Much is known regarding the frequency, prevalence, geographic manifestation, phylogenesis, etiology, physiopathology, clinical presentation, and therapy of kidney stones. Crystalline concretions are present in the kidneys of vertebrates and the equivalent excretory organs of invertebrates; the calcium constitution of the endoskeleton and exoskeleton creates the finite turnover and excretion of calcium, water conservation, and consequent low volume of urine. Thus, it is very difficult to keep calcium salts and other solutes in the urine solution since the laws of physiochemistry cannot be altered via biological evolution. Substances that promote and inhibit the calcium solution are well established in human urine, and their quality and quantity are of great importance, both in physiopathology and in a clinical setting. Urolithiasis is present in 0.5 % of US and EU populations, but its prevalence has increased from 3.2 % to 5.2 % since the 1970s; bladder stones have decreased notably in the last 20 years in developed countries. Stone recurrence remains at 50 % over 5–10 years and 75 % over 20 years; recurrence increases the probability of relapse and increases the amount of time between the two recurrences. These data are very important for what we shall go on to demonstrate here.

It is also known that it is not rare for stones to arise and grow in only one kidney, repeatedly, and for relapses to occur in the same area. It is certainly in a minority of cases in which this happens, but it does take place (no conclusive statistics on this could be found). The few authors that have addressed this topic have assumed nephrolithiasis to be the consequence of a previous illness in a part of the kidney (where it starts growing) that is capable of precipitating calcium salts, and thereby starts the stone-forming process [1, 2]. Renal stones can occur not only because of chemical processes or metabolic or genetic anomalies but also because of previous renal pathology. Recent research of various types has directly or indirectly supported the hypothesis on lithiasis occurring secondary to previous renal pathology. Firstly, so-called Darwinian medicine or evolutionistic medicine: According to the contentions of this recent branch of medicine the evolution of human phenomena occurs as a result of genes surviving so that those phenomena that have shown an advantage for the individual (food, reproduction) and the species are perpetuated. The usefulness of such (pleiotropic) genes is limited, depending on their purpose. Over time these adaptive features cease to be of any use to the organism and their presence can prove to be a source of harm. For example, it is supposed that calcium, a biophilic element that is indispensable for life, and a fundamental part of the skeletal and muscular system, is largely confined to bones, thanks to particular genes, so as to fortify them and provide them with the greatest possible resistance. This ensures that young individuals are given an advantage in enduring demanding functions like defense against predators, running, attacking, and so on. The genes that have survived are the strongest. The time scale for evolution is somewhat slower than for biology; so, in the case of calcium, the same genes once useful for surviving, over time (centuries, millennia) became risk factors for ectopic calcifications in arteries and other tissues. Calcium salt precipitation in the renal papillae and Henle’s loop could therefore be the reason for lesions on which Randall’s plaques grow.

An evolutionary anthropologist has ironically summarized the phenomenon with the phrase: “the price of not being eaten by the lion when you’re young is paid by the risk of having heart attacks or arteriosclerosis when you’re old” (or, in our case, renal stones) [1–5].

Clearly this evolutionary explanation for why stones grow and often relapse in only one kidney and area thereof can be objected to by pointing to the fact that nephrolithiasis is a disease most often found in young people, if not children. This leaves the pleiotropic genes in peace, which are probably involved in other more sophisticated situations.

Another consideration, pathogenetically linked to what has been said regarding prepapillary renal arteriole calcification, comes from research concerning extra-gastrointestinal lesions caused by Helicobacter pylori. Helicobacter pylori is presumed to be responsible for much urological pathology, such as chronic abacteric prostatitis, interstitial cystitis, and stone disease. Similar to what Helicobacter does to gastric mucosa – calcifications, arteriole thrombosis, and necrosis of mucosa epithelium, for example – it would create an analogous mechanism on the long Henle ansa and tubuli recti where the Randall’s plaque begins [6]. Randall’s plaques are invariably present in the former papillae of stones (and sometimes also in healthy people), and this structure is believed to be the nidus upon which calcium oxalate stones arise and grow. Microscopically the lesion seems to start in the basement membrane of the thin part of the loop of Henle, from where it expands through to the interstitium. Subsequently it involves renal tubules and vasa recta and eventually protrudes into the renal papilla epithelium. Biochemical studies have shown a transition from calcium phosphate to calcium oxalate in particular circumstances, such as the lesion in tubular lumen and in the collecting duct where Randall’s plaques provide the platform for calcium oxalate crystals to form a heterogeneous nucleation and become a nephrolith. A correlation exists between plaques, urine volume, hypercalciuria, and the number of stones formed. The correlation is negative for urine volume and positive for hypercalciuria and the number of stones formed. The basement membrane calcifications are certainly early events. The true relationship between urine chemistry and the functional abnormalities that create the calcium phosphate deposition around the loop of Henle before the stone formation it is not clear.