As examinations of aging go, this open access overview of kidney decline and kidney disease is more focused on the mechanics of the problem than most, which makes it an interesting read. As a bonus, it opens by touching on the thorny topic of whether aging is a disease, and where the arbitrary boundary lies between aging and disease. Kidney disease is not as large a problem in our species as heart disease and cancer, but that is only because most people are killed by something else first. Age-related fibrosis eats away at kidney tissue until there is no longer enough left fully functional to do its job. It is an unpleasant decline, and modern medicine has little in the way of effective interventions. It is to be hoped that near future therapies capable of clearing senescence cells will have a significant positive impact on fibrosis in all organs, and thus prove to be useful treatments for kidney aging, but the proof of that remains to be accomplished.
Aging is a universal biological phenomenon, except perhaps in the genus Hydra, which appears to be immortal. As such, it is difficult to label aging as a disease, at least when a departure from “normality” is a criterion for a disease. The fundamental processes responsible for aging are still incompletely understood, but environment, genes and chance all play important roles. These processes can be accelerated by diseases which tend to aggregate in older persons, such as diabetes, cancer, hypertension and atherosclerosis, largely because the aged have had more time to acquire these degenerative diseases. When one attempts to define these diseases in the older person, it is frequently necessary to adjust criteria for what might be expected from chronological aging per se; for example in the detection of osteoporosis by DEXA scanning or for detection of chronic obstructive pulmonary disease by spirometry. The disentangling of the intertwined phenomena of age-related disease and physiologic aging can be difficult and challenging. As succinctly captured by Tom Kirkwood in 1999, “grasping the correct distinction between normal aging and disease smacks of a semantic quibble, but words are powerful and the consequences of how we use them can be far-reaching”.
The kidneys age in a stereotypical fashion, affecting many aspects of their function, such as glomerular filtration rate (GFR). The aggregate GFR of both kidneys (wkGFR) is equal to the product of the number of functioning nephrons (NN) and the average GFR of single nephron (snGFR). Although difficult to study in humans, the investigation of values for the elements of this equation, according to healthy (physiologic) aging, has yielded some interesting findings. We are all born with a complement of nephrons determined in large part by the process of nephrogenesis in utero. Thus, one can only lose, not gain nephrons as one ages and the NN at any age is determined by NN at birth (nephron endowment) and the rate of post-natal loss of nephrons. Among 1638 living donors in a past study, an average adult 18-29 years old has about 1,008,000 glomeruli per kidney, 991,000 of which are presumably functioning and 17,000 of which have undergone a scarring process known as focal and global glomerulosclerosis (FGGS).
Thus, according to the equation above, if the wkGFR for two kidneys is 110ml/min, the average snGFR of the functioning nephrons in a healthy young adult is about 55 nl/min. By age 70-75 years the average number of glomeruli per kidney has declined to about 660,000, of which 520,400 are presumably functioning and 142,000 have undergone FGGS. If the normal wkGFR for a healthy 70-75 year old is about 75 ml/min (a loss of 35 ml/min over 5 decades), then the average snGFR is about 57 nl/min, not much different than an adult 50 years younger. Note that the absolute total number of non-sclerotic and sclerotic nephrons decrease by 35% with aging, so some nephrons must have been completely resorbed, as a consequence of atrophy and sclerosis. If these derived values represent the true state of renal physiology in the aging kidney, then healthy aging is associated with a substantial decline (35%) in total glomeruli, and an even greater number of functioning (non-sclerotic) glomeruli with aging about 48% (from 991,000 per kidney to 520,400 per kidney) over 50 years.
The mechanisms underlying this loss of nephrons with healthy aging remain uncertain, but unlike nephron loss accompanying surgical reduction of nephron mass or certain disease states associated with loss of function nephron number, the reduction of functioning nephrons in aging is not apparently accompanied by a compensatory increase in snGFR of surviving nephrons, at least not until the extremes of age have been attained. In addition, it seems that factors in addition to aging per se are responsible for the observed nephron loss other than age per se. The loss of nephrons is accompanied by interstitial fibrosis proportional to the severity of FGGS, and by tubular hypertrophy that somewhat attenuate the loss of cortical volume seen in aging kidneys.