Discordance Between Using Estimated and Measured Glomerular Filtration Rate for Drug Dosing in Kidney Transplant Recipients.

INTRODUCTION: Estimating glomerular filtration rate (eGFR) using different formulas is common clinical practice for evaluating kidney function and drug dosing. But, the performance of available eGFR equations is questionable during early days after kidney transplantation. METHODS: This study compared the performance of three common eGFR equations (Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) in relation with measured GFR (mGFR) using clearance of Tc-99m-diethylenetriaminepentaacetic acid, 7 to 10 days post kidney transplantation. Agreement of mGFR and different eGFR equations in the staging of kidney function and dosing of 8 common antimicrobials were assessed. RESULT: Thirty kidney and 5 simultaneous pancreas-kidney transplant recipients were included. CG applying total body weight (CGTBW) had the lowest bias (-12 mL/min/ 1.73 m2) and the highest percentage of estimation within 30% of mGFR (71.4%). MDRD showed the best precision (13.14 mL/min/ 1.73m2) and linear correlation with mGFR. CKD-EPI and MDRD acted better than CG for staging the level of kidney function. CGTBW had the lowest discordance rate with mGFR for antimicrobials dosing (33.6%). Discordance rates of drug dosing between mGFR and eGFR formulas were greater for drugs that have higher dosing levels such as (val)-ganciclovir (≥ 54.3%). CONCLUSION: Until developing more accurate methods for estimating kidney function during first 1 to 2 weeks after kidney transplantation, CGTBW method is suggested for drug dose adjustment and MDRD or CKD-EPI equation for the staging of kidney function in these patients, keeping in mind that these formulas underestimate the level of kidney function in new transplant recipients.

Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir.

BACKGROUND: The role of the antiviral therapy in treatment of COVID-19 is still a matter to be investigated. Also efficacy and safety of antiviral regimens were not compared according severity of the disease. In this study the efficacy and safety of hydroxychloroquine plus atazanavir/ritonavir was compared in patients with moderate and severe COVID-19. METHODS: We prospectively evaluated the clinical outcomes of 213 patients with COVID-19 during the hospitalization course and up to 56 days after the hospital discharge. The disease was categorized to moderate and severe based on the severity of pneumonia and peripheral oxygen saturation (SpO2). The patients received the national treatment protocol containing hydroxychloroquine (400 mg BD in first day and then 200 mg BD) plus atazanavir/ritonavir (300/100 mg daily) for 7 days. Main outcomes included discharge rates at day 7, 14 and 28, 28-day mortality, rate of intensive care unit (ICU) admission and intubation, length of hospital and ICU stay and incidence of adverse events. RESULTS: The mean (SD) age of patients was 60(14) years and 53% were male. According to WHO definition, 51.64% and 48.36% of the patients had moderate (SpO2 ≥ 90%) and severe disease (SpO2 < 90%) at baseline, respectively. The discharge rate of the moderate group was significantly higher than the severe group at day 7, 14 and 28 (HR = 0.49; 95% CI: 0.35-0.69, p = < 0.001 at day 7, HR = 0.48; 95% CI: 0.35-0.66, p = < 0.001 at day 14 and HR = 0.49; 95% CI: 0.36-0.67, p = < 0.001at day 28). The 28-day mortality of the severe group was six times higher than the moderate group (HR = 6.00; 95% CI: 2.50-14.44), p = < 0.001). The need of admission in ICU for the severe group and the moderate group was 37.86% and 18.18% of the patients. Length of hospital stay was significantly shorter in the moderate group in comparison with the severe group (5 ± 4 vs. 8 ± 6 days, p < 0.001). Patients in the moderate group experienced the serious adverse events and complications less than the severe group. The discharged patients were followed up to 56 days after discharge. Some of the patients complained of symptoms such as exertional dyspnea, weakness and new-onset hair loss. CONCLUSION: Our study did not support the use of hydroxychloroquine plus atazanavir/ritonavir in patients who had SpO2 < 90% at the time of hospital admission. SpO2 was the only predictor of clinical outcomes (duration of hospital stay, discharge from the hospital and mortality) in patients treated with hydroxychloroquine plus atazanavir/ritonavir.

Dose discordance of direct acting oral anticoagulants using different equations for estimating GFR: a literature review.

INTRODUCTION: Direct oral anticoagulants (DOACs) are widely prescribed nowadays. Available DOACs are renally eliminated to some extent and need dose adjustment in patients with kidney dysfunction. Cockcroft-Gault (CG) formula has been used to estimate creatinine clearance in DOACs trials. Nowadays, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are preferred equations for estimating glomerular filtration rate (GFR). We reviewed studies that simulated DOACs dosing in patients with atrial fibrillation by MDRD, CKD-EPI, and CG. AREAS COVERED: DOACs dose discordance varies from 28.8% underdosing to 59.2% overdosing when MDRD or CKD-EPI equations are substituted for CG. MDRD and CKD-EPI overestimate the GFR in lower thresholds of kidney function especially in elderly and females and result in overestimation of DOACs dosing or misclassifying the patients to be eligible for receiving DOACs when they are contraindicated. Compared with CG, MDRD and CKD-EPI underestimate the level of kidney function in higher GFR extremes and in these patients suggest DOACs when they are not recommended or suggest lower doses. EXPERT OPINION: Until running large clinical studies on efficacy/safety of DOACs dosing using MDRD or CKD-EPI equations, use of CG method for DOACs dosing is recommended in real practice.