Dysregulation of Laminins Plays a Role in Alport Disease
In Alportdisease, the glomerular basement membranes contain aberrantlaminins in addition to the abnormal collagenous network thatresults from mutations in the genes encoding the 3, 4, or 5chains of type IV collagen. In a mouse model of Alport disease,Abrahamson and colleagues report a significant increase in glomerularlaminin 5 that is the result of increased Lama5 gene transcription.They found that Alport glomerular basement membranes are abnormallypermeable both in thickened areas beneath effaced podocyte footprocesses as well as in otherwise normal-appearing areas. Thealtered synthesis and distribution of laminins, which may occuras a compensatory response to the disordered collagenous network,likely contribute to this dysfunction of Alport glomerular basementmembranes. See Abrahamson et al., pages 2465–2472.
Bone Marrow-Derived Stromal Cells Secrete Renoprotective Factors
Recentevidence suggests that adult bone marrow cells may be able toprotect organs from injury. Bi and colleagues found that administeringbone marrow stromal cells to mice reduces the severity of cisplatin-inducednephrotoxicity, enhances tubular cell proliferation, and reducestubular cell apoptosis. Furthermore, they observed that intraperitonealinjection of conditioned medium from cultured stromal cellsalso improves survival and reduces renal injury in this model.This suggests that marrow stromal cells secrete protective factorsthat function in an endocrine manner, providing hope for noveltherapies to treat acute kidney injury. See Bi et al., pages2486–2496.
Podocin Tethers Tight Junction Proteins to the Cytoskeleton in Nephrotic Podocytes
In nephroticsyndrome, slit diaphragms are lost and tight junctions are createdbetween effaced podocyte foot processes. Shono and colleaguesreport that podocin, a structural protein of the slit diaphragm,is recruited to newly formed tight junctions where it formsa multiprotein complex with coxsackievirus and adenovirus receptor(CAR) and zonula occludens 1 (ZO-1). Podocin facilitates thecoalescence of lipid rafts containing CAR and tethers this proteincomplex to a reorganized actin cytoskeleton. Therefore, podocinnot only serves as a structural protein in the slit diaphragmsof normal podocytes, but it also seems to secure the tight junctionsto the cytoskeleton in nephrotic foot processes. See Shono etal., pages 2525–2533.
Medicareis considering an expansion of the bundle of dialysis-relatedservices that are prospectively paid for. Hirth and colleaguesdeveloped models to explore whether case-mix adjustment couldincorporate interindividual variation in required services intothis potential payment scheme. Even after considering a broadset of patient characteristics, much of the variation in MedicareAllowable Charges per dialysis session remains unexplained.The authors note that significant gains or losses to individualproviders would occur, even though the systematic gains or losseswould be modest when compared across different classes of dialysisproviders. See Hirth et al., pages 2565–2574.
Veterans Transplanted Less Than the Privately Insured
Patientswho wish to receive a kidney transplant through the Departmentof Veteran Affairs must complete a centralized assessment todetermine eligibility and must receive their transplant at oneof four VA transplant centers nationwide. Gill and colleaguesfound that veterans without supplemental private insurance areapproximately 35% less likely to receive transplants than individualswith private insurance. Although most of this difference canbe attributed to the fact that veterans have a lower chanceof being placed on the wait-list, this does not fully explainthe disparity. See Gill et al., pages 2592–2599.
FGF23 Predicts Progression
Calcium-phosphatemetabolism is abnormal in patients with chronic kidney disease,and it is unknown whether this accelerates the decline of renalfunction. Fibroblast growth factor 23 (FGF23) is a recentlyidentified phosphaturic hormone that plays a role in phosphatehomeostasis. Fliser and colleagues prospectively followed 177nondiabetic patients with chronic kidney disease and found thatserum levels of FGF23 predict progression of renal disease.In fact, apart from glomerular filtration rate at baseline,FGF23 was the only independent predictor of progression amongseveral measures of calcium-phosphate metabolism. In the future,FGF23 levels may help guide therapy aimed at correcting derangementsin calcium-phosphate metabolism, and such therapy may modifythe progression of chronic kidney disease. See Fliser et al.,pages 2600–2608.
Related Articles
Fibroblast Growth Factor 23 (FGF23) Predicts Progression of Chronic Kidney Disease: The Mild to Moderate Kidney Disease (MMKD) Study
Danilo Fliser, Barbara Kollerits, Ulrich Neyer, Donna P. Ankerst, Karl Lhotta, Arno Lingenhel, Eberhard Ritz, Florian Kronenberg for the MMKD Study Group
J. Am. Soc. Nephrol. 2007 18: 2600-2608.
[Abstract][Full Text][PDF]
Case-Mix Adjustment for an Expanded Renal Prospective Payment System
Richard A. Hirth, Marc N. Turenne, John R.C. Wheeler, Alyssa S. Pozniak, Philip Tedeschi, Chien-Chia Chuang, Qing Pan, Kathryn Slish, and Joseph M. Messana
J. Am. Soc. Nephrol. 2007 18: 2565-2574.
[Abstract][Full Text][PDF]
Podocin Participates in the Assembly of Tight Junctions between Foot Processes in Nephrotic Podocytes
Akemi Shono, Hiroyasu Tsukaguchi, Eishin Yaoita, Masaaki Nameta, Hidetake Kurihara, Xiao-Song Qin, Tadashi Yamamoto, and Toshio Doi
J. Am. Soc. Nephrol. 2007 18: 2525-2533.
[Abstract][Full Text][PDF]
Access to Kidney Transplantation among Patients Insured by the United States Department of Veterans Affairs
John S. Gill, Syed Hussain, Caren Rose, Sundaram Hariharan, and Marcello Tonelli
J. Am. Soc. Nephrol. 2007 18: 2592-2599.
[Abstract][Full Text][PDF]
Stromal Cells Protect against Acute Tubular Injury via an Endocrine Effect
Baoyuan Bi, Roland Schmitt, Malika Israilova, Hitoshi Nishio, and Lloyd G. Cantley
J. Am. Soc. Nephrol. 2007 18: 2486-2496.
[Full Text][PDF]
Laminin Compensation in Collagen 3(IV) Knockout (Alport) Glomeruli Contributes to Permeability Defects
Dale R. Abrahamson, Kathryn Isom, Eileen Roach, Larysa Stroganova, Adrian Zelenchuk, Jeffrey H. Miner, and Patricia L. St. John
J. Am. Soc. Nephrol. 2007 18: 2465-2472.
[Abstract][Full Text][PDF]
This article has been cited by other articles:
P. Gonzales, T. Pisitkun, and M. A. Knepper Urinary exosomes: is there a future?
Nephrol. Dial. Transplant.,
June 1, 2008;
23(6):
1799 - 1801.
[Full Text][PDF]
Top
BASIC RESEARCH
CLINICAL EPIDEMIOLOGY
3, 
