Immunosuppression enhances atherogenicity of lipid profile after transplantation.
BACKGROUND
Patients after renal transplantation exhibit high cardiovascular morbidity and mortality because of the accumulation of cardiovascular risk factors such as hypertension or dyslipidemia. To elucidate the influence of immunosuppressive therapy on hyperlipidemia, we studied serum lipids and lipoproteins in renal transplant patients who received prednisone and either azathioprine or cyclosporine or triple immunosuppressive therapy.


METHODS
Serum lipids and lipoprotein levels were measured in 216 renal transplant patients (81 female and 135 male) with stable graft function of 4.8 +/- 2.3 years (range six months to eight years) after transplantation. Patients were divided into three groups according to one of the following immunosuppressive regimens: (a) prednisone and azathioprine, (b) prednisone and cyclosporine, or (c) prednisone, azathioprine, and cyclosporine. Healthy, age- and sex-matched subjects served as controls. In addition to measurement of total serum lipids, lipoproteins were isolated by preparative ultracentrifugation, and lipids were determined in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) density classes.


RESULTS
Total serum triglycerides, VLDL, and LDL triglycerides, as well as VLDL cholesterol were elevated in all renal transplant patients, but elevation was pronounced in female patients. In contrast to total serum cholesterol, which was significantly increased in only female patients, elevation of LDL-triglyceride/apo B ratio was more marked in male patients. Patients in group A exhibited only mild hypertriglyceridemia, whereas triglyceride enrichment in VLDL and LDL was more distinct in group B and was most pronounced in patients of group C. Furthermore, hypertriglyceridemia increased with the dose of administered prednisone.


CONCLUSIONS
Immunosuppressive therapy in renal transplant patients leads to accumulation of triglyceride-enriched VLDL and LDL. Triglyceride enrichment in LDL indicates the accumulation of small, dense LDLs, which are known to bear enhanced atherosclerotic risk. This study provides data that underline the use of individually adjusted immunosuppressive therapy and steroid-sparing protocols in renal transplant patients to improve their atherogenic lipoprotein profile.
Department of Medicine, University of Würzburg, Germany. quaschning@gmx.de
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Quaschning
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Mainka
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Nauck
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Rump
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Wanner
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Krämer-Guth
D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology; D001379:Azathioprine / Q000627:therapeutic use; D015243:Cholesterol, VLDL / Q000097:blood / Q000187:drug effects; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000209:etiology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood / Q000187:drug effects; D008297:Male; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012737:Sex Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D015243:Cholesterol, VLDL; D007166:Immunosuppressive Agents; D008055:Lipids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone