Table 4.
Role of major and trace elements in the formation of kidney stones with some references of recent studies
| Elements | Issue studied related to kidney stones | References | Role in lithogenesis |
|---|---|---|---|
| Calcium (Ca) | -High Ca intake has been associated with a lower risk for kidney stones. | Bihl and Meyers 2001; Stoller and Meng 2007 | Ca plays an important role in lithogenesis. |
| -Ca is the predominant element in stones which influences the distribution trace elements. Ca ion promotes the formation and growth of intrarenal crystals. | Basavaraj et al. 2005 | ||
| -Higher concentration of Ca has been observed in the center, shell and surface parts of the kidney stones. | Joost and Tessadri 1987; Barbas et al. 2002; Schubert 2006; Chaudhri et al. 2007 | ||
| Magnesium (Mg) | -Mg is the fourth most abundant element in the body; only 1 % of total Mg is found in blood and the rest is present in combination with Ca and P. | Escott-Stump 2007 | Mg acts as a potential inhibitor in formation of kidney stones. |
| -In vitro studies have demonstrated decreased nucleation and growth of calcium oxalate crystals in the presence of superphysiological concentrations of Mg. Supplementation with Mg and vitamin B6 significantly lowers the risk of kidney stone formation. | Kohri et al. 1988; Johansson et al. 1980; Lindberg et al. 1990 | ||
| -Low concentration of Mg in urine is a risk factor for kidney stone formation. | Durak et al. 1990; Meyer and Angino 1977; Scott et al. 1980 | ||
| -Dietary Mg deficiency causes experimental urolithiasis, and high levels of this element in urine reduce the concentration of oxalate available for calcium oxalate precipitation. | Robertson 1969 | ||
| -Mg inhibits calcium oxalate crystallization in human urine and it also inhibits absorption of dietary oxalate from the gut lumen. | Massey 2005 | ||
| Manganese (Mn) | -Mn is associated with bone development and plays an important role in the metabolic pathway of amino acids, lipids, carbohydrates and proteins. | Fraga 2005 | Role of Mn in kidney stone formation is still not clear. |
| -Mn levels have been found to be lower in the serum and urine of stone patients than in healthy people. | Trinchieri et al. 1991; Komleh et al. 1990 | ||
| -Low level of Mn might interfere with the fragility of urinary stones in extracorporeal shockwave lithotripsy (ESWL) therapy. | Turgut et al. 2008 | ||
| -It was suggested that Mn as well as other elements, such as Ni, Li and Cd, could be of significance in the pathological mechanism of stone formation. | Hofbauer et al. 1991 | ||
| Copper (Cu) | -Cu is an antioxidant and its highest concentration is found in the liver, kidney, heart and brain. Chronic (long-term) effect of Cu exposure can damage the liver and kidney. | New Hampshire Department of Environmental Services 2005 | Cu shows its inhibitory activity against growth of calcium phosphate crystals but not on oxalate. |
| -It was firstly pointed out by Bird et al. (1963) that Cu shows the inhibitory effect on the mineralization process of rachitic rats’ cartilage. | Bird and Thomas 1963 | ||
| -Cu and Mn urinary levels were found to be lower in stone formers than in normal subjects. | Komleh et al. 1990 | ||
| -The inhibitory activity of Cu against growth of calcium phosphate crystals was observed, but not on oxalate. | Meyer and Angino 1977 | ||
| -It has been observed that the amount of Cu stored in the stones is more relevant when compared to Zn, especially in oxalate stones. | Joost and Tessadri 1987 | ||
| Iron (Fe) | -Fe is considered to be an inhibitor of oxalate stones. However, more extensive research is needed to elucidate its role in lithogenesis. | Lieu et al. 2001; Elliot and Ribeiro 1973 | Fe is considered to be an inhibitor of oxalate stones. However, more extensive research is needed to elucidate its role in lithogenesis. |
| -Non-Ca stones have beens reported to have a lower content of Fe than Ca-containing stones. | Bazin et al. 2007; Joost and Tessadri 1987; Levinson et al. 1978 | ||
| -The Fe3+ ions have the ability to establish stable chemical interactions with oxalate ions on the surface of calcium oxalate crystals. | Durak et al. 1992; Munoz and Valiente 2005 | ||
| -An increased 24-h urinary Fe excretion was reported in calcium oxalate stone patients compared with healthy persons. | Atakan et al. 2007; Meyer and Angino 1977 | ||
| Potassium (K) | -K is important for many functions in the human body and has a role in maintaining normal Ca balance in the body as K decreases urinary loss of Ca. It is reported that the lower the K intake below 74 mmol/day, higher the relative risk of stone formation. Such an effect can be ascribed to an increase in urinary Ca and a decrease in urinary citrate excretion induced by a low K intake. | Curhan et al. 1993; Lemann et al. 1991 | K together with Mg can help prevent calcium oxalate kidney stones. |
| -A low–normal K intake and a higher NaCl intake were also observed in stone formers as compared to healthy people. | Borsatti 1991 | ||
| -A sgnificantly higher urine Na/K ratio was observed to increase the risk of stone formation. | Martini et al. 1998; Cirillo et al. 1994 | ||
| -Higher K intake was recommended in order to prevent kidney stone formation. Potassium magnesium citrate reduces the risk of developing calcium oxalate stones. | Ettinger et al. 1997 | ||
| Zinc (Zn) | -Zn is an essential trace element and its deficiency can enhance the expression of angiotensis II that constricts the blood vessels in kidneys and further aggravates the condition of individuals with obstructive kidney disease. | Yanagisawa et al. 2000 | More extensive research is needed to determine the exact role of Zn in lithogenesis. |
| -It has been described as an inhibitor of urinary stone formation but its exact role is divergent. | Hofbauer et al. 1991; Komleh et al. 1990 | ||
| -The higher content of Zn in weddellite stones than whewellite stones is reported, which may be linked to the fact that weddellite is formed during the first phase of the crystallization process and subsequently transforms to whewellite. | Bazin et al. 2007; Joost and Tessadri 1987; Hofbauer et al. 1991; Levinson et al. 1978 | ||
| -It was found in higher concentrations in Ca-containing stones but also in organic urinary stones compared to other trace elements. | Atakan et al. 2007; Bazin et al. 2007; Joost and Tessadri 1987; Levinson et al. 1978 | ||
| -Its inhibitory effect was observed only on calcium phosphate stones but not on calcium oxalate growth. | Meyer & Angino 1977 | ||
| -calcium phosphate stones were reported to have a higher Zn content than calcium oxalate stones. By contrast, brusite stones contain significantly less Zn than carbonate apatite stones. | Bazin et al. 2007; Levinson et al. 1978 | ||
| -Significantly higher amounts of Zn have also been observed in urinary excretion of stone patients. | Trinchieri et al. 1991; Komleh et al. 1990; Rangnekar and Gaur 1993; Ozgurtas et al. 2004; Kumar et al. 1984; Francois et al. 1986; Anke and Schneider 1973; Elliot and Ribeiro 1973) | ||
| -Some authors detected no differences relating to Zn urinary excretion between healthy people and stone patients. | Welshman & McGeown 1972; Hofbauer et al. 1991; Cohanim and Yendt 1975 | ||
| -In some studies, serum Zn is lower in stone patients than in healthy controls. | Pak 1998; Moe 2006; Parsons 1953 | ||
| -Healthy controls were found to have significantly high urinary and serum Zn levels than stone patients. Study documented that mean Zn levels have an inhibitory effect on calcium oxalate stone formation. | Atakan et al. 2007 | ||
| -Trace elements like Zn, Fe, and Mn appear to interfere with whewellite stone fragility. | Turgut et al. 2008 | ||
| Cadmium (Cd) | -Cd is a widely disseminated metal that can be accumulated in living cells, thereby drastically interfering with their biological mechanisms. Increased concentrations of urinary beta-2 microglobulin can be an early indicator of renal dysfunction in persons chronically exposed to low but excessive levels of environmental Cd. The urinary beta-2 microglobulin test is an indirect method of measuring Cd exposure. The long-term exposure of Cd leads to renal damage due to massive low weight tubular proteinuria. | http://www.atsdr.cdc.gov/csem/csem.asp?csem=6&po=10; Järup et al. 2000; Kjellström et al. 1977; Iwata et al. 1993 | The experimental findings clearly reveal that Cd plays an important role in kidney formation. |
| -A study of almost 2,700 renal cadaver samples showed that subjects who had died of renal disease had lower Cd concentrations. | Lyon et al. 1999 | ||
| -Its inhibitory effect on calcium oxalate crystallization was also suggested. | Hofbauer et al. 1991 | ||
| -Cd exposure has been found associated with a greater risk of kidney stone formation. | Ferraro et al. 2011 | ||
| -Recently, Swaddiwudhipong et al. (2011) found an increase in stone prevalence with increasing urinary Cd levels observed in both genders. A positive association was found between urinary Cd levels and stone prevalence. Finally, they documented that elevated calciuria induced by Cd might increase the risk of urinary stone formation in environmentally exposed population. | Swaddiwudhipong et al. 2011 | ||
| -Some authors have also noted the increased prevalence of kidney stones in workers exposed to Cd which is possibly related to the increased urinary excretion of Ca or tubular damage. | Järup et al. 1998 | ||
| Boron (B) | -B is an ultra-trace element which is essential for healthy bone and joint function and effects on the balance and absorption of Ca, Mg and P. It is efficiently absorbed and excreted in the urine. Its deficiency seems to affect Ca and Mg metabolism, and affects the composition, structure and strength of bone. Due to its effects on Ca and Mg metabolism, B deficiency may also contribute to the formation of kidney stones. | McCoy et al. 1994; Nielsen 1994 | More extensive research is needed to elucidate its role in lithogenesis. |
| -Hunt et al. (1997) reported low calcium oxalate urine excretion in postmenopausal women as a metabolic response to dietary B supplementation during low Mg intake. It is well reported that sodium borate is the most common form of supplement. B is increasingly used in Ca and bone replenishing nutritional formulas. It may be particularly useful in those whose Mg intake is low. This effect may be useful in the prevention of kidney stones. | Hunt et al. 1997 | ||
| -Low concentration of B has been observed in patients with cystine stones. | Słojewski 2011 | ||
| Selenium (Se) | -Se is an essential trace element in humans and its deficiency has been found to induce renal calcification. Experimental and clinical studies have shown that Se has an inhibitory effect on urolithiasis. | Rayman 2000; Fujieda et al. 2007; Kumar & Selvam 2003 | The experimental findings indicate that Se act as an inhibitor to the stone formation. |
| -Supplementation of Se and vitamin E prevents hyperoxaluria in experimental urolithic rats by decreasing the level of lipid peroxidation and the activities of oxalate synthesizing enzymes such as xanthine oxidase. | Kumar & Selvam 2003 | ||
| -The oxalate and Ca concentration can also be reduced and the process of crystallization can be inhibited by Se which acts as nephroprotective antioxidant. | Lahme et al. 2004 | ||
| -Recently, Sakly et al. (2003) documented that Se is one of the stone formation inhibitors which could adhere to the crystal surface and would inhibit the induction of new crystals, growth and aggregation. | Sakly et al. 2003 |