Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis

Abstract

Introduction: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. Hypothesis: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. Objective: To evaluate the main markers of atherosclerosis in patients with PG. Method: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. Results: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. Discussion and conclusion: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

The issue of atherosclerosis in primary glomerulonephritis

“…As part of the conclusion, the study by Hageman et al 3 found a significant inverse correlation between FMV and serum uric acid in the PG group, although Patients with glomerular disease and proteinuria may exhibit increased risk for cardiovascular disease, in part due to traditional risk factors such as associated hypertension, dyslipidemia, age, gender, and occasional obesity. In addition, it has been well documented that more advanced stages of chronic kidney disease (CKD) that may occur in cases of primary glomerulonephritis (PG), are associated with several nontraditional risk factors.…”

“…As part of the conclusion, the study by Hageman et al 3 found a significant inverse correlation between FMV and serum uric acid in the PG group, although information regarding serum uric acid levels in PG and control groups are lacking. The mechanisms of hyperuricemia-mediated endothelial dysfunction were recently reviewed by Wei et al 8 and include decreased nitric oxide production, oxidative stress, epithelial-to-mesenchymal transition, endothelial cell insulin resistance, and activation to release inflammatory cytokines.…”

“…In fact, previous documentation by Hutton et al 10 in which CV risk of patients with CKD and glomerulonephritis did not differ from other CKD patients from other causes, suggesting that glomerulonephritis itself does not add risk but the level of renal function does. Accordingly, in the study by Hageman et al 3 , both FMV, a marker of endothelial function, and CIMT were correlated with eGFR in the PG group.…”

“…Assessment of possible explanations for the high prevalence of atherosclerosis in PG patients is crucial for therapeutic and preventive strategies. In the present issue of BJN, Hageman and coworkers 3 initially aimed to investigate the role of MBD on atherogenesis in a group of PG patients. These patients exhibited eGFR that ranged from 48 to 105.12 mL/min/1.73m 2 with mean GFR of 80.3 mL/min/1.73m 2 per minute.…”

“…Overall, the most important message from the paper by Hageman and coworkers 3 comes from the analysis between the two groups of patients. The PG group had higher percentage of hypertensive individuals as well as lower levels of eGFR compared to control volunteers.…”