IntroductionEpidemiologyI. Epidemiology of kidney stonesI.1. Prevalence of kidney stonesI.2. An increasing trend in childrenPathophysiology II. Pathophysiology of kidney stonesII.1. LithogenesisII.1.1. Urine supersaturation : the driving force of crystallogenesisII.1.2. Promoters and inhibitors of stone formationII.2. Urine volume and composition: a necessary balanceRisk factorsIII. Risk factors for kidney stonesIII.1. Individual, non-modifiable risk factorsIII.1.1 Family historyIII.1.2. Race and ethnicityIII.1.3. Age and genderIII.1.4. Current change in gender prevalenceIII.2. Lifestyle related factorsIII.2.1. Calcium intakeIII.2.2. Emerging dietary risk factorsIII.2.3. Association with other chronic diseasesDehydrationIV. Dehydration: a risk factor for kidney stonesIV.1. Low urine volume: a key risk factor for kidney stonesIV.2. Environmental factors predisposing to low urine volumeIV.2.1. Occupational risk of kidney stonesIV.2.2. Climate and temperature as risk factorsWater & recurrenceV. Prevention of stone recurrence with high water intakeV.1. Reduction of recurrence rate with increased water intakeV.2. Water intake and urinary parameters in stone formersWater & incidenceVI. Primary prevention of stones with high water intakeVI.1. Reduction of stone incidence with increased water intakeVI.2. Water intake and urinary parameters in healthy subjectsWater & health costsVII. Water intake and health costs of kidney stonesVII.1. Reduction of stone recurrence costs via adequate water intakeVII.2. Reduction of first stone costs with adequate water intakeRecommendationsVIII. Dietary and water recommendations for stone preventionVIII.1. Guidelines for the prevention of recurrence in patientsVIII.2. Dietary and water guidelines for general populationConclusion References

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Risk factors

III. Risk factors for kidney stones 

Many factors influence the propensity of forming a kidney stone (Brenner and Rector 2008; Curhan 2007; Ramello et al. 2000; Trinchieri et al. 2008), including both individual and environmental factors (Figure 4). Main individual risk factors include age, gender and ethnicity, while the most important environmental risk factors are related to geography and climate (Brenner and Rector 2008; Curhan 2007; Ferrari et al. 2007; Ramello et al. 2000; Trinchieri et al. 2008). Body Mass Index (BMI) and a family history of kidney stones are also thought to influence the risk for kidney stones (Curhan 2007; Ramello et al. 2000). Figure 4 summarizes these factors. 

diagram: Major risk factors for nephrolithiasis

 

Figure 4. Main risk factors for kidney stones. 

 

III.1. Individual, non-modifiable risk factors

III.1.1 Family history

Family history of stones is a confirmed risk factor and it is actually reported more often among stone formers than among healthy subjects (Coe et al. 1979; Curhan et al. 1997a; Serio and Fraioli 1999; Trinchieri et al. 2008). These observations suggest a hereditary predisposition to kidney stones. Main difficulty in addressing this question is that members of a family usually share many environmental factors. Familial inheritance of kidney stones may thus be related to an environmental effect (Curhan et al. 1997a; Ramello et al. 2000; Trinchieri et al. 2008). To investigate this point, Curhan et al. published in 1997 a cohort study of 37,999 men from the Health Professionals Follow-up Study (HPFS). After adjustment for other potential risk factors (e.g. dietary factors, fluid intake or geography), men with a family history of kidney stones were at greater risk of forming a stone (relative risk of 2.57) as compared to men without a family history (Curhan et al. 1997a).

III.1.2. Race and ethnicity

Only a few epidemiological studies have evaluated race and ethnicity as risk factors for kidney stones, however there appear to be race-related differences in prevalence rates. In men, Soucie et al. found a higher prevalence among whites than blacks. The prevalence among Hispanic and Asian men was intermediate between whites and blacks (Soucie et al. 1994). This was also reported by Stamatelou et al. on data from the second and third National Health and Nutrition Examination Survey (NHANES II and III). On 15,364 and 16,115 adult United States residents, they reported a higher prevalence of kidney stones among non-Hispanic Caucasians than among non-Hispanic African Americans, or among Mexican Americans (Stamatelou et al. 2003). On data from the 2007-2010 NHANES studies, Scales et al. reported lower prevalence of kidney stones among non-Hispanic African Americans and Hispanic individuals than among non-Hispanic Caucasians (Scales, Jr. et al. 2012). 

III.1.3. Age and gender

Age and gender are established risk factors for kidneys stones; urolithiasis is more prevalent among men than among women (Brenner and Rector 2008; Ramello et al. 2000; Trinchieri et al. 2008); observations of male-to- female ratios generally vary between 1.3:1 (Scales, Jr. et al. 2007) and 3:1 (Ferrari et al. 2007). Gender prevalence of kidney stones is often attributed to differences in diet and to a suggested greater capacity of men to concentrate urine. This may lead to differences in urinary excretion of lithogenesis promoters and inhibitors. Curhan et al. have found higher urinary excretion of stone promoters such as calcium, oxalate, uric acid and sodium among men than women. On the contrary, women presented higher urinary excretion of citrate which inhibits stone formation (Curhan et al. 2001).

 

Kidney stones are also more common in middle-aged adults, with the highest prevalence rates occurring in adults aged 30 to 50 years (Brenner and Rector 2008; Ferrari et al. 2007; Trinchieri et al. 2008). Incidence peaks vary between gender, with one peak around 35 observed in men, while two peaks are observed in women at 30 and around 55 years, which corresponds to a post-menopause period (Trinchieri et al. 2008).

III.1.4. Current change in gender prevalence

During the last two decades, a decrease in male-to-female ratios has however been observed (Marickar and Vijay 2009; Scales, Jr. et al. 2007; Strope et al. 2010; Trinchieri et al. 2008). Epidemiological studies show a general increase in the incidence of urolithiasis, however interestingly Figure 5 shows that it increased at a higher rate among women (Marickar and Vijay 2009; Scales, Jr. et al. 2007; Strope et al. 2010).

 

In their prospective cohort involving 1,091 female and 7,499 male stone patients, Marickar and Vijay highlighted a change in gender prevalence over four decades: as shown in Figure 6, the percentage of females among stone formers increased from 8% in the time period of 1971-1975, to 17% in 2003-2008 (Marickar and Vijay 2009). Similarly, on 204,594 hospital discharges of urinary stone patients, Scales et al. observed a decrease of the male-to-female ratio from 1.7:1 in 1997 to 1.3:1 in 2002 (Scales, Jr. et al. 2007). Changes in urinary excretion of various compounds among women could explain this trend: over the years, female excretions of calcium and oxalate increased while excretions of magnesium decreased. These changes in excretions are often attributed to changes in living standards and in dietary habits (Marickar and Vijay 2009). 

Graphics: Evolution of the number of hospitalizations for upper urinary tract stones

 

Figure 5. Incidence inpatient admissions for upper urinary stones. 

(Strope et al. 2010). 

 

Graphics: Increased prevalence of women in lithiasic topics

 

Figure 6. Increasing prevalence of female stone formers. 

(Marickar and Vijay 2009). 

 

III.2. Lifestyle related factors 

III.2.1. Calcium intake 

The impact of nutritional habits on kidney stone risk have been widely studied and reviewed. Diet is known to influence urine composition and to play a major role in kidney stone formation (Bartoletti et al. 2007; Brenner and Rector 2008; Curhan 2007; Hughes and Norman 1992; Trinchieri et al. 2008). Specifically, in a study of 91,731 women participating in the Nurses’ Health Study I, Curhan et al. showed that women who consumed supplemental calcium were at greater risk of kidney stones, with a relative risk of 1.20 compared to women who did not (Curhan et al. 1997b).

 

Many studies have also shown that without supplemental intake of calcium, a low calcium intake was associated with a higher risk of kidney stones. On 108 stone formers and 210 healthy subjects, Leonetti et al. observed a significantly lower calcium intake in stone formers (Leonetti et al. 1998). In another study involving 45,619 men from the Health Professional Follow-up Study (HPFS) cohort, men in the highest quintile of calcium intake (1,326mg/d) were less likely to develop kidney stones (relative risk of 0.66), as compared to the lowest quintile (516mg/d). This shows that a low calcium intake may increase the risk of kidney stone formation (Curhan et al. 1993). A low calcium intake (bellow 400mg/d) is actually associated with an increased intestinal absorption of oxalate. As oxalate is a promoter of kidney stones, this may explain the increased risk of stones. Official guidelines for calcium intake therefore recommend a balanced calcium intake (Tiselius et al. 2001).

III.2.2. Emerging dietary risk factors

Fluid intake as a risk factor was long overlooked but Borghi et al. found that low fluid intake increases the risk (Borghi et al. 1999c). This topic is widely addressed in sections IV, V, VI and VII below.

 

Other dietary factors such as intakes of animal proteins, purines and sodium are emerging and may be positively correlated to the risk of kidney stones (Brenner and Rector 2008; Ferrari et al. 2007). On the contrary, a high potassium intake may decrease the risk (Curhan et al. 1993). 

III.2.3. Association with other chronic diseases 

Epidemiological studies tend to show an association between kidney stones and other chronic diseases such as diabetes, obesity and hypertension (Bartoletti et al. 2007; Brenna et al. 2013; Daudon et al. 2012; Ramello et al. 2000).

 

Overweight and obesity appear to be related to the risk of kidney stones. Using data from 89,376 women and 51,529 men who participated in the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), Curhan et al. showed a positive correlation between BMI and history as well as BMI and incidence of kidney stones (Curhan et al. 1998). In a sample of 363 male and 164 female stone formers, Siener et al. found overweight and obesity in 59.2% of men and 43.9% of women (Siener et al. 2004). BMI was actually linked to several urinary risk factors. Evaluating 807 stone formers and 237 controls from NHS I, NHS II and HPFS, Curhan et al. reported a positive correlation between body weight and urinary excretions of calcium, but found no difference in excretions of oxalate and uric acid (Curhan et al. 2001). In a study involving 527 idiopathic calcium oxalate stone formers, Siener et al. found a positive correlation between BMI and (a) urinary excretion of uric acid in both men and women, (b) urinary calcium in men, and (c) urinary oxalate in women (Siener et al. 2004).

 

Diabetes mellitus is one consequence of obesity and is also thought to be an important risk factor for kidney stones. In a cross-sectional study including more than 200,000 subjects from NHS I, NHS II and HPFS, authors found that subjects with type 2 diabetes were at greater risk of stone disease (Taylor et al. 2005). More precisely, on 2464 stone patients (272 with and 2192 without type 2 diabetes), Daudon et al. tried to investigate whether this greater risk corresponded to higher rates of calcium stones, uric acid stones, or both. They confirmed that type 2 diabetes was associated with greater risk of stone, and they found that the relative proportion of uric acid stones was higher among diabetic patients than among non-diabetic (Daudon et al. 2006). This greater incidence has been attributed to a lower urine pH (Cameron et al. 2006; Hari Kumar and Modi 2011). Yet, Daudon et al. found that uric acid stone formers with type 2 diabetes presented higher fractional excretion of uric acid, and this excretion was reduced in patients with metabolic syndrome and without diabetes (Daudon et al. 2006).

 

Hypertension was also found to be positively correlated with the risk of kidney stones. Three studies reported a higher risk of nephrolithiasis among hypertensive subjects than among normotensives (Borghi et al. 1999b; Cappuccio et al. 1999; Madore et al. 1998). Urinary analysis of hypertensive compared to normotensive subjects showed greater urinary supersaturation of calcium oxalate in women, and of calcium oxalate and calcium phosphate in men (Borghi et al. 1999b). In parallel, a higher prevalence of hypertension was noted among stone formers (Cappuccio et al. 1999). This strong association between hypertension and nephrolithiasis has been attributed to common risk factors such as overweight and high dietary intakes of animal protein and salt (Borghi et al. 1999b; Ramello et al. 2000). 

 

Take home messages

Risk factors for urolithiasis include age, gender and ethnicity, as well as geography, diet and lifestyle. Prevalence of kidney stones approaches 10% worldwide and is increasing. Epidemiological studies have suggested that obesity, diabetes and hypertension may increase the risk of developing kidney stones.

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