11 research outputs found
PCM-13THE HYPOXIA-ACTIVATED PRODRUG EVOFOSFAMIDE (TH-302) IS EFFICACIOUS IN PEDIATRIC HIGH GRADE GLIOMA CELL LINES AS A MONOTHERAPY AND IN COMBINATION WITH CHEMOTHERAPIES
STEAP1 as a predictive biomarker for antibody-drug conjugate (ADC) activity in metastatic castration resistant prostate cancer (mCRPC).
Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease
International audienc
Recovery of dialysis patients with COVID-19: health outcomes 3 months after diagnosis in ERACODA
© The Author(s) 2022.Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8–6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis
Association of obesity with 3-month mortality in kidney failure patients with COVID-19
Background: In the general population with coronavirus disease 2019 (COVID-19), obesity is associated with an increased risk of mortality. Given the typically observed obesity paradox among patients on kidney function replacement therapy (KFRT), especially dialysis patients, we examined the association of obesity with mortality among dialysis patients or living with a kidney transplant with COVID-19. Methods: Data from the European Renal Association COVID-19 Database (ERACODA) were used. KFRT patients diagnosed with COVID-19 between 1 February 2020 and 31 January 2021 were included. The association of Quetelet's body mass index (BMI) (kg/m2), divided into: <18.5 (lean), 18.5-24.9 (normal weight), 25-29.9 (overweight), 30-34.9 (obese I) and ≥35 (obese II/III), with 3-month mortality was investigated using Cox proportional-hazards regression analyses. Results: In 3160 patients on KFRT (mean age: 65 years, male: 61%), 99 patients were lean, 1151 normal weight (reference), 1160 overweight, 525 obese I and 225 obese II/III. During follow-up of 3 months, 28, 20, 21, 23 and 27% of patients died in these categories, respectively. In the fully adjusted model, the hazard ratios (HRs) for 3-month mortality were 1.65 [95% confidence interval (CI): 1.10, 2.47], 1 (ref.), 1.07 (95% CI: 0.89, 1.28), 1.17 (95% CI: 0.93, 1.46) and 1.71 (95% CI: 1.27, 2.30), respectively. Results were similar among dialysis patients (N = 2343) and among those living with a kidney transplant (N = 817) (Pinteraction = 0.99), but differed by sex (Pinteraction = 0.019). In males, the HRs for the association of aforementioned BMI categories with 3-month mortality were 2.07 (95% CI: 1.22, 3.52), 1 (ref.), 0.97 (95% CI: 0.78. 1.21), 0.99 (95% CI: 0.74, 1.33) and 1.22 (95% CI: 0.78, 1.91), respectively, and in females corresponding HRs were 1.34 (95% CI: 0.70, 2.57), 1 (ref.), 1.31 (95% CI: 0.94, 1.85), 1.54 (95% CI: 1.05, 2.26) and 2.49 (95% CI: 1.62, 3.84), respectively. Conclusion: In KFRT patients with COVID-19, on dialysis or a kidney transplant, obesity is associated with an increased risk of mortality at 3 months. This is in contrast to the obesity paradox generally observed in dialysis patients. Additional studies are required to corroborate the sex difference in the association of obesity with mortality
Clinical, Functional, and Mental Health Outcomes in Kidney Transplant Recipients 3 Months after a Diagnosis of COVID-19
Background. Kidney transplant patients are at high risk for coronavirus disease 2019 (COVID-19)-related mortality. However, limited data are available on longer-term clinical, functional, and mental health outcomes in patients who survive COVID-19. Methods. We analyzed data from adult kidney transplant patients in the European Renal Association COVID-19 Database who presented with COVID-19 between February 1, 2020, and January 31, 2021. Results. We included 912 patients with a mean age of 56.7 (±13.7) y. 26.4% were not hospitalized, 57.5% were hospitalized without need for intensive care unit (ICU) admission, and 16.1% were hospitalized and admitted to the ICU. At 3 mo follow-up survival was 82.3% overall, and 98.8%, 84.2%, and 49.0%, respectively, in each group. At 3 mo follow-up biopsy-proven acute rejection, need for renal replacement therapy, and graft failure occurred in the overall group in 0.8%, 2.6%, and 1.8% respectively, and in 2.1%, 10.6%, and 10.6% of ICU-admitted patients, respectively. Of the surviving patients, 83.3% and 94.4% reached their pre-COVID-19 physician-reported functional and mental health status, respectively, within 3 mo. Of patients who had not yet reached their prior functional and mental health status, their treating physicians expected that 79.6% and 80.0%, respectively, still would do so within the coming year. ICU admission was independently associated with a low likelihood to reach prior functional and mental health status. Conclusions. In kidney transplant recipients alive at 3-mo follow-up, clinical, physician-reported functional, and mental health recovery was good for both nonhospitalized and hospitalized patients. Recovery was, however, less favorable for patients who had been admitted to the ICU
Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy
© 2022, The Author(s).In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk
Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy
In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk
Recommended from our members
Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial
BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function
Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial
Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics