Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients with Ig deposition disease presented with acute renal failure, moderate proteinuria, and hematuria. A plasmacytoid lymphocytic infiltrate was identified in bone marrow that produced IgG4 lambda and free lambda light chains. One patient developed an anaplastic plasmacytoma (secreting only lambda light chains) 1 yr after renal biopsy. Renal biopsy in both patients demonstrated a nodular intercapillary glomerulopathy and electron dense granular deposits, associated with a linear pattern of IgG4 heavy chain deposition in vascular, tubular, and glomerular basement membranes (VBM, TBM, and GBM). In one patient this entrapped IgG4 was unassociated with detectable kappa or lambda light chains. In the second patient, lambda light chains (1+) were detected only in the GBM, but IgG4 (4+) was identified in GBM/TBM. Neither circulating (peripheral blood and bone marrow serum) nor cellular free gamma chains were present. We propose the term "pseudo-gamma heavy chain deposition disease" for the process.
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PMID:Pseudo-gamma heavy chain (IgG4 lambda) deposition disease. 157 96

Anatomical and immunological studies were performed in two brothers with membranous glomerulonephritis. The older child presented with renal failure, Fanconi syndrome and anti-TBM antibody in his plasma. Renal biopsy revealed severe tubulo-interstitial disease with membranous glomerulonephritis. Because of rapidly progressive renal insufficiency the patient was started on hemodialysis. A cadaver renal allotransplantation was performed without success. Renal transplant biopsy showed severe lesions of vascular rejection without recurrence of the primary disease. The younger child was examined at six months for a nephrotic syndrome with mild renal insufficiency, and died at nine months. Anti TBM antibodies were not detected in his serum. The patient's mother presented with asymptomatic proteinuria, and anti TBM antibodies in her plasma. In the same family the uncle died at 3 months with a steroid resistant nephrotic syndrome. The relationships between the familial membranous glomerulonephritis and the tubulo interstitial disease are discussed.
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PMID:[Membranous glomerulonephritis in two brothers associated in one with tubulo-interstitial disease, Fanconi syndrome and anti-TBM antibodies (author's transl)]. 704 46

Exposure to mercuric chloride induces the development of a membranous glomerulopathy with high proteinuria in DZB rats, in which immunoglobulin (Ig)G1 and IgG2a bound in the glomeruli were previously found to react with laminin of the EHS tumor and several unidentified glomerular basement membrane components. Monoclonal antibodies were prepared by fusing cervical and mandibular lymph node cells from a HgCl2-treated DZB rat with a nonsecreting mouse myeloma. Monoclonal antibodies were screened for reactivity with collagenase-digested glomerular basement membrane and kidney sections; upon subcloning, eight stable hybridomas were obtained, named MEC1 to MEC8. MEC2 (IgG1, kappa), MEC3 (IgM, kappa), and MEC5 (IgG1, kappa), as well as the polyclonal glomerular eluate, reacted preferentially with the P1 fragment of the laminin-1 (alpha 1 beta 1 gamma 1) isoform. MEC8 (IgM, kappa) reacted with the P1 and the E4 fragment of laminin. Both MEC6 (IgM, kappa) and MEC8 bound to actin and to various other, unidentified cellular antigens, indicating that MEC6 and MEC8 are polyreactive antibodies. MEC7 (IgM, kappa) bound to a cytoskeleton-linked cell membrane antigen, present on various epithelial cells and between heart muscle fibers and associated with small peripheral, intramuscular nerves. Several of the MEC monoclonal antibodies bound in vivo along the glomerular capillary wall. Although discrete electron-dense subepithelial immune aggregates were not detected and proteinuria was not induced, MEC3 localization changed from a continuous pattern into a fine granular pattern along the glomerular basement membrane, and focally along the TBM, upon passive transfer into naive DZB rats. These findings suggest a pathogenetic role for the P1 fragment of laminin either in the induction phase of HgCl2-induced membranous glomerulopathy as an immunogen or in the effector phase as a target antigen.
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PMID:Autoantibodies to the laminin P1 fragment in HgCl2-induced membranous glomerulopathy. 777 85

According to its immunopharmacological profile, 15-deoxyspergualin (15-DOS) has been investigated as to its disease-modifying activity on HgCl2-induced glomerulonephritis (GN) and on tubulointerstitial nephritis (TIN) in Brown-Norway rats. Both models are induced autoimmune disorders in which afflicted animals display high levels of serum autoantibodies directed against the glomerular or tubular basement membrane (GBM or TBM), respectively. The diseases are manifested by high serum creatinine and urea levels with severe proteinuria. In the model of HgCl2-GN, administration of 15-DOS clearly led to a reduction of proteinuria and decreased the amount of rat IgG attached to the GBM. Furthermore, a therapeutic effect could be demonstrated when 15-DOS was given after the appearance of clinical symptoms. Not only urine-protein values but also anti-laminin antibodies returned to normal levels. Also in the experimental TIN-model, 15-DOS, either given during the induction phase, or even late in the onset of the disease, strongly prevented the proteinuria of this autoimmune disease and inhibited the formation of autoantibodies to TBN.
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PMID:Immunosuppressive therapy of organ-specific nephritic autoimmune diseases with 15-deoxyspergualin. 827 49

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pathogenic role in experimental crescentic glomerulonephritis (GN). Renal expression of MIF is also upregulated in human GN and correlates with leukocytic infiltration, histologic damage, and renal dysfunction. The study presented here examined whether MIF can be measured in urine and if so, whether the urine MIF concentration reflects the degree of renal injury. Urine and serum MIF was measured by enzyme-linked immunosorbent assay in 10 normal healthy volunteers and in a cohort of 63 patients with GN (2 thin basement membrane disease [TBM], 15 membranous GN, 10 focal segmental glomerular sclerosis, 20 IgA glomerularnephritis, 11 crescentic GN, 10 systemic lupus erythematosis World Health Organization class IV). Renal MIF expression was assessed by immunostaining of biopsy tissue. MIF was detected in urine from normal volunteers (mean +/- SD; 191 +/- 132 pg MIF/micromol creatinine). The urine MIF concentration was unchanged in patients with nonproliferative nephropathies (343 +/- 397 pg MIF/micromol Cr) but was increased 3.4-fold in proliferative nephropathies (645 +/- 527 pg MIF/micromol Cr; P < 0.05 versus normal and nonproliferative). Stratified analysis showed the greatest increase in urine MIF in crescentic GN (4.5-fold). In contrast, serum MIF levels were not different between normal patients and any patient group. Immunostaining demonstrated a significant increase in renal MIF expression in proliferative glomerulonephritides that was associated with macrophage and T cell infiltration. There was a significant correlation between the urine MIF concentration and renal MIF expression, but not with serum MIF, indicating a renal origin for the excreted urine MIF. The urine MIF concentration also correlated with the degree of renal dysfunction, histologic damage, and leukocytic infiltration, but not with the amount of proteinuria. In conclusion, this study shows that the urine MIF concentration is significantly increased in proliferative forms of GN and correlates with the degree of renal injury. Urine MIF levels reflect MIF expression within the kidney and may be a useful noninvasive tool for monitoring patients with crescentic GN, particularly in disease exacerbation.
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PMID:Urine macrophage migration inhibitory factor reflects the severity of renal injury in human glomerulonephritis. 1179 56