title: Soluble CD40 ligand is elevated in type 1 diabetic nephropathy but not predictive of mortality, cardiovascular events or kidney function.
abstract: Soluble CD40 ligand (sCD40L) derived from platelets mediates atherothrombosis, leading to proinflammatory and proatherosclerotic responses. We investigated the predictive value of plasma sCD40L for all-cause mortality, cardiovascular mortality and morbidity, progression towards end-stage renal disease (ESRD) and rate of decline in glomerular filtration rate (GFR) in patients with type 1 diabetes (T1DM) and nephropathy. The study was a prospective, observational follow-up study of 443 T1DM patients with diabetic nephropathy (274 men; age 42.1 ± 10.5 years [mean ± SD], duration of diabetes 28.3 ± 8.9 years, GFR 76 ± 33 ml/min/1.73 m2) and a control group of 421 patients with longstanding type 1 diabetes and persistent normoalbuminuria (232 men; age 45.4 ± 11.5 years, duration of diabetes 27.7 ± 10.1 years) at baseline. sCD40L was measured by ELISA. Plasma sCD40L levels were higher in patients with diabetic nephropathy compared to normoalbuminuric patients (median (range) 1.54 (0.02-13.38) vs. 1.30 (0.04-20.65) µg/L, respectively p = 0.004). The patients were followed for 8.1 (0.0-12.9) years (median (range)). Among normoalbuminuric patients, sCD40L levels did not predict all-cause mortality (p = 0.33) or combined fatal and non-fatal cardiovascular disease (CVD) (p = 0.27). Similarly, among patients with diabetic nephropathy, the covariate adjusted sCD40L levels did not predict all-cause mortality (p = 0.86) or risk of fatal and non-fatal CVD (p = 0.08). Furthermore, high levels of sCD40L did not predict development of ESRD (p = 0.85) nor rate of decline in GFR (p = 0.69). Plasma sCD40L is elevated in T1DM nephropathy but is not a predictor of all-cause mortality, cardiovascular mortality and morbidity or deterioration of kidney function
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. Mlaj@steno.dk
authors.forename: Maria
authors.initials: M
authors.lastname: Lajer
authors.forename: Inge
authors.initials: I
authors.lastname: Tarnow
authors.forename: Alan D
authors.initials: AD
authors.lastname: Michelson
authors.forename: Anders
authors.initials: A
authors.lastname: Jorsal
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Frelinger
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
mesh_terms: D000328:Adult; D023201:CD40 Ligand / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood*; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D023201:CD40 Ligand