DESCRIPTION OF THE CONDITION
Glomerulopathy is generic disease of the renal glomerulus, impairment of which can lead to hematuria or proteinuria due to injury or dysfunction of the endothelium, glomerular filtration barrier or podocyte [1]. The Nephrotic Syndrome (proteinuria, hypoalbuminemia, edema and hyperlipidemia) develops in the context of heavy proteinuria, and the extra-renal components (edema and hyperlipidemia) have more elusive etiologies. A renal ontophylogenetic approach following Homer Smith [2] assists in establishing a firm empirical basis for further clinical investigation.
EVOLUTIONARY PERSPECTIVES
The most primitive ki dney was the pronephros, evolved as a urea-secreting organ in a multicellular animal [2] that was isotonic with its marine environment [3] some 950 million years ago (Ma) [4]. The glomerulus evolved in the mesonephric kidney of early chordate ancestors (684–824 Ma), with its primary function being the removal of excess water flooding into the body from its freshwater environment [2–5]. The metanephric kidney was a terrestrial vertebrate adaptation (350 Ma) conserving metabolic water, thus essentially reversing the earlier mesonephric adaptation [2–5]. The modern human kidney retains embryonic derivatives and remanent functions of these renal primordia. Edema resulting from glomerulopathy can be due to either reduced oncotic pressure or to increased sodium retention in the aldosterone-sensitive distal nephron [5] activated by increased plasminogen leaked by a damaged filtration barrier [7], a water-saving adaptation inherited from our terrestrial vertebrate ancestors.
FUTURE IMPLICATIONS
Diagnosing pathology and assessing etiology on the basis of dysfunction of evolutionary adaptations is a promising approach to analyzing contemporary disease and injury [8]. An evo-devo perspective has proved effective in explicating the complex etiology of edema in the nephrotic phenotype [3, 6, 7] in glomerular disease. The etiology of hyperlipidemia resulting from glomerulopathy remains unclearly explained and is a challenge for the future.
REFERENCES
- 1.Zhou W, Hildebrandt F.. Inducible podocyte injury and proteinuria in transgenic zebrafish. J Am Soc Nephrol 2012;23:1039–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Smith HS. From Fish to Philosopher. Boston: Little, Brown, 1959. [Google Scholar]
- 3.Grantham JJ, Wallace DP.. Return of the secretory kidney. Am J Physiol Renal Physiol 2002;282:F1–F9. [DOI] [PubMed] [Google Scholar]
- 4.Kumar S, Stecher G, Suleski M, Hedges SB.. TimeTree: a resource for timelines, timetrees, and divergence times. Mol Biol Evol 2017;34:1812–9. [DOI] [PubMed] [Google Scholar]
- 5.Ward P, Kirschvink J.. A New History of Life: The Radical New Discoveries about the Origins and Evolution of Life on Earth. New York: Bloomsbury, 2015. [Google Scholar]
- 6.Siddall EC, Radhakrishnan J.. The pathophysiology of edema formation in the nephrotic syndrome. Kidney Int 2012;82:635–42. [DOI] [PubMed] [Google Scholar]
- 7.Studer RA, Person E, Robinson-Rechavi M, Rossier BC.. Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport. Physiol Genomics 2011;43:844–54. [DOI] [PubMed] [Google Scholar]
- 8.Boaz NT. Evolving Health. New York: Wiley, 2002. [Google Scholar]