Lost in Translation: Evaluation of Subcutaneous Interferon-ß Treatment for SARS-CoV-2 Infection in Real Life.

Despite in vitro activity of interferon-ß (IFN-ß) against SARS-CoV-2 infection, its clinical efficacy remains controversial. We evaluated the impact of IFN-ß treatment in a cohort of 3590 patients hospitalized with COVID-19 during March−April 2020. The primary endpoint was a composed variable of admission to intensive care unit (ICU)/death. Overall, 153 patients (4%) received IFN-ß. They were significantly more severely ill, with a worse clinical and analytical situation, explaining a higher ICU admission (30% vs. 17%; p < 0.01), and a shorter time to the composed variable. In a Cox regression analysis, older age, lymphopenia, renal failure, or increased neutrophil-to-lymphocyte ratio were associated with a greater hazard ratio (HR) of admission at ICU/death. Notably, the HR of IFN-ß for the outcome variable was no longer significant after adjustment (HR, 1.03; 95% CI, 0.82−1.30), and different sensitivity analysis (early IFN use, ICU admission) showed no changes in the estimates. A propensity score matching analysis showed no association of IFN-ß therapy and outcome. In conclusion, in this large cohort of hospitalized COVID-19 patients, IFN-ß was used mainly in patients with advanced disease, reflecting an important bias of selection. After adjusting by severity, IFN-ß was not associated with a higher rate of ICU admission or mortality.

Unravelling hip-spine bone mineral density discordance in people living with HIV.

INTRODUCTION: In people living with HIV (PLWH), bone mineral density (BMD) discordance between the lumbar spine (LS) and femoral neck (FN) could be frequent given the high frequency of secondary osteoporosis, including HIV-related factors for bone disease. MATERIALS AND METHODS: Retrospective cohort of PLWH with a dual X-ray absorptiometry scan. Hip-spine BMD discordance was defined as different T-score or Z-scores categories at LS and FN. RESULTS: Overall, 865 individuals (mean 49.5 years, female 27%) were included. Osteoporosis diagnosis was four-to-seven times lower when both skeletal sites were affected than when considering the lowest T-score at any site (overall, 21% vs 4%). Hip-spine BMD discordance was observed in 381 (44%) individuals, it increased with age (from 43 to 52%, P = 0.032), and it was mainly due to lower LS-BMD. A lower FN-BMD was associated with older age, lower BMI (P < 0.01), and HIV-related factors, such as low CD4 + T-cell counts, duration of HIV infection, and time on antiretroviral therapy (ART). In a multivariate regression analysis, sex male (Odds Ratio, OR 4.901), hyperparathyroidism (OR, 2.364), and time on ART (OR 1.005 per month) were independently associated with discordance. A higher estimated fracture risk by FRAX equation was observed in individuals with BMD discordance due to lower FN-BMD compared to those with lower LS-BMD (+ 36% for major osteoporotic fracture, P = 0.04; + 135% for hip fracture, P < 0.01). CONCLUSION: Hip-spine BMD discordance is highly prevalent in PLWH and it is associated with classical and HIV-related risk factors, modifying the rate of osteoporosis and fracture risk estimation.

Colistimethate sodium and acute kidney injury: Incidence, risk factors, outcome and prognosis of renal function.

BACKGROUND: Colistimethate sodium (CMS) treatment has increased over the last years, being acute kidney injury (AKI) its main drug-related adverse event. Therefore, this study aimed to evaluate the incidence and risk factors associated with AKI, as well as identifying the factors that determine renal function (RF) outcomes at six months after discharge. MATERIALS AND METHODS: This retrospective study included adult septic patients receiving intravenous CMS for at least 48h (January 2007-December 2014). AKI was assessed using KDIGO criteria. The glomerular filtration rate (GFR) was estimated by the 4-variable MDRD equation. Logistic and linear models were performed to evaluate the risk factors for AKI and chronic kidney disease (CKD). RESULTS: Among 126 patients treated with CMS; the incidence of AKI was 48.4%. Sepsis-severe sepsis (OR 8.07, P=0.001), sepsis-septic shock (OR 42.9, P<0.001), and serum creatinine (SCr) at admission (OR 6.20, P=0.009) were independent predictors. Eighty-four patients survived; the main factors for RF evolution at the 6-month follow-up was baseline eGFR (0.58, P<0.001) and at discharge (0.34, P<0.001). Fifty-six percent (34/61) of the patients that developed AKI survived. At six months, 32% had CKD. CONCLUSIONS: The development of AKI in septic patients with CMS treatment was associated with sepsis severity and SCr at admission. Baseline eGFR and eGFR at discharge were and important determinant of the RF at the 6-month follow-up. These predictors may assist in clinical decision making for this patient population.

Changes in Kidney Function and in the Rate of Tubular Dysfunction After Tenofovir Withdrawal or Continuation in HIV-Infected Patients.

INTRODUCTION: Longitudinal data on the changes in kidney function and tubular abnormalities in case of tenofovir disoproxil fumarate (TDF) withdrawal or continuation are scarce. METHODS: Prospective study of 228 patients receiving TDF, with 3 sequential determinations of serum creatinine, estimated glomerular filtration rate (eGFR), phosphatemia, and different urinary parameters (protein, albumin, phosphaturia, uricosuria, and glycosuria). Changes were analyzed in patients who interrupted TDF as compared to those who continued the same regimen. Proximal renal tubular dysfunction (PRTD) was defined as ≥2 tubular abnormalities. RESULTS: After a median follow-up of 59.5 months, 78 patients (34%) had PRTD, mainly proteinuria (40%) and phosphaturia (61%), and time on TDF explains the severity of tubular alterations and eGFR slopes. In 35 switching patients, there was a rapid and significant eGFR improvement (median +4.1 ml/min per 1.73 m; P = 0.02), leading to a 39%-83% reduction in the prevalence of tubular abnormalities and of PRTD in less than 1 year (66%-39%). In comparison, 193 patients continuing the same regimen for 21.2 months had a small but significant and progressive eGFR decrease (-2.9 mL·min·1.73 m; P < 0.01), and a progressive rise in the prevalence of phosphaturia, uricosuria, and glycosuria (+9%-56%). In linear mixed-effect model, subsequent eGFR impairment was associated with proteinuria and time on TDF, and eGFR improvement with TDF discontinuation. CONCLUSIONS: Our data support the role of use and time on TDF in eGFR decline and tubular dysfunction. In contrast, TDF withdrawal is followed by a rapid and significant, although partial, recovery of eGFR and tubular abnormalities.

Preoperative hydration with 0.9% normal saline to prevent acute kidney injury after major elective open abdominal surgery: A randomised controlled trial.

BACKGROUND: Postoperative acute kidney injury (AKI) is the second leading cause of hospital-acquired AKI. Although many preventive strategies have been tested, none of them has been totally effective. OBJECTIVE: We investigated whether preoperative intravenous hydration with 0.9% normal saline could prevent postoperative AKI. DESIGN: Randomised controlled trial. SETTING: University Ramón y Cajal Hospital, Spain, from June 2006 to February 2011. PATIENTS: Total 328 inpatients scheduled for major elective open abdominal surgery. INTERVENTION: 0.9% normal saline at a dose of 1.5 ml kg h for 12 h before surgery. MAIN OUTCOME MEASURES: The primary outcome was the overall postoperative AKI incidence during the first week after surgery defined by risk, injury, failure, loss, end-stage kidney disease (RIFLE) and AKI network (AKIN) creatinine criteria. Secondary endpoints were the need for ICU admission, renal replacement therapy during the study period and adverse events and hospital mortality during hospital admission. RESULTS: There was no difference in the incidence of AKI between groups: 4.7% in the normal saline group versus 5.0% in the control group and 11.4% in the 0.9% normal saline group versus 7.9% in the control group as assessed by the RIFLE and AKIN creatinine criteria, respectively. Absolute risk reductions (95% confidence interval) were -0.3% (-5.3 to 4.7%) for RIFLE and 3.5% (-10.2 to 3.6%) for AKIN. ICU admission after surgery was required in 44.5% of all participants. Only 2 (0.7%) patients required renal replacement therapy during the first week after surgery. The analysis of adverse events did not show statistically significant differences between the groups except for pain. In our population, 8 (2.4%) patients died during their hospital admission. CONCLUSION: Intravenous hydration with 0.9% normal saline before major open abdominal surgery was not effective in preventing postoperative AKI. No safety concerns were identified during the trial. TRIAL REGISTRATIONS: Clinical trials.gov: NCT00953940 and EUDRA CT: 2005-004755-35.

Prevalence and significance of proximal renal tubular abnormalities in HIV-infected patients receiving tenofovir.

OBJECTIVES: Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction (PRTD), but contributing factors and its clinical significance remain controversial. DESIGN AND METHODS: Cross-sectional evaluation of different urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria) in 200 HIV-infected patients receiving TDF, 26 following TDF discontinuation, and 22 never treated with TDF, included in a prospective cohort study. PRTD was defined as two or more tubular abnormalities. RESULTS: After a median of 65 months (interquartile range, 42.7-84.7), at least one tubular alteration was found in 72% of patients, mostly proteinuria (42, 50, and 14% in current, previous and never TDF use; P=0.02) and phosphaturia (46, 42, and 14%; respectively, P < 0.01). PRTD was found in 63 patients (32%) receiving TDF, ranging from 14 to 46% according to concomitant hepatitis C virus coinfection, diabetes mellitus or hypertension arterial, in contrast with six (23%) following TDF discontinuation, and zero cases in no TDF-treated patients. The use of TDF [odds ratio (OR) 13.2; 95% confidence interval (CI) 1.4-22.7; P = 0.01], cumulative time on combination antiretroviral therapy (OR 1.011; 95% CI 1.07-1.019 per month; P = 0.01), and baseline estimated glomerular filtration rate (eGFR, OR 0.97; 95% CI 0.94-0.99 per ml/min per 1.73 m higher; P = 0.04) were associated with PRTD. The number of tubular abnormalities was linearly associated with eGFR decline since TDF initiation (ß-coefficient -0.15, P = 0.02), together with age (-0.18; P = 0.01), baseline eGFR (0.49, P = 0.01), diabetes mellitus (-0.19, P = 0.02), and time on TDF (-0.23; P = 0.01). CONCLUSION: The use of TDF leads to an increased rate of tubular dysfunction, and modulated by age, baseline eGFR, and classical factors, is associated with kidney function decline.

Impact of a new definition of acute kidney injury based on creatinine kinetics in cardiac surgery patients: a comparison with the RIFLE classification.

OBJECTIVES: Acute kidney injury (AKI) after cardiac surgery is associated with adverse patient outcome. A new definition and staging system for AKI based on creatinine kinetics (CKs) has been proposed recently. Their proponents hypothesize that early absolute increases in serum creatinine (sCr) after kidney injury are superior to percentage increases, especially in patients with chronic kidney disease (CKD). The aims of our study were to measure agreement between CK definition and the current consensus definition [risk, injury, failure, loss and end-stage renal disease (RIFLE) system], and to compare time to diagnosis and prognostic value between both systems. METHODS: Retrospective cohort study. Agreement on AKI diagnosis by both classifications, time to diagnosis and prognostic value of both systems were compared in cardiac surgeries performed during a 6-year period (2002-2007) in a single centre. RESULTS: We found substantial agreement between both classifications (0.67). More patients were diagnosed with AKI by the CK definition than by RIFLE criteria both globally (28.2 vs 13.9%) and in every category (16.5 vs 8.4% for CK-1 vs RIFLE-R; 8.4 vs 3.6% for CK-2 vs RIFLE-I and 3.2 vs 2.0% for CK-3 vs RIFLE-F). Time to diagnosis was shorter for the CK definition (1.8 vs 2.5 days). Prognostic value in terms of information about in-hospital death and need for renal replacement was comparable between classifications. CONCLUSIONS: In cardiac surgery, the CK definition and classification system showed substantial agreement with the current standard, was more sensitive than RIFLE and detected AKI earlier without loss of prognostic information.