The Diamant Alpin Dialysis cohort study: clinico-biological characteristics and cardiovascular genetic risk profile of incident patients.
BACKGROUND
Clinical and therapeutic characteristics of chronic dialysis patients vary widely at national and/or regional levels. Their increased cardiovascular (CV) mortality is not explained by traditional cardiovascular disease (CVD) risk factors only. Therefore, this study aimed to investigate and compare the characteristics of patients starting dialysis in a homogeneous Alpin region and possibly to identify new biological parameters (phenotypes or genotypes), which eould be responsible for the increased CVD seen in end-stage renal disease (ESRD) patients.


METHODS
A cohort of 279 non-selected consecutive patients entering a dialysis program was prospectively investigated in eight centers of three adjacent regions in France, Italy and Switzerland. In addition to the usual demographic, clinical and biological data, we analyzed at study entry the blood levels of homocysteine, lipoprotein(a) (Lp(a)) and antioxidized low density lipoprotein (LDL) antibodies, vitamin B12 status, Lp(a) and haptoglobin phenotypes, methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), allele epsilon E4 of apolipoprotein (ApoE4) and plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism.


RESULTS
At entry, 90.3% of patients were hypertensive, 30% had type 2 diabetes mellitus and 17.6% were current smokers; 42% of patients had already experienced at least one CV event: peripheral artery disease (26% of the cohort), coronary artery disease (22%) or ischemic cerebro-vascular disease (16%). Forty-two patients had had > or =2 CV events or documented atherosclerotic localizations. Anemia was not optimally treated: mean hemoglobin (Hb) was at 97.7 g/L and, while overall 62% of patients received erythropoietin (EPO) prior to dialysis, large national differences were observed. Compared to the reference population, ESRD patients exhibited increased homocysteinemia, Lp(a) levels and ApoE4 allele prevalence. Conversely, the distribution of Lp(a) phenotype, MTHFR TT, ACE DD and PAI-1 4G/4G was equivalent to that of the reference population. In addition, none of the analyzed phenotypical or genotypical parameters, except for the haptoglobin 2.2 phenotype, could be associated with the existence of a previous adverse CV event.


CONCLUSIONS
(1) The clinical characteristics of the ESRD patients entering dialysis in our region were comparable to the currently observed dialysis populations in most European countries with the deleterious role of advancing age, diabetes, previous CVD, smoking and hypertension evident (2). Except for anemia therapy, there were no regional or national differences observed at dialysis start. (3) An analysis of the phenotypic and genotypic CV risk factors demonstrated differences with the reference population only for hyperhomocysteinemia, Lp(a) and ApoE4 allele prevalence, with no notable differences among the participating centers.
Pernod
Gilles
G
CHU Grenoble, France.
Bosson
Jean-Luc
JL
Golshayan
Dela
D
Barro
Claire
C
Alloatti
Sandro
S
Turc-Baron
Cécile
C
Quarello
Francesco
F
Jeantet
Alberto
A
Von Albertini
Beat
B
Forêt
Michel
M
Lauren
Guy
G
Cordonnier
Daniel
D
Piccoli
Giuseppe
G
Wauters
Jean-Pierre
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011110:Polymorphism, Genetic; D006435:Renal Dialysis / Q000009:adverse effects*; D012307:Risk Factors
D006242:Haptoglobins; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D007703:Peptidyl-Dipeptidase A