Glomerular injury after trauma, burn, and sepsis

Abstract

Acute kidney injury development after trauma, burn, or sepsis occurs frequently but remains a scientific and clinical challenge. Whereas the pathophysiological focus has mainly been on hemodynamics and the downstream renal tubular system, little is known about alterations upstream within the glomerulus post trauma or during sepsis. Particularly for the glomerular endothelial cells, mesangial cells, basal membrane, and podocytes, all of which form the glomerular filter, there are numerous in vitro studies on the molecular and functional consequences upon exposure of single cell types to specific damage- or microbial-associated molecular patterns. By contrast, a lack of knowledge exists in the real world regarding the orchestrated inflammatory response of the glomerulus post trauma or burn or during sepsis. Therefore, we aim to provide an overview on the glomerulus as an immune target but also as a perpetrator of the danger response to traumatic and septic conditions, and present major players involved in the context of critical illness. Finally, we highlight research gaps of this rather neglected but worthwhile area to define future molecular targets and therapeutic strategies to prevent or improve the course of AKI after trauma, burn, or sepsis. Graphical abstract

Kidney damage in burn disease. Part 1. Pathomorphophysiology (literature review)

“…To balance the hypotonic state, cardiac output increases due to activation of the sympathetic and reninangiotensin-aldosterone systems. For sepsis, significant tubular inflammation and microvascular damage, rapid and frequent development of bacteremia are typical [12,13,18,25,30,[37][38][39]. Plasma toxins in patients with burns caused by septic shock and AKI can increase the permeability of renal vessels for albumin, reduce the expression of nephrin and have a pro-apoptotic effect on podocytes and tubular cells; 10 % of burn patients develop an infectious complication of BD -pyelonephritis [27, 32,39].…”

“…In general, kidney function gradually declines with age ontogenetically. As patients with mild kidney disease age and experience some risk factors or accidental injury, kidney function further will decline rapidly, eventually progressing to CKD, sometimes even end-stage renal disease [8, 18,39]. Renal damage is due in part to aging-related, profibrotic and inflammatory factors that contribute to renal fibrosis and vascular damage, which accelerates the progression of CKD [18].…”

“…Renal proximal tubular epithelial cells are capable of repair by proliferation, but damage to podocytes is usually permanent. Therefore, in the long term, it is believed that severe burns can lead to renal dysfunction due to glomerulopathy [18,39].…”