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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.
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PMID:Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis. 4 5

Ischemic injury is invoked as a mechanism contributing to end-organ damage and other complications of sickle cell disease (SCD). However, the intrinsic sensitivity of tissues in SCD to ischemic insults has never been addressed. We examined the effect of renal ischemia in a transgenic mouse expressing human sickle hemoglobin. Twenty-four hours after bilateral, total renal artery occlusion for 15 minutes, transgenic sickle mice exhibited worse renal function and more marked histological injury. With bilateral renal ischemia of greater duration (22.5 minutes), and after 6 hours, transgenic sickle mice exhibited massive vascular congestion, sickling of red blood cells, more marked histological injury in the kidney, and more prominent congestion in the capillary beds in the lungs and heart. Additionally, serum amyloid P-component, the murine homologue of C-reactive protein, was markedly increased in transgenic sickle mice as compared to wild-type mice. Twenty-four hours after bilateral renal ischemia for 22.5 minutes, transgenic sickle mice exhibited 28% mortality, with no mortality observed in any other group. With bilateral renal ischemia of short or long duration, renal expression of caspase-3 was most prominent in transgenic sickle mice subjected to ischemia. Thus, renal ischemia in this murine model induces more severe renal injury and extrarenal complications. We conclude that tissues in SCD exhibit heightened vascular congestion and sensitivity to ischemia and that clinically apparent or silent episodes of ischemia may contribute to the complications of SCD.
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PMID:Transgenic sickle mice are markedly sensitive to renal ischemia-reperfusion injury. 1579 78

In human and murine models of sickle cell disease (SCD), heme oxygenase-1 (HO-1) is induced in the kidney, an organ commonly involved in SCD. The present study assessed the role of HO-1 by using a competitive inhibitor of HO activity, tin protoporphyrin (SnPP), in protocols affording a composite, clinically relevant analysis of the kidney in SCD under unstressed and stressed conditions. Whereas short-term administration of SnPP exerted comparable renal hemodynamic effects in wild-type and sickle mice, chronic administration of SnPP exerted divergent effects: SnPP provoked tubulointerstitial inflammation and up-regulation of injury-related genes in wild-type mice, whereas in sickle mice SnPP reduced expression of injury-related genes and vascular congestion without provoking tubulointerstitial inflammation. SnPP also protected against the heightened sensitivity to renal ischemia observed in sickle mice, preventing ischemia-induced worsening of renal injury in sickle mice above that observed in wild-type mice. Effective and comparable inhibition of HO activity by SnPP in wild-type and sickle mice was confirmed. These findings suggest that induction of HO-1, at least as assessed by this approach, may contribute to renal injury in this murine model of SCD and uncover an experimental maneuver that protects the kidney in murine SCD.
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PMID:Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease. 1681 58

Sickle cell disease (SCD) is a major health problem in many countries. Sickle cell nephropathy (SCN) is now a well-characterized entity with specific manifestations, risk factors and prognosis. The presence of sickled erythrocytes in the renal medullary vessels is the hallmark of the disease with a variety of renal complications. Renal manifestations of SCD include renal ischemia, microinfarcts, renal papillary necrosis and renal tubular abnormalities with variable clinical presentations. Proximal tubule dysfunction generally impairs urinary concentration, while more distal tubule dysfunction may impair potassium excretion, leading to hyperkalemia. Glomerular disease with proteinuria may develop due to ischemia and results in a compensatory increase in the renal blood flow and glomerular filtration rate; such hyperfiltration, combined with glomerular hypertrophy, probably contributes to glomerulosclerosis. Acute and chronic kidney disease are the expected outcomes of the disease. Both dialysis and kidney transplantation are effective renal replacement therapies for end-stage renal disease due to SCN, with a higher advantage for transplantation. Whether bone marrow transplantation in the early stage of the disease can halt the progression of SCN is unknown and awaits clinical studies.
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PMID:An update on sickle cell nephropathy. 2462 90