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Lupus nephritis is a severe organ manifestation in systemic lupus erythematosus leading to kidney failure in a subset of patients. In lupus-prone mice, controlled infection with Plasmodium parasites protects against the progression of autoimmune pathology including lethal glomerulonephritis. Here, we demonstrate that parasite-induced protection was not due to a systemic effect of infection on autoimmunity as previously assumed, but rather to specific alterations in immune cell infiltrates into kidneys and renal draining lymph nodes. Infection of lupus-prone mice with a Plasmodium parasite did not reduce the levels or specificities of autoreactive antibodies, vasculitis, immune complex-induced innate activation, or hypoxia. Instead, infection uniquely reduced kidney-infiltrating CCL17-producing bone marrow-derived type 2 inflammatory dendritic cells (iDC2s). Bone marrow reconstitution experiments revealed that infection with Plasmodium caused alterations in bone marrow cells that hindered the ability of DC2s to infiltrate the kidneys. The essential role for CCL17 in lupus nephritis was confirmed by in vivo depletion with a blocking antibody, which reduced kidney pathology and immune infiltrates, while bypassing the need for parasitic infection. Therefore, infiltration into the kidneys of iDC2s, with the potential to prime local adaptive responses, is an essential regulated event in the transition from manageable glomerulonephritis to lethal tubular injury., Introduction Lupus nephritis is one of the most severe organ manifestations of systemic lupus erythematosus (SLE) and a main cause of morbidity in patients who progress to end-stage kidney disease [...]

Autoantibody-mediated diseases like myasthenia gravis, autoimmune hemolytic anemia and systemic lupus erythematosus represent a therapeutic challenge. In particular, long-lived plasma cells producing autoantibodies resist current therapeutic and experimental approaches. Recently, we showed that the sensitivity of myeloma cells toward proteasome inhibitors directly correlates with their immunoglobulin synthesis rates. Therefore, we hypothesized that normal plasma cells are also hypersensitive to proteasome inhibition owing to their extremely high amount of protein biosynthesis. Here we show that the proteasome inhibitor bortezomib, which is approved for the treatment of multiple myeloma, eliminates both short- and long-lived plasma cells by activation of the terminal unfolded protein response. Treatment with bortezomib depleted plasma cells producing antibodies to double-stranded DNA, eliminated autoantibody production, ameliorated glomerulonephritis and prolonged survival of two mouse strains with lupus-like disease, NZB/W F1 and MRUIpr mice. Hence, the elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases., The treatment of antibody-mediated diseases such as autoimmune hemolytic anemia, myasthenia gravis, cryoglobulinemia and systemic lupus erythematosus (SLE) represents a serious challenge. In spite of aggressive therapies including high-dose glucosteroids [...]

Abstract Idiopathic tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon condition, characterized by acute tubulointerstitial nephritis (TIN) with a favorable course and uveitis with a chronic relapsing course. The [...]

Abstract To evaluate the effect of azathioprine with steroids on the clinical course and histologic parameters of severe Henoch-Schonlein nephritis (HSN), 20 patients with a median age of 9.3 years [...]

Byline: Lois J. Arend (1), James E. Springate (2,3) Keywords: 5-Aminosalicylic acid; Renal failure; Nephrotoxicity; Inflammatory bowel disease Abstract: We report a new case of biopsy-confirmed mesalazine-induced interstitial nephritis in an 18-year-old male with ulcerative colitis. His renal function improved with drug discontinuation and corticosteroid treatment. An English literature review revealed an additional 22 cases of this complication that, taken together, showed (1) a male predominance, (2) an absence of specific symptoms or findings on urinalysis, (3) a 61% frequency of residual chronic renal insufficiency with 13% of patients developing end-stage renal disease, and (4) an apparent favorable response to steroid therapy. We conclude that patients receiving 5-aminosalicylates should be routinely monitored with serum creatinine measurements to prevent this uncommon but potentially serious adverse drug reaction. Author Affiliation: (1) Department of Pathology, University of Rochester School of Medicine, New York, USA (2) Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, New York, USA (3) Division of Nephrology, Women's and Children's Hospital of Buffalo, 219 Bryant Street, Buffalo, New York 14222, USA Article History: Registration Date: 08/01/2004 Received Date: 23/09/2003 Accepted Date: 17/12/2003 Online Date: 09/03/2004

Byline: D. Muller (1), D. Greve (3), P. Eggert (3) Keywords: Key wordsaTubular proteinuria; Henoch-Schonlein purpura; Nephritis Abstract: The prognosis of Henoch-Schonlein purpura (HSP) is mainly determined by the involvement of the kidney, but prognostic markers have not been established. To study the extent of tubular involvement in HSP and its relationship to the development of HSP nephritis, we measured the urinary excretion of two tubular marker proteins in 36 children with HSP. After admission, urinary N-acetyl-[beta]-D-glucosaminidase (NAG) was determined in 20 children and [alpha].sub.1-microglobulin ([alpha].sub.1-MG) in 16 children respectively. These values were compared with the biochemical data on admission, 1 month, 6 months, and 12 months later. A total of 198 24-h urine samples from healthy children were used for the establishment of reference data for NAG and [alpha].sub.1-MG (mean+-2 SD). Twenty-one patients had elevated excretion of either NAG (&gt mean+2 SD, n=12) or [alpha].sub.1-MG (&gt mean+2 SD, n=9). The highest values (&gt mean+4 SD) were found in patients with early kidney involvement. Normal values were accompanied by a benign further clinical course. Children with intermediate high values (&gt mean+2 SD, &lt mean+4 SD) developed signs of renal involvement during follow-up. Hence, tubular proteinuria is common during the early stages of HSP. NAG and [alpha].sub.1-MG levels correlate well with the extent of early and late renal involvement. Tubular marker proteins may be prognostic markers for the development of HSP nephritis. Author Affiliation: (1) University of Nijmegen, 162 Cell Physiology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands e-mail: d.mueller@celfys.kun.nl Tel.: +31-24-3614202, Fax: +31-24-3540525, NL (2) Department of Cell Physiology, University of Nijmegen, The Netherlands, NL (3) Children's Hospital, University of Kiel, Germany, DE Article note: Received: 21 December 1999 / Revised: 28 February 2000 / Accepted: 27 March 2000

Abstract Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass without frank abscess formation, which may represent a relatively early stage [...]

Byline: J.P. Dieleman (1), M. van der Feltz (2), C.H. Bangma (3), B.H.C. Stricker (4), M.E. van der Ende (5) Keywords: Key Words Papillary necrosis; Indinavir; Nephrolithiasis Abstract: The HIV protease inhibitor indinavir may cause nephrolithiasis and interstitial nephritis. The renal consequences of indinavir-associated nephrotoxicity are uncertain. We report a case of papillary necrosis in a patient treated with indinavir. An asymptomatic HIV-infected woman experienced right-sided renal colicky pain during treatment with indinavir. She passed a non-solid stone and continued indinavir treatment. Intravenous pyelogram performed 20 months later following an episode of left-sided colicky pain showed right-sided papillary necrosis. Indinavir-associated nephrolithiasis and chronic interstitial nephritis were the only possible causes identified in this patient. Physicians should be aware that indinavir nephrolithiasis may cause papillary necrosis. Author Affiliation: (1) Pharmaco-Epidemiology Unit, L-448, Dept. of Internal Medicine II, Erasmus University Medical Center Rotterdam, Postbox 2040, 3000 CA Rotterdam, The Netherlands Phone: (+31/10)408-8123, Fax: -9447 e-mail: dieleman@inw2.azr.nl, NL (2) Dept. of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands, NL (3) Dept. of Urology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands, NL (4) Drug Safety Unit, Inspectorate for Healthcare, The Hague, The Netherlands, NL (5) Dept. of Internal Medicine II, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands, NL Article note: Received: July 25, 2000 * Revision accepted: March 2, 2001