title: Effect of CD40 and sCD40L on renal function and survival in patients with renal artery stenosis.
abstract: Activation of the CD40 receptor on the proximal tubular epithelium of the kidney results in fibrosis and inflammation in experimental models of kidney injury. Soluble CD40 ligand is released by activated platelets. The role of CD40-soluble CD40 ligand in patients with ischemic renal disease is unknown. Plasma levels of CD40 and soluble CD40 ligand were measured by enzyme-linked immunosorbent assay in a single center cohort of 60 patients with renal artery stenosis recruited from Salford Royal Hospital, Manchester, United Kingdom. A natural log transformation of CD40 and soluble CD40 ligand was performed to normalize the data. Estimated glomerular filtration rate was used as the primary indicator of renal function. By univariate analysis, low baseline levels of circulating CD40 (R(2)=0.06; P<0.05) and baseline creatinine (R(2)=0.08; P=0.022) were associated with loss of kidney function at 1-year follow-up, whereas soluble CD40 ligand was not (R(2)=0.02; P=ns). In a multiple linear regression model, CD40 (P<0.02) and baseline creatinine (P<0.01) continued to be significantly associated with a decline in renal function (model R(2)=0.17; P<0.005). Baseline CD40 levels were somewhat lower in patients who died during follow-up (survivors, 7.3±0.9 pg/mL, n=48 versus nonsurvivors, 6.7±1.0 pg/mL, n=12; P=0.06). The CD40/soluble CD40 ligand signaling cascade may be a novel mechanism contributing to the development and progression of renal injury in patients with atherosclerotic renal artery stenosis.
authors: Department of Medicine, University of Toledo, 3000 Arlington Ave, MS 1036, Toledo, OH 43614, USA. steven.haller@utoledo.edu
authors: Steven T
authors: ST
authors: Haller
authors: Philip A
authors: PA
authors: Kalra
authors: James P
authors: JP
authors: Ritchie
authors: Tina
authors: T
authors: Chrysochou
authors: Pamela
authors: P
authors: Brewster
authors: Wencan
authors: W
authors: He
authors: Haifeng
authors: H
authors: Yu
authors: Joseph I
authors: JI
authors: Shapiro
authors: Christopher J
authors: CJ
authors: Cooper
mesh_terms: D000368:Aged; D019013:CD40 Antigens / Q000097:blood*; D023201:CD40 Ligand / Q000097:blood*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D012078:Renal Artery Obstruction / Q000097:blood / Q000401:mortality* / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand
references: Am J Physiol Renal Physiol. 2009 Feb;296(2):F438-45
references: 18667484
references: Transplantation. 2008 Jan 15;85(1):125-34
references: 18192922
references: Clin J Am Soc Nephrol. 2011 Sep;6(9):2185-91
references: 21817131
references: Nephrol Dial Transplant. 2000 May;15(5):631-6
references: 10809803
references: N Engl J Med. 2003 Mar 20;348(12):1104-11
references: 12646667
references: Hypertension. 1990 Mar;15(3):318-26
references: 2406201
references: Kidney Int Suppl. 2008 Dec;(111):S60-3
references: 19034329
references: Am J Cardiol. 1968 Jan;21(1):60-71
references: 5634745
references: Kidney Int. 1998 Jul;54(1):2-13
references: 9648058
references: J Hypertens. 1997 Dec;15(12 Pt 2):1791-6
references: 9488241
references: Nephron Exp Nephrol. 2007;107(1):e22-9
references: 17671397
references: Circulation. 1998 Dec 22-29;98(25):2866-72
references: 9860789
references: Semin Nephrol. 1996 Jan;16(1):21-32
references: 8720083
references: Circulation. 2001 Nov 6;104(19):2266-8
references: 11696462
references: J Leukoc Biol. 2000 Jan;67(1):2-17
references: 10647992
references: J Am Soc Nephrol. 2007 Apr;18(4):1323-30
references: 17314326
references: J Vasc Surg. 1991 Sep;14(3):327-31
references: 1880841
references: Kidney Int. 2003 Oct;64(4):1265-72
references: 12969144
references: Kidney Int. 2000 Nov;58(5):1841-50
references: 11044203
references: N Engl J Med. 1983 Feb 17;308(7):373-6
references: 6337327
references: Circulation. 2008 May 27;117(21):2752-60
references: 18490527
references: Radiology. 1968 Nov;91(5):881-7
references: 5681323
references: N Engl J Med. 2006 Jun 8;354(23):2473-83
references: 16760447
references: Immunology. 2003 Sep;110(1):131-40
references: 12941150
references: Clin J Am Soc Nephrol. 2006 Mar;1(2):172-81
references: 17699206
references: Hypertension. 1994 Mar;23(3):346-50
references: 8125561
references: Kidney Int. 1999 Apr;55(4):1543-52
references: 10201021
references: Lab Invest. 1990 Dec;63(6):770-9
references: 2255186
references: Prog Cardiovasc Dis. 2009 Nov-Dec;52(3):196-203
references: 19917330
references: J Am Coll Cardiol. 2009 Aug 18;54(8):669-77
references: 19679244
references: Platelets. 2010;21(7):525-32
references: 20701458
references: JAMA. 2002 Nov 20;288(19):2421-31
references: 12435255
references: Nephrol Dial Transplant. 2010 Mar;25(3):717-30
references: 19889873
references: J Am Soc Nephrol. 2006 Mar;17(3):627-36
references: 16452499
references: Nephrology (Carlton). 2008 Dec;13(8):677-83
references: 19019166
references: J Thromb Haemost. 2010 May;8(5):914-22
references: 20180823
references: Bull Acad Natl Med. 1999;183(1):33-45; discussion 45-6
references: 10371763
references: Clin Biochem. 2010 Dec;43(18):1393-8
references: 20846521
references: Nephrol Dial Transplant. 2007 Apr;22(4):1002-6
references: 17210599
references: Lancet. 1974 Apr;1(7859):653-6
references: 4132316
references: Am J Physiol Renal Physiol. 2006 Jun;290(6):F1408-15
references: 16434573
references: J Atheroscler Thromb. 2010 Jul 30;17(7):705-11
references: 20065610