An evolutionary approach to kidney function and disease

Robert L. Chevalier
Division of Pediatric Nephrology
University of Virginia

Evmedreview is very pleased to feature a paper on evolutionary nephrology by Robert L. Chevalier. Robert joined the University of Virginia in 1978 where he established the now internationally recognized Division of Pediatric Nephrology. Since 2010 he has devoted himself full-time to studying chronic kidney disease progression from birth to senescence. Finding his study limited by a conventional training in medicine and physiology he turned to evolutionary medicine for explanations based on ultimate causes. We believe this paper is the first comprehensive application of evolutionary medicine to understanding progressive chronic kidney disease. Chevalier traces his evolutionary perspective back to Homer W. Smith who did pioneering work on kidney evolution in the late 1930s. In his book From Fish to Philosopher, Chevalier says, Smith argued that the complex structure of the kidney can be explained by a series of evolutionary adaptations in our vertebrate ancestors, who transitioned from marine to fresh water environments and ultimately to survival on land. Written by the leading American renal physiologist of the mid- 20th century, says Chevalier, that book revealed how an evolutionary perspective explains the dependence of renal excretory function on filtration of 180 liters of plasma per day and reclamation of 99% of the filtrate. Many of the early advances in renal physiology were based on animal studies that required an understanding of evolution to apply the results to human beings.

Why is evolutionary medicine important? According to Chevalier, the primary challenge to the adoption of an evolutionary approach to disease rests on the practice of medicine itself: physicians are charged with the responsibility for diagnosing and treating a particular disorder in an individual patient, a process that appears far removed from evolutionary concerns. However, the history (present illness, past history, and family history) is the key component in diagnosis. Seeking concordance with established medical sciences (genetics, anatomy, physiology, biochemistry), evolutionary medicine relies on evolutionary biology to create a “deep” history of human populations. The rationale for the evolutionary perspective is that rather than causing disease, our evolutionary history determines our risk of disease in a given environment, a context that overlaps with public health, global health, and health care disparities.

The featured image illustrates Homer Smith’s account of the more important steps in the evolution of the vertebrate kidney in relation to saltwater (darkly shaded) and freshwater (lightly shaded) environment. The evolutionary tree is followed through primitive fish, amphibians, reptiles, birds and mammals showing the adaptation to a terrestrial environment.

Chevalier’s paper is published in Kidney International Reports and simply titled Evolutionary Nephrology. To whet your appetites here is the abstract:

“Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as “maladaptive.” In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic) adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or from evolutionary tradeoffs. Evolutionary adaptation to a terrestrial environment resulted in a vulnerable energy-consuming renal tubule and a hypoxic, hyperosmolar microenvironment. Natural selection favors successful energy investment strategy: energy is allocated to maintenance of nephron integrity through reproductive years, but this declines with increasing senescence after ~40 years of age. Risk factors for chronic kidney disease include restricted fetal growth or preterm birth (life history tradeoff resulting in fewer nephrons), evolutionary selection for APOL1 mutations (which provide resistance to trypanosome infection, a tradeoff), and modern life experience (Western diet mismatch leading to diabetes and hypertension). Current advances in genomics, epigenetics, and developmental biology have revealed proximate causes of kidney disease, but attempts to slow kidney disease remain elusive. Evolutionary medicine provides a complementary approach by addressing ultimate causes of kidney disease. Marked variation in nephron number at birth, nephron heterogeneity, and changing susceptibility to kidney injury throughout the life history are the result of evolutionary processes. Combined application of molecular genetics, evolutionary developmental biology (evo-devo), developmental programming, and life history theory may yield new strategies for prevention and treatment of chronic kidney disease.”