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LITTLE ROCK, AR, United States

Alexander M.P.,Mayo Medical School | Larsen C.P.,Nephropathology Associates | Gibson I.W.,University of Manitoba | Nasr S.H.,Mayo Medical School | And 7 more authors.
Kidney International | Year: 2013

IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that typically manifests as fibro-inflammatory masses that can affect nearly any organ system. Renal involvement by IgG4-RD usually takes the form of IgG4-related tubulointerstitial nephritis, but cases of membranous glomerulonephritis (MGN) have also been described. Here we present a series of 9 patients (mean age at diagnosis 58 years) with MGN associated with IgG4-RD. All patients showed MGN on biopsy, presented with proteinuria (mean 8.3 g/day), and most had elevated serum creatinine (mean 2.2 mg/dl). Seven patients had known extrarenal involvement by IgG4-RD, with 5 patients having concurrent IgG4-related tubulointerstitial nephritis. Immunohistochemical analysis for the phospholipase A2 receptor, a marker of primary MGN, was negative in all 8 biopsies so examined. Six of 7 patients with available follow-up (mean 39 months) were treated with immunosuppressive agents; one untreated patient developed end-stage renal disease and underwent transplantation, without recurrence at 12 years after transplant. All 6 treated patients showed decreased proteinuria (mean 1.2 g/day), and most showed decreased serum creatinine (mean 1.4 mg/dl). Thus, MGN should be included in the spectrum of IgG4-RD and should be suspected in proteinuric IgG4-RD patients. Conversely, patients with MGN and an appropriate clinical history should be evaluated for IgG4-RD. © 2012 International Society of Nephrology. Source


Murphy C.L.,Alcoa | Wang S.,Alcoa | Kestler D.,Alcoa | Larsen C.,Nephropathology Associates | And 3 more authors.
American Journal of Kidney Diseases | Year: 2010

Background Renal amyloidosis is characterized by the pathologic deposition within glomeruli and/or interstitium of congophilic fibrils, most often composed of either immunoglobulin light chains or serum amyloid Arelated protein and, less commonly, mutated forms of apolipoproteins AI or AII, lysozyme, fibrinogen, gelsolin, or transthyretin. Study Design Case series. Setting & Participants 10 patients with renal amyloidosis who had an amyloidogenic protein that was not identified using routine immunohistochemistry. Outcomes Clinical, pathologic, biochemical, and genetic characteristics. Measurements Tandem mass spectrometry was used to analyze fibrils extracted from sections of formalin-fixed paraffin-embedded amyloid-containing kidney biopsy specimen blocks. Results Chemical analyses showed peptides corresponding to the carboxy-terminal portion of the leukocyte chemotactic factor 2 (LECT2) molecule. In addition, deposits were immunostained using an antihuman LECT2 monoclonal antibody. Plasma specimens were available from 2 individuals for whom LECT2 concentration in these samples was within the reference range. Additionally, in 4 of the cases analyzed at the molecular level, isolation of genomic DNA and polymerase chain reaction amplification of LECT2-encoding exons showed no mutations. However, all were homozygous for the G allele encoding valine at position 40 in the mature protein, a finding confirmed using restriction enzyme analysis of the polymorphic site. Limitations Causality is not addressed. Conclusions Based on our studies, we posit that LECT2-associated renal amyloidosis represents a unique and perhaps not uncommon disease, especially in Mexican Americans. The pathogenesis, extent, and prognosis remain to be determined. © 2010 National Kidney Foundation, Inc. Source


Rodriguez E.F.,Mayo Medical School | Nasr S.H.,Mayo Medical School | Larsen C.P.,Nephropathology Associates | Sethi S.,Mayo Medical School | And 2 more authors.
American Journal of Kidney Diseases | Year: 2014

Background Membranous nephropathy (MN) with crescents is rare and, in the absence of lupus, usually is associated with anti-glomerular basement membrane (anti-GBM) nephritis or antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis. Only rare cases of crescentic MN without ANCA or anti-GBM have been reported. Study Design Case series. Setting & Participants 19 patients with ANCA- and anti-GBM-negative crescentic MN and no clinical evidence of systemic lupus. Outcomes Clinical features, kidney biopsy findings, laboratory results, treatment, and follow-up of patients with crescentic MN. Results Mean age was 55 (range, 5-86) years. All patients presented with proteinuria (mean protein excretion, 11.5 [range, 3.3-29] g/d) and nearly all had hematuria; 16 of 19 (84%) patients had decreased estimated glomerular filtration rates (eGFRs; mean serum creatinine, 2.9 [range, 0.4-10] mg/dL; mean eGFR, 39.7 [range, 4 to >100] mL/min/1.73 m2). Glomeruli showed on average 25% (range, 2%-73%) involvement by crescents. All showed a membranous pattern; 7 showed mesangial and 2 showed segmental endocapillary proliferation. By immunofluorescence, all cases showed granular subepithelial immunoglobulin G (IgG) and κ and λ light chains, and all but one showed C3; 5 showed C1q or IgA. Electron microscopy revealed stages I-III MN; 38% of cases were M-type phospholipase A2 receptor (PLA2R) associated, indicating that at least some were primary MN. Follow-up clinical data were available for all patients (mean, 22 [range, 1.5-138] months). 14 patients received immunosuppressive therapy, and 2, only angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy. 4 patients (21%) progressed to end-stage renal disease, at 0-9 months postbiopsy. Mean serum creatinine level of those without end-stage renal disease at follow-up was 1.7 (range, 0.5-4.1) mg/dL; mean eGFR was 53.3 (range, 16-103) mL/min/1.73 m2. 67% of patients had proteinuria with protein excretion ≥ 1 (mean, 3.2) g/d at follow-up. Limitations Retrospective study. Conclusions Crescentic MN is a rare variant of MN that usually presents with heavy proteinuria, hematuria, and decline in GFR. The prognosis is variable and the disease may respond to therapy, but most patients develop a long-term decline in GFR. © 2014 by the National Kidney Foundation, Inc. Source


Raissian Y.,Mayo Medical School | Nasr S.H.,Mayo Medical School | Larsen C.P.,Nephropathology Associates | Colvin R.B.,Massachusetts General Hospital | And 9 more authors.
Journal of the American Society of Nephrology | Year: 2011

IgG4-related systemic disease is an autoimmune disease that was first recognized in the pancreas but also affects other organs. This disease may manifest as tubulointerstitial nephritis (IgG4-TIN), but its clinicopathologic features in the kidney are not well described. Of the 35 patients with IgG4-TIN whose renal tissue specimens we examined, 27 (77%) had acute or progressive chronic renal failure, 29 (83%) had involvement of other organ systems, and 18 of 23 (78%) had radiographic abnormalities. Elevated total IgG or IgG4 serum levels were present in 79%. All pathologic specimens featured plasma cell - rich TIN, with most showing diffuse, expansile interstitial fibrosis. Immune complexes along the tubular basement membranes were present in 25 of 30 (83%). All specimens had a moderate to marked increase in IgG4+ plasma cells by immunohistochemistry. We used a control group of 175 pathologic specimens with plasma cell - rich interstitial infiltrates that can mimic IgG4-TIN to examine the diagnostic utility of IgG4 immunostaining. Excluding pauci-immune necrotizing and crescentic glomerulonephritis, IgG4 immunohistochemistry had a sensitivity of 100% (95% CI 90-100%) and a specificity of 92% (95% CI 86-95%) for IgG4-TIN. Of the 19 patients with renal failure for whom treatment and follow-up data were available, 17 (89%) responded to prednisone. In summary, because no single test definitively diagnoses IgG4-related systemic disease, we rely on a combination of histologic, immunophenotypic, clinical, radiographic, and laboratory features. When the disease manifests in the kidney, our data support diagnostic criteria that can distinguish IgG4-TIN from other types of TIN. Copyright © 2011 by the American Society of Nephrology. Source


Cossey L.N.,University of Arkansas for Medical Sciences | Cossey L.N.,Nephropathology Associates | Rahim F.,Idaho Kidney Institute | Larsen C.P.,University of Arkansas for Medical Sciences | Larsen C.P.,Nephropathology Associates
American Journal of Kidney Diseases | Year: 2013

Oxalate nephropathy is a rare condition characterized by extensive calcium oxalate deposition in the renal tubules, resulting in kidney injury. There are primary forms of the disease that arise from genetic mutation causing overproduction of oxalate. More commonly, this condition is seen as a secondary phenomenon. The clinical presentation is nonspecific, with acute kidney injury and normal serologic study results. The characteristic finding on kidney biopsy is the presence of acute tubular injury associated with polarizable crystals in the tubular lumen and epithelial cytoplasm. We present a case of acute oxalate nephropathy in a patient with underlying systemic lupus erythematosus who recently received intravenous vitamin C. © 2013 National Kidney Foundation, Inc. Source

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