Incidence Of Nephrotoxicity Research Articles

Incidence and Risk Factors for Vancomycin Nephrotoxicity in Acutely Ill Pediatric Patients.

Background: Particularly with the current increased vancomycin dosing trends, the true risk of the agent's nephrotoxicity is not well characterized and remains of concern. Objective: To determine the incidence of vancomycin nephrotoxicity in acutely ill hospitalized children and to secondarily characterize the risk factors for this complication. Methods: A single-center retrospective cohort study conducted at UCSF Benioff Children's Hospital from June 2012 to June 2015. Inpatients 3 months to <19 years who received intravenous vancomycin for ≥48 hours were included. The primary outcome was incidence of nephrotoxicity, defined as an increase in serum creatinine by ≥50% from baseline. Univariate and multivariate analyses were conducted to identify risk factors for vancomycin nephrotoxicity. Results: A total of 291 patients (272 nonnephrotoxic and 19 nephrotoxic) were included in the analysis. Of the 19 patients, 12 (4.1%) were found to have moderate to severe toxicity. The median duration of therapy was 3 (3-5) and 4 (3-6) days for the group with "no nephrotoxicity" and "nephrotoxicity," respectively. The mean time for the serum creatinine to return to normal in patients with nephrotoxicity was 5.1 days. In the multivariate analysis, only final trough concentration ≥15mg/dL (odds ratio = 3.49, 95% confidence interval = 1.2-10.1; P = .021) and receipt of piperacillin/tazobactam (odds ratio = 3.14, 95% confidence interval = 1.02-9.6; P = .046) were significantly associated with nephrotoxicity. Conclusion: The rate of moderate to severe vancomycin-associated nephrotoxicity in acutely ill children is relatively uncommon and reversible. Kidney injury is associated with increased vancomycin trough concentrations and concomitant receipt of nephrotoxins, particularly piperacillin/tazobactam.

Colistin-induced nephrotoxicity and the role of N-acetylcysteine: a retrospective cohort study.

Colistin is associated with dose-dependent nephrotoxicity. N-acetylcycteine (NAC) may reduce the risk of concomitant acute kidney injury (AKI) due to its antioxidant properties. We report a retrospective cohort study evaluating the role of N-acetylcysteine (NAC) in the development of colistin (COL) associated nephrotoxicity. A single centre retrospective cohort study was conducted in a university hospital between January 2014 and June 2015. Nephrotoxicity was defined and staged per the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. We evaluated the association between NAC use and COL-related nephrotoxicity by comparing the incidence of nephrotoxicity in patients receiving colistin with or without adjunctive NAC. Forty-six patients received intravenous (IV) COL and 46 patients received IV NAC+COL. The cumulative COL doses did not differ between the two groups (p = 0.802). The initial creatinine value doubled in 29 (63%) patients undergoing NAC+COL therapy and in 27 (58.7%) patients in the COL group (p = 0.669). The median doubling time of baseline creatinine was 6 and 7 days in the NAC+COL and COL groups, respectively. The mean hospital stay, potentially nephrotoxic agent use, and mortality rates were statistically higher for the patients receiving NAC+COL (p < 0.005). The present study was not able to reveal any beneficial effect of NAC for patients undergoing COL therapy. The NAC+COL group had a higher baseline risk for development of AKI. However, the incidence of AKI was comparable between the groups. The results of the study would not solely exhibit the protective effect of adjunctive NAC therapy.

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

Incidence of Nephrotoxicity Among Patients Initiated on Vancomycin and Β-lactam Combination Therapies

Abstract Background Vancomycin and β-lactam combinations are used to provide empiric coverage in hospitalized patients. Recent literature has illustrated an increased incidence of nephrotoxicity with such combinations, predominantly with piperacillin-tazobactam and vancomycin. The objective of this study is to evaluate the incidence of nephrotoxicity among patients receiving vancomycin and piperacillin-tazobactam vs., cefepime, or aztreonam. Methods A retrospective, observational, cohort study was conducted at Hahnemann University Hospital in adult patients who received vancomycin plus piperacillin-tazobactam, cefepime, or aztreonam for at least 48 hours between June 2013 and August 2016. Patients were excluded if they had chronic kidney disease Stage III or higher or on continuous renal replacement therapy. The following data were collected: demographics, renal function, number of concomitant nephrotoxic agents, total duration of combination therapy, and vancomycin levels. The primary outcome was the incidence of nephrotoxicity according to the Risk Injury Failure End Stage Renal Disease (RIFLE) criteria. Secondary outcomes were the total length of hospital (LOS) and intensive care unit (ICU) LOS. Statistical analyses were conducted using the Analysis of Variance and the Chi-square test. Results A total of 757 charts were reviewed of which 203 were included in the analysis; 69 in the piperacillin-tazobactam arm, 74 in the cefepime arm, and 60 in the aztreonam arm. The incidence of nephrotoxicity as assessed by the RIFLE criteria was higher in the piperacillin-tazobactam arm (41%) compared with cefepime (15%) and aztreonam arms (17%); P = 0.052. Majority of patients with nephrotoxicity experienced injury according to the RIFLE criteria. No differences were found in the total LOS, ICU LOS, or duration of nephrotoxicity. Patients who experienced nephrotoxicity in the piperacillin-tazobactam arm occurred earlier upon antibiotic initiation at 48 hours compared with the other arms extending past 72 hours; P = 0.004. Conclusion There was a trend towards more patients experiencing nephrotoxicity in the piperacillin-tazobactam arm compared with the other groups. Clinicians should remain vigilant when utilizing combination therapy. Disclosures T. Bias, Merck: Grant Investigator, Research grant. The Medicines Company: Speaker’s Bureau, Speaker honorarium.

Assessing the Risk of Nephrotoxicity Associated With Non-renally Adjusted Intravenous Polymyxin B Compared with Traditional Dosing

BackgroundPrior data states that polymyxin B is renally cleared and thus required renal adjustments, however newer data suggests that polymyxin B undergoes non-renal clearance. With more aggressive dosing, potential for increased nephrotoxicity is of concern. This study aims to determine whether time to acute kidney injury (AKI) differs between renally adjusted and non-adjusted doses of intravenous (IV) polymyxin B. Secondary objectives aim to evaluate incidence of AKI, length of stay (LOS), adverse reactions, and potential role of ascorbic acid in decreasing nephrotoxicity.MethodsThis retrospective chart review compared time to AKI in patients receiving renally adjusted and non-adjusted IV polymyxin B between Jan 2012 and Nov 2016. This study included patients who are at least 18 years old, received IV polymyxin B, and have creatinine clearance below 80 mL/minute. Patients were excluded if they had AKI (RIFLE criteria), received renal replacement therapy, or are pregnant prior to receipt of IV polymyxin B. Fine and Gray’s model for competing risks was used to predict the cumulative incidence function of AKI. Descriptive statistics, two-sample t-test, and Chi-square test were used as appropriate.ResultsOf the 132 patients screened, 54 met inclusion criteria (23 in the renally adjusted vs. 31 in the non-adjusted group). There was no statistical association between dosing type and time to AKI (P = 0.13). Incidence of nephrotoxicity was higher in the renally adjusted vs. non-adjusted groups (21.7% vs. 6.5% respectively). Mortality was higher in the renally adjusted vs. non-adjusted groups (17.4% vs. 6.5% respectively). LOS was greater in the renally adjusted vs. non-adjusted groups (16 vs. 14 days respectively, P = 0.26). All patients in the study received concomitant nephrotoxic agents (e.g., vancomycin, aminoglycosides). Ascorbic acid use was infrequent but, in the 4 patients who did receive it, none developed AKI. No difference in neurotoxicity, respiratory arrest, Clostridium difficile infections was seen.ConclusionNo significant association between IV polymyxin B dosing type and time to AKI was found. Incidence of AKI, LOS, and mortality was higher in the renally adjusted group compared with the non-adjusted group. Ascorbic acid may mitigate the nephrotoxic potential of IV polymyxin B, but further studies are needed.Disclosures All authors: No reported disclosures.

Relationship between Vancomycin Area Under the Concentration-Time Curve (AUC) and Nephrotoxicity in Adults

Abstract Background While recent data correlate vancomycin’s ratio of the area under the 24 hour time-concentration curve (AUC0−24h) to the pathogen’s minimal inhibitory concentration (MIC) of &amp;gt; 400 mg*hours/L with a favorable clinical outcome, data are sparse to correlate vancomycin AUC0−24h to nephrotoxicity. Our primary objective was to evaluate the relationship between vancomycin AUC0−24h and nephrotoxicity. Methods This single-center, retrospective cohort study was conducted at a large US tertiary-care hospital. Adults hospitalized between 08/01/13 and 08/31/14 with normal baseline renal function receiving intravenous vancomycin ≥ 72 hours were included. Vancomycin AUC0−24h was calculated for each subject utilizing computer-based Bayesian pharmacokinetic methods (BestDose™). Subjects were divided into AUC0−24h of &amp;lt; 700 and &amp;gt; 700 mg*hours/L groups. The primary endpoint of nephrotoxicity (defined as a 50% relative increase or &amp;gt; 0.5 mg/dl absolute increase in SCr over at least 2 consecutive days) was compared between exposure groups. Secondary objectives were to compare the incidence of nephrotoxicity with and without the following risk factors: sepsis, concomitant nephrotoxins, vancomycin troughs &amp;gt; 20 mg/L or doses ≥ 4 g/day, and Charlson Comorbidity Index scores. Results Table 1. Multivariate Model of Nephrotoxicity and Clinical Characteristics Conclusion A significant increase in nephrotoxicity was observed in patients with a vancomycin AUC0−24h ≥ 700 mg*hours/L. Given that this exposure threshold is within the target for efficacy for organisms with elevated MICs, further studies should be conducted to better delineate the AUC0−24h values associated with nephrotoxicity. Disclosures All authors: No reported disclosures.

Vancomycin vs. Vancomycin/Piperacillin-Tazobactam-Associated Acute Kidney Injury in Noncritically Ill Patients at a Tertiary Care Military Treatment Facility.

Broad-spectrum antibiotics are often used as initial empiric therapy in patients at risk for infections by multidrug-resistant organisms. Emerging literature and anecdotal reports within Tripler Army Medical Center indicate an increased incidence of vancomycin-associated acute kidney injury when used in combination with piperacillin-tazobactam. This is a retrospective, single-center study comparing the incidence of acute kidney injury in noncritically ill patients receiving either vancomycin or vancomycin in combination with piperacillin-tazobactam in a 206-bed tertiary care military training facility. Data were collected from electronic medical records between May 2012 and October 2014 and evaluated via multivariable logistic regression models. Patients included for analysis were 17 years of age and older, were admitted to medical/surgical wards, and received vancomycin or vancomycin in combination with piperacillin-tazobactam for at least 48 hours. A vancomycin trough level, baseline serum creatinine level, and at least two follow-up serum creatinine levels were required for inclusion. Patients were excluded if they were pregnant, admitted to an intensive care unit while on antimicrobial therapy, or their baseline serum creatinine was equal to or greater than 1.5 mg/dL. Of 1,133 patients evaluated retrospectively, 455 were included for analysis. Of 202 patients, 49 (24%) taking vancomycin in combination with piperacillin-tazobactam developed acute kidney injury in contrast to 28 of the 253 patients (11%) given vancomycin without piperacillin-tazobactam (unadjusted odds ratio 2.57 [95% confidence interval (CI) 1.55-4.28], p < 0.001). Dual therapy remained significant after adjusting for age, sex, body mass index, concomitant nephrotoxic agents, and preexisting comorbid status as evaluated by Charlson comorbidity index (adjusted odds ratio 2.14 [95% CI 1.26-3.6], p = 0.005). Contrast administration (p < 0.001), fluoroquinolone administration (p < 0.001), and Charlson Comorbidity Index > 6 (p = 0.008) were also found to be independent risk factors for acute kidney injury. Significant increased incidence of nephrotoxicity was noted with vancomycin and piperacillin-tazobactam as compared to vancomycin within Tripler Army Medical Center. This finding influenced our institution's decision to add ceftaroline as a formulary agent in the treatment of skin and soft-tissue infections and further supported the need for rapid de-escalation of antibiotics within our military training facility.

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m2), obesity class I and II (BMI 30-39.9kg/m2), and obesity class III (BMI≥40 kg/m2) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

Incidence and prognostic significance of nephrotoxicity in patients receiving eshap as salvage therapy for lymphoma

Nephrotoxicity is a well-known side effect of platinum-based chemotherapy. We retrospectively assessed the incidence and prognostic impact of nephrotoxicity with ESHAP rescue chemotherapy in 74 lymphoma patients (61 aggressive lymphomas). A higher incidence of nephrotoxicity (estimated glomerular filtration rate <60mL/min) was found when ESHAP was administred on an outpatient vs. inpatient basis (14/39 vs. 4/35). Patients submitted to ASCT with renal failure had a lower overall survival (OS) than those with normal renal function (2-yr OS probability [95%CI]: 88% [77%–99%] vs. 50% [22%–78%]). Outpatient administration of ESHAP may not be optimal for all patients and the impact of ESHAP-induced renal failure on ASCT outcomes in lymphoma needs to be assessed in prospective studies.

Safety and effectiveness of colistin compared with non-colistin combinations in the treatment of multi drug resistant bacterial infections

Background: Multi drug resistant (MDR) bacteria are usually defined as when it is resistant to three or more group of antibiotics. The objective of this study was to determine the efficacy and safety of colistin when compared with other antibiotics for the treatment of infections caused by MDR Acinetobacter baumannii and Pseudomonas aeruginosa.Methods: A single centre, prospective cohort study was conducted at Krishna Institute of medical Sciences, Hyderabad, India between September 2016 to March 2017. Seventy-four patients (74) were included in the study. Primary outcome were good clinical response and thirty days’ mortality, secondary outcome were microbiological response and adverse drug reactions of the drug.Results: A total of 74 patients were enrolled into the study. Forty patients (40) were received intravenous colistin dose of 2.5mg-5mg/kg/day. Remaining thirty-four patients (34) received other antibiotics which includes carbapenem, aminoglycosides. etc. The mean age, gender, underlying conditions and severity of illness of the patients in both groups were significantly same. In colistin group 27 (67.5%) patients and 11 (32.3%) patients had good clinical response. The overall mortality of the patients in the colistin group was 17.5% and that in the non-colistin group was 38.2%. The incidence of nephrotoxicity in colistin was 15% and 35.2% in non colistin group. No neurotoxicity was observed in present study.Conclusions: Our study concludes treatment with colistin decreases patient mortality and increase the clinical response in multidrug-resistant A. baumannii and P. aeruginosa infected patients. However large multicentric clinical trials are needed to demonstrate the safety and efficacy of colistin.

Lower blood pressure and risk of cisplatin nephrotoxicity: a retrospective cohort study

BackgroundThe pathophysiological mechanisms of cisplatin nephrotoxicity include the reduction of renal blood flow, as well as tubular epithelial cell toxicity. The objective of this study was to investigate the influence of lower blood pressure and decreased food intake on the incidence of cisplatin nephrotoxicity.MethodsWe conducted a retrospective cohort study at a university hospital between 2011 and 2012. We identified hospitalized adult patients with head and neck cancer, esophageal cancer, or gastric cancer, who received intravenous cisplatin administration. The primary outcome was the incidence of cisplatin nephrotoxicity defined as the increase in serum creatinine after cisplatin administration more than 1.5 times from baseline.ResultsThe study participants included 182 patients, in whom we observed a total of 442 cycles of cisplatin chemotherapy. The incidence of cisplatin nephrotoxicity was observed in 41 of 182 cycles with initial administration. Multivariate logistic regression analysis showed that systolic blood pressure was independently associated with cisplatin nephrotoxicity (adjusted odds ratio 0.75, 95% confidence interval 0.57 to 0.95 for each 10 mmHg). The use of renin-angiotensin system (RAS) inhibitors was also associated with cisplatin nephrotoxicity (3.39, 1.30 to 8.93). Among quartiles of systolic blood pressure in all cycles of chemotherapy, the incidence of nephrotoxicity in the lower blood pressure group was significantly higher than that in the higher blood pressure group for patients taking non-solid food (P = 0.037), while there was no significant difference for patients taking solid food (P = 0.67).ConclusionsLower blood pressure and the use of RAS inhibitors were associated with the incidence of cisplatin nephrotoxicity, and lower blood pressure had a greater influence on nephrotoxicity in patients who could not take solid food. Discontinuation of antihypertensive medication including RAS inhibitors before cisplatin chemotherapy should be considered, which may be beneficial for patients with lower blood pressure.

Pharmacoepidemiology of Severe Systemic Infection and Need of Netilmicin Monotherapy or Combination Therapy: Systemic Review and Meta-Analysis

In this systematic review and meta-analysis we compared the efficacy and safety in patient with severe systemic infection (SSF) who has been either on netilmicin (NL) monotherapy or combination of netilmicin with other antibiotics (NLC). A systematic review of the literature was performed in accordance with PRISMA guidelines in Medline and Embase. A comprehensive search was performed from 1978 to 2017. Total 17 studies were identified that include 976 randomized patients with SSF. 489 patients enrolled in 11 studies for NL while 487 in NLC group. The meta-analysis showed that there was a statistically significant difference in rate of clinical efficacy (rate of failure) between NL (13.09%) and comparator NLC (20.91%). Nephrotoxicity associated with the therapy showed minor difference between both group, NL (13.80%) and NLC (10.09%). The study was further compare on the basis of dose regimen viz once a day (OD) and three times a day (TID). 184 patients of 4 studies received once in a day netilmicin monotherapy (OD-NL) while 259 patients of 7 studies received three times a day netilmicin monotherapy (TID-NL). Result of dose regimen group showed 11.04% rate of failure and 11.78% incidence of nephrotoxicity in (OD-NL) and 12.5% and 13.84% respectively in (TID-NL). The paucity of data from this evidence based systematic review and meta-analysis, favors NL monotherapy, if the slightly more chances of nephrotoxicity than comparator NLC neglected.

P2.03a-012 Nephrotoxicity in Patients with Advanced NSCLC Receiving Pemetrexed-Based Chemotherapy

In patients with advanced non-small cell lung cancer (NSCLC) pemetrexed (PEM) is increasingly used as maintenance therapy after induction PEM/platinum treatment. Despite the extensive use of PEM, the incidence of nephrotoxicity during (maintenance) PEM therapy has not been systematically evaluated. Knowledge about nephrotoxicity during PEM-based treatment could determine the need for adapted renal protective strategies. We assessed the occurrence of nephrotoxicity and its influence on treatment continuation in NSCLC patients receiving PEM-based therapy. In a prospective observational multi-center study, treatment-naive patients with stage IIIB or IV NSCLC were enrolled. Patients were treated with PEM-cisplatin (PEMCIS; PEM 500mg/m2 and CIS 75mg/m2) or PEM-carboplatin (PEMCAR; CAR AUC=5). Patients with at least disease stabilization after four cycles and a favorable toxicity profile were eligible for PEM maintenance therapy. Prior to the initial PEM/platinum cycle, baseline serum creatinine (μmol/l) was obtained. Subsequently, prior to and weekly after each administration of PEM(/platinum) serum creatinine was measured. Glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboriation (CKD-EPI) formula. Acute kidney disease (AKD) was defined as >1.5-fold increase of serum creatinine and/or decrease in GFR >35% or GFR<60mL/min within 3 months (KDIGO). Of the 151 patients starting PEM-based therapy, the majority of patients had stage IV disease (86.8%) and they were treated with PEMCIS (64.2%) or PEMCAR (35.8%). During the first four cycles, treatment was discontinued in four patients (2.6%) due to AKD. Patients starting maintenance therapy (n=44, 29.1%) received a median number of 4 PEM cycles. During maintenance treatment with PEM, 12 patients developed AKD (27.3%): three patients could continue treatment after recovery of renal function and in one patient AKD was a part of septic shock. The remaining eight patients (18.2%) stopped treatment due to renal impairment. From patients with a decreased renal function at baseline (eGFR<90mL/min) a significantly higher proportion of patients stopped maintenance therapy due to renal impairment compared to patients with an eGFR≥90mL/min at baseline (6/11 vs. 2/33, p<0.05). Patients have a significant risk of developing nephrotoxicity leading to treatment discontinuation during maintenance therapy, especially if the renal clearance is impaired at the start of induction PEM/platinum therapy. In those patients a cumulative systemic dose of PEM or increased susceptibility may play a role in the development of nephrotoxicity. Patients might benefit from altered renal protective strategies, like continuation of hydration during maintenance therapy or dose-adjustment based on renal function. This study was funded by ZonMw, the Netherlands.

Active surveillance for adverse events among patients who underwent renal transplantation: A prospective observational study.

Aim:Renal transplantation is the treatment of choice for end-stage renal disease patients. Renal transplant recipients, however, have to be on lifelong therapy with immunosuppressants, which are associated with a number of adverse events (AEs). The safety profile of these immunosuppressants is not clear with respect to the Indian population. This study was conducted to find the frequency and pattern of all AEs experienced by Indian renal transplant recipients during the initial 3 months posttransplantation.Methods:Adults undergoing their first renal transplantation were enrolled in the study. All enrolled subjects were followed up for a maximum period of 3 months. All AEs were graded for severity and classified according to the Common Terminology Criteria for AEs criteria.Results:Ninety-eight renal transplant recipients enrolled in the study. There was a loss of follow-up of 7%. Five subjects died during the study. Subjects experienced on an average 9 AEs during the study. There was no difference in frequency of AEs between those on tacrolimus and cyclosporine. Most commonly observed AEs belonged to “Investigational” and “Metabolism and Nutrition” system organ classes. The most common AE was hypokalemia. New-onset diabetes after transplantation (NODAT) developed in 28% of subjects. There were 27 episodes of acute nephrotoxicity.Conclusion:The incidence of NODAT in the Indian population is substantially higher than that observed in the Western population. The incidence of nephrotoxicity may indicate higher sensitivity of the Indian population to calcineurin inhibitors.

Incidence of Nephrotoxicity Among Antiretroviral Therapy-naïve Patients with Human Immunodeficiency Virus Infection Taking Tenofovir at the Philippine General Hospital

Incidence of Nephrotoxicity Among Antiretroviral Therapy-naïve Patients with Human Immunodeficiency Virus Infection Taking Tenofovir at the Philippine General Hospital

Comparison of Rates of Acute Kidney Injury with Vancomycin/Piperacillin-Tazobactam vs. Vancomycin/Meropenem Combination Therapy

BackgroundVancomycin is historically correlated with renal toxicity, especially in conjunction with other nephrotoxins. Recent reports have identified nephrotoxicity associated with vancomycin in conjunction with β-lactam antibiotic therapy, reporting increased rates of acute kidney injury (AKI) with vancomycin/piperacillin-tazobactam (VPT) therapy as compared with vancomycin monotherapy. Similarly, increased rates of AKI have been reported with VPT as compared with vancomycin/cefepime. Little data exists comparing VPT to the combination of vancomycin/meropenem (VM). The purpose of this study was to compare the incidence of nephrotoxicity between these two antibiotic combinations.MethodsA single-center cohort study was performed at a large tertiary care community hospital utilizing retrospective review of electronic medical records. Adult in-patients treated from June to October of 2015 were included. Evaluable patients received at least 48 hours of either VPT or VM combination therapy and were followed for up to 10 days of combination therapy. Data collection included patient demographics, AKI risk factors, days of antibiotic therapy, and serum creatinine. The primary endpoint was incidence of AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included time to AKI and incidence of new dialysis treatment.ResultsOf 564 patients screened, a total of 202 patients met inclusion criteria, with 101 patients in each combination therapy group. Baseline serum creatinine and estimated creatinine clearance were not different between groups. The incidence of AKI was higher in the VPT group as compared with the VM group (17.82% vs. 4.95%, respectively, P = 0.004). Time to AKI onset was longer in the VPT group compared with the VM group (3.2 days vs. 1.4 days, P = 0.045). Patients in the VM group had a higher incidence of ICU admissions (56.4% vs. 40.6%, P = 0.024) and mean arterial pressure (MAP) less than 65mmHg (60.4% vs. 44.6%, P = 0.029). No patients in either group required new dialysis therapy.ConclusionDespite a greater incidence of AKI risk factors in the VM group, VPT therapy was associated with an increased risk of AKI as compared with VM therapy. Prospective studies are needed to further evaluate this finding.Disclosures All authors: No reported disclosures.

Randomized Controlled Trial to Determine the Efficacy of Early Switch From Vancomycin to Vancomycin Alternatives as a Strategy to Prevent Nephrotoxicity in Patients With Multiple Risk Factors for Adverse Renal Outcomes (STOP-NT).

Use of alternative antimicrobials to vancomycin is a potential strategy to reduce acute kidney injury (AKI) in high-risk patients, but current data do not support widespread adoption of this practice. To determine the efficacy of early switch to a nonnephrotoxic alternative for prevention of AKI in high-risk patients who receive vancomycin. This was an IRB-approved, prospective randomized controlled trial in a single, tertiary care academic medical center. Patients initially prescribed vancomycin between October 2011 to April 2013 with at least 2 risk factors for AKI were included. Treatment randomization was stratified by indication for therapy. Patients were randomized to continuation of dose-optimized vancomycin or early switch to an alternative antimicrobial agent. The primary end point was nephrotoxicity by consensus guideline definition adjudicated by blinded review; the secondary end point was AKI network-defined AKI. A total of 103 patients were randomized; 100 were included in the modified intent-to-treat population, 51 in the vancomycin group and 49 in the alternative group. The incidence of nephrotoxicity was 6.1% in the alternative therapy arm and 9.8% in the vancomycin group ( P = 0.72). The incidence of AKI was 32.7% in the alternative therapy group and 31.4% in the vancomycin group ( P = 0.89). No significant difference in nephrotoxicity or AKI was detected among patients treated with alternative antimicrobials compared with vancomycin. The use of alternative antimicrobial therapy instead of vancomycin solely for the purpose of preventing AKI in high-risk patients does not appear to be warranted.

Validation of a colistin plasma concentration breakpoint as a predictor of nephrotoxicity in patients treated with colistin methanesulfonate

Nephrotoxicity limits the effective use of colistin for the treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections. We previously defined a steady-state colistin plasma concentration (Css) of 2.42 mg/L that predicted nephrotoxicity at end of treatment (EOT). The objective of this study was to validate this breakpoint in a prospective cohort. This was a multicentre, prospective, observational study conducted at three hospitals with a cohort of patients treated for MDR-GNB infection with colistin methanesulfonate from September 2011 until January 2015. Nephrotoxicity was evaluated at Day 7 and at EOT using the RIFLE criteria. Css values were measured and analysed using HPLC. Taking the previously defined breakpoint for colistin concentration as a criterion, patients were divided into two groups (Css, ≤2.42 mg/L vs. >2.42 mg/L). Sixty-four patients were included. Seven patients (10.9%) had a Css > 2.42 mg/L and were compared with the remaining patients. Bivariate analysis showed that patients with a Css > 2.42 mg/L were older and had a significantly higher incidence of nephrotoxicity at Day 7 and EOT. Although not statistically significant, nephrotoxicity occurred earlier in these patients (6.2 days vs. 9.2 days in patients with lower Css; P = 0.091). Multivariate analysis of nephrotoxicity showed that Css > 2.42 mg/L was the only predictive factor. Nephrotoxicity was more frequent and occurred earlier in patients with colistin plasma concentrations higher than the previously defined breakpoint (2.42 mg/L). Colistin therapeutic drug monitoring should be routinely considered to avoid reaching this toxicity threshold and potential clinical consequences.

The effect of CYP3A5 genetic polymorphisms on adverse events in patients with ulcerative colitis treated with tacrolimus

BackgroundTacrolimus is an immunosuppressive agent, used in the remission induction therapy of ulcerative colitis (UC). AimsWe investigated the correlation between CYP3A5 genetic polymorphisms and the adverse events in patients with UC. The pharmacokinetics of tacrolimus after oral administration were also analyzed. MethodsWe enrolled 29 hospitalized patients with UC received oral tacrolimus. Genotyping for CYP3A5 A6986G (rs776746) was performed using Custom TaqMan® SNP genotyping assays. Adverse events, concentration and dose (C/D) ratios and clinical outcomes were investigated. ResultsCYP3A5 expressers and non-expressers were 16 and 13, respectively. C/D ratios of CYP3A5 expressers were significantly lower compared to non-expressers. The response rate in CYP3A5 non-expressers was relatively higher in the early phase of treatment compared to expressers, but not statistically significant. The incidence of overall adverse events was significantly higher in CYP3A5 expressers than in non-expressers (P=0.034, chi-squared test). In particular, the incidence of nephrotoxicity was significantly higher in CYP3A5 expressers compared to non-expressers (P=0.027, chi-squared test). All of the nephrotoxicity were reversible and resolved by discontinuation or dose reduction of tacrolimus. ConclusionThe adverse events especially nephrotoxicity were frequently observed in CYP3A5 expressers. CYP3A5 expressers should be paid attention to the onset of nephrotoxicity.

Impact of a Clinical Solid Organ Transplant Pharmacist on Tacrolimus Nephrotoxicity, Therapeutic Drug Monitoring, and Institutional Revenue Generation in Adult Kidney Transplant Recipients.

Tacrolimus requires close therapeutic drug monitoring (TDM) to ensure efficacy and minimize adverse effects. Pharmacists are uniquely positioned on transplant teams to interpret levels and recommend therapy modifications. Their impact in the immediate postoperative setting has not been described previously. To evaluate the impact of a clinical solid organ transplant pharmacist on nephrotoxicity, TDM, and revenue generation in adult kidney transplant recipients on tacrolimus. Retrospective assessment of adult kidney transplant recipients at University of Florida Health Shands Hospital. A transplant pharmacist rounded 5 days a week and made medication recommendations on transplant recipients-including tacrolimus dose modifications based on levels. Pharmacy services were expanded to include medication reconciliation, medication counseling, and delivery of discharge medications to bedside. Incidence of nephrotoxicity during tacrolimus exposure. Of the 70 kidney transplant recipients in the postpharmacist cohort, 18 (25.7%) experienced nephrotoxicity while on tacrolimus, compared to 18 (25%) of the 72 in the prepharmacist cohort ( P = .922). A significantly greater proportion of recipients who experienced nephrotoxicity were male, had hypertension, or experienced delayed or slow graft function. The rate of appropriately drawn tacrolimus troughs significantly increased from 23.4% to 30.3% in the postpharmacist cohort ( P < .001). The median outpatient pharmacy revenue generated per recipient significantly increased from US$345.49 (interquartile range [IQR]: 0-4727.56) to US$4834.95 per recipient (IQR: 3592.78-6224.60; P < .001). The length of stay (7 days, IQR: 6-9, vs 8 days, IQR: 6-9; P = .107) and the 30-day readmission rate were similar between groups (20.8% vs 21.4%; P = .931).