IFN-,an immunomodulatory cytokine, has been shown to reduce proteinuria,improve renal function, and prolong survival in a mouse modelof lupus. Satchell and colleagues report that IFN- significantlyreduces proteinuria in three rat models of glomerulonephritis,but this does not seem to be a result of reduced glomerularinflammation. Instead, IFN- decreases albumin flux and increaseselectrical resistance across glomerular endothelial cells andpodocytes. They suggest that IFN- may hold promise for the treatmentof proteinuric renal diseases, in part by tightening the glomerularfiltration barrier. See Satchell et al., pages 2875–2884.
Glycocalyx Contributes to Glomerular Permselectivity
Glycocalyxcoats the luminal surface of all endothelia. Singh and colleaguesconfirm the presence of a 200-nm coat of glycocalyx on conditionallyimmortalized human glomerular endothelial cells. Incubationwith heparanase, which degrades a component of the glycocalyx,increases albumin flux across these cells but does not affecttranscellular passage of water and solute. Therefore, glycocalyxseems to contribute to the selective permeability of the glomerularbasement membrane, and heparanase may contribute to the pathogenesisof proteinuric renal disease by disturbing this barrier. SeeSingh et al., pages 2885–2893.
Renoprotective Stem Cells Secrete IGF-1
Administrationof bone marrow–derived mesenchymal stem cells improvesrenal structure and function in mice with cisplatin-inducedkidney injury. Coculture experiments by Imberti and colleaguesdemonstrate that IGF-1 produced by stem cells protects cisplatin-treatedproximal tubule cells by promoting cellular proliferation andreducing apoptosis. In mice, this renoprotective effect wasremoved when the IGF-1 gene was silenced. Mesenchymal stem cellsmay be used to treat acute kidney injury in the future, andtheir beneficial effect may result, in part, from the releaseof IGF-1 in the damaged microenvironment. See Imberti et al.,pages 2921–2928.
Littleis known about the risk of ESRD among patients infected withthe HIV. Choi and colleagues analyzed data from >2 millionU.S. veterans and report that diabetes and HIV confer similarincreased risks of ESRD among blacks. Among whites, diabeteswas associated with an increased risk of ESRD but HIV was not.In addition, the age- and sex-adjusted incidence of ESRD wasnearly 10 times higher among HIV-infected blacks than HIV-infectedwhites. These findings should encourage new strategies to treatrenal disease among HIV-infected blacks. See Choi et al., pages2968–2974.
Cardiovasculardisease is the most common cause of death among young adultswith chronic kidney disease. Shroff and colleagues report thatchildren with ESRD and levels of PTH more than twice the upperlimit of normal have greater carotid intima-media thickness,stiffer vessels, and increased cardiac calcification comparedwith age-matched controls. A strong dose-dependent correlationexists between vitamin D therapy and all vascular measures.Although causation cannot be claimed from this observationalstudy, uncontrolled secondary hyperparathyroidism and exogenousvitamin D may contribute to vascular damage and calcificationamong children on dialysis. See Shroff et al., pages 2996–3003.
Classicteaching suggests that thin basement membrane nephropathy carriesan excellent prognosis. Voskarides and colleagues diagnosedconcomitant FSGS and thin basement membrane nephropathy in 20renal biopsies from 13 families. In 10 of these families, theauthors identified mutations in the COL4A3/COL4A4 locus. Of82 patients harboring mutations, 38% developed chronic renalfailure, and 20% developed ESRD. Although the identified mutationshave not been shown to cause FSGS directly, it can be concludedthat "benign familial hematuria" is a misnomer for some casesof thin basement membrane nephropathy. See Voskarides et al.,pages 3004–3016.
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’s Antiproteinuric Effect
