Update in Nephrology

Most clinically important advances in nephrology reported in 1997 occurred in four areas: hypertension and the role of simple treatment measures, delay of progression of end-stage renal disease in nondiabetic patients, screening for microalbuminuria, and effects of common hospital practices on electrolyte metabolism. Each article reviewed here was chosen by one of the authors and reviewed by the other. The importance of the study results to clinical practice and sound research methods were the major guides to study selection. Hypertension Many advances in the field of hypertension in 1997 focused on basic issues. Dietary measures were found to be effective for patients with mild hypertension. Thiazide diuretics were found to be safe and effective in diabetic and nondiabetic persons. Finally, a study of ambulatory blood pressure monitoring may change the way we study and measure blood pressure. Diet Was Effective in the Treatment of Mild Hypertension Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997; 336:1117-24. Therapy for hypertension often centers on pharmacologic treatment, but attempts to decrease body weight, decrease intake of sodium and alcohol, and increase consumption of potassium and calcium are now receiving more attention [1]. The actual effectiveness of these dietary measures has not been known. The DASH (Dietary Approaches to Stop Hypertension) trial tested whether some dietary measures altered blood pressure. All participants (459 healthy adults with mild hypertension) received a diet low in fruit, vegetables, and calcium for 3 weeks. They were then randomly assigned to receive one of three diets for 8 weeks: a controlled diet, which included one serving of fruit or vegetables and one serving of calcium; a diet high in fruits and vegetables, which contained 5 servings of fruit or vegetables; and a combination diet, which was high in both fruits and vegetables and contained some calcium in the form of low-fat milk products. Sodium intake was kept at 3 g for all volunteers, and body weights were kept constant. At baseline, the mean blood pressure was 131/85 mm Hg. In participants receiving the combination diet, the decrease in systolic blood pressure was 5.5 mm Hg greater and the decrease in diastolic blood pressure was 3.0 mm Hg greater than the decreases in participants receiving the controlled diet. In participants receiving the high-fruit, high-vegetable diet, the decrease in systolic blood pressure was 2.8 mm Hg greater and the decrease in diastolic blood pressure was 1.1 mm Hg greater than the decreases in participants receiving the controlled diet. The diets had the greatest effect among those with the highest blood pressures at baseline. It seems that a diet rich in fruits, vegetables, and calcium and low in saturated fat can reduce blood pressure in patients with mild hypertension. These findings support the results of previous studies that show beneficial effects of potassium and calcium intake [2, 3]. The diets used by Appel and colleagues were easier to comply with than many previously recommended diet plans. For patients with mild hypertension, dietary therapy such as that described here should be a major component of treatment. Thiazides Were Effective and Safe in Older Diabetic Patients Curb JD, Pressel SL, Cutler JA, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA. 1996; 276:1886-92. Isolated systolic hypertension in the elderly is now routinely treated, but controversy remains about whether the use of diuretic therapy in older persons is safe. Clinicians worry about hypokalemia and adverse effects on low-density lipoprotein cholesterol levels. In addition, a previous study of patients with diabetes [4] suggested that persons who received diuretics had excess mortality. Curb and colleagues sought to end the controversy with a clinical trial to assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular events in older, non-insulin-treated diabetic patients with isolated systolic hypertension. They enrolled 4736 persons 60 years of age or older, 583 of whom had type 2 diabetes mellitus. All had isolated systolic hypertension, which was defined as a systolic blood pressure of 160 mm Hg or more and a diastolic blood pressure less than 90 mm Hg. Patients were randomly assigned to receive either placebo or 12.5 to 25 mg of chlorthalidone per day. The blood pressure of patients receiving placebo was then managed by their physicians. The treatment group received, if necessary, atenolol or reserpine in addition to the thiazide diuretic. The outcome measures were 5-year rates of all major cardiac and cerebrovascular events, fatal cardiac events, and all-cause mortality. Blood pressure decreased for both diabetic and nondiabetic patients in the treatment group. The 5-year rate of major cardiovascular events was reduced by 34% in both diabetic and nondiabetic patients receiving chlorthalidone (number needed to treat to prevent one adverse outcome, 10 for diabetic patients and 20 for nondiabetic patients). The greatest effect seemed to be on coronary artery events. The risk reductions for various outcomes are shown in Table 1. Table 1. Morbidity and Mortality in Diabetic and Nondiabetic Persons with Hypertension Receiving Chlorthalidone* This study shows that therapy with a thiazide diuretic-a simple regimen-is effective and well tolerated in older diabetic and nondiabetic patients with isolated systolic hypertension. Ambulatory Monitoring Resulted in Use of Fewer Drugs Staessen JA, Byttebier G, Buntinx F, et al. Antihypertensive treatment based on conventional or ambulatory blood pressure measurement. A randomized, controlled trial. Ambulatory Blood Pressure Monitoring and Treatment of Hypertension Investigators. JAMA. 1997; 278:1065-72. In theory, ambulatory blood pressure measurement should be superior to the conventional measurements of blood pressure. It is reproducible because it avoids observer bias. It is also done during the day and night, mitigating some of the issues about diurnal variation and white-coat hypertension. But does it actually improve patient care? One difficulty involved in answering that question is that almost all clinical outcomes data about control of hypertension are based on standard monitoring in the office. We must ask whether ambulatory blood pressure monitoring has a role in patient care. These Belgian researchers compared conventional and ambulatory blood pressure measurement to determine whether the latter affects the treatment and management of hypertensive patients. They recruited 419 healthy adults whose untreated diastolic blood pressure, by conventional measurement, averaged 95 mm Hg or more. Patients were randomly assigned to receive conventional or ambulatory blood pressure monitoring. Antihypertensive drug treatment was adjusted in a stepwise fashion on the basis of either the average daytime ambulatory diastolic blood pressure or the average of three diastolic blood pressure readings taken while patients were seated. Blinded physicians based therapy on whether diastolic blood pressure was greater than (>89 mm Hg), equal to (80 to 89 mm Hg), or less than (<80 mm Hg) the target pressure. Compared with patients assigned to conventional blood pressure measurement, more of those assigned to the ambulatory method discontinued antihypertensive drug treatment (26.3% compared with 7.3%) and fewer progressed to sustained multidrug treatment (27.2% compared with 42.7%). Blood pressure control, left ventricular mass, and reported symptoms were similarly improved. Ambulatory monitoring saved money because it resulted in less intensive drug treatment and fewer physician visits, but these savings were offset by the cost of the equipment. Much can be inferred from this study. First, the findings on cost may not be generalizable to the United States. Ambulatory blood pressure evaluations in Europe cost about $30; in the United States, they cost up to five times that amount. In addition, the drugs used were lisinopril, hydrochlorothiazide, and amlodipine-an expensive regimen. Second, the study raises the possibility of increased use of home monitoring of blood pressure, which is relatively inexpensive. Patients may be able to monitor blood pressure at home and then use those readings to guide therapy [5]. If the results of home monitoring mirror those of ambulatory assessment, fewer patients may need pharmacologic therapy. Third, the investigators excluded patients with serious comorbid disease, so it is unclear whether these findings can be generalized to patients with renal failure or heart failure. Finally, we expect that over the next 5 years, many studies will investigate clinical outcomes on the basis of either home monitoring or more formal ambulatory monitoring, and this study may be a turning point in our approach to the diagnosis and monitoring of hypertension. Of course, whether treatment based on ambulatory blood pressure readings prevents adverse clinical outcomes remains unknown. Progression of Renal Disease In primary care, many patients have low-grade renal insufficiency. What can be done to prevent advancement to end-stage renal disease? The use of angiotensin-converting enzyme (ACE) inhibitors has become standard in diabetic patients, but much less is known about prevention of progression of disease in patients with other causes of renal disease. Angiotensin-Converting Enzyme Inhibitors Seemed To Slow Disease Progression Giatras I, Lau J, Levey AS. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin-Converting-Enzyme Inh