Role of T cells and dendritic cells in glomerular immunopathology.

Inappropriate T cell responses cause the four classical types of hypersensitivity immune reactions. All of these can target the kidney and cause distinct forms of glomerulonephritis. CD4(+) T cells can mediate glomerular immunopathology by cytokine secretion, by activating effector cells such as macrophages or by inducing auto-antibodies or immune-complexes.

CCN3 is a novel endogenous PDGF-regulated inhibitor of glomerular cell proliferation.

CCN proteins affect cell proliferation, migration, attachment, and differentiation. We identified CCN3 as a suppressed gene following platelet-derived growth factor (PDGF)-BB or -DD stimulation in a cDNA-array analysis of mesangial cells. In vitro growth-arrested mesangial cells overexpressed and secreted CCN3, whereas the addition of the recombinant protein inhibited cell growth.

The map kinase ERK regulates renal activity of cyclin-dependent kinase 2 in experimental glomerulonephritis.

Background: In vitro, the extracellular signal-regulated kinase (ERK) is an intracellular convergence point of multiple stimuli, which affect the cell cycle. However, the role of ERK in cell cycle regulation in vivo is unknown.

Methods: To address this issue, ERK activity was blocked both in vitro in mesangial cells (MC) and in vivo in experimental glomerulonephritis (GN) by a pharmacological inhibitor (U0126) of the ERK-activating kinase.

Identification of central venous hemodialysis catheter-related infection by a semiquantitative culture method.

Background: Central venous hemodialysis catheter-related infection is a major cause of morbidity and mortality in the hemodialysis (HD) population. Due to an impaired immune response, symptoms and signs of infection may not be obvious, and thus bacteremia is often diagnosed and treated protractedly. In contrast, induction of the acute phase response is frequently observed in HD patients even without infection.

[Is there a correlation between C-reactive protein and calcification inhibitors with cardiovascular parameters and risk factors in hemodialysis patients?].

Background And Objective: Patients on hemodialysis exhibit a drastically increased cardiovascular mortality. Inflammation, hyperphosphatemia and lack of calcification inhibitors are uremia-associated risk factors for vascular calcification. Functional and morphological vascular parameters are used to assess cardiovascular risk.

Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview.

Background And Objectives: The dramatically high rates of mortality and cardiovascular morbidity observed among dialysis patients highlights the importance of identifying and implementing strategies to lower cardiovascular risk in this population. Results from clinical trials undertaken thus far, including trials on lipid reduction, normalization of hematocrit, and increased dialysis dosage, have been unsuccessful. Available data indicate that abnormalities in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism alone or the therapeutic measures used to manage secondary hyperparathyroidism, are associated with an increased risk for death and cardiovascular events.

The management of CKD: a look into the future.

The increasing global prevalence of chronic kidney disease (CKD) and end-stage renal disease with the associated spiraling cost has profound public health and economic implications. This has made slowing the progression of CKD, a major health-care priority. CKD is invariably characterized by progressive kidney fibrosis and at present, treatment aiming to slow the progression of CKD is limited to aggressive blood pressure control, with few therapies targeting the fibrotic process itself.

L-carnosine, a substrate of carnosinase-1, influences glucose metabolism.

Objective: Carnosinase 1 (CN1) is a secreted dipeptidase that hydrolyzes L-carnosine. Recently, we have identified an allelic variant of human CN1 (hCN1) that results in increased enzyme activity and is associated with susceptibility for diabetic nephropathy in human diabetic patients. We therefore hypothesized that L-carnosine in the serum represents a critical protective factor in diabetic patients.

[Daily problems involving contact with terminally ill patients with renal failure].

Practitioners and physicians working in emergency rooms are often confronted with dialysis patients or patients who have received a kidney transplant. For dialysis patients, the mode of dialysis treatment needs to be assessed and dialysis access should be secured. Furthermore, the indications for the next dialysis treatment need to be determined.

Podocyte damage resulting in podocyturia: a potential diagnostic marker to assess glomerular disease activity.

A decrease in podocyte number contributes to the development of glomerulosclerosis in most forms of glomerular disease [1, 2, 3, 4, 5]. Traditionally, it has been argued that this decrease may be caused by the inability of podocytes to proliferate and replace those lost following immune, metabolic, toxic or hemodynamic injury. These data contrast with recent studies showing that podocytes are able to enter the cell cycle after injury, to progress through the different phases of the cell cycle and even enter mitosis.

Sticky platelet syndrome: an underrecognized cause of graft dysfunction and thromboembolic complications in renal transplant recipients.

Sticky platelet syndrome (SPS) leads to hyperaggregabilty of platelets in response to physiologic stimuli. In this report we describe three patients with clinical symptoms of SPS after renal transplantation. The first patient developed an infarction of her transplant kidney with additional, subsequent renal microinfarctions.

Differentially spliced isoforms of FAT1 are asymmetrically distributed within migrating cells.

Cadherin FAT1 is localized along the leading edge of mammalian cells and is necessary for polarization and directed migration. It is essential for maintenance of the complex cytoarchitecture of the glomerular filtration barrier within the kidney. In this study, three novel splice isoforms of FAT1 with important functional differences in comparison with wild-type FAT1, FAT1(WT), were identified.

The role of PDGF-D in mesangioproliferative glomerulonephritis.

In view of increasing numbers of patients with end-stage renal disease (ESRD), new approaches to common underlying diseases, such as mesangioproliferative glomerulonephritis, including IgA nephropathy, are urgently needed. Whereas the role of the platelet-derived growth factor (PDGF) B chain in mediating mesangioproliferative changes is well established, the role of the PDGF-D chain has only recently been elucidated. The PDGF-D chain, like PDGF-B, signals through the PDGF beta-receptor and therefore shares a number of biological activities with PDGF-B.

Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes.

Glomerulonephritis (GN) is a major cause of renal failure. This study sought to determine whether intrarenal injection of rat mesenchymal stem cells (MSC) can preserve renal function in a progressive rat model of GN. Early in GN (day 10), fluorescently labeled rat MSC localized to more than 70% of glomeruli, ameliorated acute renal failure, and reduced glomerular adhesions.

Pro-fibrogenic potential of PDGF-D in liver fibrosis.

Background/aims: We analyzed the expression of platelet-derived growth factor D (PDGF-D) in an experimental bile duct-ligated (BDL) rat model and assessed its biological function in cultured hepatic stellate cells (HSC) and myofibroblasts (MFB).

Methods: The mRNA for PDGF-A, -B, -C, -D and for PDGF receptor-alpha and -beta chains (PDGFRalpha and PDGFRbeta) in normal and fibrotic rat livers was assessed quantitatively. Protein levels of PDGF-D were quantified by immunoblotting and immunohistochemistry.

Complement C5 mediates experimental tubulointerstitial fibrosis.

Renal fibrosis is the final common pathway of most progressive renal diseases. C5 was recently identified as a risk factor for liver fibrosis. This study investigated the role of C5 in the development of renal tubulointerstitial fibrosis by (1) induction of renal fibrosis in wild-type and C5(-/-) mice by unilateral ureteral ligation (UUO) and (2) investigation of the effects of a C5a receptor antagonist (C5aRA) in UUO.

Fetuin-A (AHSG) prevents extraosseous calcification induced by uraemia and phosphate challenge in mice.

Background: Chronic kidney disease (CKD) is associated with vascular and tissue calcification. The extent of vascular calcification has been identified as an independent risk factor of cardiovascular death in patients on haemodialysis.

Methods: We studied the role of fetuin-A in CKD-associated calcification using a mouse model of graded renal insufficiency generated by nephrectomy and high phosphate diet.

PDGF-B gene single-nucleotide polymorphisms are not predictive for disease onset or progression of IgA nephropathy.

Background: Few genetic factors have been identified that determine susceptibility to and progression of IgA-nephropathy (IgAN). Given that IgAN is usually characterized by mesangioproliferative glomerulonephritis and that PDGF-B is of central pathophysiological relevance in this process, we analyzed four single-nucleotide polymorphisms (SNPs) of the PDGF-B gene to evaluate a possible association of these SNPs with disease onset and progression, histological grading and responses to ACE inhibitor (ACEi) therapy.

Methods: The total study population consisted of 195 IgAN patients (127 from southern Italy and 68 from northern Germany) and 200 healthy controls (100 from each region).

PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis.

Background: Arresting or regressing kidney scarring is of major clinical relevance. Platelet-derived growth factor D (PDGF-D) is widely expressed in fibrotic kidneys. Administration of the PDGF-D neutralizing fully human monoclonal antibody CR002 in the acute phase of progressive anti-Thy 1.

Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, but its etiologic mechanisms are still poorly understood. Different prevalences among ethnic groups and familial aggregation, together with an increased familial risk, suggest important genetic influences on its pathogenesis. A locus for familial IgAN, called "IGAN1," on chromosome 6q22-23 has been described, without the identification of any responsible gene.