Glomerulonephritis after hematopoietic cell transplantation: IgA nephropathy with increased excretion of galactose-deficient IgA1.

We report the development of IgA nephropathy (IgAN) following full myeloablative allogeneic hematopoietic cell transplantation in two patients with human leukocyte antigen (HLA) matched sibling donors, unrelated to active or chronic graft-versus-host disease. Both recipients had elevated urinary levels of galactose-deficient IgA1, and one donor-recipient pair had elevated serum levels of galactose-deficient IgA1. We propose that IgAN developed after bone marrow transplantation due to a non-graft-versus-host-disease-related multi-hit process associated with glomerular deposition of galactose-deficient IgA1.

Candesartan suppresses chronic renal inflammation by a novel antioxidant action independent of AT1R blockade.

Reactive oxygen species are thought to be critical inducers of renal inflammation and destruction. We examined the effects of candesartan, a highly selective angiotensin II type I receptor (AT1R) blocker, on renal inflammation and oxidative stress. Candesartan suppressed TNF-induced chemokine expression and NFkappaB activation independent of AT1R blockade in cultured renal tubular epithelial cells.

Hepatocyte growth factor suppresses proinflammatory NFkappaB activation through GSK3beta inactivation in renal tubular epithelial cells.

Activation of NFkappaB is a fundamental cellular event central to all inflammatory diseases. Hepatocyte growth factor (HGF) ameliorates both acute and chronic inflammation in a multitude of organ systems through modulating NFkappaB activity; nevertheless, the exact molecular mechanism remains uncertain. Here we report that HGF through inactivation of GSK3beta suppresses NFkappaB p65 phosphorylation specifically at position Ser-468.

Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease: targeting the inflamed vascular endothelium.

Recent studies show that hepatocyte growth factor (HGF) has potent anti-inflammatory effects in multiple animal models of disease in various organ systems, including the kidney, suggesting that HGF may suppress a common proinflammatory process. The aim of this study was to examine the molecular mechanism of HGF's anti-inflammatory actions in a model of chronic kidney disease. Beginning 2 wk after subtotal nephrectomy, rats received a continuous infusion of recombinant HGF, neutralization of endogenous HGF by daily injection of an anti-HGF antibody, or preimmune IgG for an additional 2 wk.

Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure.

Background: Rise in cellular calcium is associated with acute tubular necrosis, the most common cause of acute renal failure (ARF). The mechanisms that calcium signaling induce in the quiescent tubular cells to proliferate and differentiate during acute tubular necrosis have not been elucidated.

Methods: Acute tubular necrosis induced in mice by single intravenous injection of uranyl nitrate and examined after 1, 3, 7, and 14 days.

Glomerular crescent-related biomarkers in a murine model of chronic graft versus host disease.

Background: We examined the alterations in gene expression associated with the development of crescentic glomerulonephritis in murine chronic graft-versus-host disease, a model for human systemic lupus erythematosus.

Methods: The disease was induced in (C57BL/6 x DBA/2) F(1) hybrids by injection of DBA/2 lymphocytes leading to deposition of auto-antibodies in the glomeruli, and a lupus type of nephritis morphologically. After extensive crescent formation at week 9 of disease, cDNA microarray analysis was performed and highly expressed genes were evaluated as molecular markers by real-time reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, immunohistochemistry and immunoassay of urine proteins.

Activation of PI3K-Akt-GSK3beta pathway mediates hepatocyte growth factor inhibition of RANTES expression in renal tubular epithelial cells.

Hepatocyte growth factor (HGF) was recently reported to ameliorate renal inflammation in a rat model of chronic renal failure. HGF exerted its action through suppression of RANTES expression in renal tubules. In the present study, we utilized an in vitro model of human kidney proximal tubule epithelial cells (HKC) to elucidate the mechanisms of RANTES suppression by HGF.

Hepatocyte growth factor ameliorates renal interstitial inflammation in rat remnant kidney by modulating tubular expression of macrophage chemoattractant protein-1 and RANTES.

Hepatocyte growth factor (HGF) has been shown to reduce renal injury in a variety of animal models of chronic renal disease. Suggested mechanisms to explain this action include prevention of tubular cell apoptosis, blocking epithelial-to-mesenchymal transition, and promotion of extracellular matrix degradation. Inflammation is another common finding in kidneys that progress to end-stage renal failure; however, the effect of HGF on inflammation has hardly been investigated.

Hepatocyte growth factor ameliorates progression of interstitial fibrosis in rats with established renal injury.

Background: Hepatocyte growth factor (HGF) has been reported to prevent injury in several models of renal disease; however, whether HGF can also retard progression of established renal disease is not known.

Methods: The aim of the present study was to examine the effects of HGF on progression of chronic renal disease in rats with remnant kidneys and established injury. Studies were performed in rats that underwent subtotal nephrectomy, were observed for two weeks without therapy, and then randomized to receive HGF or vehicle by continuous infusion for an additional two weeks.

Hepatocyte growth factor modulates matrix metalloproteinases and plasminogen activator/plasmin proteolytic pathways in progressive renal interstitial fibrosis.

Evidence suggests that hepatocyte growth factor (HGF) ameliorates renal fibrosis in animal models of chronic renal disease by promoting extracellular matrix catabolism. This study examined the molecular mechanisms of HGF-induced alterations in matrix degradation both in vitro and in vivo. In vitro, HGF increased the collagen catabolizing activity of human proximal tubular epithelial cells (HKC) that were treated with TGF-beta1.