Chronic viral hepatitis in renal transplant recipients with allografts functioning for more than 20 years.

BACKGROUND: The impact of infection with hepatotropic viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]) on morbidity and mortality, and allograft function in renal transplant recipients with allografts functioning for >20 years is not known. METHODS AND RESULTS: Seventy-nine of 511 renal transplants performed at the Cleveland Clinic Foundation from January 1963 to January 1978 are known to have functioned for at least 20 years (level 5A). Fifty-four of these patients had hepatitis testing updated after their 19th year of transplantation. Fifteen patients had evidence of ongoing viral infection: persistent hepatitis B surface antigen in three (6%), HCV antibody (enzyme-linked immunosorbent assay II supplemented by recombinant immunoblot assay) in 11 (20%), and both viruses in one (2%). Of the 10 surviving patients, 8 were tested further for viral replication. HCV RNA (polymerase chain reaction; Amplicore) was positive in 6/7 (86%), and HBV DNA (hybridization) was positive in 1/2 (50%). An elevated alanine aminotransferase (>35 U/L) was present in all hepatitis patients, alpha-fetoprotein >10 ng/ml in 2/8 (25%), and cryoglobulins >50 microg/ml in 3/6 (50%) infected with HCV. No hepatocellular carcinoma was detected by hepatic ultrasound. In patients with chronic viral hepatitis, probable cirrhosis developed in 20% (3/15) compared to one patient in the group without hepatitis, but there was no mortality from liver failure in either group. Diabetes mellitus was significantly more common in those with than without hepatitis (11/15 vs. 10/39; P=0.002), but severe infection was not (9/15 vs. 15/39). Five hepatitis patients (33%) have died of non-hepatic causes (one from meningitis, one from unknown cause, and three from coronary heart disease [CHD] vs. only two individuals without hepatitis [5%]; P= 0.014). Although the more frequent occurrence of CHD among those with hepatitis was not significant (7/15 vs. 8/39; P=0.09), CHD as a cause of death in those with HCV was significantly increased (P=0.03). CONCLUSIONS: Twenty-year renal transplant recipients infected with hepatotropic viruses (HBV and HCV) have a high rate of active viral replication (88%), a greater frequency of diabetes (P=0.01), and a higher overall mortality (P=0.014).

New hypertension guidelines set aggressive goals based on risk factors. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Physicians and public health officials need to intensify their efforts to detect and treat high blood pressure, because the incidence of hypertension-related morbidity and mortality has stopped declining, and fewer than 30% of hypertensive patients have their blood pressure under control. The JNC VI report outlines the current standard of care for treating hypertension.

Antihypertensive therapy. Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium antagonists.

ACEIs, angiotensin II receptor antagonists, and calcium antagonists are effective and well-tolerated antihypertensive agents but, except in special situations, should be considered alternative drugs for first line therapy until randomized trials show that they are at least as effective as diuretics and beta-blockers in preventing cardiovascular morbidity and mortality for a broad spectrum of hypertensive patients. ACEIs are particularly indicated for managing patients with congestive heart failure due to systolic dysfunction and patients with diabetic nephropathy, especially in Type I diabetes. Theoretically, the AII receptor antagonists will be equally effective for these indications, and randomized trials are now underway to demonstrate this. Special indications for calcium antagonists in the management of hypertension include angina pectoris, and for the non-dihydropyridine calcium antagonists, paroxysmal supraventricular tachycardia, and atrial fibrillation with rapid ventricular rate. Isolated systolic hypertension in the elderly is a special indication for long-acting dihydropyridine calcium antagonists, although diuretics are preferred. Calcium antagonists have been particularly effective in managing hypertension induced by cyclosporine. They are contraindicated in CHF due to systolic dysfunction and in the management of acute myocardial infarction. The long-term cardioprotective effect of calcium antagonists after a myocardial infarction has been demonstrated only for verapamil and diltiazem in patients with no evidence of LV dysfunction during their infarction. Calcium antagonists should be prescribed for this purpose only when beta-blockers are poorly-tolerated or contraindicated.

What's new in the treatment of hypertension.

Twenty-five years after the establishment of the National High Blood Pressure Education Program, hypertension is still underdiagnosed and often inadequately treated. This article argues for more aggressive treatment and outlines a practical, office-based approach.

Choice of initial therapy for hypertension.

Hypertension is one of the most common conditions treated by the clinician, yet accurate diagnosis and selection of the appropriate treatment can be challenging and recommendations regarding antihypertensive medications continue to evolve. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommends diet and exercise for the initial treatment of mild hypertension, followed by a diuretic or beta-blocker if necessary, unless contraindicated. This recommendation is based on outcome studies using these drugs that demonstrate reductions in major diseases that treatment of hypertension is intended to prevent: stroke and cardiovascular morbidity and mortality. Other antihypertensive drugs, while not tested in large trials evaluating outcomes, have unique advantages for certain patients. Consideration of the patient's medical conditions and needs, including the cost of medication, is essential to ensuring optimal treatment of hypertension.

FDR and hypertension: if we'd only known then what we know now.

Fifty years ago, when President Roosevelt died of complications from severe hypertension, there was no effective medication to reduce elevated blood pressure. Since then, three breakthroughs have contributed significantly to the successful management of hypertension: actuarial and observational studies that have identified risk factors for cardiovascular disease; the development of safe and effective antihypertensive drugs; and prospective, randomized trials that have shown the effectiveness of antihypertensive therapy. Mortality from stroke has decreased by almost 60% and mortality from heart attack by almost 50%. Even so, many hypertensives remain unidentified and untreated, a challenge for today's physicians.

The fate of renal allografts functioning for a minimum of 20 years (level 5A)--indefinite success or beginning of the end? A proposed classification of long-term allograft survivals.

Fifty-five renal allografts (44 from living-related and 11 from cadaver donors) that have functioned for at least 20 years (mean 22.9 +/- 2.3, range 20.1 to 30.7 years) were evaluated in three groups based on renal function: group I (n = 26), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl and no proteinuria; group II (n = 9), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl but > 150 mg proteinuria/24 hr; and group III (n = 20), with a GFR < 60 ml/min/1.73 m2 and/or serum creatinine > 1.4 mg/dL with or without proteinuria. Allograft factors, including acute rejection (AR) in 62% (34/55) and delayed function (DF) in 55% (6/11) of the cadaver grafts, did not preclude 20-year success and the prospect of continued survival since they were not significantly more frequent in group I, II, or III. However, AR was confined to a limited period within the first three months posttransplant in 18/18 recipients in groups I and II but only in 7/16 of group III (P = 0.0002). In groups I and II AR was treated with IVMP in 14/18 cases and only 6/16 in group III (P = 0.035). Donor age < or = 50 years and recipient age < or = 40 years each occurred in 87% (48/55) of these transplants. One- or two-HLA haplotype matching was present in 98% (43/44) of living related transplants. Major risks to the recipient were coronary artery disease (11 cases and 3 deaths), malignancy (18 cases and 1 death), and severe infection and hepatitis (35 cases and 3 deaths, 2 of whom also had coronary artery disease). Hypertension occurred in 25 recipients and diabetes mellitus in 12. Potential open-end success was compromised by renal dysfunction in groups II and III, but appeared possible in 12 of the 26 patients in group I. There is no apparent "safe-haven" point of time for immunosuppressed renal allograft recipients, who remain at increased risk for eventual renal allograft dysfunction, as well as cardiovascular, neoplastic, infectious, and metabolic diseases. In order to clarify and standardize the words "long-term," a simple classification of long-term allograft survivals is proposed.

Managing hypertension in the elderly: dispelling the myths.

BACKGROUND: There are now more than 31 million people 65 years of age or older in the United States, at least half of whom have systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher or both. By the year 2050, 16 million Americans will be over age 85. OBJECTIVE: To review the current data and recommendations regarding treating hypertension in elderly patients. SUMMARY: Randomized clinical trials have dispelled some of the myths that surround treatment of hypertension in the elderly by showing that judicious treatment of elevated blood pressure, both systolic and diastolic, will reduce the risk of cardiovascular morbidity and mortality, with an acceptable trade-off in terms of side effects and without sacrificing quality of life. CONCLUSIONS: Because most of the trials have used a diuretic as initial therapy, it is recommended that one of these agents be prescribed in low doses if life-style modifications do not reduce blood pressure to acceptable levels, unless there is a contraindication to diuretics or an indication for another class of agents.

Pheochromocytoma.

None of the endocrine causes for hypertension is more fascinating and challenging for the clinician than pheochromocytoma. Its protean manifestations can make diagnosis difficult, yet its sinister prognostic implications demand prompt recognition and expert management. Diagnosis depends on clinical suspicion, demonstration of high levels of free catecholamines in the plasma or urine, or high localization of the tumor by appropriate imaging techniques that include CT scanning, MR imaging, and 131I-MIBG scintigraphy. Surgical extirpation is the treatment of choice unless the risk of operation is overwhelming or distant metastasis has already occurred. Successful outcome demands a team approach, taking advantage of the experience, skill, and expertise of the surgeon, anesthesiologist, and internist.