Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary defects in either podocytes or the glomerular basement membrane (GBM) cause proteinuria, a fact that complicates defining the barrier to albumin. Laminin beta2 (LAMB2) is a GBM component required for proper functioning of the glomerular filtration barrier. To investigate the GBM's role in glomerular filtration, we characterized GBM and overlying podocyte architecture in relation to development and progression of proteinuria in Lamb2-/- mice, which model Pierson syndrome, a rare congenital nephrotic syndrome. We found ectopic deposition of several laminins and mislocalization of anionic sites in the GBM, which together suggest that the Lamb2-/- GBM is severely disorganized, although it is ultrastructurally intact. Importantly, albuminuria was detectable shortly after birth and preceded podocyte foot process effacement and loss of slit diaphragms by at least 7 days. Expression and localization of slit diaphragm and foot process-associated proteins appeared normal at early stages. GBM permeability to the electron-dense tracer ferritin was dramatically elevated in Lamb2-/- mice, even before widespread foot process effacement. Increased ferritin permeability was not observed in nephrotic CD2-associated protein-null (Cd2ap-/-) mice, which have a primary podocyte defect. Together these data show that the GBM serves as a barrier to protein in vivo and that the glomerular slit diaphragm alone is not sufficient to prevent the passage of albumin into the urinary space.
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PMID:Proteinuria precedes podocyte abnormalities inLamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier. 1688 57

In conclusion, the most important priority is to shift thinking to ESA dose exposure and away from focusing on the target Hb level. More attention needs to be spent on developing strategies to minimize exposure to high doses of ESAs. Possible strategies might include the subcutaneous administration of ESAs, treating a patient with an elevated ferritin, identifying sources of blood losses, treating infections and/or an inflammatory focus, and the use of computerized protocols. An equally important goal should be to change the CMS QIP anemia measure to a target Hb >9 g/dL. This modification in the QIP anemia measure is supported by the evidence from both the Normal Hematocrit trials and TREAT. If one models the effect of this QIP on the dialysis patient population as a whole, the majority of achieved Hb concentrations will likely be <11 g/dL (similar to the reported findings in the Normal Hematocrit study--see Figure 1). Lastly, translational studies and clinical trials are necessary to test whether exposure to high doses of ESAs explains the higher risk observed in CHOIR, TREAT, and the Normal Hematocrit study.
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PMID:Should we keep hemoglobin levels as a viable outcome measure? 2036 93

We have examined trends in hemodialysis practice from August 2010 to August 2011, a time frame spanning the implementation of the bundled PPS, a major ESA label change by the FDA, and announcements from CMS on the proposed and final rules for the first year of the Quality Incentive Program (QIP) plus the proposed rules for the second and third years of the QIP. Although many hemodialysis practices have remained stable during this 1-year time period, substantial changes have been seen. These include a decline in epoetin dose and hemoglobin levels, an increase in IV iron use and serum ferritin levels, and an increase in PTH levels. The rates of decline in hemoglobin and epoetin dosing levels were greatest in the 2 months after the ESA label change in June 2011. Trends in anemia care in ensuing months, with more follow-up time after the label change, will be of great interest. In view of declining hemoglobin levels, a mechanism for comprehensive monitoring of transfusion rates is warranted to understand this important aspect of care for hemodialysis patients. Regarding clinical outcomes, no trend in all-cause mortality has been evident during this 1-year time period. Additional follow-up is warranted to understand if findings reported here persist over time, and require confirmation with national data as these become available. Trends in clinical care may not necessarily affect patient outcomes, and careful evaluation is required to understand effects on patient outcomes.
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PMID:The DOPPS Practice Monitor for US dialysis care: trends through August 2011. 2256 Jul 43

The FDA first licensed erythropoiesis stimulating agents (ESA) for use in patients with ESRD in 1989. Hemoglobin targets for treatment with ESAs were established at the outset on the basis of descriptive pre-ESA literature and Phase I-III data in patients with ESRD. Postrelease literature in ESA-treated patients accumulating over time initially supported improvement in indices of both cardiovascular and other organ function as well as quality of life with therapy. Recommended treatment targets for hemoglobin would evolve further in the United States from four iterations of evidence- and opinion-based practice guidelines appearing between 1997 and 2007. Several randomized, controlled trials published from 1998 to 2009 examined normalization and near-normalization of hemoglobin in patients with both ESRD and CKD; they raised fundamental questions as to the safety of robust correction of anemia. These findings, taken together with subsequent actions of the FDA in ESA labeling and CMS's quality expectations for hemoglobin in payment for dialysis treatments, would result in a comprehensive reassessment of the hemoglobin targets in ESA therapy. A marked decrease in both national ESA utilization and hemoglobin attainment has ensued as a result. This discussion addresses the history of the striking changes in enthusiasm for hemoglobin-targeted anemia therapy from 1989 to the present, and similarly examines the evolution of ferritin-targeted iron administration, which has followed different-and markedly slower-historical development.
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PMID:Target-based Anemia Management with Erythropoiesis Stimulating Agents (Risks and Benefits Relearned) and Iron (Still More to Learn). 2808 17