Increased Lipoproteins and Fibrinogen in Chronic Renal Allograft Dysfunction

Abstract

Chronic rejection – also called chronic renal allograft dysfunction (CRAD) – is the main cause of long-term loss of the transplanted kidney, but its pathogenesis is not well known. The aim of this study was to know if lipoproteins, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and platelet aggregation show more abnormalities in renal transplant patients with CRAD than in those with stable renal function. Sixty patients with renal allograft have been studied; 20 patients with CRAD and 40 controls matched for age, gender and time after transplantation. In a univariate analysis patients with CRAD had higher total serum triglycerides (214 ± 153 vs. 133 ± 39 mg/dl; p = 0.04) and very-low-density lipoprotein (VLDL) triglycerides (128 ± 116 vs. 59 ± 29 mg/dl; p = 0.04). Apolipoprotein B levels were also increased in patients with CRAD although this difference was only borderline significant (131 ± 58 vs. 98 ± 16 mg/dl; p = 0.05). Similarly, there was a trend toward increased total, VLDL, and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol in CRAD patients, but these differences did not reach statistical significance. Apolipoprotein A-1 and lipoprotein(a) levels were similar in both groups. Neither platelet aggregation nor PAI-1 levels differed between both groups. In contrast, fibrinogen was increased in patients with CRAD (373 ± 81 vs. 322 ± 62 mg/dl; p = 0.01). In a multivariate analysis triglycerides and fibrinogen were positively correlated to CRAD. These findings add further support to the hypothesis that lipid abnormalities may be involved in the pathophysiology of CRAD. In addition, this is the first report showing that fibrinogen levels are increased in patients with CRAD. Further studies are needed to evaluate a potential role of fibrinogen in the development of CRAD.

Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial

“…None of the lipid parameters measured in this study appeared to be related to the effect of fluvastatin on the incidence of renal end points, which is in contrast with previous reports indicating that lipids are risk factors for renal allograft [18][19][20]30]. The commonly accepted hypothesis that lipoproteins are implicated in the pathogenesis of glomerulosclerosis is supported by the observation that patients with pretransplant hypercholesterolemia have an increased number of acute rejection episodes, worse graft function, and more graft losses during up to three years of follow-up [19].…”

Improved Cardiovascular Risk Profile and Renal Function in Renal Transplant Patients after Randomized Conversion from Cyclosporine to Tacrolimus

“…Also, in a cross-sectional study, high fibrinogen levels have been associated with chronic renal allograft dysfunction (37). With regard to determinants of the fibrinolytic system, a reduction in the level of the plasma uPA level was observed in the tacrolimus group.…”

Living Donation Mitigates Poorer Outcomes in Marginal Recipients

“…Posttransplant elevated lipid profiles are also associated with poor renal allograft outcomes. In addition, post-transplant hypertriglyceridemia [43,44] and fibrinogenemia [44] were independent risk factors for chronic allograft dysfunction. A more recent study showed pretransplant and post-transplant triglyceride, and lipoprotein A levels were both associated with chronic allograft dysfunction [45].…”