The prevalence of kidney stone disease (and other stone diseases) is increasing in all western societies. In the USA, the prevalence of stone disease increased from affecting 3.6% of the population in the period 1976–1980 to 5.2% between 1988 and 1994.
While some of this increase may reflect better diagnostic tests (e.g. the advent of CTU) diagnosing asymptomatic stones, much of this increase is likely to be real. Certainly in the UK, rates of treatment for stones have shown a very substantial rise over the last 10y at a time when there have been no substantial changes in technology or technique of stone treatment.
Thus, the use of ESWL for treating upper tract stones increased by 55% between 2000 and 2010 with a 127% increase in the number of ureteroscopic stone treatments, 49% of this increase occurring between the periods 2007–8 and 2009–10.
Of 5047 men and women (mean age 57y) undergoing CT colonography screening in 2004–2008 and with no symptoms of stone disease, a staggering 395 (7.8%) had stones (an average of 2 stones per patient, mean stone size 3mm).
The prevalence in men was 9.7% and in women 6.3%, but was not (surprisingly) related to diabetes, obesity, and age >60. A substantial proportion of these initially asymptomatic stones became symptomatic over time. Over 10y of follow-up, 81 of these 395 patients (21%) went on to develop at least one symptomatic stone event.
The driving force behind stone formation is the supersaturation of urine. Supersaturation is expressed as the ratio of urinary calcium oxalate (for example) to its solubility. Below a supersaturation of 1, crystals of calcium oxalate remain soluble. Above a supersaturation of 1, crystals of calcium oxalate nucleate and grow, thereby promoting stone formation.
Urine is said to be saturated with, for example, calcium and oxalate when the product of the concentrations of calcium and oxalate exceeds the solubility product (Ksp). Below Ksp, crystals of calcium and oxalate will not form and the urine is said to be undersaturated. Above Ksp, crystals of calcium and oxalate should form, but they do not because of the presence of inhibitorsof crystal formation.
However, above a certain concentration of calcium and oxalate, inhibitors of crystallization become ineffective and crystals of calcium oxalate start to form. The concentration of calcium and oxalate at which this is reached (i.e. at which crystallization starts) is known as the formation product (Kf) and the urine is said to be supersaturated with the substance or substances in question at concentrations above this level.
Urine is described as being metastable for calcium and oxalate at concentrations between the Ksp of calcium and oxalate and the Kf (Box 9.1).
The ability of urine to hold more solute in solution than can pure water is due partly to the presence of various inhibitors of crystallization (e.g. citrate forms a soluble complex with calcium, preventing it from combining with oxalate or phosphate to form calcium oxalate or calcium phosphate stones). Other inhibitors of crystallization include magnesium, glycosaminoglycans, and Tamm–Horsfall protein.
From a practical perspective, the only inhibitor of stone formation that is open to manipulation is citrate. Periods of intermittent supersaturation of urine with various substances can occur as a consequence of dehydration and following meals.
The earliest phase of crystal formation is known as nucleation. Crystal nuclei usually form on the surfaces of epithelial cells or on other crystals. Crystal nuclei form into clumps—a process known as aggregation. Citrate and magnesium not only inhibit crystallization, but also inhibit aggregation. Calcium oxalate stones form over a nucleus of calcium phosphate (Randall’s plaques on the surface of a renal papilla).
What is the risk of recurrent kidney stone (and other stones) forming in those who have already had a stone?
Once a stone has formed, the risk of future stone disease is very substantially increased and treatment becomes more complicated. Within 1y of a calcium oxalate stone, 10% of men will form another calcium oxalate stone, 727–50% will have formed another stone within a mean of 7.54 to 9 years.
Once a second stone has formed, the frequency of recurrences increases and the interval between relapses becomes smaller.
Factors affecting kidney stone (and other stones) formation…
The prevalence of renal tract stone disease is determined by factors intrinsic to the individual and by extrinsic (environmental) factors. A combination of factors often contributes to risk of stone formation.
The prevalence of stone disease and incidence of new stone events, including kidney stones, is increasing. Much of this change may relate to the epidemic of obesity sweeping western societies (obesity is associated with increased urinary excretion of stone-promoting substances, e.g. calcium, oxalate, uric acid, and decreased excretion of stone-preventing substances, e.g. citrate).
Obese patients have a lower urinary pH which encourages urate stone formation.
Age: the peak incidence of stones occurs between the ages of 20–50y.
Sex: males are affected three times as frequently as females, but the gender gap is closing, at least in the USA so that between 1997 and 2002, the male : female ratio for treated stones fell from 1.7:1 to 1.3:1.6.
Testosterone may cause increased oxalate production in the liver (predisposing to calcium oxalate stones) and women have higher urinary citrate concentrations (citrate inhibits calcium oxalate stone formation).
Genetic: kidney stones are relatively uncommon in Native Americans, Black Africans, and American Blacks and more common in Caucasians and Asians (including Singapore). About 25% of patients with kidney stones report a family history of stone disease (the relative risk of stone formation remaining high after adjusting for dietary calcium intake). Familial renal tubular acidosis (predisposing to calcium phosphate stones) and cystinuria (predisposing to cystine stones) are inherited.
Geographical location, climate, and season: the relationship between these factors and stone risk is complex. While renal stone disease is more common in hot climates, some indigenous populations of hot climates have a low incidence of stones (e.g. Black Africans, Aborigines) and many temperate areas have a high incidence of stones (e.g. Northern Europe and Scandinavia).
This may relate to western lifestyle—excess food, inadequate fl uid intake, limited exercise — combined with a genetic predisposition to stone formation.
Ureteric stones become more prevalent during the summer: the highest incidence occurs a month or so after peak summertime temperatures, presumably because of higher urinary concentration in the summer (encourages crystallization). The number of patients presenting acutely with urinary calculi increases by 2.8% for each degree increase in temperature and 0.2% for each hour increase in sunlight hours.
Concentrated urine has a lower pH, encouraging cystine and uric acid stone formation. Exposure to sunlight may also increase endogenous vitamin D production, leading to hypercalciuria.
Water intake: low fluid intake (<1200mL/day) predisposes to stone formation and patients who relapse after experiencing a stone are less likely to have increased their fluid intake than those who remain stonefree. Increasing water ‘hardness’ (high calcium content) may reduce the risk of stone formation, by decreasing urinary oxalate.
Diet: high animal protein intake increases the risk of stone disease (high urinary oxalate, low pH, low urinary citrate).
High salt intake causes hypercalciuria (through a sodium: calcium co-transport mechanism). Contrary to conventional teaching, epidemiological studies show that in populations, low calcium diets predispose to calcium stone disease and high calcium intake is protective.
Occupation: sedentary occupations predispose to stones compared with manual workers.
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