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.

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.

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.

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.

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.

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.

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.

Performance of methods to assess kidney function in a predominantly overweight sample of patients with liver disease.

The assessment of glomerular filtration rate (GFR) in patients with liver disease is necessary to make decisions about organ allocation. Creatinine is widely used as a marker of GFR; however, it is not reliable in patients with liver disease. The aims of this study were to (1) determine if iodine 125-labeled iothalamate ((125)I-iothalamate) clearance calculated using the plasma decay method is equal to renal clearance of (125)I-iothalamate and (2) estimate kidney function using the creatinine-based Cockcroft-Gault and the Modification of Diet in Renal Disease equations, a cystatin C-based equation, the urine collection method for creatinine clearance, and plasma clearance of vancomycin (V) and compare these estimates to renal clearance of (125)I-iothalamate in adult patients with liver disease. Adults with liver disease received (125)I-iothalamate and V and had a catheter placed for urine collection. Blood and urine samples were collected over 8 h for analysis of (125)I-iothalamate, creatinine, and V to determine kidney function. Estimates were compared to renal (125)I-iothalamate clearance. Eight patients classified as Child-Pugh class B were enrolled: age was 52 ± 6 years; body mass index was 36.5 ± 19 kg/m(2); and Model for End-Stage Liver Disease score was 13 ± 3. Mean estimates of kidney function did not differ significantly from mean renal (125)I-iothalamate clearance (74 ± 38 mL/min/1.73 m(2)). Other methods overestimated kidney function at lower levels of GFR (<60 mL/min/1.73 m(2)) and underestimated kidney function at higher GFR levels. Given the variability in performance of methods to assess kidney function in this population, direct measurement of GFR may be preferable to indirect estimates based on marker compounds such as creatinine and cystatin C until more accurate methods are developed.

Evaluation of vancomycin and gentamicin dialysis clearance using in vivo and in vitro systems.

Advances in hemodialysis (HD) techniques have increased the potential for drug removal. Quantifying drug clearance in clinical studies for all possible dialysis conditions is impractical, given the variability in dialysis conditions. The purpose of this study was to determine the dialysis clearance (CL(D)) of vancomycin and gentamicin using in vitro and in vivo methods and evaluate the applicability of in vitro data. In vitro dialysis was used to determine the CL(D) of vancomycin and gentamicin under conditions of intermittent HD (IHD) and sustained low-efficiency dialysis (SLED). Two Fresenius polysulfone dialyzers were studied: F180NR for IHD and F50 for SLED. Data were compared with in vivo CL(D) determined in patients with end-stage renal disease receiving IHD and from the literature for SLED. Under IHD conditions, in vitro CL(D) of vancomycin and gentamicin was 131 ± 3 and 154 ± 3 mL/min, respectively, and under SLED condition it was 72 ± 9 and 84 ± 11 mL/min, respectively. These values were 11-27% higher than in vivo CL(D) for IHD (103 ± 15 mL/min for vancomycin and 132 ± 25 mL/min for gentamicin) and SLED (63 mL/min for vancomycin and 76 ± 38 mL/min for gentamicin). There was a statistically significant difference in vancomycin clearance by IHD for the in vitro study compared with in vivo data (p = 0.012), but not for gentamicin (p = 0.18). In vitro methods overestimated in vivo CL(D), but are reasonable to assist with drug regimen design if one considers the limitations.

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.

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.

Use of estimated glomerular filtration rate for drug dosing in the chronic kidney disease patient.

PURPOSE OF REVIEW: Assessment of kidney function is necessary to stage chronic kidney disease (CKD) and appropriately dose medications. The Cockcroft-Gault equation provides an estimate of creatinine clearance (eClCr) and is the method commonly referenced in pharmacokinetic studies. The Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology Collaboration (EPI) equations provide an estimate of glomerular filtration rate (eGFR), with the MDRD eGFR now automatically reported by most clinical laboratories. This review describes the differences in the Cockcroft-Gault, MDRD, and CKD-EPI equations and considerations when applying estimates from these equations for drug dosing. RECENT FINDINGS: Studies evaluating drug-dosing regimens using eClCr and eGFR differ in their results depending on the population in which the equation is applied, the adjustment factors used to account for body size, and the number of dosing levels for a particular medication. The largest study to evaluate drug regimen design by method concluded that either the eGFR or Cockcroft-Gault estimates could be used for drug dosing. Differences in methodology among studies are a key factor in evaluating these results and will be highlighted in this review. SUMMARY: The Cockcroft-Gault, MDRD, and CKD-EPI equations provide reasonable estimates of kidney function; however, clinicians must understand the limitations when using these estimates for drug regimen design.

Estimates of kidney function in obese African Americans with chronic kidney disease.

BACKGROUND/AIMS: Methods for assessing glomerular filtration rate (GFR) are controversial in obese individuals. This study compared clinical estimates of GFR in African Americans (AA) with chronic kidney disease (CKD) overall and by body mass index (BMI). METHODS: The estimated GFR was determined in AA with CKD using (1) the 4-variable Modification of Diet in Renal Disease equation (MDRD4), (2) the Cockcroft-Gault equation with ideal, adjusted and total body weight (TBW, with and without normalization for body surface area), and (3) urine collection methods. Differences in mean values and CKD staging were compared for all patients and for subgroups with a BMI above and below 30. RESULTS: The mean GFR by MDRD4 for individuals with a BMI of >30 was 35 ± 14 ml/min/1.73 m(2) and ranged from 32 to 53 ml/min by other methods. Estimates using TBW differed significantly from the MDRD4, a finding not observed for the lower BMI subgroup or when using adjusted weights. The obese patients were more often categorized into a less severe CKD stage, whereas the lower BMI subgroup was commonly grouped into a more severe CKD stage compared to MDRD4 staging. CONCLUSION: Significant variations in estimated GFR between methods exist in the obese. Until other assessment methods are adequately evaluated, clinicians must be critical in applying clinical estimates of kidney function to patient care.

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.

Assessment of eptifibatide clearance by hemodialysis using an in vitro system.

BACKGROUND/AIMS: Eptifibatide is a parenteral glycoprotein IIb-IIIa inhibitor that prevents platelet aggregation. Although contraindicated in dialysis patients due to limited safety and dialysis data, eptifibatide is prescribed in this population and is associated with bleeding complications. This study was done to determine dialysis clearance (CL(D)) of eptifibatide using an in vitro system. METHODS: Three common dialyzers were tested. In vitro dialysis was performed at a dialysate flow rate of 500 ml/min, 'blood' flow rate (Q(B)) of 200 and 400 ml/min, and the minimal ultrafiltration rate. Eptifibatide CL(D) and fraction removed were calculated for each condition. RESULTS: CL(D) ranged from 122 to 225 ml/min and was not significantly different among the dialyzers tested. CL(D) was flow dependent with higher clearances observed at higher Q(B). The estimated fraction of eptifibatide removed was 73-83%. CONCLUSIONS: These data suggest that hemodialysis is an effective method to decrease the effects of eptifibatide in patients with impaired kidney function.

Hypercalcemia associated with tertiary hyperparathyroidism managed conservatively with pamidronate in a hemodialysis patient.

Secondary hyperparathyroidism and the associated metabolic abnormalities are common complications of chronic kidney disease. When these disorders cannot be managed by conventional measures, including phosphate restriction, phosphate binders, vitamin D therapy, and calcimimetics, tertiary hyperparathyroidism and the associated metabolic abnormalities may develop. In such cases parathyroidectomy is required. We report a case in which a patient with tertiary hyperparathyroidism and refractory hypercalcemia who was not a surgical candidate was managed with the bisphosphonate pamidronate. This patient had failed conventional measures to manage hypercalcemia and presented with mental status changes. Pamidronate therapy was associated with a sustained decrease in serum calcium concentration and improvement in clinical symptoms. This is the first case, to our knowledge, in which pamidronate was used in a patient refractory to all other reasonable medical management, including calcimimetics.

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.

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.