Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patient's kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.

The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2. The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter.

Chromium supplements may cause serious renal impairment when ingested in excess. Medication histories should include attention to the use of OTC nutritional supplements often regarded as harmless by the public and lay media.

Medication regimen simplification may improve adherence in end-stage kidney disease. The effect of nocturnal home hemodialysis (NHHD) on medication burden is unknown. A retrospective pilot study of NHHD patients was conducted. Medication information was collected at baseline, NHHD start, and at 3, 6, 12, 18, and 24 months. SF-36 scores were collected at baseline, 6, 12, and 24 months. The number of medications, pill burden, and number of administrations per day were determined. Medication Regimen Complexity Index was used at each time point as a comparator. Medications for anemia, mineral and bone disorders (MBD), cardiovascular (CV) disease, infection, and vitamins were analyzed for number of medications and pill burden. Thirty-five patients were included. Patients used 10.5 ± 4.4 medications at baseline and 11.8 ± 4.7 at the end of the study (P=NS). Regarding the number of medications, anemia medications, anti-infectives, and vitamins increased; MBD and CV medications decreased by the end of the study. Total pill burden did not change over 24 months, nor did anemia pill burden. Mineral bone disorder and CV pill burden decreased, and vitamins and anti-infective pill burden increased. Daily medication administration times decreased significantly from 5.0 ± 1.5 to 3.6 ± 1.5 by 24 months. Switching to NHHD was associated with a significant increase in Medication Regimen Complexity Index at 24 months (P<0.05). SF-36 scores increased significantly once patients began on NHHD. No measure of medication regimen complexity was correlated with the SF-36 score. Medication burden changes over time after starting NHHD. It is unknown what effect NHHD has on adherence or medication costs, and warrants further study in a prospective comparative investigation.

This study identified optimal daptomycin dosing for patients receiving thrice-weekly hemodialysis (HD). Twelve adult patients on HD received daptomycin at 6 mg/kg of body weight intravenously (i.v.) one time; plasma and dialysate samples were collected over 3 days. A 2-compartment model with separate HD and non-HD clearance terms was fit to the data. A series of 9,999-subject Monte Carlo simulations (MCS) was performed to identify HD dosing schemes providing efficacy and toxicity profiles comparable to those obtained for MCS employing the daptomycin population pharmacokinetic (PK) model derived from patients in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. For efficacy, we selected the HD dosing scheme which generated an area-under-the-curve (AUC) exposure profile comparable to that for the SAB-IE population model. For toxicity, we selected HD dosing schemes that minimized trough concentrations of >24. Daptomycin is a lipopeptide approved for the treatment of Staphylococcus aureus bacteremia and complicated skin and skin structure infections, both of which are common in patients receiving hemodialysis (HD) (1,4,(14)(15)(16)(17)(18). While the pharmacokinetic (PK) properties of daptomycin are well described for the general population, there are scant data for patients on HD (12, 13). An understanding of how PK changes during HD is essential to determining optimal dosing schemes for these patients. Furthermore, such dosage adjustments necessitate cognizance of interactions between antibiotic exposure, efficacy, and toxicity. Given the dearth of treatment options available against methicillin-resistant S. aureus (MRSA), it is imperative that daptomycin regimens be optimized for those on HD.The two objectives of this study were (i) to characterize the PK profile of daptomycin in patients receiving traditional thrice-weekly hemodialysis and (ii) to identify the optimal dosing scheme for daptomycin among patients on HD. With respect to the latter, the intent was to identify HD dosing schemes with efficacy and toxicity profiles comparable to those obtained from Monte Carlo simulations (MCS) employing the daptomycin population PK model derived from patients enrolled in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) clinical study for doses of 4 mg/kg of body weight given intravenously (i.v.) every 24 h (q24h) and 6 mg/kg given i.v. q24h (2, 7).Separate dosing schemes were developed for both FDAapproved daptomycin dosing regimens (4 mg/kg i.v. q24h and 6 mg/kg i.v. q24h) and for the two interdialytic periods (48 and 72 h). For efficacy, the primary exposure target was the area under the curve (AUC). Animal model data suggest that daptomycin is a concentration-dependent antibiotic, and the AUC/ MIC ratio is the pharmacodynamic (PD) parameter that best describes its activity (3,5,9,11). However, the AUC/MIC ratio associated with maximal effect has varied (3,5,9,11). Given the lack of a definitive AUC/MIC threshold, especially for patients with bloodstream infections, the ...