Low birth weight is associated with impaired murine kidney development and function.

BackgroundLow birth weight (LBW) neonates have impaired kidney development that leaves them susceptible to kidney disease and hypertension during adulthood. The study here identifies events that blunt nephrogenesis and kidney development in the murine LBW neonate.MethodsWe examined survival, kidney development, GFR, gene expression, and cyto-/chemokines in the LBW offspring of malnourished (caloric and protein-restricted) pregnant mice.ResultsMalnourished pregnant mothers gave birth to LBW neonates that had 40% reduced body weight and 54% decreased survival. Renal blood perfusion was reduced by 37%, whereas kidney volume and GFR were diminished in the LBW neonate. During gestation, the LBW neonatal kidney had 2.2-fold increased apoptosis, 76% decreased SIX2+ progenitor cells, downregulation of mesenchymal-to-epithelial signaling factors Wnt9b and Fgf8, 64% less renal vesicle formation, and 32% fewer nephrons than controls. At birth, increased plasma levels of IL-1ß, IL-6, IL-12(p70), and granulocyte-macrophage colony-stimulating factor in the LBW neonate reduced SIX2+ progenitor cells.ConclusionIncreased pro-inflammatory cytokines in the LBW neonate decrease SIX2+ stem cells in the developing kidney. Reduced renal stem cells (along with the decreased mesenchymal-to-epithelial signaling) blunt renal vesicle generation, nephron formation, and kidney development. Subsequently, the mouse LBW neonate has reduced glomeruli volume, renal perfusion, and GFR.

The relationship between obesity, hemoglobin A1c and the severity of COVID-19 at an urban tertiary care center in New York City: a retrospective cohort study.

OBJECTIVES: To determine if obesity and diabetes are risk factors for severe outcomes in COVID-19 and to compare patient outcomes in those two conditions. DESIGN: Retrospective cohort study. SETTING: Urban tertiary care center in New York City. PARTICIPANTS: 302 patients admitted in an inpatient setting, ≥18 years old, with a laboratory-confirmed diagnosis of COVID-19 via nasal PCR swab were randomly selected. Patients were separated into two cohorts based on their body mass index and hemoglobin A1c. 150 patients were placed in the non-obese, non-diabetic cohort and 152 patients were placed in the corresponding cohort (obesity alone, obesity and diabetes, and diabetes alone). MEASUREMENTS: Primary outcomes were development of acute kidney injury, commencement of renal replacement therapy, aminotransferase elevation, troponin elevation, lactic acidosis, development of septic shock, use of vasopressors, presence of acute respiratory distress syndrome (ARDS) and intubation. The secondary outcomes were length of stay in days and mortality. RESULTS: Patients with obesity and/or diabetes were more likely to develop ARDS (79 patients vs 57 patients, p<0.0001) and to be intubated (71 patients vs 45 patients, p=0.0031). Patients with obesity and/or diabetes were more likely to require vasopressors (60 patients vs 41 patients, p=0.0284) and to develop lactic acidosis (median 3.15 mmol/L, IQR 1.8 to 5.2 mmol/L, p=0.0432). When comparing patients with diabetes with and without obesity against patients with obesity alone, they were more likely to develop ARDS (87.5%, p=0.0305). Despite these findings, there was no difference in mortality. CONCLUSIONS: In patients hospitalised with COVID-19, those with obesity and/or diabetes were more likely to suffer severe complications, but had negligible differences in mortality. This highlights the importance of close monitoring of patients with these conditions and additional areas of research needed to explain the mortality findings.