Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients

Abstract

To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low-dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62 +/- 0.35 vs 1.62 +/- 0.23 mmol/l (P less than 0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.44 +/- 0.32 vs 5.84 +/- 0.25 (P less than 0.02). CsA/P patients had higher serum levels of LDL-C (4.79 +/- 0.20 vs 3.43 +/- 0.19 mmol/l (P less than 0.001) and apolipoprotein B concentrations (191 +/- 13 vs 128 +/- 9 mg/dl: P less than 0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73 +/- 0.13 vs 1.52 +/- 0.09 mmol/l: NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P.

Hyperlipidemia in Children: The Role of Uremia, Steroids and Cyclosporine Therapy

“…These findings are also corro borated by earlier studies by Hricik et al [19] in 79 adults, which showed a significant reduction of serum cholesterol after steroid withdrawal. However, our findings are in contrast to those of Schom et al [20] who showed that patients reccivingcyclosporineand prednisone have high er levels of triglycerides, total cholesterol and low-density lipoprotein levels as compared to a group of adult patients receiving azathioprine and prednisone. The limitation of that study [26] is that it did not have a population receiv ing cyclosporine alone and/or in combination with pred- eride removal [23].…”

Cyclosporin A-Induced Hyperlipidemia

“…Immunosuppressive therapy has been reported to increase, decrease or leave HDL levels unaffected [5,10,11,24]. Parallel changes in plasma apoA-I levels are usually observed.…”

“…Plasma LDL levels appear to be consistently elevated by CsA [4,5,6,7,9,10,13,14] even in patients where plasma VLDL levels are not altered [5,6,9,13]. A correlation between CsA levels and plasma LDL-C has been described in some studies [19], but was not observed in others [5,20].…”

“…Studies investigating plasma lipids after CsA monotherapy are limited [4,5,6,7,8,9] and only a few studies have directly compared the combination of CsA therapy with low dose prednisolone with other immune suppressing strategies in combination with low dose steroids [10,11]. In general, these studies indicate that CsA treatment can independently lead to elevated plasma triglyceride and cholesterol levels in humans and that these effects are reversible upon cessation of immunosuppression therapy (Table 1).…”

“…IDL can be further hydrolyzed by lipases to low density lipoprotein (LDL). CsA increases plasma VLDL levels in transplant recipients and a concomitant increase in plasma apoB levels is observed [4,10,11]. It is unclear whether both plasma VLDL1 and VLDL2 levels are elevated.…”