Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study.

BACKGROUND: Continued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism. METHODS: This single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary ß2 microglobulin (Uß2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uß2MG and factors affecting eGFR decline were examined. RESULTS: Sixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uß2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uß2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uß2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uß2MG had no effect on the eGFR decline. CONCLUSIONS: Switching from TDF to TAF for the long term slows eGFR decline, decreases Uß2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.

Renal function in Japanese HIV-1-positive patients who switch to tenofovir alafenamide fumarate after long-term tenofovir disoproxil fumarate: a single-center observational study.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF. METHODS: A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF. RESULTS: Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF. CONCLUSIONS: In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored.

A simple scoring method to predict augmented renal clearance in haematologic malignancies.

WHAT IS KNOWN AND OBJECTIVE: Augmented renal clearance (ARC; hyperfiltration with over 130 mL/min/1.73 m2 of creatinine clearance (CLcr )) commonly occurs in critically ill patients. Recent reports indicate that ARC also occurs in haematologic malignancies. However, the risk factors for ARC in haematologic malignancies remain unknown, and there is no established method to predict ARC in haematologic malignancies. Our objective was to explore the risk factors for ARC retrospectively and develop a scoring method to predict ARC. METHODS: A single-centre, retrospective, observational cohort study was conducted at the Sendai Medical Center (Sendai, Japan); 133 patients (April 2017-March 2019) and 41 patients (April-November 2019) with haematopoietic tumours who were administered vancomycin were enrolled in the analysis and validation cohorts, respectively. To define ARC, we calculated the vancomycin serum concentration when CLcr  = 130 mL/min/1.73 m2 using a one-compartment model. Patients with ARC were defined as those whose actual concentration of vancomycin remained lower than the calculated concentration. Using the analysis cohort, we explored risk factors of ARC and developed a scoring method to predict ARC in haematologic malignancies. The reproducibility of the scoring system was demonstrated using the validation cohort. RESULTS AND DISCUSSION: Through multivariate analysis, young age (P < .001), leukaemia (P = .001) and low serum creatinine (P < .001) were identified as risk factors. According to this result, we established the ARC detection method: age ≤ 50 years = 3 points, 50 years < age ≤65 years = 1 point, leukaemia = 2 points, low SCr = 2 points; patients scoring ≥ 5 points represent the ARC high-risk group. Using this scoring system, we could detect ARC with a sensitivity and specificity of 60.0% and 89.7% in the analysis cohort and 90.0% and 90.9% in the validation cohort, respectively. WHAT IS NEW AND CONCLUSION: Our scoring method could predict ARC in haematologic malignancies and is useful as a simple screening tool for ARC.

Effect of plantar subcutaneous administration of bergamot essential oil and linalool on formalin-induced nociceptive behavior in mice.

This study investigated the effect of bergamot essential oil (BEO) or linalool, a major volatile component of BEO, on the nociceptive response to formalin. Plantar subcutaneous injection of BEO or linalool into the ipsilateral hindpaw reduced both the first and late phases of the formalin-induced licking and biting responses in mice. Plantar subcutaneous injection of BEO or linalool into the contralateral hindpaw did not yield an antinociceptive effect, suggesting that the antinociceptive effect of BEO or linalool in the formalin test occurred peripherally. Intraperitoneal and plantar subcutaneous injection pretreatment with naloxone hydrochloride, an opioid receptor antagonist, significantly attenuated both BEO- and linalool-induced antinociception. Pretreatment with naloxone methiodide, a peripherally acting opioid receptor antagonists, also significantly antagonized the antinociceptive effects of BEO and linalool. Our results provide evidence for the involvement of peripheral opioids in antinociception induced by BEO and linalool. These results suggest that activation of peripheral opioid receptors may play an important role in reducing formalin-induced nociception.