Disease relevance of Nephritis

• Thromboxane antagonism in lupus nephritis [1].
• Three structural aberrations were found in COL4A5, in intragenic deletion, a Pst I site variant, and an uncharacterized abnormality, which appear to cause nephritis and deafness, with allele-specific severity, in three Alport syndrome kindreds in Utah [2].
• Anasarca with pronounced hypoalbuminemia developed in a young woman 15 months after the onset of a mild, arthralgic type of systemic lupus erythematosus (SLE) without evidence of active nephritis [3].
• To investigate the functional role that the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES play in inflammation and the progression to fibrosis during crescentic nephritis we have developed and characterized a murine model for this syndrome [4].
• To assess the role of VEGF(165) in glomerular disease, we administered a novel antagonist - a high-affinity, nuclease-resistant RNA aptamer coupled to 40-kDa polyethylene glycol (PEG) - to normal rats and to rats with mesangioproliferative nephritis, passive Heymann nephritis (PHN), or puromycin aminonucleoside nephrosis (PAN) [5].

High impact information on Nephritis

• The CD45 E613R mutation causes polyclonal lymphocyte activation leading to lymphoproliferation and severe autoimmune nephritis with autoantibody production, resulting in death [6].
• CONCLUSIONS: For the treatment of diffuse proliferative lupus nephritis, the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone but is less toxic [7].
• We carried out a randomized, controlled trial comparing a standard-therapy regimen of prednisone and cyclophosphamide (standard therapy) with a regimen of standard therapy plus plasmapheresis in 86 patients with severe lupus nephritis in 14 medical centers [8].
• Improvement of renal function with selective thromboxane antagonism in lupus nephritis [9].
• We therefore investigated serum neuraminidase activity and serum and urinary free neuraminic acid levels, using the thiobarbituric acid method, in 39 patients with acute poststreptococcal nephritis [10].

Chemical compound and disease context of Nephritis

• Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide [11].
• Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs [12].
• In a four-year follow-up study there was a higher incidence (P approximately 0.04) and average rate (P approximately 0.02) of clinical recurrence of nephritis in the group initially given only steroid than in the group initially given both drugs [11].
• Ribavirin, a drug with known antiviral activity, was given to mice with established lupus nephritis [13].
• Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis [14].

Biological context of Nephritis

• These data indicate that Gas6 induces glomerular cell proliferation in NTN and suggest that this factor contributes to glomerular injury and the progression of chronic nephritis [15].
• IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis [16].
• Interestingly, a distal chromosome 4 locus, Nba1, was linked with nephritis but not with any of the autoantibodies measured, suggesting that it contributes to renal disease at a checkpoint distal to autoantibody production [17].
• The RR genotype was more frequent in SLE patients as a whole (OR 1.30, 95% CI 1.10-1.52) and in SLE patients without nephritis (OR 1.27, 95% CI 1.04-1.55) compared with disease-free controls [18].
• Thus cytokine-mediated upregulation of ICAM-1 in lupus nephritis may promote interaction of immune cells with renal tissue [19].

Anatomical context of Nephritis

• In vivo, in a model of acute antiglomerular basement membrane nephritis in which immune complexes are accessible to circulating neutrophils, Fc gamma RIII-deficient mice had a significant reduction in neutrophil recruitment [20].
• Mice that are transgenic for BLyS show B cell accumulation, activation and autoimmune lupus-like nephritis [21].
• To investigate the relevance of Mac-1-FcgammaR interactions in IC-mediated injury in vivo, we induced a model of Fc-dependent anti-glomerular basement membrane (GBM) nephritis in wild-type and Mac-1-deficient mice by the intravenous injection of anti-GBM antibody [22].
• We investigated whether mesangial of mesangial proliferative nephritis induced with antibody to the Thy-1 antigen present on mesangial cells [23].
• Nonneoplastic lesions included cystic hyperplasia of the uterus, nephritis, ovarian and uterine cysts, inflammatory lesions of the lung, mineralization in the brain, and focal hyperplasias in several tissues [24].

Gene context of Nephritis

• Essential role of Gas6 for glomerular injury in nephrotoxic nephritis [15].
• Lack of chemokine receptor CCR1 enhances Th1 responses and glomerular injury during nephrotoxic nephritis [25].
• Using the rat model of anti-glomerular basement membrane (GBM) nephritis, we found that mRNA for the chemokine CINC (cytokine-induced neutrophil chemoattractant) was induced in the kidney, and the corresponding protein was elaborated by isolated inflamed glomeruli [26].
• The protein also corresponds to the mouse protein LN1, which could be involved in the progress of lupus nephritis [27].
• The epistatic interactions of Sle1 with other susceptibility loci to cause severe nephritis cannot be accounted, however, by these three loci alone, suggesting the existence of an additional locus, termed Sle1d [28].

Analytical, diagnostic and therapeutic context of Nephritis

• In an effort to clarify the role of immunosuppressive drugs in the management of lupus nephritis, we pooled data from all published clinical trials in which patients had been randomly assigned to receive either prednisone alone or prednisone plus cyclophosphamide or azathioprine [29].
• To further investigate these relationships, we compare the variable genes and primary structure of eight anti-DNA mAbs previously obtained from an MRL/MpJ-lpr/lpr mouse along with the ability of three representative mAbs to induce nephritis in nonautoimmune mice using established adoptive transfer protocols [30].
• CONCLUSIONS: Patients with systemic lupus erythematosus and end-stage renal failure are excellent candidates for renal transplantation; disease activity after transplantation is sporadic and low, and the recurrence of lupus nephritis is rare [31].
• Rheumatoid arthritis, lupus nephritis, and risks of lymphoid irradiation [32].
• Histologic analysis of the kidneys revealed that GF-AF mice had much lower levels of nephritis, while immunofluorescence analysis demonstrated no difference in Ig deposits but did reveal a paucity of C3 deposition in the kidneys of GF-AF mice [33].

References