Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Kidney stones

A Correction to this article was published on 12 January 2017

Abstract

Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. They contain crystalline and organic components and are formed when the urine becomes supersaturated with respect to a mineral. Calcium oxalate is the main constituent of most stones, many of which form on a foundation of calcium phosphate called Randall's plaques, which are present on the renal papillary surface. Stone formation is highly prevalent, with rates of up to 14.8% and increasing, and a recurrence rate of up to 50% within the first 5 years of the initial stone episode. Obesity, diabetes, hypertension and metabolic syndrome are considered risk factors for stone formation, which, in turn, can lead to hypertension, chronic kidney disease and end-stage renal disease. Management of symptomatic kidney stones has evolved from open surgical lithotomy to minimally invasive endourological treatments leading to a reduction in patient morbidity, improved stone-free rates and better quality of life. Prevention of recurrence requires behavioural and nutritional interventions, as well as pharmacological treatments that are specific for the type of stone. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more-effective drugs.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Macroscopic and microscopic morphology of human kidneys and location of stones.
Figure 2: Calcium oxalate kidney stones examined using scanning electron microscopy.
Figure 3: Scanning electron microscopy and transmission electron microscopy of kidney stones.
Figure 4: The renal interstitium of a calcium oxalate stone former with Randall's plaque.
Figure 5: The renal papillary surface of a calcium oxalate monohydrate stone former examined using scanning electron microscopy.
Figure 6: Randall's plaque and calcium oxalate stone formation.
Figure 7: Algorithm for the most common approaches to surgical treatment of kidney stones.
Figure 8: Potential methods to interfere with abnormal crystallization and stone formation.

References

  1. 1

    Khan, S. R. Nephrocalcinosis in animal models with and without stones. Urol. Res. 38, 429–438 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2

    Finlayson, B. Physicochemical aspects of urolithiasis. Kidney Int. 13, 344–360 (1978).

    Article  CAS  PubMed  Google Scholar 

  3. 3

    Evan, A. P. Physiopathology and etiology of stone formation in the kidney and the urinary tract. Pediatr. Nephrol. 25, 831–841 (2010).

    Article  PubMed  Google Scholar 

  4. 4

    Tattevin, P. et al. Increased risk of renal stones in patients treated with atazanavir. Clin. Infect. Dis. 56, 1186 (2013).

    Article  PubMed  Google Scholar 

  5. 5

    Izzedine, H., Lescure, F. X. & Bonnet, F. HIV medication-based urolithiasis. Clin. Kidney J. 7, 121–126 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Raheem, O. A. et al. Prevalence of nephrolithiasis in human immunodeficiency virus infected patients on the highly active antiretroviral therapy. J. Endourol. 26, 1095–1098 (2012).

    Article  PubMed  Google Scholar 

  7. 7

    Bischoff, K. & Rumbeiha, W. K. Pet food recalls and pet food contaminants in small animals. Vet. Clin. North Am. Small Anim. Pract. 42, 237–250 (2012).

    Article  PubMed  Google Scholar 

  8. 8

    Cianciolo, R. E. et al. Clinicopathologic, histologic, and toxicologic findings in 70 cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid. J. Am. Vet. Med. Assoc. 233, 729–737 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. 9

    Gabriels, G., Lambert, M., Smith, P., Wiesner, L. & Hiss, D. Melamine contamination in nutritional supplements — is it an alarm bell for the general consumer, athletes, and ‘Weekend Warriors’? Nutr. J. 14, 69 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Ding, J. Childhood urinary stones induced by melamine-tainted formula: how much we know, how much we don't know. Kidney Int. 75, 780–782 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. 11

    Fink, H. A. et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann. Intern. Med. 158, 535–543 (2013).

    Article  PubMed  Google Scholar 

  12. 12

    Scales, C. D., Smith, A. C., Hanley, J. M. & Saigal, C. S. Prevalence of kidney stones in the United States. Eur. Urol. 62, 160–165 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13

    Obligado, S. H. & Goldfarb, D. S. The association of nephrolithiasis with hypertension and obesity: a review. Am. J. Hypertens. 21, 257–264 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. 14

    Brikowski, T. H., Lotan, Y. & Pearle, M. S. Climate-related increase in the prevalence of urolithiasis in the United States. Proc. Natl Acad. Sci. USA 105, 9841–9846 (2008).

    Article  PubMed  Google Scholar 

  15. 15

    Taylor, E. N., Stampfer, M. J. & Curhan, G. C. Obesity, weight gain, and the risk of kidney stones. JAMA 293, 455–462 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. 16

    Daudon, M. & Jungers, P. Diabetes and nephrolithiasis. Curr. Diab. Rep. 7, 443–448 (2007).

    Article  PubMed  Google Scholar 

  17. 17

    Lieske, J. C. et al. Diabetes mellitus and the risk of urinary tract stones: a population-based case–control study. Am. J. Kidney Dis. 48, 897–904 (2006).

    Article  PubMed  Google Scholar 

  18. 18

    Taylor, E. N., Stampfer, M. J. & Curhan, G. C. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. 68, 1230–1235 (2005).

    Article  PubMed  Google Scholar 

  19. 19

    Strazzullo, P. et al. Past history of nephrolithiasis and incidence of hypertension in men: a reappraisal based on the results of the Olivetti Prospective Heart study. Nephrol. Dial. Transplant. 16, 2232–2235 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. 20

    Johri, N. et al. An update and practical guide to renal stone management. Nephron Clin. Pract. 116, c159–c171 (2010).

    Article  PubMed  Google Scholar 

  21. 21

    Cappuccio, F. P., Strazzullo, P. & Mancini, M. Kidney stones and hypertension: population based study of an independent clinical association. BMJ 300, 1234–1236 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Rule, A. D., Krambeck, A. E. & Lieske, J. C. Chronic kidney disease in kidney stone formers. Clin. J. Am. Soc. Nephrol. 6, 2069–2075 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23

    El-Zoghby, Z. M. et al. Urolithiasis and the risk of ESRD. Clin. J. Am. Soc. Nephrol. 7, 1409–1415 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24

    Shoag, J., Halpern, J., Goldfarb, D. S. & Eisner, B. H. Risk of chronic and end stage kidney disease in patients with nephrolithiasis. J. Urol. 192, 1440–1445 (2014).

    Article  PubMed  Google Scholar 

  25. 25

    Keddis, M. T. & Rule, A. D. Nephrolithiasis and loss of kidney function. Curr. Opin. Nephrol. Hypertens. 22, 390–396 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26

    Department of Health and Human Services USA, National Institutes of Health & National Institute of Diabetes and Digestive and Kidney Diseases. Urologic Diseases in America (US Government Printing Office, 2012).

  27. 27

    Romero, V., Akpinar, H. & Assimos, D. G. Kidney stones: a global picture of prevalence, incidence, and associated risk factors. Rev. Urol. 12, e86–e96 (2010).

    PubMed  PubMed Central  Google Scholar 

  28. 28

    Stamatelou, K. K., Francis, M. E., Jones, C. A., Nyberg, L. M. & Curhan, G. C. Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int. 63, 1817–1823 (2003).

    Article  PubMed  Google Scholar 

  29. 29

    Turney, B. W., Reynard, J. M., Noble, J. G. & Keoghane, S. R. Trends in urological stone disease. BJU Int. 109, 1082–1087 (2012).

    Article  PubMed  Google Scholar 

  30. 30

    Scales, C. D. et al. Changing gender prevalence of stone disease. J. Urol. 177, 979–982 (2007).

    Article  PubMed  Google Scholar 

  31. 31

    Lieske, J. C. et al. Renal stone epidemiology in Rochester, Minnesota: an update. Kidney Int. 69, 760–764 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. 32

    Strope, S. A., Wolf, J. S. & Hollenbeck, B. K. Changes in gender distribution of urinary stone disease. Urology 75, 543–546.e1 (2010).

    Article  PubMed  Google Scholar 

  33. 33

    Ordon, M. et al. A population based study of the changing demographics of patients undergoing definitive treatment for kidney stone disease. J. Urol. 193, 869–874 (2015).

    Article  PubMed  Google Scholar 

  34. 34

    Curhan, G. C., Rimm, E. B., Willett, W. C. & Stampfer, M. J. Regional variation in nephrolithiasis incidence and prevalence among United States men. J. Urol. 151, 838–841 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. 35

    Soucie, J. M., Thun, M. J., Coates, R. J., McClellan, W. & Austin, H. Demographic and geographic variability of kidney stones in the United States. Kidney Int. 46, 893–899 (1994).

    Article  CAS  PubMed  Google Scholar 

  36. 36

    Mandel, N. S. & Mandel, G. S. Urinary tract stone disease in the United States veteran population. II. Geographical analysis of variations in composition. J. Urol. 142, 1516–1521 (1989).

    Article  CAS  PubMed  Google Scholar 

  37. 37

    Mandel, N. S. & Mandel, G. S. Urinary tract stone disease in the United States veteran population. I. Geographical frequency of occurrence. J. Urol. 142, 1513–1515 (1989).

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Curhan, G. C., Willett, W. C., Rimm, E. B., Speizer, F. E. & Stampfer, M. J. Body size and risk of kidney stones. J. Am. Soc. Nephrol. 9, 1645–1652 (1998).

    CAS  PubMed  Google Scholar 

  39. 39

    Sorensen, M. D. et al. Activity, energy intake, obesity, and the risk of incident kidney stones in postmenopausal women: a report from the Women's Health Initiative. J. Am. Soc. Nephrol. 25, 362–369 (2014).

    Article  PubMed  Google Scholar 

  40. 40

    Chung, S.-D., Chen, Y.-K. & Lin, H.-C. Increased risk of diabetes in patients with urinary calculi: a 5-year followup study. J. Urol. 186, 1888–1893 (2011).

    Article  PubMed  Google Scholar 

  41. 41

    West, B. et al. Metabolic syndrome and self-reported history of kidney stones: the National Health and Nutrition Examination Survey (NHANES III)1988–1994. Am. J. Kidney Dis. 51, 741–747 (2008).

    Article  PubMed  Google Scholar 

  42. 42

    Jeong, I. G. et al. Association between metabolic syndrome and the presence of kidney stones in a screened population. Am. J. Kidney Dis. 58, 383–388 (2011).

    Article  PubMed  Google Scholar 

  43. 43

    Ferraro, P. M. et al. History of kidney stones and the risk of coronary heart disease. JAMA 310, 408–415 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Alexander, R. T. et al. Kidney stones and cardiovascular events: a cohort study. Clin. J. Am. Soc. Nephrol. 9, 506–512 (2014).

    Article  PubMed  Google Scholar 

  45. 45

    Rule, A. D. et al. Kidney stones associate with increased risk for myocardial infarction. J. Am. Soc. Nephrol. 21, 1641–1644 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46

    Khan, S. R. & Hackett, R. L. Role of organic matrix in urinary stone formation: an ultrastructural study of crystal matrix interface of calcium oxalate monohydrate stones. J. Urol. 150, 239–245 (1993).

    Article  CAS  PubMed  Google Scholar 

  47. 47

    Ryall, R. L., Chauvet, M. C. & Grover, P. K. Intracrystalline proteins and urolithiasis: a comparison of the protein content and ultrastructure of urinary calcium oxalate monohydrate and dihydrate crystals. BJU Int. 96, 654–663 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. 48

    McKee, M. D., Nanci, A. & Khan, S. R. Ultrastructural immunodetection of osteopontin and osteocalcin as major matrix components of renal calculi. J. Bone Miner. Res. 10, 1913–1929 (1995).

    Article  CAS  PubMed  Google Scholar 

  49. 49

    Khan, S. R. & Kok, D. J. Modulators of urinary stone formation. Front. Biosci. 9, 1450–1482 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. 50

    Atmani, F. & Khan, S. R. Role of urinary bikunin in the inhibition of calcium oxalate crystallization. J. Am. Soc. Nephrol. 10, S385–S388 (1999).

    CAS  PubMed  Google Scholar 

  51. 51

    Ryall, R. L. Macromolecules and urolithiasis: parallels and paradoxes. Nephron Physiol. 98, 37–42 (2004).

    Article  Google Scholar 

  52. 52

    Khan, S. R. et al. Lipids and membranes in the organic matrix of urinary calcific crystals and stones. Calcif. Tissue Int. 59, 357–365 (1996).

    Article  CAS  PubMed  Google Scholar 

  53. 53

    Khan, S. R. & Glenton, P. A. Increased urinary excretion of lipids by patients with kidney stones. Br. J. Urol. 77, 506–511 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. 54

    Khan, S. R., Glenton, P. A., Backov, R. & Talham, D. R. Presence of lipids in urine, crystals and stones: implications for the formation of kidney stones. Kidney Int. 62, 2062–2072 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. 55

    Khan, S. R., Shevock, P. N. & Hackett, R. L. In vitro precipitation of calcium oxalate in the presence of whole matrix or lipid components of the urinary stones. J. Urol. 139, 418–422 (1988).

    Article  CAS  PubMed  Google Scholar 

  56. 56

    Khan, S. R., Shevock, P. N. & Hackett, R. L. Membrane-associated crystallization of calcium oxalate in vitro. Calcif. Tissue Int. 46, 116–120 (1990).

    Article  CAS  PubMed  Google Scholar 

  57. 57

    Hunter, G. K. Role of osteopontin in modulation of hydroxyapatite formation. Calcif. Tissue Int. 93, 348–354 (2013).

    Article  CAS  PubMed  Google Scholar 

  58. 58

    Khan, S. R., Johnson, J. M., Peck, A. B., Cornelius, J. G. & Glenton, P. A. Expression of osteopontin in rat kidneys: induction during ethylene glycol induced calcium oxalate nephrolithiasis. J. Urol. 168, 1173–1181 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. 59

    Khan, S. R., Joshi, S., Wang, W. & Peck, A. B. Regulation of macromolecular modulators of urinary stone formation by reactive oxygen species: transcriptional study in an animal model of hyperoxaluria. Am. J. Physiol. Renal Physiol. 306, F1285–F1295 (2014). This is the first study to demonstrate the involvement of reactive oxygen species in the regulation of macromolecular production.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Aihara, K., Byer, K. J. & Khan, S. R. Calcium phosphate-induced renal epithelial injury and stone formation: involvement of reactive oxygen species. Kidney Int. 64, 1283–1291 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. 61

    Daudon, M., Doré, J.-C., Jungers, P. & Lacour, B. Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach. Urol. Res. 32, 241–247 (2004).

    Article  PubMed  Google Scholar 

  62. 62

    Khan, S. R. & Hackett, R. L. Identification of urinary stone and sediment crystals by scanning electron microscopy and X-ray microanalysis. J. Urol. 135, 818–825 (1986).

    Article  CAS  PubMed  Google Scholar 

  63. 63

    Siener, R., Netzer, L. & Hesse, A. Determinants of brushite stone formation: a case–control study. PLoS ONE 8, e78996 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Sakhaee, K., Adams-Huet, B., Moe, O. W. & Pak, C. Y. C. Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int. 62, 971–979 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. 65

    Fellström, B. et al. The influence of a high dietary intake of purine-rich animal protein on urinary urate excretion and supersaturation in renal stone disease. Clin. Sci. (Lond.) 64, 399–405 (1983).

    Article  Google Scholar 

  66. 66

    Grases, F., Villacampa, A. I., Costa-Bauzá, A. & Söhnel, O. Uric acid calculi: types, etiology and mechanisms of formation. Clin. Chim. Acta 302, 89–104 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. 67

    Khan, S. R., Hackett, R. L. & Finlayson, B. Morphology of urinary stone particles resulting from ESWL treatment. J. Urol. 136, 1367–1372 (1986).

    Article  CAS  PubMed  Google Scholar 

  68. 68

    Griffith, D. P. & Osborne, C. A. Infection (urease) stones. Miner. Electrolyte Metab. 13, 278–285 (1987).

    CAS  PubMed  Google Scholar 

  69. 69

    Biyani, C. S. & Cartledge, J. J. Cystinuria — diagnosis and management. EAU–EBU Updat. Ser. 4, 175–183 (2006).

    Article  Google Scholar 

  70. 70

    Robertson, W. G., Peacock, M. & Nordin, B. E. Calcium oxalate crystalluria and urine saturation in recurrent renal stone-formers. Clin. Sci. 40, 365–374 (1971).

    Article  CAS  PubMed  Google Scholar 

  71. 71

    Finlayson, B. & Reid, F. The expectation of free and fixed particles in urinary stone disease. Invest. Urol. 15, 442–448 (1978).

    CAS  PubMed  Google Scholar 

  72. 72

    Robertson, W. G. Measurement of ionized calcium in biological fluids. Clin. Chim. Acta 24, 149–157 (1969).

    Article  CAS  PubMed  Google Scholar 

  73. 73

    Werness, P. G., Brown, C. M., Smith, L. H. & Finlayson, B. EQUIL2: a BASIC computer program for the calculation of urinary saturation. J. Urol. 134, 1242–1244 (1985).

    Article  CAS  PubMed  Google Scholar 

  74. 74

    May, P. M. & Muray, K. JESS, a joint expert speciation system-II. The thermodynamic database. Talanta 38, 1419–1426 (1991).

    Article  CAS  PubMed  Google Scholar 

  75. 75

    Brown, C. M., Ackermann, D. K. & Purich, D. L. EQUIL93: a tool for experimental and clinical urolithiasis. Urol. Res. 22, 119–126 (1994).

    Article  CAS  PubMed  Google Scholar 

  76. 76

    Robertson, W. G. Factors affecting the precipitation of calcium phosphate in vitro. Calcif. Tissue Res. 11, 311–322 (1973).

    Article  CAS  PubMed  Google Scholar 

  77. 77

    Kok, D. J. & Khan, S. R. Calcium oxalate nephrolithiasis, a free or fixed particle disease. Kidney Int. 46, 847–854 (1994).

    Article  CAS  PubMed  Google Scholar 

  78. 78

    Robertson, W. G. Potential role of fluctuations in the composition of renal tubular fluid through the nephron in the initiation of Randall's plugs and calcium oxalate crystalluria in a computer model of renal function. Urolithiasis 43 (Suppl. 1), 93–107 (2015).

    Article  CAS  PubMed  Google Scholar 

  79. 79

    Fleisch, H. & Bisaz, S. The inhibitory effect of pyrophosphate on calcium oxalate precipitation and its relation to urolithiasis. Experientia 20, 276–277 (1964).

    Article  CAS  PubMed  Google Scholar 

  80. 80

    Fleisch, H. & Bisaz, S. Isolation from urine of pyrophosphate, a calcification inhibitor. Am. J. Physiol. 203, 671–675 (1962).

    Article  CAS  PubMed  Google Scholar 

  81. 81

    Asplin, J. R., Mandel, N. S. & Coe, F. L. Evidence of calcium phosphate supersaturation in the loop of Henle. Am. J. Physiol. 270, F604–F613 (1996).

    CAS  PubMed  Google Scholar 

  82. 82

    Khan, S. R. & Hackett, R. L. Developmental morphology of calcium oxalate foreign body stones in rats. Calcif. Tissue Int. 37, 165–173 (1985).

    Article  CAS  PubMed  Google Scholar 

  83. 83

    Khan, S. R. & Hackett, R. L. Urolithogenesis of mixed foreign body stones. J. Urol. 138, 1321–1328 (1987).

    Article  CAS  PubMed  Google Scholar 

  84. 84

    Linnes, M. P. et al. Phenotypic characterization of kidney stone formers by endoscopic and histological quantification of intrarenal calcification. Kidney Int. 84, 818–825 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Wang, X. et al. Distinguishing characteristics of idiopathic calcium oxalate kidney stone formers with low amounts of Randall's plaque. Clin. J. Am. Soc. Nephrol. 9, 1757–1763 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Khan, S. R. Experimental calcium oxalate nephrolithiasis and the formation of human urinary stones. Scanning Microsc. 9, 89–100; discussion 100–101 (1995).

    CAS  PubMed  Google Scholar 

  87. 87

    Randall, A. The etiology of primary renal calculus. Int. Abstr. Surg. 71, 209–240 (1940).

    Google Scholar 

  88. 88

    Khan, S. R. & Canales, B. K. Unified theory on the pathogenesis of Randall's plaques and plugs. Urolithiasis 43 (Suppl. 1), 109–123 (2015).

    Article  CAS  PubMed  Google Scholar 

  89. 89

    Bushinsky, D. A., Frick, K. K. & Nehrke, K. Genetic hypercalciuric stone-forming rats. Curr. Opin. Nephrol. Hypertens. 15, 403–418 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. 90

    Khan, S. R. & Canales, B. K. Ultrastructural investigation of crystal deposits in Npt2a knockout mice: are they similar to human Randall's plaques? J. Urol. 186, 1107–1113 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. 91

    Khan, S. R. & Hackett, R. L. Retention of calcium oxalate crystals in renal tubules. Scanning Microsc. 5, 707–711; discussion 711–712 (1991).

    CAS  PubMed  Google Scholar 

  92. 92

    Khan, S. R., Finlayson, B. & Hackett, R. L. Experimental calcium oxalate nephrolithiasis in the rat. Role of the renal papilla. Am. J. Pathol. 107, 59–69 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Evan, A. P. et al. Crystal-associated nephropathy in patients with brushite nephrolithiasis. Kidney Int. 67, 576–591 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. 94

    Evan, A. P. et al. Renal crystal deposits and histopathology in patients with cystine stones. Kidney Int. 69, 2227–2235 (2006).

    Article  CAS  PubMed  Google Scholar 

  95. 95

    Evan, A. P. et al. Renal intratubular crystals and hyaluronan staining occur in stone formers with bypass surgery but not with idiopathic calcium oxalate stones. Anat. Rec. (Hoboken) 291, 325–334 (2008).

    Article  Google Scholar 

  96. 96

    Coe, F. L., Evan, A. P., Lingeman, J. E. & Worcester, E. M. Plaque and deposits in nine human stone diseases. Urol. Res. 38, 239–247 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  97. 97

    Evan, A. P., Worcester, E. M., Coe, F. L., Williams, J. & Lingeman, J. E. Mechanisms of human kidney stone formation. Urolithiasis 43 (Suppl. 1), 19–32 (2015).

    Article  PubMed  Google Scholar 

  98. 98

    Evan, A. E. et al. Histopathology and surgical anatomy of patients with primary hyperparathyroidism and calcium phosphate stones. Kidney Int. 74, 223–229 (2008).

    Article  CAS  PubMed  Google Scholar 

  99. 99

    Khan, S. R., Finlayson, B. & Hackett, R. Renal papillary changes in patient with calcium oxalate lithiasis. Urology 23, 194–199 (1984).

    Article  CAS  PubMed  Google Scholar 

  100. 100

    Khan, S. R., Rodriguez, D. E., Gower, L. B. & Monga, M. Association of Randall plaque with collagen fibers and membrane vesicles. J. Urol. 187, 1094–1100 (2012). This is the first study to discuss the initiation of Randall's plaque through the deposition of CaP in membrane-bound vesicles and plaque growth via the renal interstitium by mineralization of collagen fibres.

  101. 101

    Coe, F. L., Evan, A. P., Worcester, E. M. & Lingeman, J. E. Three pathways for human kidney stone formation. Urol. Res. 38, 147–160 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  102. 102

    Randall, A. Recent advances in knowledge relating to the formation, recognition and treatment of kidney calculi. Bull. N. Y. Acad. Med. 20, 473–484 (1944).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Cooke, S. A. The site of calcification in the human renal papilla. Br. J. Surg. 57, 890–896 (1970).

    Article  CAS  PubMed  Google Scholar 

  104. 104

    Evan, A. P. et al. Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle. J. Clin. Invest. 111, 607–616 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. 105

    Stoller, M. L., Low, R. K., Shami, G. S., McCormick, V. D. & Kerschmann, R. L. High resolution radiography of cadaveric kidneys: unraveling the mystery of Randall's plaque formation. J. Urol. 156, 1263–1266 (1996). This paper provided the first suggestion that plaques might start in the vasa recta.

    Article  CAS  PubMed  Google Scholar 

  106. 106

    Stoller, M. L., Meng, M. V., Abrahams, H. M. & Kane, J. P. The primary stone event: a new hypothesis involving a vascular etiology. J. Urol. 171, 1920–1924 (2004).

    Article  PubMed  Google Scholar 

  107. 107

    Haggitt, R. C. & Pitcock, J. A. Renal medullary calcifications: a light and electron microscopic study. J. Urol. 106, 342–347 (1971).

    Article  CAS  PubMed  Google Scholar 

  108. 108

    Weller, R. O., Nester, B. & Cooke, S. A. Calcification in the human renal papilla: an electron-microscope study. J. Pathol. 107, 211–216 (1972).

    Article  CAS  PubMed  Google Scholar 

  109. 109

    Miller, N. L. et al. A formal test of the hypothesis that idiopathic calcium oxalate stones grow on Randall's plaque. BJU Int. 103, 966–971 (2009).

    Article  CAS  PubMed  Google Scholar 

  110. 110

    Evan, A. P. et al. Apatite plaque particles in inner medulla of kidneys of calcium oxalate stone formers: osteopontin localization. Kidney Int. 68, 145–154 (2005).

    Article  CAS  PubMed  Google Scholar 

  111. 111

    Evan, A. P. et al. Renal inter-α-trypsin inhibitor heavy chain 3 increases in calcium oxalate stone-forming patients. Kidney Int. 72, 1503–1511 (2007).

    Article  CAS  PubMed  Google Scholar 

  112. 112

    Evan, A., Lingeman, J., Coe, F. L. & Worcester, E. Randall's plaque: pathogenesis and role in calcium oxalate nephrolithiasis. Kidney Int. 69, 1313–1318 (2006).

    Article  CAS  PubMed  Google Scholar 

  113. 113

    Carpentier, X. et al. High Zn content of Randall's plaque: a μ-X-ray fluorescence investigation. J. Trace Elem. Med. Biol. 25, 160–165 (2011).

    Article  CAS  PubMed  Google Scholar 

  114. 114

    Evan, A. P., Lingeman, J. E., Coe, F. L. & Worcester, E. M. Role of interstitial apatite plaque in the pathogenesis of the common calcium oxalate stone. Semin. Nephrol. 28, 111–119 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Khan, S. R. & Gambaro, G. Role of osteogenesis in the formation of Randall's plaques. Anat. Rec. (Hoboken) 299, 5–7 (2015).

    Article  Google Scholar 

  116. 116

    Mezzabotta, F. et al. Spontaneous calcification process in primary renal cells from a medullary sponge kidney patient harbouring a GDNF mutation. J. Cell. Mol. Med. 19, 889–902 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 117

    Khan, S. R., Glenton, P. A. & Byer, K. J. Modeling of hyperoxaluric calcium oxalate nephrolithiasis: experimental induction of hyperoxaluria by hydroxy-l-proline. Kidney Int. 70, 914–923 (2006).

    Article  CAS  PubMed  Google Scholar 

  118. 118

    Meyer, J. L., Bergert, J. H. & Smith, L. H. Epitaxial relationships in urolithiasis: the calcium oxalate monohydrate–hydroxyapatite system. Clin. Sci. Mol. Med. 49, 369–374 (1975).

    CAS  PubMed  Google Scholar 

  119. 119

    Sethman, I., Grohe, B. & Kleebe, H.-J. Replacement of hydroxyapatite by whewellite: implications for kidney stone formation. Miner. Mag. 78, 91–100 (2014).

    Article  CAS  Google Scholar 

  120. 120

    Højgaard, I., Fornander, A. M., Nilsson, M. A. & Tiselius, H. G. The effect of pH changes on the crystallization of calcium salts in solutions with an ion composition corresponding to that in the distal tubule. Urol. Res. 27, 409–416 (1999).

    Article  PubMed  Google Scholar 

  121. 121

    Tiselius, H.-G. A hypothesis of calcium stone formation: an interpretation of stone research during the past decades. Urol. Res. 39, 231–243 (2011).

    Article  PubMed  Google Scholar 

  122. 122

    Borden, T. A. & Lyon, E. S. The effects of magnesium and pH on experimental calcium oxalate stone disease. Invest. Urol. 6, 412–422 (1969).

    CAS  PubMed  Google Scholar 

  123. 123

    Meyer, J. L. & Smith, L. H. Growth of calcium oxalate crystals. II. Inhibition by natural urinary crystal growth inhibitors. Invest. Urol. 13, 36–39 (1975).

    CAS  PubMed  Google Scholar 

  124. 124

    Meyer, J. L., McCall, J. T. & Smith, L. H. Inhibition of calcium phosphate crystallization by nucleoside phosphates. Calcif. Tissue Res. 15, 287–293 (1974).

    Article  CAS  PubMed  Google Scholar 

  125. 125

    Howard, J. E., Thomas, W. C., Barker, L. M., Smith, L. H. & Wadkins, C. L. The recognition and isolation from urine and serum of a peptide inhibitor to calcification. Johns Hopkins Med. J. 120, 119–136 (1967).

    CAS  PubMed  Google Scholar 

  126. 126

    Robertson, W. G., Peacock, M. & Nordin, B. E. Inhibitors of the growth and aggregation of calcium oxalate crystals in vitro. Clin. Chim. Acta 43, 31–37 (1973).

    Article  CAS  PubMed  Google Scholar 

  127. 127

    Ryall, R. L., Harnett, R. M. & Marshall, V. R. The effect of urine, pyrophosphate, citrate, magnesium and glycosaminoglycans on the growth and aggregation of calcium oxalate crystals in vitro. Clin. Chim. Acta 112, 349–356 (1981).

    Article  CAS  PubMed  Google Scholar 

  128. 128

    Robertson, W. G., Scurr, D. S. & Bridge, C. M. Factors influencing the crystallisation of calcium oxalate in urine — critique. J. Cryst. Growth 53, 182–194 (1981).

    Article  CAS  Google Scholar 

  129. 129

    Worcester, E. M., Nakagawa, Y. & Coe, F. L. Glycoprotein calcium oxalate crystal growth inhibitor in urine. Miner. Electrolyte Metab. 13, 267–272 (1987).

    CAS  PubMed  Google Scholar 

  130. 130

    Nakagawa, Y., Ahmed, M., Hall, S. L., Deganello, S. & Coe, F. L. Isolation from human calcium oxalate renal stones of nephrocalcin, a glycoprotein inhibitor of calcium oxalate crystal growth. Evidence that nephrocalcin from patients with calcium oxalate nephrolithiasis is deficient in gamma-carboxyglutamic acid. J. Clin. Invest. 79, 1782–1787 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. 131

    Hess, B., Nakagawa, Y. & Coe, F. L. Inhibition of calcium oxalate monohydrate crystal aggregation by urine proteins. Am. J. Physiol. 257, F99–F106 (1989).

    CAS  PubMed  Google Scholar 

  132. 132

    Shiraga, H. et al. Inhibition of calcium oxalate crystal growth in vitro by uropontin: another member of the aspartic acid-rich protein superfamily. Proc. Natl Acad. Sci. USA 89, 426–430 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. 133

    Tsuji, H. et al. Urinary concentration of osteopontin and association with urinary supersaturation and crystal formation. Int. J. Urol. 14, 630–634 (2007).

    Article  CAS  PubMed  Google Scholar 

  134. 134

    Pillay, S. N., Asplin, J. R. & Coe, F. L. Evidence that calgranulin is produced by kidney cells and is an inhibitor of calcium oxalate crystallization. Am. J. Physiol. 275, F255–F261 (1998).

    CAS  PubMed  Google Scholar 

  135. 135

    Morse, R. M. & Resnick, M. I. A new approach to the study of urinary macromolecules as a participant in calcium oxalate crystallization. J. Urol. 139, 869–873 (1988).

    Article  CAS  PubMed  Google Scholar 

  136. 136

    Dussol, B. et al. Analysis of the soluble organic matrix of five morphologically different kidney stones. Evidence for a specific role of albumin in the constitution of the stone protein matrix. Urol. Res. 23, 45–51 (1995).

    Article  CAS  PubMed  Google Scholar 

  137. 137

    Stapleton, A. M. et al. Further evidence linking urolithiasis and blood coagulation: urinary prothrombin fragment 1 is present in stone matrix. Kidney Int. 49, 880–888 (1996).

    Article  CAS  PubMed  Google Scholar 

  138. 138

    Grover, P. K. & Ryall, R. L. Inhibition of calcium oxalate crystal growth and aggregation by prothrombin and its fragments in vitro: relationship between protein structure and inhibitory activity. Eur. J. Biochem. 263, 50–56 (1999).

    Article  CAS  PubMed  Google Scholar 

  139. 139

    Dawson, C. J., Grover, P. K. & Ryall, R. L. Inter-alpha-inhibitor in urine and calcium oxalate urinary crystals. Br. J. Urol. 81, 20–26 (1998).

    Article  CAS  PubMed  Google Scholar 

  140. 140

    Robertson, W. G. A risk factor model of stone-formation. Front. Biosci. 8, s1330–s1338 (2003).

    Article  CAS  PubMed  Google Scholar 

  141. 141

    Spector, A. R., Gray, A. & Prien, E. L. Kidney stone matrix. Differences in acidic protein composition. Invest. Urol. 13, 387–389 (1976).

    CAS  PubMed  Google Scholar 

  142. 142

    Lian, J. B., Prien, E. L., Glimcher, M. J. & Gallop, P. M. The presence of protein-bound gamma-carboxyglutamic acid in calcium-containing renal calculi. J. Clin. Invest. 59, 1151–1157 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. 143

    Jones, W. T. & Resnick, M. I. The characterization of soluble matrix proteins in selected human renal calculi using two-dimensional polyacrylamide gel electrophoresis. J. Urol. 144, 1010–1014 (1990).

    Article  CAS  PubMed  Google Scholar 

  144. 144

    Rose, G. A. & Sulaiman, S. Tamm–Horsfall mucoproteins promote calcium oxalate crystal formation in urine: quantitative studies. J. Urol. 127, 177–179 (1982).

    Article  CAS  PubMed  Google Scholar 

  145. 145

    Robertson, W. G. & Scurr, D. S. Modifiers of calcium oxalate crystallization found in urine. I. Studies with a continuous crystallizer using an artificial urine. J. Urol. 135, 1322–1326 (1986).

    Article  CAS  PubMed  Google Scholar 

  146. 146

    Grover, P. K., Ryall, R. L. & Marshall, V. R. Does Tamm–Horsfall mucoprotein inhibit or promote calcium oxalate crystallization in human urine? Clin. Chim. Acta 190, 223–238 (1990).

    Article  CAS  PubMed  Google Scholar 

  147. 147

    Bagga, H. S., Chi, T., Miller, J. & Stoller, M. L. New insights into the pathogenesis of renal calculi. Urol. Clin. North Am. 40, 1–12 (2013).

    Article  PubMed  Google Scholar 

  148. 148

    Fabris, A. et al. The relationship between calcium kidney stones, arterial stiffness and bone density: unraveling the stone–bone–vessel liaison. J. Nephrol. 28, 549–555 (2015).

    Article  CAS  PubMed  Google Scholar 

  149. 149

    Gambaro, G. et al. Crystals, Randall's plaques and renal stones: do bone and atherosclerosis teach us something? J. Nephrol. 17, 774–777 (2004).

    PubMed  Google Scholar 

  150. 150

    Reiner, A. P. et al. Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study. J. Urol. 185, 920–925 (2011).

    Article  PubMed  Google Scholar 

  151. 151

    Taylor, E. R. & Stoller, M. L. Vascular theory of the formation of Randall plaques. Urolithiasis 43 (Suppl. 1), 41–45 (2015).

    Article  PubMed  Google Scholar 

  152. 152

    Moe, S. M. & Chen, N. X. Mechanisms of vascular calcification in chronic kidney disease. J. Am. Soc. Nephrol. 19, 213–216 (2008).

    Article  CAS  PubMed  Google Scholar 

  153. 153

    Shanahan, C. M. Mechanisms of vascular calcification in renal disease. Clin. Nephrol. 63, 146–157 (2005).

    Article  CAS  PubMed  Google Scholar 

  154. 154

    Shanahan, C. M., Crouthamel, M. H., Kapustin, A. & Giachelli, C. M. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ. Res. 109, 697–711 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. 155

    Kapustin, A. N. et al. Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization. Circ. Res. 109, e1–e12 (2011).

    Article  CAS  PubMed  Google Scholar 

  156. 156

    Shroff, R. C. & Shanahan, C. M. The vascular biology of calcification. Semin. Dial. 20, 103–109 (2007).

    Article  PubMed  Google Scholar 

  157. 157

    Tada, Y. et al. Advanced glycation end products-induced vascular calcification is mediated by oxidative stress: functional roles of NAD(P)H-oxidase. Horm. Metab. Res. 45, 267–272 (2013).

    CAS  PubMed  Google Scholar 

  158. 158

    Byon, C. H. et al. Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J. Biol. Chem. 283, 15319–15327 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. 159

    Murshed, M. & McKee, M. D. Molecular determinants of extracellular matrix mineralization in bone and blood vessels. Curr. Opin. Nephrol. Hypertens. 19, 359–365 (2010).

    Article  CAS  PubMed  Google Scholar 

  160. 160

    Jia, Z. et al. Does crystal deposition in genetic hypercalciuric rat kidney tissue share similarities with bone formation? Urology 83, 509.e7–509.14 (2014).

    Article  Google Scholar 

  161. 161

    Naito, Y. et al. Morphological analysis of renal cell culture models of calcium phosphate stone formation. Urol. Res. 25, 59–65 (1997).

    Article  CAS  PubMed  Google Scholar 

  162. 162

    Kageyama, S. et al. Microlith formation in vitro by Madin Darby canine kidney (MDCK) cells. Int. J. Urol. 3, 23–26 (1996).

    Article  CAS  PubMed  Google Scholar 

  163. 163

    Thamilselvan, S., Byer, K. J., Hackett, R. L. & Khan, S. R. Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J. Urol. 164, 224–229 (2000).

    Article  CAS  PubMed  Google Scholar 

  164. 164

    Thamilselvan, S., Hackett, R. L. & Khan, S. R. Lipid peroxidation in ethylene glycol induced hyperoxaluria and calcium oxalate nephrolithiasis. J. Urol. 157, 1059–1063 (1997).

    Article  CAS  PubMed  Google Scholar 

  165. 165

    Joshi, S., Saylor, B. T., Wang, W., Peck, A. B. & Khan, S. R. Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study. PLoS ONE 7, e47738 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. 166

    Zuo, J., Khan, A., Glenton, P. A. & Khan, S. R. Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-l-proline-induced hyperoxaluria in the male Sprague-Dawley rats. Nephrol. Dial. Transplant. 26, 1785–1796 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. 167

    Khan, S. R., Khan, A. & Byer, K. J. Temporal changes in the expression of mRNA of NADPH oxidase subunits in renal epithelial cells exposed to oxalate or calcium oxalate crystals. Nephrol. Dial. Transplant. 26, 1778–1785 (2011).

    Article  CAS  PubMed  Google Scholar 

  168. 168

    Joshi, S., Clapp, W. L., Wang, W. & Khan, S. R. Osteogenic changes in kidneys of hyperoxaluric rats. Biochim. Biophys. Acta 1852, 2000–2012 (2015). The results of this study show osteogenic changes in the kidneys of hyperoxaluric rats.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. 169

    Kanno, T. et al. The efficacy of ultrasonography for the detection of renal stone. Urology 84, 285–288 (2014).

    Article  PubMed  Google Scholar 

  170. 170

    Kanno, T. et al. Determining the efficacy of ultrasonography for the detection of ureteral stone. Urology 84, 533–537 (2014).

    Article  PubMed  Google Scholar 

  171. 171

    Heidenreich, A., Desgrandschamps, F. & Terrier, F. Modern approach of diagnosis and management of acute flank pain: review of all imaging modalities. Eur. Urol. 41, 351–362 (2002).

    Article  PubMed  Google Scholar 

  172. 172

    Johnston, R., Lin, A., Du, J. & Mark, S. Comparison of kidney–ureter–bladder abdominal radiography and computed tomography scout films for identifying renal calculi. BJU Int. 104, 670–673 (2009).

    Article  PubMed  Google Scholar 

  173. 173

    Worster, A., Preyra, I., Weaver, B. & Haines, T. The accuracy of noncontrast helical computed tomography versus intravenous pyelography in the diagnosis of suspected acute urolithiasis: a meta-analysis. Ann. Emerg. Med. 40, 280–286 (2002).

    Article  PubMed  Google Scholar 

  174. 174

    Wiesenthal, J. D., Ghiculete, D., D' A Honey, R. J. & Pace, K. T. Evaluating the importance of mean stone density and skin-to-stone distance in predicting successful shock wave lithotripsy of renal and ureteric calculi. Urol. Res. 38, 307–313 (2010).

    Article  PubMed  Google Scholar 

  175. 175

    Primiano, A. et al. FT-IR analysis of urinary stones: a helpful tool for clinician comparison with the chemical spot test. Dis. Markers 2014, 176165 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. 176

    Gambaro, G., Reis-Santos, J. M. & Rao, N. Nephrolithiasis: why doesn't our ‘learning’ progress? Eur. Urol. 45, 547–556; discussion 556 (2004).

    Article  PubMed  Google Scholar 

  177. 177

    Eisner, B. H., Sheth, S., Dretler, S. P., Herrick, B. & Pais, V. M. Abnormalities of 24-hour urine composition in first-time and recurrent stone-formers. Urology 80, 776–779 (2012).

    Article  PubMed  Google Scholar 

  178. 178

    Rodgers, A. L., Allie-Hamdulay, S., Jackson, G. & Tiselius, H.-G. Simulating calcium salt precipitation in the nephron using chemical speciation. Urol. Res. 39, 245–251 (2011).

    Article  PubMed  Google Scholar 

  179. 179

    Sakhaee, K., Maalouf, N. M., Kumar, R., Pasch, A. & Moe, O. W. Nephrolithiasis-associated bone disease: pathogenesis and treatment options. Kidney Int. 79, 393–403 (2011). This is an updated overview of the epidemiology and mechanisms of MBD in patients with nephrolithiasis. The effect of treatments for renal stone prevention on the associated MBD and the effect of treatments addressing the bone-on-the-stone disease are thoroughly discussed.

    Article  CAS  PubMed  Google Scholar 

  180. 180

    Ferraro, P. M., D'Addessi, A. & Gambaro, G. When to suspect a genetic disorder in a patient with renal stones, and why. Nephrol. Dial. Transplant. 28, 811–820 (2013).

    Article  CAS  PubMed  Google Scholar 

  181. 181

    Kang, H. W. et al. Effect of renal insufficiency on stone recurrence in patients with urolithiasis. J. Korean Med. Sci. 29, 1132–1137 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. 182

    Kristensen, C., Parks, J. H., Lindheimer, M. & Coe, F. L. Reduced glomerular filtration rate and hypercalciuria in primary struvite nephrolithiasis. Kidney Int. 32, 749–753 (1987).

    Article  CAS  PubMed  Google Scholar 

  183. 183

    Evan, A. P. et al. Contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite, brushite, or calcium oxalate stones. Anat. Rec. (Hoboken) 297, 731–748 (2014).

    Article  CAS  Google Scholar 

  184. 184

    Ascenti, G. et al. Stone-targeted dual-energy CT: a new diagnostic approach to urinary calculosis. AJR Am. J. Roentgenol. 195, 953–958 (2010).

    Article  PubMed  Google Scholar 

  185. 185

    Halbritter, J. et al. Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J. Am. Soc. Nephrol. 26, 543–551 (2015).

    Article  CAS  PubMed  Google Scholar 

  186. 186

    Gambaro, G. et al. Genetics of hypercalciuria and calcium nephrolithiasis: from the rare monogenic to the common polygenic forms. Am. J. Kidney Dis. 44, 963–986 (2004).

    Article  CAS  PubMed  Google Scholar 

  187. 187

    Pak, C. Y. et al. Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions. J. Urol. 169, 465–469 (2003).

    Article  CAS  PubMed  Google Scholar 

  188. 188

    Fabris, A. et al. Bone disease in medullary sponge kidney and effect of potassium citrate treatment. Clin. J. Am. Soc. Nephrol. 4, 1974–1979 (2009). Treatment with potassium citrate not only decreased stone recurrences but also improved mineral bone density in a cohort of patients with medullary sponge kidney. The effect was probably due to the amelioration of the subtle metabolic acidosis in patients with medullary sponge kidney.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. 189

    Hosking, D. H., Erickson, S. B., Van den Berg, C. J., Wilson, D. M. & Smith, L. H. The stone clinic effect in patients with idiopathic calcium urolithiasis. J. Urol. 130, 1115–1118 (1983).

    Article  CAS  PubMed  Google Scholar 

  190. 190

    Borghi, L. et al. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. J. Urol. 155, 839–843 (1996).

    Article  CAS  PubMed  Google Scholar 

  191. 191

    Borghi, L. et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N. Engl. J. Med. 346, 77–84 (2002).

    Article  CAS  PubMed  Google Scholar 

  192. 192

    Meschi, T. et al. The effect of fruits and vegetables on urinary stone risk factors. Kidney Int. 66, 2402–2410 (2004).

    Article  CAS  PubMed  Google Scholar 

  193. 193

    Ferraro, P. M., Taylor, E. N., Gambaro, G. & Curhan, G. C. Soda and other beverages and the risk of kidney stones. Clin. J. Am. Soc. Nephrol. 8, 1389–1395 (2013). This is a robust observational study in the general population (the three health professionals Channing cohorts) that showed that soda beverages increase the risk of becoming a stone former.

    Article  PubMed  PubMed Central  Google Scholar 

  194. 194

    Bushinsky, D. A. et al. Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats. Kidney Int. 55, 602–612 (1999).

    Article  CAS  PubMed  Google Scholar 

  195. 195

    Pearle, M. S. et al. Medical management of kidney stones: AUA guideline. J. Urol. 192, 316–324 (2014).

    Article  PubMed  Google Scholar 

  196. 196

    Yendt, E. R. & Cohanim, M. Prevention of calcium stones with thiazides. Kidney Int. 13, 397–409 (1978).

    Article  CAS  PubMed  Google Scholar 

  197. 197

    Ettinger, B., Tang, A., Citron, J. T., Livermore, B. & Williams, T. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N. Engl. J. Med. 315, 1386–1389 (1986).

    Article  CAS  PubMed  Google Scholar 

  198. 198

    Arowojolu, O. & Goldfarb, D. S. Treatment of calcium nephrolithiasis in the patient with hyperuricosuria. J. Nephrol. 27, 601–605 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. 199

    Pak, C. Y., Sakhaee, K. & Fuller, C. J. Physiological and physiochemical correction and prevention of calcium stone formation by potassium citrate therapy. Trans. Assoc. Am. Physicians 96, 294–305 (1983).

    CAS  PubMed  Google Scholar 

  200. 200

    Barcelo, P., Wuhl, O., Servitge, E., Rousaud, A. & Pak, C. Y. Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J. Urol. 150, 1761–1764 (1993).

    Article  CAS  PubMed  Google Scholar 

  201. 201

    Ettinger, B. et al. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J. Urol. 158, 2069–2073 (1997).

    Article  CAS  PubMed  Google Scholar 

  202. 202

    Sakhaee, K., Nicar, M., Hill, K. & Pak, C. Y. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts. Kidney Int. 24, 348–352 (1983).

    Article  CAS  PubMed  Google Scholar 

  203. 203

    Preminger, G. M., Sakhaee, K., Skurla, C. & Pak, C. Y. Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. J. Urol. 134, 20–23 (1985).

    Article  CAS  PubMed  Google Scholar 

  204. 204

    Fabris, A. et al. Long-term treatment with potassium citrate and renal stones in medullary sponge kidney. Clin. J. Am. Soc. Nephrol. 5, 1663–1668 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. 205

    Skolarikos, A. et al. Metabolic evaluation and recurrence prevention for urinary stone patients: EAU guidelines. Eur. Urol. 67, 750–763 (2015).

    Article  PubMed  Google Scholar 

  206. 206

    Daudon, M. et al. Cystine crystal volume determination: a useful tool in the management of cystinuric patients. Urol. Res. 31, 207–211 (2003).

    Article  CAS  PubMed  Google Scholar 

  207. 207

    Goldfarb, D. S., Coe, F. L. & Asplin, J. R. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 69, 1041–1047 (2006).

    Article  CAS  PubMed  Google Scholar 

  208. 208

    Dello Strologo, L., Laurenzi, C., Legato, A. & Pastore, A. Cystinuria in children and young adults: success of monitoring free-cystine urine levels. Pediatr. Nephrol. 22, 1869–1873 (2007).

    Article  PubMed  Google Scholar 

  209. 209

    Prot-Bertoye, C. et al. CKD and its risk factors among patients with cystinuria. Clin. J. Am. Soc. Nephrol. 10, 842–851 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  210. 210

    Ordon, M. et al. The surgical management of kidney stone disease: a population based time series analysis. J. Urol. 192, 1450–1456 (2014).

    Article  PubMed  Google Scholar 

  211. 211

    Scales, C. D. et al. Comparative effectiveness of shock wave lithotripsy and ureteroscopy for treating patients with kidney stones. JAMA Surg. 149, 648–653 (2014). This is one of the few studies comparing large head-to-head data in SWL versus ureteroscopy.

    Article  PubMed  Google Scholar 

  212. 212

    Lingeman, J. E. et al. Extracorporeal shock wave lithotripsy: the Methodist Hospital of Indiana experience. J. Urol. 135, 1134–1137 (1986).

    Article  CAS  PubMed  Google Scholar 

  213. 213

    Wignall, G. R., Canales, B. K., Denstedt, J. D. & Monga, M. Minimally invasive approaches to upper urinary tract urolithiasis. Urol. Clin. North Am. 35, 441–454 (2008). This is a solid review of preoperative considerations and surgical techniques for urologists who perform SWL, ureteroscopy and PCNL.

    Article  PubMed  Google Scholar 

  214. 214

    Albala, D. M. et al. Lower pole I: a prospective randomized trial of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for lower pole nephrolithiasis-initial results. J. Urol. 166, 2072–2080 (2001).

    Article  CAS  PubMed  Google Scholar 

  215. 215

    Pearle, M. S. et al. Prospective, randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less. J. Urol. 173, 2005–2009 (2005).

    Article  PubMed  Google Scholar 

  216. 216

    Wiesenthal, J. D., Ghiculete, D., D' A Honey, R. J. & Pace, K. T. A comparison of treatment modalities for renal calculi between 100 and 300 mm2: are shockwave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy equivalent? J. Endourol. 25, 481–485 (2011).

    Article  PubMed  Google Scholar 

  217. 217

    Gupta, N. P., Ansari, M. S., Kesarvani, P., Kapoor, A. & Mukhopadhyay, S. Role of computed tomography with no contrast medium enhancement in predicting the outcome of extracorporeal shock wave lithotripsy for urinary calculi. BJU Int. 95, 1285–1288 (2005).

    Article  PubMed  Google Scholar 

  218. 218

    Wang, L.-J. et al. Predictions of outcomes of renal stones after extracorporeal shock wave lithotripsy from stone characteristics determined by unenhanced helical computed tomography: a multivariate analysis. Eur. Radiol. 15, 2238–2243 (2005).

    Article  PubMed  Google Scholar 

  219. 219

    El-Nahas, A. R., El-Assmy, A. M., Mansour, O. & Sheir, K. Z. A prospective multivariate analysis of factors predicting stone disintegration by extracorporeal shock wave lithotripsy: the value of high-resolution noncontrast computed tomography. Eur. Urol. 51, 1688–1693; discussion 1693–1694 (2007).

    Article  PubMed  Google Scholar 

  220. 220

    Müller-Mattheis, V. G., Schmale, D., Seewald, M., Rosin, H. & Ackermann, R. Bacteremia during extracorporeal shock wave lithotripsy of renal calculi. J. Urol. 146, 733–736 (1991).

    Article  PubMed  Google Scholar 

  221. 221

    Dhar, N. B., Thornton, J., Karafa, M. T. & Streem, S. B. A multivariate analysis of risk factors associated with subcapsular hematoma formation following electromagnetic shock wave lithotripsy. J. Urol. 172, 2271–2274 (2004).

    Article  PubMed  Google Scholar 

  222. 222

    Aboumarzouk, O. M., Kata, S. G., Keeley, F. X., McClinton, S. & Nabi, G. Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for ureteric calculi. Cochrane Database Syst. Rev. 5, CD006029 (2012).

    Google Scholar 

  223. 223

    Preminger, G. M. et al. 2007 guideline for the management of ureteral calculi. J. Urol. 178, 2418–2434 (2007).

    Article  PubMed  Google Scholar 

  224. 224

    Kourambas, J., Delvecchio, F. C., Munver, R. & Preminger, G. M. Nitinol stone retrieval-assisted ureteroscopic management of lower pole renal calculi. Urology 56, 935–939 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. 225

    Kamphuis, G. M., Baard, J., Westendarp, M. & de la Rosette, J. J. M. C. H. Lessons learned from the CROES percutaneous nephrolithotomy global study. World J. Urol. 33, 223–233 (2015).

    Article  PubMed  Google Scholar 

  226. 226

    Akman, T. et al. Tubeless procedure is most important factor in reducing length of hospitalization after percutaneous nephrolithotomy: results of univariable and multivariable models. Urology 77, 299–304 (2011).

    Article  PubMed  Google Scholar 

  227. 227

    Preminger, G. M. et al. Percutaneous nephrostolithotomy vs open surgery for renal calculi. A comparative study. JAMA 254, 1054–1058 (1985).

    Article  CAS  PubMed  Google Scholar 

  228. 228

    Xue, W. et al. Management of single large nonstaghorn renal stones in the CROES PCNL global study. J. Urol. 187, 1293–1297 (2012).

    Article  PubMed  Google Scholar 

  229. 229

    Holdgate, A. & Pollock, T. Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst. Rev. 2, CD004137 (2005).

    Google Scholar 

  230. 230

    Afshar, K., Jafari, S., Marks, A. J., Eftekhari, A. & MacNeily, A. E. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst. Rev. 6, CD006027 (2015).

    Google Scholar 

  231. 231

    Serinken, M. et al. Intravenous paracetamol versus morphine for renal colic in the emergency department: a randomised double-blind controlled trial. Emerg. Med. J. 29, 902–905 (2012).

    Article  PubMed  Google Scholar 

  232. 232

    Papadopoulos, G. et al. Hyoscine N-butylbromide (Buscopan®) in the treatment of acute ureteral colic: what is the evidence? Urol. Int. 92, 253–257 (2014).

    Article  CAS  PubMed  Google Scholar 

  233. 233

    Worster, A. S. & Bhanich Supapol, W. Fluids and diuretics for acute ureteric colic. Cochrane Database Syst. Rev. 2, CD004926 (2012).

    Google Scholar 

  234. 234

    Picozzi, S. C. M. et al. Management of ureteral calculi and medical expulsive therapy in emergency departments. J. Emerg. Trauma Shock 4, 70–76 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  235. 235

    Campschroer, T., Zhu, Y., Duijvesz, D., Grobbee, D. E. & Lock, M. T. W. T. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst. Rev. 4, CD008509 (2014).

    Google Scholar 

  236. 236

    Pickard, R. et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 386, 341–349 (2015). Perhaps the most controversial publication of the decade in the kidney stone arena, the authors of this extremely well-done randomized controlled trial (of tamsulosin, nifedipine and placebo) showed that medical expulsive therapy does not alter stone interventions for patients after 4 weeks of stone passage and declared that these agents should not be offered to patients with ureteric colic who are managed expectantly.

    Article  PubMed  Google Scholar 

  237. 237

    Furyk, J. S. et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann. Emerg. Med. 67, 86–95.e2 (2016).

    Article  PubMed  Google Scholar 

  238. 238

    Moran, M. E., Abrahams, H. M., Burday, D. E. & Greene, T. D. Utility of oral dissolution therapy in the management of referred patients with secondarily treated uric acid stones. Urology 59, 206–210 (2002).

    Article  PubMed  Google Scholar 

  239. 239

    Trinchieri, A., Esposito, N. & Castelnuovo, C. Dissolution of radiolucent renal stones by oral alkalinization with potassium citrate/potassium bicarbonate. Arch. Ital. Urol. Androl. 81, 188–191 (2009).

    PubMed  Google Scholar 

  240. 240

    Koide, T., Yoshioka, T., Yamaguchi, S., Utsunomiya, M. & Sonoda, T. A strategy of cystine stone management. J. Urol. 147, 112–114 (1992).

    Article  CAS  PubMed  Google Scholar 

  241. 241

    Gonzalez, R. D., Whiting, B. M. & Canales, B. K. The history of kidney stone dissolution therapy: 50 years of optimism and frustration with renacidin. J. Endourol. 26, 110–118 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  242. 242

    Pearle, M. S., Calhoun, E. A. & Curhan, G. C. Urologic diseases in America project: urolithiasis. J. Urol. 173, 848–857 (2005).

    Article  PubMed  Google Scholar 

  243. 243

    Ware, J. E., Kosinski, M. & Gandek, B. SF-36 Health Survey: Manual and Interpretation Guide (Quality Metric Inc., 2003).

  244. 244

    Bensalah, K. et al. Determinants of quality of life for patients with kidney stones. J. Urol. 179, 2238–2243; discussion 2243 (2008).

    Article  PubMed  Google Scholar 

  245. 245

    Bryant, M. et al. Health related quality of life for stone formers. J. Urol. 188, 436–440 (2012).

    Article  PubMed  Google Scholar 

  246. 246

    Penniston, K. L. & Nakada, S. Y. Health related quality of life differs between male and female stone formers. J. Urol. 178, 2435–2440; discussion 2440 (2007).

    Article  PubMed  Google Scholar 

  247. 247

    Modersitzki, F., Pizzi, L., Grasso, M. & Goldfarb, D. S. Health-related quality of life (HRQoL) in cystine compared with non-cystine stone formers. Urolithiasis 42, 53–60 (2014).

    Article  CAS  PubMed  Google Scholar 

  248. 248

    Arafa, M. A. & Rabah, D. M. Study of quality of life and its determinants in patients after urinary stone fragmentation. Health Qual. Life Outcomes 8, 119 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  249. 249

    Rabah, D. M., Alomar, M., Binsaleh, S. & Arafa, M. A. Health related quality of life in ureteral stone patients: post-ureterolithiasis. Urol. Res. 39, 385–388 (2011).

    Article  PubMed  Google Scholar 

  250. 250

    Kurahashi, T. et al. Health-related quality of life in patients undergoing lithotripsy for urinary stones. Int. Urol. Nephrol. 40, 39–43 (2008).

    Article  PubMed  Google Scholar 

  251. 251

    Joshi, H. B. et al. Indwelling ureteral stents: evaluation of symptoms, quality of life and utility. J. Urol. 169, 1065–1069; discussion 1069 (2003).

    Article  CAS  PubMed  Google Scholar 

  252. 252

    Damiano, R. et al. Does the size of ureteral stent impact urinary symptoms and quality of life? A prospective randomized study. Eur. Urol. 48, 673–678 (2005).

    Article  PubMed  Google Scholar 

  253. 253

    Joshi, H. B., Adams, S., Obadeyi, O. O. & Rao, P. N. Nephrostomy tube or ‘JJ’ ureteric stent in ureteric obstruction: assessment of patient perspectives using quality-of-life survey and utility analysis. Eur. Urol. 39, 695–701 (2001).

    Article  CAS  PubMed  Google Scholar 

  254. 254

    Sahin, C. et al. Do the residual fragments after shock wave lithotripsy affect the quality of life? Urology 84, 549–554 (2014).

    Article  PubMed  Google Scholar 

  255. 255

    Lingeman, J. E., McAteer, J. A., Gnessin, E. & Evan, A. P. Shock wave lithotripsy: advances in technology and technique. Nat. Rev. Urol. 6, 660–670 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  256. 256

    Rajaian, S. et al. Outcome of shock wave lithotripsy as monotherapy for large solitary renal stones (>2 cm in size) without stenting. Indian J. Urol. 26, 359–363 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  257. 257

    Zanetti, G., Trinchieri, A., Montanari, E. & Rocco, F. SWL: our twenty-four year experience. Arch. Ital. Urol. Androl. 80, 21–26 (2008).

    PubMed  Google Scholar 

  258. 258

    Srisubat, A., Potisat, S., Lojanapiwat, B., Setthawong, V. & Laopaiboon, M. Extracorporeal shock wave lithotripsy (ESWL) versus percutaneous nephrolithotomy (PCNL) or retrograde intrarenal surgery (RIRS) for kidney stones. Cochrane Database Syst. Rev. 11, CD007044 (2014).

    Google Scholar 

  259. 259

    Skolarikos, A. et al. Outcomes of flexible ureterorenoscopy for solitary renal stones in the CROES URS global study. J. Urol. 194, 137–143 (2015).

    Article  PubMed  Google Scholar 

  260. 260

    Donaldson, J. F. et al. Systematic review and meta-analysis of the clinical effectiveness of shock wave lithotripsy, retrograde intrarenal surgery, and percutaneous nephrolithotomy for lower-pole renal stones. Eur. Urol. 67, 612–616 (2015).

    Article  PubMed  Google Scholar 

  261. 261

    Ozgor, F. et al. Clinically insignificant residual fragments after flexible ureterorenoscopy: medium-term follow-up results. Urolithiasis 42, 533–538 (2014).

    Article  PubMed  Google Scholar 

  262. 262

    Thalji, N. K., Richards, N. G., Peck, A. B. & Canales, B. K. Enzymatic dissolution of calcium and struvite crystals: in vitro evaluation of biochemical requirements. Urology 78, 721.e13–721.e17 (2011).

    Article  Google Scholar 

  263. 263

    Qaseem, A., Dallas, P., Forciea, M. A., Starkey, M. & Denberg, T. D. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians. Ann. Intern. Med. 161, 659–667 (2014).

    Article  PubMed  Google Scholar 

  264. 264

    Tiselius, H.-G. Recurrence prevention in patients with urinary tract stone disease. ScientificWorldJournal 4, 35–41 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  265. 265

    Türk, C. et al. Guidelines on urolithiasis. European Association of Urology [online], http://uroweb.org/wp-content/uploads/22-Urolithiasis_LR_full.pdf (2015).

  266. 266

    Chiong, E. et al. Randomized controlled study of mechanical percussion, diuresis, and inversion therapy to assist passage of lower pole renal calculi after shock wave lithotripsy. Urology 65, 1070–1074 (2005).

    Article  PubMed  Google Scholar 

  267. 267

    Lee, S. W.-H., Chaiyakunapruk, N., Chong, H.-Y. & Liong, M.-L. Comparative effectiveness and safety of various treatment procedures for lower pole renal calculi: a systematic review and network meta-analysis. BJU Int. 116, 252–264 (2015).

    Article  PubMed  Google Scholar 

  268. 268

    Leong, W. S., Liong, M. L., Liong, Y. V., Wu, D. B.-C. & Lee, S. W. H. Does simultaneous inversion during extracorporeal shock wave lithotripsy improve stone clearance: a long-term, prospective, single-blind, randomized controlled study. Urology 83, 40–44 (2014).

    Article  PubMed  Google Scholar 

  269. 269

    Pace, K. T., Tariq, N., Dyer, S. J., Weir, M. J. & D' A Honey, R. J. Mechanical percussion, inversion and diuresis for residual lower pole fragments after shock wave lithotripsy: a prospective, single blind, randomized controlled trial. J. Urol. 166, 2065–2071 (2001).

    Article  CAS  PubMed  Google Scholar 

  270. 270

    Albanis, S. et al. Inversion, hydration and diuresis during extracorporeal shock wave lithotripsy: does it improve the stone-free rate for lower pole stone clearance? Urol. Int. 83, 211–216 (2009).

    Article  PubMed  Google Scholar 

  271. 271

    Bailey, M. et al. Ultrasonic propulsion of kidney stones: preliminary results of human feasibility study. IEEE Int. Ultrason. Symp. 2014, 511–514 (2014).

    PubMed  PubMed Central  Google Scholar 

  272. 272

    Schulz, E. et al. Disturbed urinary transport in the pelvi–calyceal system in calcium-oxalate stone patients. Urol. Res. 15, 109–113 (1987).

    CAS  PubMed  Google Scholar 

  273. 273

    Ahlstrand, C. & Tiselius, H. G. Recurrences during a 10-year follow-up after first renal stone episode. Urol. Res. 18, 397–399 (1990).

    Article  CAS  PubMed  Google Scholar 

  274. 274

    Coe, F. L., Evan, A. & Worcester, E. Pathophysiology-based treatment of idiopathic calcium kidney stones. Clin. J. Am. Soc. Nephrol. 6, 2083–2092 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  275. 275

    Evan, A. P. et al. Mechanism of formation of human calcium oxalate renal stones on Randall's plaque. Anat. Rec. (Hoboken) 290, 1315–1323 (2007).

    Article  CAS  Google Scholar 

  276. 276

    Tiselius, H.-G., Lindbä ck, B., Fornander, A.-M. & Nilsson, M.-A. Studies on the role of calcium phosphate in the process of calcium oxalate crystal formation. Urol. Res. 37, 181–192 (2009).

    Article  CAS  PubMed  Google Scholar 

  277. 277

    Tsujihata, M. Mechanism of calcium oxalate renal stone formation and renal tubular cell injury. Int. J. Urol. 15, 115–120 (2008).

    Article  CAS  PubMed  Google Scholar 

  278. 278

    Krambeck, A. E. et al. Current computed tomography techniques can detect duct of Bellini plugging but not Randall's plaques. Urology 82, 301–306 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  279. 279

    Tiselius, H.-G. Should we modify the principles of risk evaluation and recurrence preventive treatment of patients with calcium oxalate stone disease in view of the etiologic importance of calcium phosphate? Urolithiasis 43 (Suppl. 1), 47–57 (2015).

    Article  PubMed  Google Scholar 

  280. 280

    Bandeira, F. et al. Bone markers and osteoporosis therapy. Arq. Bras. Endocrinol. Metabol. 58, 504–513 (2014).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Research funding to S.R.K. is provided by NIH grant numbers RO1-DK078602 and RO1-DK092311. S.R.K. thanks P. J. Khan for her assistance in preparing the manuscript.

Author information

Affiliations

Authors

Contributions

Introduction (S.R.K.); Epidemiology (M.S.P.); Mechanism/pathophysiology (W.G.R. and S.R.K.); Diagnosis, screening and prevention (G.G.); Management (G.G. and B.K.C.); Quality of life (S.D. and O.T.); Outlook (H.G.T.); Overview of the Primer (S.R.K.).

Corresponding author

Correspondence to Saeed R. Khan.

Ethics declarations

Competing interests

The authors declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Khan, S., Pearle, M., Robertson, W. et al. Kidney stones. Nat Rev Dis Primers 2, 16008 (2016). https://doi.org/10.1038/nrdp.2016.8

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing