Late hypertension after liver transplantation: A comparison of cyclosporine and tacrolimus (FK 506)

Abstract

Hypertension frequently develops early after liver transplantation when cyclosporine-based immunosuppression is used. However, initial experience with tacrolimus has suggested that its use leads to a lower early incidence of hypertension. In this study, the blood pressure status of patients treated with cyclosporine (n ‫؍‬ 131) and those treated with tacrolimus (n ‫؍‬ 28) was compared 24 months after liver transplantation. At this time interval, the prevalence of hypertension in the cyclosporine and tacrolimus groups were 82% and 64%, respectively (P F .05). For those patients who were hypertensive by 24 months, onset was delayed in the tacrolimus group compared with the cyclosporine group: 40% versus 71% and 73% versus 93% at 1 and 12 months, respectively (P F .05). Within the cyclosporine group, patients with hypertension were heavier than those with normal blood pressure, 84.7 ؎ 1.8 versus 73.4 ؎ 4.0 kg, respectively (P F .05). Within the tacrolimus group, hypertensive patients had lower glomerular filtration rates and higher renal vascular resistances compared with normotensive patients, 74 ؎ 12 versus 47 ؎ 6 mL/min and 15,711 ؎ 2,445 versus 28,830 ؎ 4,310 dyne/s/cm 5 / m 2 , respectively (P F .05). There were no withingroup differences for age, gender, pretransplant history of hypertension, family history of hypertension, graft function, or daily doses of prednisone, cyclosporine, or tacrolimus. These results indicate that, compared with cyclosporine, the onset of hypertension after liver transplantation is delayed and less prevalent with tacrolimus. Additionally, hypertension is associated with increased body weight in cyclosporine-treated patients and with more severe renal dysfunction in patients receiving tacrolimus. The relationships of these findings to the development of posttransplant hypertension requires further study. Copyright 1998 by the American Association for the Study of Liver DiseasesH ypertension frequently occurs early after liver transplantation when immunosuppression with cyclosporine plus prednisone is used, amounting to a prevalence of 75% to 85% by 24 months. 1-3 Several reports have suggested that the incidence of hypertension in patients treated with tacrolimus (also called FK 506) is lower than that in patients treated with cyclosporine within the first year or two after kidney transplantation, 4-6 up to 3 years after heart transplantation, 7-9 and during the first year after liver transplantation. [10][11][12] We have observed, however, that the prevalence of hypertension in tacrolimus-treated patients increases in the second year after liver transplantation and may approach that observed in patients treated with cyclosporine. 3 We examined the development of hypertension in patients treated with cyclosporine or tacrolimus and followed up for 24 months after liver transplantation. The goals of this study were to assess the prevalence of hypertension in these two patient groups and to compare clinical and laboratory characteristics that might be associated with the development of...

Effects of Immunosuppressive Drugs on Platelet Aggregation and Soluble P-Selectin Levels in Renal Transplant Patients

“…[1] Studies including liver transplant recipients revealed that cyclosporine immunosuppression is associated with a higher likelihood of post-transplant weight gain compared with tacrolimus. [13] Our data reporting an increase of serum triglyceride and LDL cholesterol levels and a decrease of serum HDL levels in cyclosporinetreated patients support post-transplant dyslipidemia. We agree that conventional coronary risk factors in the posttransplant setting should be identified and managed aggressively to decrease the cardiovascular morbidity and mortality in this high-risk population.…”

Long-term management of the liver transplant patient: Diabetes, hyperlipidemia, and obesity

“…15 Similar variability has been described for such indicators of morbidity as infection, rejection, renal impairment, graft survival, and length of hospital stay. Even in studies in which there were no differences in mortality, diabetics more often experienced bacterial, 13,40 viral, 13 and fungal 13,40 infection, renal impairment, 40 and episodes of rejection 17 and steroid-resistant rejection 19 than nondiabetics. Among the other possible adverse effects of diabetes in transplantation has been the suggestion of an increased frequency or rapid progression of diabetic nephropathy in type 1 insulindependent diabetic recipients.…”

“…The other immunosuppressives (azathioprine, mycophenolate mofetil, and sirolimus) are not diabetogenic. The diabetogenic potential of tacrolimus appears to be greater than that of cyclosporine in renal transplant patients, 30 whereas they appear equal in liver transplant recipients, 19,31,32 even though a change from tacrolimus to cyclosporine can completely reverse tacrolimus-induced diabetes in the occasional patient. 33 …”

“…16 In other studies, there was no discernible increase in diabetes prevalence over baseline. 18,19 When de novo posttransplant insulin-dependent diabetes is strictly defined as diabetes presenting beyond the first postoperative month but within 30 days of discharge, the prevalence is 5.2%, but a need for long-term insulin therapy does not necessarily ensue. 20 In fact, when patients who develop de novo posttransplant diabetes are followed for 3 years, the prevalence of insulin use falls progressively from 26% at 1 year, to 9% at 2 years, and to 1% at 3 years.…”

“…42,49 Tacrolimus appears less likely to cause hypercholesterolemia than does cyclosporine. 19,44,47,48 Indeed, conversion of patients from cyclosporine-based to tacrolimus-based therapy improves hyperlipidemia safely and dramatically. 51,51a Pretransplant risk factors predictive of posttransplant hypercholesterolemia include female gender, cholestatic liver disease, and the pretransplant cholesterol level.…”