Lupus nephropathy beyond immunosuppression: Searching for nephro and cardioprotection

Abstract

Renal involvement in systemic lupus erythematosus (SLE) represents one of the most frequent organ manifestations, often leading to end-stage kidney disease (ESKD). Several therapies have been tested in patients with lupus nephritis (LN) to prevent further organ damage. The effectiveness of immunosuppressive therapy as a treatment for LN is abundant, supported by multiple clinical trials that have shown its efficacy in preventing the development of chronic kidney disease (CKD). In addition to immunosuppressive therapy, several traditional and recent therapies aimed at nephroprotection in patients with proteinuric chronic kidney disease are gaining importance in the setting of LN. Thus, immunosuppressive therapy should be accompanied by nephro- and cardioprotective measures to control cardiovascular risk factors and proteinuria to ensure a better renal prognosis. Despite this, the literature on these specific measures is relatively scarce, with recommendations focused on the blockade of the renin-angiotensin-aldosterone system (RAAS). This review explores the pharmacological options available for cardiovascular and renal protection outside the usual treatment schemes.

Sodium-glucose cotransporter 2 inhibitors: are they ready for prime time in the management of lupus nephritis?

“…Kidney function in all these patients remained stable. Similarly, Morales reported the use of empagliflozin in five patients with lupus nephritis resulting in a mean decrease in proteinuria from 2.2 to 1.2 g per day [41 ▪ ]. Observation extended to two months only.…”

The Inflammatory Profile Orchestrated by Inducible Nitric Oxide Synthase in Systemic Lupus Erythematosus

“…SLE is a multisystemic disease, with hematological, skin, heart, lung, kidney, joint, and cerebral involvement and with a complex pathogenicity, intensively studied in previous decades [ 6 , 8 , 15 ]. The present study evaluated the inflammatory profile orchestrated by inducible nitric oxide synthase in systemic lupus erythematosus and lupus nephritis, showing that renal lesions could be a consequence of inflammation-associated hypoxia.…”

“…Inflammation, oxidative imbalance, immune activation, autoantibody production, overstimulation of type 1 interferon (IFN), generation of inflammatory mediators, and tissue damage are fundamental contributors to SLE pathogenesis [ 1 , 2 , 3 ]. A series of experimental data have suggested that reactions mediated by inducible synthase of nitric oxide (NOS2 or iNOS) could be involved in the pathogenesis of SLE [ 4 , 5 , 6 , 7 , 8 ]. An inflammatory stimulus triggers iNOS production, further orchestrating inflammation, angiogenesis, and tissue fibrosis [ 9 , 10 ].…”

“…SLE affects several organs and tissues, such as the skin, kidneys, joints, blood cells, heart, lungs, and brain [ 6 , 8 , 15 ]. Skin and mucous involvement includes skin rashes, photosensitivity, mucosal ulcers, and alopecia.…”

“…Skin and mucous involvement includes skin rashes, photosensitivity, mucosal ulcers, and alopecia. Patients with SLE frequently develop lupus nephritis (LN), which can evolve to end-stage renal disease [ 5 , 7 , 8 ]. NL development is multifactorial, involving genetic susceptibility, environmental factors, and systemic inflammation [ 4 , 16 , 17 , 18 ].…”