Primary Focal Segmental Glomerulosclerisis: Clinical Characteristics Of Common Complications And Evaluation Of Endothelial Dysfunction

Focal segmental glomerulosclerosis (FSGS) is now one of the most common causes of primary glomerular disease, which accounts for 10-15% of patients undergoing an evaluation for proteinuria. A significant percentage of patients will remain heavily proteinuric despite vigorous attempts to modify its course with specific, therapeutic regimens, which makes them more susceptible to common complications of nephrotic syndrome (NS), including acute kidney injury (AKI), infection and thromboembolisms, the development of which may have negative effects on their prognosis. How to prevent or reduce the incidences of these complications has become a worrying challenge for nephrologists. This study was performed to better describe the spectrum and incidences of these complications and to identify clinical variables predictive of the risk of them.In addition, previous studies have demonstrated that patients with NS have endothelial injury, which plays a key role in the process of vascular complications such as venous thromboembolisms and atherosclerosis. This study also investigated the endothelial function of FSGS patients and made a preliminary observation on the relationship between endothelial injury, venous thromboembolisms and disease activity.Part 1. Primary focal segmental glomerulosclerosis in nephrotic patients: common complications and risk factorsObjective:Focal segmental glomerulosclerosis (FSGS) presents a range of potentially serious complications, including acute kidney injury (AKI), infection and thromboembolisms. This study aimed to find out the incidences and risk factors of these complications in nephrotic FSGS patients.Methods:Patients with biopsy-proven primary FSGS and nephrotic-range proteinuria were involved in this cross-sectional study. Clinical characteristics were prospectively recorded upon enrollment. AKI was diagnosed as an absolute increase in serum creatinine of≥0.3 mg/dl or a percentage increase of≥50%; infection, by a combination of clinical manifestations, laboratory tests and imaging examinations; and thromboembolisms, by imaging methods. Risk factors for complications were evaluated by logistic regression model.Results:The study population included 90 FSGS patients (63 males; mean age 28.9±12.9 years). The incidences of AKI, infection and thromboembolisms were 44.4%,23.3% and 12.2%, respectively. Patients with AKI were more likely to be male with lower serum albumin, greater proteinuria and more severe acute tubulointerstitial damage. Patients with infection had higher proteinuria and lower serum albumin, globulin and IgG. There was a tendency towards a difference in hemoglobin (P=0.057) between patients with and without thromboses. Logistic regression showed that acute tubulointerstitial injury, decreased serum albumin and IgG, and increased hemoglobin were independent risk factors for AKI, infection and thromboembolisms, respectively.Conclusions:AKI, infection and thromboembolisms are common among FSGS patients. Awareness of risk factors and prevention of these complications are important for the prognosis of these patients.Part 2. Biomarkers of endothelial dysfunction in patients with primary focal segmental glomerulosclerosisObjective: Endothelial dysfunction occurs in nephrotic syndrome (NS) and may constitute a link between NS and vascular complications. Focal segmental glomerulosclerosis (FSGS) is a common cause of NS. This study aimed to assess endothelial markers at different stages of FSGS and define whether they were associated with thromboembolic complications and disease activity.Methods:Fifty-three patients with nephrotic-range proteinuria and biopsy-proven primary FSGS were included in this study. Nine of them had concurrent thromboembolisms. Thirty-two sex- and age- matched healthy volunteers served as controls. Markers of endothelial dysfunction, including circulating endothelial cells (CECs), soluble thrombomodulin (sTM), von Willebrand factor (vWf), vascular cell adhesion molecule (VCAM) and E-selectin (ES), were assessed at the commencement of the study in all participates and were repeated at 2,6,12 months of follow-up in patients without thromboembolisms.Results:Patients with FSGS during active stage showed significantly higher levels of CECs, sTM, vWf, VCAM and ES when compared to controls. Moreover, patients with thromboembolisms had higher CECs and vWf than those without thromboembolisms, indicating more severe endothelial injury. In patients without thromboembolisms, endothelial markers had inverse correlations with serum albumin and were positively related to cholesterol. At follow-up, they systematically decreased as the disease went into remission, but the increase in vWf and VCAM persisted even in patients obtaining complete remission for nearly a year. In patients with no response, levels of endothelial markers exhibited no obvious change.Conclusions:Patients with FSGS had elevated markers of endothelial dysfunction, which were largely related to the activity of the disease. Endothelial injury was more severe in patients concurrent with thromboembolisms.