Polycythemia, capillary rarefaction, and focal glomerulosclerosis in two adolescents born extremely low birth weight and premature.

BACKGROUND: Low birthweight infants have a reduced number of nephrons and are at high risk of chronic kidney disease. Preterm birth and/or intrauterine growth restriction (IUGR) may also affect peritubular capillary development, as has been shown in other organs. CASE-DIAGNOSIS/TREATMENT: We report two patients with a history of preterm birth and extremely low birthweight who showed polycythemia and renal capillary rarefaction. Patient 1 and 2, born at 25 weeks of gestation with a birthweight of 728 and 466 g, showed mild proteinuria at age 8 and 6 years, respectively. In addition to increasing proteinuria, hemoglobin levels became elevated towards adolescence and their serum erythropoietin (EPO) was high despite polycythemia. Light microscopic examination of renal biopsy specimens showed glomerular hypertrophy, focal segmental glomerulosclerosis, and only mild tubulointerstitial fibrosis. A decrease in the immunohistochemical staining of CD31 and CD34 endothelial cells in renal biopsy specimens was consistent with peritubular capillary rarefaction. CONCLUSIONS: Since kidney function was almost normal and fibrosis was not severe, we consider that the capillary rarefaction and polycythemia associated with elevated EPO levels were largely attributable to preterm birth and/or IUGR.

Fasting Glucose Variation Predicts Microvascular Risk in ACCORD and VADT.

AIMS: The association of glycemic variability with microvascular disease complications in type 2 diabetes (T2D) has been under-studied and remains unclear. We investigated this relationship using both Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the Veteran Affairs Diabetes Trial (VADT). METHODS: In ACCORD, fasting plasma glucose (FPG) was measured 1 to 3 times/year for up to 84 months in 10 251 individuals. In the VADT, FPG was measured every 3 months for up to 87 months in 1791 individuals. Variability measures included coefficient of variation (CV) and average real variability (ARV) for fasting glucose. The primary composite outcome was time to either severe nephropathy or retinopathy event and secondary outcomes included each outcome individually. To assess the association, we considered variability measures as time-dependent covariates in Cox proportional hazard models. We conducted a meta-analysis across the 2 trials to estimate the risk of fasting glucose variability as well as to assess the heterogenous effects of FPG variability across treatment arms. RESULTS: In both ACCORD and the VADT, the CV and ARV of FPG were associated with development of future microvascular outcomes even after adjusting for other risk factors, including measures of average glycemic control (ie, cumulative average of HbA1c). Meta-analyses of these 2 trials confirmed these findings and indicated FPG variation may be more harmful in those with less intensive glucose control. CONCLUSIONS: This post hoc analysis indicates that variability of FPG plays a role in, and/or is an independent and readily available marker of, development of microvascular complications in T2D.

Altered ellipsoid zone reflectivity and deep capillary plexus rarefaction correlate with progression in Best disease.

AIMS: To evaluate the effects of neurovascular damage in patients with the typical vitelliform lesion of Best vitelliform macular dystrophy (BVMD) in the attempt to identify different progression patterns. METHODS: Prospective, observational case series. Patients in the vitelliform stage of BVMD and healthy controls underwent complete ophthalmological examination on a yearly basis, including best-corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT) and OCT angiography (OCT-A). 4.5×4.5 mm OCT-A slabs were imported into ImageJ software and their vessel density (VD) was calculated. Similarly, the ellipsoid zone (EZ) was manually outlined and the reflectivity was measured above the vitelliform lesion and in the 500 µm external to it. Retinal pigment epithelium-Bruch's membrane complex was taken as internal reference. RESULTS: 34 eyes (24 patients) and 34 matched controls were included in the study. Mean follow-up was of 28.4±5.8 months, with 12 eyes showing signs of stage progression at the end follow-up. The EZ overlying the vitelliform lesion and in the peri-lesional area disclosed a significant reduction in reflectivity when compared with the foveal and para-foveal EZ of controls, respectively. VD resulted meaningfully decreased only at the deep capillary plexus. Of notice, more extensive EZ (reflectivity <0.7) and vascular alterations (VD <0.4) at baseline strongly correlated with worse BCVA and were associated with a more rapid progression at follow-up. CONCLUSIONS: Both EZ reflectivity and VD at deep capillary plexus may prove valuable biomarkers to assess BVMD severity and detect progression. In this view, 'rapid progressors' might benefit the most from timely genetic therapies in the future.