Resident Kidney Cells and Their Involvement in Glomerulonephritis

Abstract

Each year, worldwide, there is an increasing number of patients with chronic kidney disease that progress to end-stage renal disease. Glomerulonephritis (GN) is the commonest single cause of end-stage renal failure in the world. GN can be a manifestation of primary renal injury or may be a secondary feature of a systemic disease process, for example Systemic Lupus Erythematosus (SLE) and Anti-Neutrophilic Cytoplasmic Antibody (ANCA) associated vasculitis. Understanding of the immunopathogenesis of GN has advanced considerably over the last 25 years, particularly the immune system's role. The injurious role of infiltrating leukocytes and humoral mediators has been emphasised, however, the contribution of intrinsic renal cells has proved difficult to define. Most evidence for the pro-inflammatory capacity of intrinsic renal cells has been derived from in vitro studies. Although cytokine production by intrinsic renal cells has been demonstrated by immunohistochemistry and in situ hybridisation studies in renal tissue during the development of GN, the functional contribution of this cytokine production to renal injury was unknown. Little was known about direct and specific interactions between different glomerular cell types and infiltrating leukocytes in the pathogenesis of GN. The development of mice with genetic deficiencies of pro-inflammatory mediators and cytokines, and the technique of bone marrow transplantation into irradiated recipients to produce chimeric mice with restricted cytokine expression has allowed in vivo assessment of the functional contribution made by intrinsic renal cells. Studies have demonstrated the significant contribution of intrinsic renal cell derived cytokines (e.g. TNF) in mediating GN, whereas others (IL-1beta) have a relatively minor role.

Inflammatory Mediators Release in Urine from Mice Injected withCrotalus durissus terrificusVenom

“…Total urine protein excretion was determined as previously described by Timoshanko and Tipping [25]. In brief, mice were housed individually in cages to collect urine before administration of Cdt , and spontaneously voided urine was collected over different times.…”

Lupus nephritis: current update

“…These intrinsic renal cells represent both the cause and the victim of various insults leading to GN [69,70]. Perhaps the most compelling evidence that intrinsic renal cells play an important role in immune-meditated GN has come from bone-marrow transfer or kidney- transplant studies in mice subjected to anti-glomerular basement membrane nephritis.…”

Urine Annexin A1 as an Index for Glomerular Injury in Patients

“…Recently, there has been great interest in strategies aimed at identifying novel biomarkers that can be easily detected in a noninvasive way (such as the use of urine samples) and can predict renal damage during the earlier stages [3]. Glomerular disorders represent a major health care problem because of their high mortality and morbidity rates [4]. Several studies have demonstrated that glomerular disorders are a multifactorial process caused by immune and nonimmune mechanisms that lead to glomerulosclerosis, tubulointerstitial fibrosis, inflammatory infiltration, loss of renal parenchyma, and renal vascular changes [5, 6].…”