Reversal of endothelial dysfunction post-immunosuppressive therapy in adult-onset podocytopathy and primary membranous nephropathy. (February 2020)

• Record Type: Journal Article
• Authors: Inamdar, Neeraj; Tomer, Shallu; Kalmath, Sunil; Bansal, Akash; Yadav, Ashok Kumar; Sharma, Vishal; Bahuguna, Pankaj; Gorsi, Ujjwal; Arora, Sunil; Lal, Anupam; Kumar, Vivek; Rathi, Manish; Kohli, Harbir Singh; Gupta, Krishan Lal; Ramachandran, Raja
• Is Part Of: Atherosclerosis. Volume 295(2020)
• Page Start: 38
• Page End: 44
• Publication Date: 2020-02
• Subjects: CD4+CD28nullT cells -- Endothelial dysfunction -- E-selectin -- FMD -- Podocytopathy; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2019.08.013
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: The effect of nephrotic syndrome (NS) and its treatment on endothelial dysfunction is not evident. This study assessed endothelial dysfunction in adult-onset NS and its impact of immunosuppressive therapy. Methods: Newly diagnosed patients with adult-onset NS (podocytopathy and primary membranous nephropathy (PMN)) and normal renal function were enrolled. Flow mediated vasodilatation (FMD) assessed endothelial function and CD4 + CD28null T cells, E-selectin and pulse wave velocities (PWV) were measured at baseline and after treatment to characterize this further. Monitoring included monthly proteinuria, serum albumin, creatinine and lipid profile at baseline and post-treatment. The healthy control (HC) included 25 voluntary kidney donors who were assessed for markers of endothelial dysfunction. Results: Fifty participants with new-onset NS were studied. Amongst the NS group, 26 (52%) patients had PMN, while the remaining 24 (48%) had podocytopathy. Twenty-one (88%) patients in the podocytopathy and 18 (69%) patients in the PMN cohort were in either complete or partial remission at the end of 8 months. FMD at baseline in NS patients was significantly lower as compared to HC ( p = 0.002) while PWV ( p = 0.007), E-selectin ( p < 0.001) and CD4 + CD28null T cells ( p = 0.003) were significantly higher as compared with HC. Following treatment with immunosuppressive medication, FMD increased from 3 to 8% ( p < 0.001). PWV also improved from a baseline of 7.70 to 6.65 m/s ( p = 0.001). At the end of 8 months, E-selectin decreased significantly from 127 to 82 ng/ml ( p = 0.002) while the CD4 + CD28null T cell population reduced from 5.20 to 3.70% ( p = 0.032) of total CD4 + cells. In the PMN cohort, despite significant reduction, E-selectin and CD4 + CD28null T cells at follow-up remained higher than in healthy controls. Conclusion: Immunosuppressive treatment contributes substantially to the improvement of endothelial dysfunction present at baseline in NS patients. Persistent subtle endothelial dysfunction remains in the sub-group of patients with PMN. Graphical abstract: Image 1 Highlights: As compared to healthy controls, patients with nephrotic syndrome have endothelial dysfunction at presentation. Immunosuppressive drugs contribute substantially to improvement in endothelial dysfunction. Despite treatment, subtle endothelial dysfunction persists in primary membranous nephropathy.