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Background: Idiopathic membranous nephropathy (i-MN) is a leading cause of nephrotic syndrome in adults and results in end-stage renal disease in approximately one third of patients. There are few large, long-term US studies evaluating clinical and histologic prognostic factors in i-MN., Methods: We describe 132 patients with biopsy-proven i-MN who were followed for a mean period of 68 months at our tertiary referral center from 1977 to 2009, and we analyzed clinical and histologic features that predicted renal outcomes., Results: The presence of hypertension and treating physician's decision to institute immunosuppression were negative predictors of attaining complete or partial remission. Among clinical variables, impaired renal function (eGFR <60 ml/min/1.73 m(2)) at time of presentation was the only variable at presentation associated with an increased risk of reaching end-stage renal disease. The use of statins and RAAS blockers were protective. The choice of corticosteroids as the initial immunosuppressive agent by referring physicians decreased over time but even in the most recent era (2000-2008) was significant (33%)., Conclusion: Renal function at presentation and non-white race were the main predictors of a worse renal outcome. Corticosteroid therapy is still being adopted as first-line therapy in a significant number of patients in this era. The development of guidelines may help clarify the treatment strategies of i-MN., (Copyright © 2012 S. Karger AG, Basel.)

We report two cases of nephrotic syndrome presenting 18 and 20 months after allogeneic stem cell transplantation (alloSCT) with chronic myelogenous leukemia. Both patients had acute and chronic graft-versus-host disease (GVHD) and renal biopsy findings of membranous glomerulopathy (MG). A review of the literature revealed 10 additional cases of immune-complex-mediated glomerular disease following alloSCT, 8 of which were diagnostic of MG. All patients showed evidence of acute or chronic GVHD. Patients typically presented with preserved renal function (mean creatinine 1.2 mg/dl) and full nephrotic syndrome including heavy proteinuria (mean 9.2 g/24 h), edema, hypoalbuminemia (mean 2.1 g/dl) and hypercholesterolemia (mean 472 mg/dl). Most patients showed stabilization of renal function and significant decreases in proteinuria when treated with steroids and/or cyclosporine. The close temporal association as well as evidence from murine models of GVHD support a pathogenetic association between GVHD and the development of MG., (Copyright 2001 S. Karger AG, Basel)

The anatomic heterogeneity of the nephron poses obstacles to microdissection of individual renal compartments for analysis of gene expression. We have systematically analyzed the effects of fixation time and nuclear staining on the ability to recover nucleic acid from individual renal compartments by laser capture microdissection (LCM). Formalin-fixed kidney sections from Wistar rats and archival human renal biopsies were used for DNA analysis. From 1 to 10 individual glomeruli and from 1 to 10 individual proximal tubules were captured sequentially onto polymer films. DNA for beta-globin could be amplified by PCR from even a single glomerulus or tubule. Optimal conditions for DNA amplification were brief (1- or 2-day) formalin fixation. Use of nuclear counterstains, including Weigert's hematoxylin, Harris's hematoxylin, Mayer's hematoxylin, or methyl green, did not adversely affect the ability to extract and amplify DNA. For RNA extraction, glomeruli and tubules were microdissected from renal cryostat sections stored for up to 6 months. By RT-PCR, mRNA expression of the glomerulus-specific gene, Wilms' tumor-1, was identified in as few as 5 microdissected glomeruli and of the tubule-specific gene, aminopeptidase N, in as few as 5 microdissected tubules, with no cross-contamination between renal compartments. Our findings indicate that the LCM method can successfully microdissect pure glomerular and tubular tissue compartments and that the optimal fixation and staining conditions are those employed routinely for renal biopsies, namely overnight formalin fixation and hematoxylin counterstain for DNA extraction, and cryostat sectioning with hematoxylin counterstain for RNA extraction. The specificity of LCM coupled with the sensitivity of RT-PCR should prove a powerful tool for the analysis of gene expression in specific renal compartments from archival human renal biopsies., (Copyright 2001 S. Karger AG, Basel)

Tenascin, a large oligomeric glycoprotein, is a recent addition to a list of increasing extracellular matrix proteins. Previous studies have documented the strong expression of tenascin in embryonic kidney and in both normal and abnormal mature glomeruli implicating an important role of this extracellular matrix protein in nephrogenesis and glomerular scarring. Whether tenascin plays any role in interstitial fibrosis, a common final pathway of tubulointerstitial nephritis, is no known; on the other hand, a detailed knowledge of the structural components of interstitial fibrosis is essential for further studies on other fundamental aspects of this biologically and clinically important process. In this study, the expression of tenascin in the renal interstitium was immunohistochemically evaluated in 208 renal specimens during normal kidney (23 cases), acute tubular necrosis (8), acute tubulointerstitial nephritis (8), chronic primary tubulointerstitial nephritis (30), tubulointerstitial nephritis secondary to glomerular diseases of mild (46) and severe (55) degree, ischemic damage (24), and rejection (14). It was found that in normal kidney tenascin expression was limited to the medullary interstitium. In kidney with tubulointerstitial nephritis, tenascin was ubiquitously and constantly expressed in any areas with tubulointerstitial damage regardless of diagnosis, etiology, the cortical vs. medullary location of the lesions, stage of the fibrogenetic process, density of fibroblasts, or severity of interstitial inflammation in the affected areas. Indeed, strong tenascin expression was seen in areas where there was only interstitial edema or inflammation as judged by routine light microscopic preparations. In summary, this study systematically documents tenascin as a novel extracellular matrix protein selectively expressed in the medullary interstitium in normal kidney, and ubiquitously present in areas with interstitial fibrosis.

A patient receiving adoptive immunotherapy with recombinant interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells for metastatic melanoma developed acute renal insufficiency out of proportion to the decrease in her renal perfusion after 4 days of receiving IL-2. On the 8th day of IL-2 and the 3rd day of LAK cell infusion she expired suddenly from an acute intra-abdominal hemorrhage due to rupture of a metastasis. Postmortem examination of the kidneys showed an interstitial infiltrate consisting largely of lymphocytes and concomitant tubulitis. Immunoperoxidase staining of the infiltrating cells with a panel of lymphocyte-specific monoclonal antibodies showed the majority of cells to be T lymphocytes (70-75%), with a more focal infiltrate of B lymphocytes (25-30%) and rare monocytes, granulocytes and natural killer cells. This patient represents the first reported case of acute interstitial nephritis associated with IL-2 immunotherapy. Our finding is consistent with the hypothesis that the acute renal failure that accompanies this therapy may sometimes be due to intrinsic renal disease as well as the usual pre-renal failure. Nephritis may be caused by IL-2-mediated effects on lymphocytes, resulting in renal parenchymal infiltration.

We report the first case of membranous lupus nephritis occurring in a child with congenital AIDS. Hypocomplementemia, elevated titers of anti-nuclear antibody and antibody to double-stranded DNA supported the diagnosis of associated systemic lupus erythematosus (SLE). The pathogenetic implications of this coexistence of AIDS and SLE are discussed.

Cat scratch disease is a generally benign, self-limited disease characterized by fever and regional lymphadenitis. Systemic complications are rare and most frequently affect the central nervous system, bone, liver or spleen. We report the first case of glomerulonephritis associated with cat scratch disease which resolved spontaneously concurrent with the resolution of lymphadenitis and constitutional symptoms. Immunopathologic and ultrastructural studies suggest a form of immune-mediated postinfectious glomerulonephritis.

An 82-year-old female developed hemolytic uremic syndrome (HUS) after a prodromal illness of bloody diarrhea. No specific enteric pathogen was isolated. A renal biopsy performed 5 days after the onset of azotemia revealed typical thrombotic microangiopathy. By electron microscopy, massive annular-tubular deposits admixed with fibrillar fibrin were demonstrated in glomerular capillaries. Immunofluorescent staining of the intracapillary material was positive for IgG, IgM, C3, C1q and fibrin-related antigens. No evidence of plasma cell dyscrasia, cryoglobulinemia or systemic lupus erythematosus was found, and the patient recovered renal function uneventfully in 2 months. Organized immune deposits appear to have played a role in the pathogenesis of HUS in this patient.

A patient with a single kidney and oliguric renal failure for 47 days experienced dramatic restoration of glomerular filtration and renal function following graft bypass of an occluded renal artery. There was very little evidence of acute tubular necrosis. The case emphasizes the importance of the renal collateral circulation in the maintenance of tissue viability, even when the hydrostatic pressure of collateral flow is inadequate for glomerular ultrafiltrate formation. The differentiation of oliguric renal failure due to renal arterial occlusion from that due to acute tubular necrosis following arterial injection of radiocontrast material is imperative because of the dramatic response to reconstructive vascular surgery.

The interrelationships between tubulointerstitial immune deposits (TID), interstitial inflammation, glomerular changes, renal function, and prognosis were assessed in the renal biopsies from 93 patients with lupus nephritis. The prevalence of TID was 33% by immunofluorescence and 23% by electron microscopy. Although predominantly detected along and within tubular basement membranes, extraglomerular immune deposits were also present in the wall of renal interstitial capillaries and small arteries as well as in Bowman's capsule. The prevalence of TID correlated with the activity of glomerular lesions and, to a lesser extent, with the severity of proliferative lupus nephritis (WHO classes II-IV). TID were much less common in the membranous form (WHO class V). The severity of interstitial inflammation correlated with the degree of renal insufficiency and was an accurate prognostic indicator of progressive deterioration of renal function. However, there was no correlation between prevalence of TID and prevalence and severity of interstitial inflammation, suggesting that the latter is not necessarily secondary to the presence of immune complexes and that other pathogenetic mechanisms may be involved.