Case series of idiopathic intracranial hypertension in three patients with immune-complex glomerulonephritis

Background Idiopathic intracranial hypertension (IIH) is defined by an increased cerebrospinal fluid pressure in the absence of inflammation, structural obstructions, or mass lesions. Although the underlying pathogenesis of IIH is not fully understood, associations with specific risk factors as obesity, obstruction of cerebral venous sinuses, medications, endocrine or systemic conditions and chronic kidney disease have been described. Immune-complex glomerulonephritis as IgA-nephropathy is a frequent cause of chronic kidney failure, which was reported previously in one IIH patient. To date, there is no knowledge about the variable relation of immune-complex nephritis, kidney function and the course of IIH. Case presentation We report three cases (two females) of concurrent diagnosis of IIH and immune-complex glomerulonephritis. All patients presented with typical IIH symptoms of headache and visual disturbances. Two patients had been diagnosed with IgA-nephropathy only few weeks prior to IIH diagnosis. The third patient had been diagnosed earlier with terminal kidney failure due to a cryoglobulin glomerulonephritis. Conclusion We propose a possible link between renal deposition of immune-complexes and increased cerebrospinal fluid pressure. Pathophysiological hypotheses and clinical implications are discussed. We recommend clinical awareness and further systematic research to obtain more information on the association of IIH and immune-complex glomerulonephritis.

The Rare First Manifestation Of Mantle Cell Lymphoma As Immune Complex Glomerulonephritis With Crescents And Membranoproliferative Features

Introduction/Objective Initial presentation of Non-Hodgkin Lymphoma (NHL) with immune complex glomerulonephritis (ICGN) is rare. Mantle cell lymphoma (MCL) is a rare aggressive lymphoma comprising 3–7 % of all NHL and ICGN as the first manifestation of MCL is very unusual. Methods We report a 73 year-old-man with increased serum creatinine (2.1 mg/dl) from normal baseline 3 months ago. Urinalysis showed the presence of dysmorphic RBCs, RBC casts and 300 mg/dl of protein. Physical examination revealed diffuse lymphadenopathy. Hepatitis C and B Ab, HIV screen, ANA, ANCA, Anti dsDNA Ab, Anti GBM Ab, and Serum protein electrophoresis were normal or negative. Results The renal biopsy showed Immune complex glomerulonephritis with (25%) fibrocellular/cellular crescents and focal membranoproliferative (MPGN) features. There were foci of dense monomorphic lymphoid aggregates of small lymphocytes and 30% interstitial fibrosis with corresponding tubular atrophy. No tubulitis was present. Direct Immunofluorescence showed 2+ to 4+ granular mesangial and capillary loop staining for Total Ig, IgG, IgA, IgM, C1q, C3 and C4. The lymphoid aggregate was monoclonal Kappa. Electron microscopy showed widespread podocyte foot process effacement, subendothelial and rare mesangial dense deposits. Excisional lymph node biopsy flow cytometry showed a monoclonal population of CD19+, CD20+, CD22+, CD5+, skappa-restricted, CD10-, CD11c-, CD23-, CD25- CD38-, CD103-, CD200- B- cells. Cyclin D1 was positive on immunostain, consistent with stage IV (renal) MCL. He received chemotherapy with steroids, bendamustine, and rituximab leading to resolution of lymphadenopathy and proteinuria and improvement in serum creatinine. Conclusion It is important to recognize that the first manifestation of MCL may present as renal involvement in the form of ICGN and, as in this case, with fibrocellular/cellular crescents and a focal MPGN pattern. This is an extremely rare, but important, cause of renal insufficiency that can be successfully treated with lymphoma chemotherapy.

MicroRNA-146a-deficient mice develop immune complex glomerulonephritis

MicroRNAs (miRNAs) play an important role in the kidneys under physiological and pathological conditions, but their role in immune glomerulonephritis is unclear. miR-146a has been identified as a key player in innate immunity and inflammatory responses, and in the kidney, this miRNA is involved in the response of injured tubular cells. We studied the renal and immune phenotypes of miR-146a+/+ and miR-146a−/− mice at 12 months of age, and the results showed that miR-146a−/− mice developed autoimmunity during aging, as demonstrated by circulating antibodies targeting double-stranded DNA and an immune complex-mediated glomerulonephritis associated with a mild renal immune infiltrate. In addition, miR-146a−/− mice showed reduced expression of the transmembrane protein Kim1/Tim1, a key regulator of regulatory B cell (Breg) homeostasis, in the kidney and the immune cells. The numbers of memory B cells and plasmablasts were increased in miR-146a−/− mice compared with the numbers in wild-type mice, whereas Bregs were decreased in number and displayed an altered capacity to produce IL-10. Finally, we showed that miR-146a−/− mice develop an autoimmune syndrome with increasing age, and this syndrome includes immune complex glomerulonephritis, which might be due to altered B cell responses associated with Kim1/Tim1 deficiency. This study unravels a link between miR-146a and Kim1 and identifies miR-146a as a significant player in immune-mediated glomerulonephritis pathogenesis.