oxalate nephropathy in patients with pre-existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. Hereby we report a case where a young man with previously normal renal function presented with AKI that was attributable to consumption of star fruit. This write up illustrates the importance of obtaining the patient’s history with respect to ingestion of star fruit in case of sudden and unexplained development of renal impairment.J MEDICINE Jan 2018; 19 (1) : 63-65

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