RESUMO
Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.
Assuntos
Injúria Renal Aguda , COVID-19 , Apolipoproteína L1/genética , Humanos , Rim , Estudos Retrospectivos , SARS-CoV-2RESUMO
INTRODUCTION: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in several regions for the treatment of anemia of chronic kidney disease (CKD). DENALI, a phase 3b study, evaluated the efficacy, safety, and feasibility of roxadustat in patients with anemia of CKD receiving in-center or home dialysis. METHODS: Eligible patients received open-label roxadustat, dosed three times weekly for 24 weeks, with an optional extension of ≤1 year. Initial dosing depended on erythropoiesis-stimulating agent (ESA) dose at screening for patients receiving ESAs (≥6 weeks) and weight-based for those not (total <6 weeks). Primary efficacy endpoints were proportion of patients with mean hemoglobin (Hb) ≥10.0 g/dL averaged over Weeks 16-24, and mean Hb change from baseline to the average during Weeks 16-24. Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) were assessed. FINDINGS: Of 281 patients screened, 203 were treated and 201 included in the full analysis set. Overall, 166 patients completed the 24-week treatment period and 126 continued into the extension period. Mean baseline Hb was 10.4 g/dL and 82.6% received in-center hemodialysis. Overall, 84.6% of patients achieved a mean Hb ≥ 10.0 g/dL averaged Weeks 16-24. Mean (standard deviation) Hb change from baseline averaged Weeks 16-24 was 0.5 (1.0) g/dL. Prespecified subgroup analyses were consistent with primary analyses. Dosing adherence was 94%. Overall, 3.0% of patients received a red blood cell transfusion at up to Week 24. TEAEs and TESAEs were reported by 71.4% and 25.6% of patients, respectively. The most frequently reported TESAEs were COVID-19 (n = 5; 2.5%), and acute myocardial infarction, pneumonia, and sepsis (each n = 4; 2.0%). DISCUSSION: Roxadustat effectively achieved and/or maintained mean Hb levels ≥10.0 g/dL in patients receiving dialysis. The feasibility of incorporating oral roxadustat into dialysis organizations was successfully demonstrated with high dosing adherence. No new safety signals were identified.
Assuntos
Anemia , Hematínicos , Insuficiência Renal Crônica , Humanos , Diálise Renal , Anemia/tratamento farmacológico , Anemia/etiologia , Hemoglobinas/análise , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Hematínicos/uso terapêutico , Hematínicos/efeitos adversos , Glicina/efeitos adversos , Isoquinolinas/uso terapêutico , Isoquinolinas/efeitos adversosRESUMO
Residential segregation is associated with poor health-including poor birth outcomes-among African Americans in US cities and metropolitan areas. However, the few existing studies of this relationship among Mexican-origin women have produced mixed results. In this study, the relationship between segregation and very preterm birth was examined with National Center for Health Statistics (NCHS) data on singleton births to African American women (n = 400,718) in 238 metropolitan areas and to Mexican-origin women (n = 552,382) in 170 metropolitan areas. The study evaluated 1) whether residential segregation is positively associated with very preterm birth among both African American and Mexican-origin women and 2) if so, whether exposure to neighborhood poverty accounts for these associations. Results from multi-level analysis indicate that residential segregation is positively associated with very preterm birth among both groups of women. However, this association is robust across different measures of segregation only for African Americans. Conversely, differences across metropolitan areas in average levels of exposure to neighborhood poverty account for the positive association between segregation and very preterm birth among Mexican-origin women, but not among African American women.