| Kidney disease is an important and understudied correlate of aging; reduced kidney function is associated with substantially increased morbidity and mortality. This dissertation improves our understanding of the process and determinants of decline in kidney function. The effect of normal aging on kidney function has not been well described due to the inaccuracy of creatinine-based measures of kidney function in the elderly, and the inclusion of persons with comorbidites known to affect kidney function in prior studies. In the present research, I use a novel marker of kidney function, cystatin C, which is more accurate in studies of aging compared to traditional creatinine-based measures. Based on cross-sectional data on participants aged 28-100, I found a substantial, non-linear association between age and cystatin C concentrations even in participants without diabetes, hypertension, obesity, history of smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease, and heart failure. These findings provide important evidence that kidney function worsens considerably with age, even among apparently healthy persons. Next, I applied novel statistical methods, marginal structural models, to characterize more accurately the effect of the most important known risk factors for kidney disease, namely obesity, diabetes, and hypertension, on kidney function across the age-spectrum. I found hypertension has the strongest effect on kidney function, and the deleterious effects of hypertension are evident even in early to middle adulthood. Finally, I examined the effect of antihypertensive medications on prevention of decline in kidney function in elderly persons. Based on marginal structural models to account for bias in observational data, my research provides important evidence of a protective effect of antihypertensive medication on kidney function in older adults with a history of hypertension. In summary, I demonstrate that antihypertensive medications and other interventions to prevent hypertension have the greatest public health potential to prevent decline in kidney function. Future research should aim to identify the optimal intervention regimens to prevent decline in kidney function across different stages and causes of disease. In addition to the treatment of disease, a better understanding of the aging process is needed to improve the quality of the final years of life. |
