Serial creatinine clearances (5 to 14 studies) were obtained for 446 normal volunteers in the Baltimore Longitudinal Study of Aging followed between 1958 and 1981. When those subjects with possible renal or urinary tract disease and subjects on diuretics and antihypertensives were removed from the study, leaving a group of 254 "normal" subjects, the mean decrease in creatinine clearance was 0.75 ml/min/year. The slopes of the creatinine clearance vs. time fell into a normal (Gaussian) distribution around this mean. One third of all subjects followed had no absolute decrease in renal function (positive slope of creatinine clearance vs. time) and there was a small group of patients who showed a statistically significant increase (P less than 0.05) in creatinine clearance with age.

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Standard true 24-hour creatinine clearance determinations were performed on 884 subjects of the Baltimore Longitudinal Study. On the basis of clinical data, subjects were placed in categories indicating the presence of specific diseases or medications which might alter glomerular filtration rate. Subjects not included in these categories were considered normal (N=548). In the normals, cross-sectional analysis by 10-year age groups showed a progressive linear decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80. Three or more serial clearances were obtained at 12- to 18-mo. intervals on 293 normal subjects. These longitudinal data showed an acceleration of the rate of decline in creatinine clearance with advancing age. The decrease in creatinine clearance with age seen in this study represents true renal aging and is not secondary to diseases which become increasingly prevalent in the elderly. A nomogram constructed from these data provides normative age-corrected standards for creatinine clearance.

In the first of two papers, the details and results of a systematic, carefully standardized application of dye dilution technic to the measurement of cardiac output are reporte(l. A substantially reduced output was a consistent finding in older subjects. Fa(tors responsible for this are analyzed in this article, and further interpretations are made in the succeedinig a1rticle. One result of the analysis of time-concentration curves of dye provides an interesting relationship to (linical estimates of circulation time.INVESTIGATIONS of cardiac output ill older, but presumably "normal," adults were made by Starr and his coworkers,1 by Lewis2 and by Aperia3 16 to 20 years ago, using the indirect gas methods then available. Although the insensitivity of these methods could mask a sizeable change, Starr and his associates noted that in the "period before 20 years the average cardiac index is higher than at any time later, after 50 it slowly declines. The number of cases was too small to demonstrate the significance of the difference." Their series included only nine cases over 50 years of age; the oldest was 76. Lewis, in a systematic agewise study, found a small decrease in cardiac index in 100 male subjects between 40 and 89 years of age. He considered that the observed changes represented neither statistically nor physiologically a significant decline and that they were predominantly the result of a decrease in oxygen consumption. A decrease of about the same order may be calculated from the data reported by Aperia,3 utilizing the acetylene technic of Grollman. These indirect Fick gas methods are now recognized as yielding values which are approximately 25 per cent too low, but even allowing for this, a sizeable decrease in cardiac output cannot be said to have been demonstrated by these studies, despite a consistent suggestion in this direction.Age comparisons, using the Fick principle with right heart catheterization, were sought in the studies of Stead and his colleagues,4