Muscle fibrosis and maladaptation occur progressively in CKD and are rescued by dialysis.

BACKGROUNDSkeletal muscle maladaptation accompanies chronic kidney disease (CKD) and negatively affects physical function. Emphasis in CKD has historically been placed on muscle fiber-intrinsic deficits, such as altered protein metabolism and atrophy. However, targeted treatment of fiber-intrinsic dysfunction has produced limited improvement, whereas alterations within the fiber-extrinsic environment have scarcely been examined.METHODSWe investigated alterations to the skeletal muscle interstitial environment with deep cellular phenotyping of biopsies from patients with CKD and age-matched controls and performed transcriptome profiling to define the molecular underpinnings of CKD-associated muscle impairments. We examined changes in muscle maladaptation following initiation of dialysis therapy for kidney failure.RESULTSPatients with CKD exhibited a progressive fibrotic muscle phenotype, which was associated with impaired regenerative capacity and lower vascular density. The severity of these deficits was strongly associated with the degree of kidney dysfunction. Consistent with these profound deficits, CKD was associated with broad alterations to the muscle transcriptome, including altered ECM organization, downregulated angiogenesis, and altered expression of pathways related to stem cell self-renewal. Remarkably, despite the seemingly advanced nature of this fibrotic transformation, dialysis treatment rescued these deficits, restoring a healthier muscle phenotype. Furthermore, after accounting for muscle atrophy, strength and endurance improved after dialysis initiation.CONCLUSIONThese data identify a dialysis-responsive muscle fibrotic phenotype in CKD and suggest the early dialysis window presents a unique opportunity of improved muscle regenerative capacity during which targeted interventions may achieve maximal impact.TRIAL REGISTRATIONNCT01452412FUNDINGNIH, NIH Clinical and Translational Science Awards (CTSA), and Einstein-Mount Sinai Diabetes Research Center.

Tuberculosis during pregnancy in the United States: Racial/ethnic disparities in pregnancy complications and in-hospital death.

BACKGROUND: Despite decades of efforts to eliminate tuberculosis (TB) in the United States (US), TB still contributes to adverse ill health, especially among racial/ethnic minorities. According to the Centers for Disease Control and Prevention, in 2016, about 87% of the TB cases reported in the US were among racial and ethnic minorities. The objective of this study is to explore the risks for pregnancy complications and in-hospital death among mothers diagnosed with TB across racial/ethnic groups in the US. METHODS: This retrospective cohort study utilized National Inpatient Sample data for all inpatient hospital discharges in the US. We analyzed pregnancy-related hospitalizations and births in the US from January 1, 2002 through December 31, 2014 (n = 57,393,459). Multivariable logistic regression was applied to generate odds ratios for the association between TB status and the primary study outcomes (i.e., pregnancy complications and in-hospital death) across racial/ethnic categories. RESULTS: The prevalence of TB was 7.1 per 100,000 pregnancy-related hospitalizations. The overall prevalence of pregnancy complications was 80% greater among TB-infected mothers than their uninfected counterparts. Severe pre-eclampsia, eclampsia, placenta previa, post-partum hemorrhage, sepsis and anemia occurred with greater frequency among mothers with a TB diagnosis than those without TB, irrespective of race/ethnicity. The rate of in-hospital death among TB patients was 37 times greater among TB-infected than in non-TB infected mothers (468.8 per 100,000 versus 12.6 per 100,000). A 3-fold increased risk of in-hospital death was observed among black TB-negative mothers compared to their white counterparts. No racial/ethnic disparities in maternal morbidity or in-hospital death were found among mothers with TB disease. CONCLUSION: TB continues to be an important cause of morbidity and mortality among pregnant women in the US. Resources to address TB disease should also target pregnant women, especially racial/ethnic minorities who bear the greatest burden of the disease.