Validation of Two Scoring Tools to Predict Risk of Augmented Renal Clearance in Trauma Patients.

INTRODUCTION: Augmented renal clearance (ARC) is prevalent in trauma populations. Identification is underrecognized by calculated creatinine clearance or estimated glomerular filtration rate equations. Predictive scores may assist with ARC identification. The goal of this study was to evaluate validity of the ARCTIC score and ARC Predictor to predict ARC in critically ill trauma patients. METHODS: This single center, retrospective study was performed at an academic level 1 trauma center. Critically ill adult trauma patients undergoing 24-h urine-collection were included. Patients with serum creatinine >1.5 mg/dL, kidney replacement therapy, suspected rhabdomyolysis, chronic kidney disease, or inaccurate urine collection were excluded. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for ARCTIC Score and ARC Predictor were calculated. Receiver operating characteristic curves were created for ARCTIC score and ARC Predictor models. RESULTS: One-hundred and twenty-two patients with ARC and 78 patients without ARC were included. The ARCTIC score sensitivity, specificity, PPV, and NPV were 89%, 54%, 75%, and 75%, respectively. The ARC Predictor demonstrated sensitivity, specificity, PPV, and NPV of 77%, 88%, 91%, and 71%, respectively. Regression analyses revealed both ARCTIC score ≥6 and ARC Predictor threshold >0.5 as significant risk factors for ARC in presence of traumatic brain injury, obesity, injury severity score, and negative nitrogen balance (ARCTIC ≥6: odds ratio 8.59 [95% confidence interval 3.90-18.92], P < 0.001; ARC Predictor >0.5: odds ratio 20.07 [95% confidence interval 8.53-47.19], P < 0.001). CONCLUSIONS: These findings corroborate validity of two pragmatic prediction tools to identify patients at high risk of ARC. Future studies evaluating correlations between ARCTIC score, ARC Predictor, and clinical outcomes are warranted.

The Use of Intraperitoneal Ampicillin in a Patient With Enterococcus faecalis Peritonitis.

INTRODUCTION: Peritoneal dialysis (PD) - associated peritonitis is a serious complication of peritoneal dialysis (PD). The 2022 International Society of Peritoneal Dialysis (ISPD) guidelines do not recommend intraperitoneal (IP) ampicillin for treatment of Enterococcal PD - associated peritonitis. To date, there is no in vivo data to support use of IP ampicillin for the treatment of Enterococcus faecalis. CASE DESCRIPTION: A 69-year-old man with a past medical history of end stage kidney disease (ESKD) requiring continuous cycling peritoneal dialysis (CCPD) was admitted to the hospital and treated for peritonitis with E. faecalis. The patient's CCPD prescription was 2.5% Dianeal with 5 total exchanges. IP ampicillin was added to the first 4 exchanges and additional ampicillin was added to the last fill. The patient successfully completed the treatment course with clinical cure. DISCUSSION: The use of IP ampicillin for E. faecalis peritonitis is controversial and previously lacked compelling clinical evidence for or against its use. This case demonstrates treatment of peritonitis using a modified dosing strategy with ampicillin added to each CCPD exchange and last fill. The loss of ampicillin antimicrobial activity reported in vitro with E. faecalis was not supported by this case.

Removal of common antimicrobial agents by sustained low-efficiency dialysis.

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin-tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life (t1/2) on-SLED and off-SLED, and the fraction of removal by SLED (fD). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin-tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10-211). The t1/2 on-SLED was substantially lower than the off-SLED t1/2 for all antimicrobials, and the SLED fD varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.

Education Standards for Pharmacists Providing Comprehensive Medication Management in Outpatient Nephrology Settings.

Chronic kidney disease is a public health problem that has generated renewed interest due to poor patient outcomes and high cost. The Advancing American Kidney Health initiative aimed to transform kidney care with goals of decreasing the incidence of kidney failure and increasing the number of patients receiving home dialysis or a kidney transplant. New value-based models of kidney care that specify inclusion of pharmacists as part of the kidney care team were developed to help achieve these goals. To support this Advancing American Kidney Health-catalyzed opportunity for pharmacist engagement, the pharmacy workforce must have a fundamental knowledge of the core principles needed to provide comprehensive medication management to address chronic kidney disease and the common comorbid conditions and secondary complications. The Advancing Kidney Health through Optimal Medication Management initiative was created by nephrology pharmacists with the vision that every person with kidney disease receives optimal medication management through team-based care that includes a pharmacist to ensure medications are safe, effective, and convenient. Here, we propose education standards for pharmacists providing care for individuals with kidney disease in the outpatient setting to complement proposed practice standards.

Gabapentinoid dosing and adverse events in patients with chronic kidney disease.

BACKGROUND: Gabapentinoids (GPs) are frequently prescribed in individuals with chronic kidney disease (CKD); however, their exclusive renal elimination warrants dose adjustments to decrease risk of toxicity. This study evaluated GP prescribing patterns and whether excessive dosing was associated with increased incidence of gabapentinoid-related adverse events (GRAEs). MATERIALS AND METHODS: A retrospective analysis of adult CKD and end-stage kidney disease (ESKD) patients hospitalized from 2014 to 2020 and receiving GPs was conducted. Patients were grouped based on whether the average daily dose prescribed was higher than recommended (inappropriately dosed, (ID)) or as recommended (appropriately dosed (AD)) for CKD stage. The occurrence of GRAEs was compared between groups. Patient characteristics, CKD stage, and hospital length of stay (LOS) were evaluated to determine association with GRAEs. RESULTS: The 200 patients included were predominantly female (51%), black (72%), CKD 5/ESKD (84%), and prescribed gabapentin (90%) with a mean age 61 ± 14 years. For the 111 (55%) patients in the AD group and 89 (45%) in the ID group there was no statistically significant difference in GRAEs (18 vs. 19%, p = 0.84). GRAEs were associated with older age (66 vs. 61 years; p < 0.001), seizure history (14% for GRAE vs. 3% for no GRAE, p = 0.02), and concomitant antipsychotic use (24% for GRAE vs. 5% for no GRAE; p < 0.001) but not with CKD severity. LOS was significantly longer for patients experiencing a GRAE (8.5 vs. 5.3 days; p < 0.001). CONCLUSION: Appropriate dosing of GPs is particularly important to minimize the risk of adverse events in patients of older age, with a history of seizures, or concomitant antipsychotic use. There is a need for prescriber education given the high frequency of inappropriate GP dosing observed in patients with advanced kidney disease.

Evaluation of Hospitalized Patients Receiving High versus Low-Dose Opioids for Non-Cancer Pain.

Limited studies suggest that opioid-related adverse effects (ORAEs) may worsen hospitalized patient outcomes, but there is insufficient data related to the impact of high-dose opioids compared to low-dose on adverse patient events. Given the paucity of data, our study aims to evaluate these ORAEs in the general hospitalized patient with non-cancer pain. A retrospective study of adult patients receiving opioids with a primary diagnoses of myocardial infarction, chronic obstructive pulmonary disease, heart failure, pneumonia, sepsis, or diabetes was conducted. Average oral morphine milligram equivalents (MMEs) administered over the entire LOS was collected, and patients were categorized as high-dose (≥50 MMEs/day) or low-dose (<50 MMEs/day). The primary composite endpoint was the incidence of ORAEs (naloxone use, decreased oxygen saturations, nausea/vomiting). Secondary outcomes included LOS, 30-day readmission, ORAEs with >100 MMEs/day. A total of 100 patients were included (n = 58 low-dose group; n = 42 high-dose group). For the primary outcome, more patients in the high-dose group experienced ORAEs (50% high-dose vs. 22.4% low-dose; p < 0.006). No statistically significant differences in LOS or 30-day readmission rates were identified between the groups. For patients receiving >100 MMEs/day, ORAEs occurred in 61% of patients. Hospitalized patients receiving high-dose opioids for non-cancer pain may have an increased incidence of ORAEs.

Review of Anticoagulation in Continuous Renal Replacement Therapy.

Continuous renal replacement therapy is an important, yet challenging, treatment of critically ill patients with kidney dysfunction. Clotting within the dialysis filter or circuit leads to time off therapy and impaired delivery of prescribed treatment. Anticoagulation can be used to prevent this complication; however, doing so introduces risk for unintended complications such as bleeding or metabolic derangements in patients who are already critically ill. A thorough understanding of indications, therapeutic options, and monitoring principles is necessary for safe and effective use of this strategy. This review provides clinicians important information regarding when to anticoagulate, differences in pharmacologic agents, recommended doses, routes of drug delivery, and appropriate laboratory monitoring for patients receiving anticoagulation to support continuous renal replacement therapy.

Levetiracetam pharmacokinetics in critically ill patients undergoing renal replacement therapy.

PURPOSE: To determine clearance of levetiracetam in patients requiring continuous renal replacement therapy (CRRT) or sustained low efficiency dialysis (SLED). MATERIALS AND METHODS: Adult patients with acute kidney injury or end stage renal disease requiring either CRRT or SLED and levetiracetam were eligible for inclusion. Simultaneous arterial, venous, and effluent samples for analysis of levetiracetam concentrations were collected every two hours for up to 6-8 h. Levetiracetam clearance (CL) and half-life (t1/2) were calculated for each modality. RESULTS: Eight CRRT patients and 4 SLED patients completed the study: 67% male, mean age 50 ± 13 years, and 83% had AKI. Seven CRRT patients received continuous venovenous hemodiafiltration (CVVHDF) [median pre-replacement rate 700 mL/h (range 500-1000), post-replacement rate 500 mL/h (range 200-1000), effluent rate 2500 mL/h (range 1700-3650) and delivered CRRT dose 27 mL/kg/h (range 19-54)] and one patient received CVV hemofiltration (CVVH). The mm mean levetiracetam CL during CVVHDF was 31.2 ± 8.5 mL/min, and the and the mean t1/2 was 10.4 ± 2.2 h. For the patient requiring CVVH, clearance and t1/2 were 22.5 mL/min and 9.5 h, respectively. Mean levetiracetam CL during SLED performed at a blood flow rate of 250 mL/min and a dialysate flow rate of 100 mL/min was 74.0 ± 25.3 mL/min and t1/2 was 4.8 ± 2.3 h. CONCLUSIONS: Levetiracetam clearance was substantial with both modalities under the operating conditions reported. There is the potential for subtherapeutic concentrations with current recommended dosing strategies that account only for kidney function and not these extracorporeal routes of elimination.

Predictors of Hypophosphatemia and Outcomes during Continuous Renal Replacement Therapy.

INTRODUCTION: Hypophosphatemia occurs in up to 80% of patients undergoing continuous renal replacement therapy (CRRT) and has been associated with poor outcomes. Whether preemptive phosphate supplementation is warranted in select patients has not been adequately explored. This single-center, retrospective cohort study evaluates predictors of hypophosphatemia and characterizes treatment approaches in adult patients undergoing at least 12 h of CRRT. METHODS: Patients were divided into 2 groups based on the presence or absence of hypophosphatemia as defined by serum phosphorus <2.5 mg/dL. Select laboratory values at baseline and during CRRT, medications and nutritional sources affecting phosphorus, and CRRT parameters were compared. Patient outcomes including resolution of acute kidney injury (AKI), freedom from renal replacement therapy at hospital discharge, duration of intensive care unit (ICU) and hospital stay, duration of mechanical ventilation, and ICU mortality were evaluated. RESULTS: Seventy-two patients were included. The group was 43% female and 51% African American. CRRT was ordered for AKI in 83% and for end-stage renal disease in 15%. Hypophosphatemia occurred in 45 patients (63%). Mean time to development of hypophosphatemia was 34 ± 22 h. Patients who developed hypophosphatemia received a longer duration of CRRT (p = 0.001), were more likely to have a diet ordered (p = 0.005), less likely to have received calcium infusions (p = 0.045), and had lower phosphorus (p = 0.017) and potassium levels (p = 0.038) and higher calcium levels at baseline (p = 0.048). Development of hypophosphatemia was associated with an increased duration of ICU stay (p = 0.014) but not with the other patient outcomes evaluated. Twenty-seven of the 45 patients (60%) who developed hypophosphatemia received phosphorus supplementation with near equal use of intravenous, oral, and combination routes. Only 17 patients (38%) achieved resolution of hypophosphatemia while on CRRT. CONCLUSION: Hypophosphatemia is common, difficult to correct, and contributes to longer ICU stays in patients requiring CRRT. A preemptive approach to address hypophosphatemia including aggressive supplementation strategies to correct phosphorus is warranted in patients requiring CRRT.

Factors Associated With Increased Hospital Length of Stay in Peritoneal Dialysis Patients With Peritonitis: A Need for Antimicrobial Stewardship?

Background: Peritonitis remains a complication of peritoneal dialysis (PD) and contributes to morbidity. Adherence to evidence-based recommendations should resolve peritonitis within 5 days; however, hospital length of stay (LOS) for patients with PD-associated peritonitis (PDAP) varies. Factors contributing to increased LOS and vigilance with antimicrobial stewardship (ASP) in this population are not well described. Methods: This was a system-wide, retrospective cohort of adult patients presenting with PDAP from August 2012 to August 2017. Patients were divided into 2 groups based on LOS: <7 days (reduced LOS) versus ≥7 days (prolonged LOS). Patient demographics, resolution of peritonitis by day 5, intensive care unit (ICU) admission, infectious diseases (ID) consultation, changes in dialysis modality, blood glucose, and pathogen/antimicrobial characteristics were compared. In-hospital mortality and 30-day readmissions were also evaluated. Results: Of the 401 patients screened, 90 were included: 53% women, 88% African American, age 52 ± 2 years (reduced LOS: 46 patients; prolonged LOS: 44 patients). Increased LOS was associated with ICU admission (P = .014), ID consultation (P = .015), PD catheter removal (P = .001), hemodialysis conversion (P < .001), antifungal therapy (P = .021), and days with blood glucose >180 mg/dL (P = .028). Opportunities for antimicrobial de-escalation were identified in 24 (52%) and 22 (50%) patients in the reduced and prolonged LOS groups, respectively; however, de-escalation occurred in only 5 (21%) and 6 (27%) of these patients. There were no differences in mortality or 30-day readmissions. Conclusions: Longer LOS was influenced by acuity of illness and possibly lack of enforced ASP. Improvement of ASP within the PDAP population is necessary.

Disagreement in Estimates of Kidney Function for Drug Dosing in Obese Inpatients.

BACKGROUND:: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are used to estimate kidney function. However, utility has been questioned in the obese population. OBJECTIVE:: To evaluate differences in estimates of kidney function in obese patients and implications for drug dosing. METHODS:: This was a retrospective study of adult inpatients with a body mass index ≥30 kg/m2 and stable kidney function. Patients were categorized based on creatinine clearance (CrCl): group 1-CrCl ≥ 60 mL/min and group 2-CrCl 15 to 59 mL/min. Mean estimates of kidney function and recommended doses of 8 renally eliminated medications were compared. RESULTS:: For the 166 patients included, mean estimates using CG, MDRD, and CKD-EPI for group 1 were 87 (23) mL/min, 91 (21) mL/min, and 96 (23) mL/min, respectively. Group 2 estimates were 42 (13) mL/min, 51 (15) mL/min, and 51 (16) mL/min, respectively. MDRD and CKD-EPI estimates were significantly higher than CG in 125 (75%) and 140 (84%) patients, respectively. Dose discrepancies were most often due to higher dose recommendations using MDRD or CKD-EPI compared to CG. CONCLUSION:: Careful consideration of the method used to estimate kidney function, the method used for developing dosing recommendations, and the risk-benefit profile is warranted when designing drug regimens in obese individuals.

Inadequate antibiotic dosing in patients receiving sustained low efficiency dialysis.

Background Patients requiring SLED are often critically ill and/or hemodynamically unstable, and often need antibiotic therapy for life-threatening infections. Antibiotic dosing recommendations for intermittent hemodialysis and continuous renal replacement therapy are not appropriate for SLED and there is substantial concern for under dosing. Objective To characterize the adequacy of antibiotic dosing during SLED. Setting: Inpatient adult acute care hospital. Methods A retrospective chart review was performed for the period of October 2010 to August 2013 to identify patients who received SLED and at least one of the selected antibiotics: cefepime, daptomycin, piperacillin/tazobactam, meropenem, and vancomycin. Dosing regimens were evaluated each day the patient was receiving one of these antibiotics concurrently with SLED. The administered antibiotic dosing regimens were defined as "adequate" or "inadequate" based on recommendations available in the literature. Main outcome measure The percentage of adequate antibiotic days for each antibiotic. Results Antibiotic regimens were evaluated for a total of 51 patients: 35 (69%) with acute kidney injury, 16 (31%) with end-stage renal disease, mean SLED duration 9.3 ± 1.7 h. The total percent of adequate antibiotic days were: vancomycin 86%, cefepime 62%, daptomycin 58%, meropenem 35%, and piperacillin/tazobactam 20%. Under dosing accounted for 63% of the days antibiotic dosing was considered inadequate. Conclusion: Antibiotic dosing was frequently inadequate, especially for antibiotics requiring more frequent dosing, suggesting a high potential for subtherapeutic levels during the majority of time critically ill patients are requiring SLED.

Pragmatic Use of Kidney Function Estimates for Drug Dosing: The Tide Is Turning.

Creatinine clearance has been the most common method of estimating kidney function for the purpose of drug dosing for decades. The availability and extensive clinical use of estimated glomerular filtration rate (eGFR) now provides clinicians a potential alternative. Currently, data demonstrating the validity of eGFR-based drug dosing is limited, but proof of principle has been established and the tide related to use of eGFR for drug dosing appears to be turning. Use of the same kidney function estimate for management of kidney disease, drug development and dosing, and harmonization in all clinical arenas would be ideal. Use of multiple equations can lead to differences in kidney function estimates and corresponding drug dosing regimens, which necessitates clinical judgment and a pragmatic approach when rendering drug dosing decisions. Careful consideration of the risk-benefit ratio of individual drugs and dosing regimens within each patient is warranted. Going forward, FDA guidance will likely incentivize pharmaceutical manufacturers to generate eGFR-based dosing recommendations in addition to creatinine clearance for inclusion in the label of newly approved drugs. However, dosing information for currently approved drugs will continue to be based on creatinine clearance alone, so clinicians must be vigilant in the assessment of kidney function in order to provide optimal pharmacotherapy.

Assessing Guideline-Directed Medication Therapy for Heart Failure in End-Stage Renal Disease.

BACKGROUND: Treatment of heart failure with reduced ejection fraction (HFrEF) requires guideline-directed medication therapy (GDMT) consisting of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker in combination with an indicated beta-blocker. There is concern that end-stage renal disease (ESRD) patients are not being prescribed GDMT. The study aim was to determine whether outcomes differ for patients with HFrEF and ESRD receiving GDMT compared to those not receiving GDMT. MATERIALS AND METHODS: Adult patients with ESRD and HFrEF admitted to a tertiary teaching hospital over a 2-year period were included. Patients were categorized into GDMT or non-GDMT groups based on their home medications. The length of stay (LOS), mortality, and 30-day hospital readmissions were compared between groups. The incidence of hyperkalemia, hypotension and bradycardia were also evaluated. RESULTS: A total of 109 patients were included: 88% African-American, 61% males, median age 63 (28-93) years with 25 in the GDMT group and 84 in the non-GDMT group. The LOS did not differ between the GDMT (5 days; 3-14) compared to the non-GDMT group (7 days; 3-28), P = 0.14. Thirty-day hospital readmission and in-hospital mortality were also similar. Hypotension occurred less frequently in the GDMT group compared to the non-GDMT group, 4% versus 27% (P = 0.01). CONCLUSIONS: Although there were no differences in the primary outcomes, the shorter LOS in the GDMT group may be clinically significant. The fact that most patients with ESRD and HFrEF were not receiving GDMT is a finding that requires further evaluation.

Predictors of adherence to a new erythropoiesis-stimulating agent inpatient ordering policy: A cross-sectional study.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are recommended for treating anemia in patients with chronic kidney disease and end-stage renal disease. However, misappropriate and over-use of these agents can be costly and unnecessary in some settings. OBJECTIVE: The primary aim was to identify predictors of adherence to a newly approved ESA inpatient ordering policy. The secondary aims were to evaluate the impact of a 5-day delay in the initiation of ESA therapy on ESA usage, hemoglobin (Hb) levels, and costs. METHODS: This retrospective observational record review included a sample of adult patients admitted to four tertiary care hospitals from November 1, 2013 to August 31, 2014. Multivariable logistic and linear regression analyses were used to calculate the odds of adherence to the new ESA inpatient ordering policy and the impact of this policy on discharge Hb level, respectively. RESULTS: A total of 242 patients were included. The majority of the prescribers (77%) adhered to the new ESA ordering policy. Hemoglobin (OR = 1.306; 95% CI: 1.03-1.65) and ferritin (OR = 3.91; 95% CI: 1.23-12.51) levels at admission and length of hospital stay were positively correlated with the odds of patients receiving ESAs after day 5 (OR = 1.12; 95% CI:1.05-1.20). Furthermore, adherence to the new policy did not have a significant impact on discharge Hb level (ß = 0.02349; P = 0.895). CONCLUSIONS: Prescribers were adherent to a 5-day delay in the initiation of ESA therapy policy which resulted in a reduction in ESA usage, did not impact the discharge Hb levels, and was proven to be cost effective.

End-Stage Renal Disease Increases Rates of Adverse Glucose Events When Treating Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic State.

IN BRIEF Treatment guidelines for diabetic emergencies are well described in patients with normal to moderately impaired kidney function. However, management of patients with end-stage renal disease (ESRD) is an ongoing challenge. This article describes a retrospective study comparing the rates of adverse glucose events (defined as hypoglycemia or a decrease in glucose >200 mg/dL/h) between patients with ESRD and those with normal kidney function who were admitted with diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). These results indicate that current treatment approaches to DKA or HHS in patients with ESRD are suboptimal and require further evaluation.

A Review of Phosphate Binders in Chronic Kidney Disease: Incremental Progress or Just Higher Costs?

As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.

Simultaneous assay of multiple antibiotics in human plasma by LC-MS/MS: importance of optimizing formic acid concentration.

AIM: Optimal dosing of antibiotics in critically ill patients is complicated by the development of resistant organisms requiring treatment with multiple antibiotics and alterations in systemic exposure due to diseases and extracorporeal drug removal. Developing guidelines for optimal antibiotic dosing is an important therapeutic goal requiring robust analytical methods to simultaneously measure multiple antibiotics. METHODS: An LC-MS/MS assay using protein precipitation for cleanup followed by a 6-min gradient separation was developed to simultaneously determine five antibiotics in human plasma. RESULTS: The precision and accuracy were within the 15% acceptance range. The formic acid concentration was an important determinant of signal intensity, peak shape and matrix effects. CONCLUSION: The method was designed to be simple and successfully applied to a clinical pharmacokinetic study.

Acute Kidney Injury in Patients Continued on Renin-Angiotensin System Blockers During Hospitalization.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with adverse outcomes. This study aimed to evaluate patient characteristics and interventions during hospitalization associated with the development of AKI in patients continued on renin-angiotensin system (RAS) blockers during hospitalization. METHODS: A retrospective study of 184 adult patients admitted between January 2012 and September 2014 and continued on RAS blockers was conducted. Risk factors for AKI were compared between AKI (n = 92) and non-AKI (n = 92) groups. RESULTS: Patients who developed hospital-acquired AKI had a higher baseline serum creatinine (1.2 ± 0.4 versus 1 ± 0.3mg/dL, P < 0.001) and lower estimated glomerular filtration rate (54 ± 10 versus 57 ± 7mL/minute/1.73m2, P = 0.03) compared with patients who did not develop AKI. Patients who developed AKI were also more likely to be admitted to the intensive care unit, have surgical procedures, have hypotension and be prescribed loop diuretics. The presence of chronic kidney disease and hypotension were risk factors associated with AKI development. In addition, the AKI group had a significantly longer length of stay (14 days versus 8 days, P < 0.0001) and had a higher rate of all-cause hospital mortality (9% versus 1%, P = 0.03). CONCLUSIONS: Patients with chronic kidney disease, hypotension and those undergoing surgeries were more likely to develop AKI while receiving RAS blockers. During hospitalization, temporary discontinuation of these medications may be warranted in patients with these characteristics.