Extrarenal determinants of kidney filter function

Abstract

The kidney is an organ involved in cross talk with many human organs. The link between the immune system and the kidney has been studied in some detail, although data precisely elucidating their interaction are sparse, in particular with regard to the function of the kidney filter apparatus. Current research suggests that an understanding of the impairment of this cross talk between the bone marrow, as a fundament of the immune system and the kidney will provide meaningful insights into the pathophysiological mechanisms of impaired kidney filter function. Circulating factors have long been implicated in the pathogenesis of idiopathic nephrotic syndrome, particularly focal segmental glomerulosclerosis (FSGS) and its recurrence. Soluble urokinase receptor (suPAR) has emerged as a circulating factor responsible for FSGS and also as an early predictive marker for the development of various renal diseases. The bone marrow has recently been revealed as a predominant source of suPAR with deleterious effects on the kidney filter. These new findings have led to bone marrow or hematopoietic stem cell transplants being considered as potential therapeutic options for preventing the post-transplantation recurrence of FSGS or even as a treatment for the original disease associated with high suPAR levels. Whereas bone marrow transplantation for patients with preexisting chronic kidney disease is challenging, recent clinical trials have demonstrated the promising outcome of combined bone marrow and kidney transplantation in patients with kidney failure. In this review, with its brief update on suPAR, we describe the critical new role of the bone marrow in the pathogenesis of the kidney disease process and the functional connection between these two organs through the soluble mediator, suPAR. We also comment on the feasibility of bone marrow transplants for the treatment of patients with chronic renal failure arising from recurrent FSGS.

Diagnostic and Prognostic Value of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) in Focal Segmental Glomerulosclerosis and Impact of Detection Method

“…As suPAR has a high affinity to protein A immunoapheresis columns, it is removable from the circulation, at least in part, but also rebounds within days 16 . An established therapy for recurrence of FSGS after transplantation is plasmapheresis or immunoadsorption, in combination with steroids, cyclosporine A and rituximab or alone 15,38 .…”

“…Several proteins have been suggested as the causative circulating factors responsible for the occurrence of primary FSGS or recurrence of disease after kidney transplantation, including cardiotrophin-like cytokine-1 (CLC-1) 11 , vasodilator-stimulated phosphoprotein (VASP) 12 , anti-CD40 antibodies 13 and soluble urokinase-type plasminogen activator receptor (suPAR) 14 . The most investigated factor in this context to date is suPAR 15 .…”

From genetics to personalized nephrology: kidney research at a tipping point

“…The manner in which the kidney interacts in molecular terms with other tissues and cross talks with the immunological system has seen substantial advances in recent years, especially in the form of circulating factors tentatively identified in the pathogenesis of idiopathic nephrotic syndrome. In their review article BExtrarenal determinants of kidney filter function^, Hahm et al (2017) provide comprehensive insight into the derivation of suPAR (from the bone-marrow), its regulation and its promise not only as a target, but also as a potential high-value diagnostic biomarker for the management of this devastating kidney disease.…”