Hypertension, creatinine, and plasma renin activity in heart transplant recipients.

Development of de novo hypertension in a large proportion of orthotopic heart transplant recipients receiving cyclosporine has previously been reported. This hypertension is characterized by a persistence of increased peripheral resistance, sodium retention, and loss of nocturnal decline in BP. Vascular nephropathy with plasma renin activity (PRA) elevation from cyclosporine (CsA) may also be major factor in the progress of hypertension. To investigate this hypothesis, observations of BP, creatinine (Cr), and PRA were made in 144 heart transplant recipients followed for up to four and a half years. Median Cr was 133 mumol/l. Average diastolic BP and mean PRA values were significantly higher in patients with Cr greater than or equal to the median. Cr and PRA were significantly correlated (r = 0.4; P less than 0.001) in recipients with Cr greater than or equal to 133 mumols/l but not in those with Cr less than 133 mumols/l. In a selected subsample of heart transplant recipients with repeated Cr and PRA values, Cr and PRA appeared to increase longitudinally after transplant. These data are derived from a case series of patients managed on a variety of antihypertensive agents (excluding ACE inhibitors) needed to control the persistent hypertension.

Hypertension following orthotopic cardiac transplantation.

It seems established that hypertension, to some degree, is a frequent consequence of cardiac transplantation. The hypertension occurs de novo and is not related to whether hypertension was present in association with the heart disease that led to the need for transplantation. The etiology of this hypertension is multifactorial and varies depending on the time that has ensued after transplantation. Acutely, it is primarily a problem related to intravascular volume expansion and persistently increased systemic vascular resistance. Although it may be modest in severity, it seems to be particularly resistant to therapy with most antihypertensive drugs. Moreover, the total "hyperbaric impact" of the hypertension is rendered greater because the blood pressure and heart rate in these patients with denervated hearts fails to show the usual 10 to 15 percent fall when recumbent/asleep at night, which occurs in normotensive individuals and in most with hypertension of other etiologies. The major factor in the persistence of the hypertension through the later stages post-transplantation appears to be the cyclosporine that is used as an immunosuppressive. Although cyclosporine has been the major contributor to reduced rejection in these individuals, and to their increasingly prolonged survival, it inevitably produces slowly progressive impairment of renal function. The damage to the kidney is reflected both in tubular as well as glomerular and vascular damage, with a steady fall in glomerular filtration and a rise in creatinine. From our studies it appears that the renal alterations are associated with a gradual rise in plasma renin activity and angiotensin II, which perhaps further damages the kidney and causes persistence of the increased systemic vascular resistance. The use of lower doses of cyclosporine during the ischemic phase in the kidney that immediately follows surgery and of reduced doses over time, often with azathioprine added, seems to minimize the renal damage, or at least to stabilize it and to slow progression of the renal dysfunction and hypertension. Treatment of the hypertension with conventional drugs has definite but limited value. Diuretics and vasodilators have been the mainstay of our approach during the early phases of the hypertension but our recent data indicate that ACE inhibitors may become relatively specific in management during the later phases of the post-transplantation period as PRA levels rise in response to vascular damage by cyclosporine. ACE inhibitors have inherent dangers that require careful monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)