Independent and interactive effects of kidney stone formation and conventional risk factors for chronic kidney disease: a follow-up study of Japanese men



To assess the impact of interactions between kidney stone formation and conventional risk factors on incident chronic kidney disease (CKD).


A total of 11,402 subjects (men 30–69 years of age, Japanese) without CKD at baseline were observed over an average period of 4 years. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to determine the association between incident CKD, kidney stone formation, and conventional risk factors (diabetes mellitus, hypertension, overweight/obesity, dyslipidemia, and hyperuricemia/gout). We also examined the interactions of renal stones and the conventional risk factors for CKD.


In total, 2301 men (20.2%) developed incident CKD during the follow-up period. After multivariable adjustment, kidney stones were found to increase the risk of incident CKD (HR 1.16; 95% CI 1.03–1.32). Kidney stone formers with hypertension, dyslipidemia, or hyperuricemia/gout presented a greater risk for incident CKD than those who had either kidney stones or other risk factors. However, no significant interactions between kidney stones and other risk factors were found to increase CKD risk. On the other hand, a negative interactive effect between kidney stones and overweight/obesity was observed, leading to reversed risk of incident CKD in coexistence of both factors.


Kidney stones were linked to a higher risk for the development of CKD. However, no positive interactive effects were identified between renal stones and conventional risk factors on the risk of incident CKD.

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  1. 1.

    Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS et al (2016) Global prevalence of chronic kidney disease—a systematic review and meta-analysis. PLoS ONE 11:e0158765.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Nagata M, Ninomiya T, Doi Y, Yonemoto K, Kubo M, Hata J et al (2010) Trends in the prevalence of chronic kidney disease and its risk factors in a general Japanese population: the Hisayama Study. Nephrol Dial Transplant 25:2557–2564.

    Article  PubMed  Google Scholar 

  4. 4.

    Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298:2038–2047.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Brown WW, Peters RM, Ohmit SE, Keane WF, Collins A, Chen S-C et al (2003) Early detection of kidney disease in community settings: the kidney early evaluation program (KEEP). Am J Kidney Dis 42:22–35.

    Article  PubMed  Google Scholar 

  6. 6.

    Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF et al (2013) Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382:339–352.

    Article  PubMed  Google Scholar 

  7. 7.

    Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63:1817–1823

    Article  Google Scholar 

  8. 8.

    Hesse A, Brandle E, Wilbert D, Kohrmann KU, Alken P (2003) Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000. Eur Urol 44:709–713

    CAS  Article  Google Scholar 

  9. 9.

    Sakamoto S, Miyazawa K, Yasui T, Iguchi T, Fujita M, Nishimatsu H et al (2018) Chronological changes in the epidemiological characteristics of upper urinary tract urolithiasis in Japan. Int J Urol 25:373–378.

    Article  PubMed  Google Scholar 

  10. 10.

    Hamamoto S, Unno R, Taguchi K, Naiki T, Ando R, Okada A et al (2018) Determinants of health-related quality of life for patients after urinary lithotripsy: ureteroscopic vs. shock wave lithotripsy. Urolithiasis 46:203–210.

    Article  PubMed  Google Scholar 

  11. 11.

    Raja A, Wood F, Joshi HB (2020) The impact of urinary stone disease and their treatment on patients’ quality of life: a qualitative study. Urolithiasis 48:227–234.

    Article  PubMed  Google Scholar 

  12. 12.

    Rule AD, Bergstralh EJ, Melton LJ 3rd, Li X, Weaver AL, Lieske JC (2009) Kidney stones and the risk for chronic kidney disease. Clin J Am Soc Nephrol 4:804–811.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Morgan C, Samuel S et al (2012) Kidney stones and kidney function loss: a cohort study. BMJ 345:e5287.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Ando R, Nagaya T, Suzuki S, Takahashi H, Kawai M, Okada A et al (2013) Kidney stone formation is positively associated with conventional risk factors for coronary heart disease in Japanese men. J Urol 189:1340–1346.

    Article  PubMed  Google Scholar 

  15. 15.

    Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K et al (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Gillen DL, Worcester EM, Coe FL (2005) Decreased renal function among adults with a history of nephrolithiasis: a study of NHANES III. Kidney Int 67:685–690.

    Article  PubMed  Google Scholar 

  17. 17.

    Khan SR (2012) Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome? Urol Res 40:95–112.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Yamagata K, Ishida K, Sairenchi T, Takahashi H, Ohba S, Shiigai T et al (2007) Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study. Kidney Int 71:159–166.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ (2010) The clinical significance of hyperfiltration in diabetes. Diabetologia 53:2093–2104.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Melsom T, Mathisen UD, Ingebretsen OC, Jenssen TG, Njolstad I, Solbu MD et al (2011) Impaired fasting glucose is associated with renal hyperfiltration in the general population. Diabetes Care 34:1546–1551.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Tomaszewski M, Charchar FJ, Maric C, McClure J, Crawford L, Grzeszczak W et al (2007) Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int 71:816–821.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Saucier NA, Sinha MK, Liang KV, Krambeck AE, Weaver AL, Bergstralh EJ et al (2010) Risk factors for CKD in persons with kidney stones: a case-control study in Olmsted County, Minnesota. Am J Kidney Dis 55:61–68.

    Article  PubMed  Google Scholar 

  23. 23.

    Vupputuri S, Soucie JM, McClellan W, Sandler DP (2004) History of kidney stones as a possible risk factor for chronic kidney disease. Ann Epidemiol 14:222–228.

    Article  PubMed  Google Scholar 

  24. 24.

    Ferraro PM, Taylor EN, Eisner BH, Gambaro G, Rimm EB, Mukamal KJ et al (2013) History of kidney stones and the risk of coronary heart disease. JAMA 310:408–415.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Xu C, Zhang C, Wang XL, Liu TZ, Zeng XT, Li S et al (2015) Self-fluid management in prevention of kidney stones: a PRISMA-compliant systematic review and dose-response meta-analysis of observational studies. Medicine (Baltimore) 94:e1042.

    CAS  Article  Google Scholar 

  26. 26.

    Pedro RN, Aslam AU, Bello JO, Bhatti KH, Philipraj J, Sissoko I et al (2020) Nutrients, vitamins, probiotics and herbal products: an update of their role in urolithogenesis. Urolithiasis 48:285–301.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    The National Nutrition Survey in Japan (2018) Ministry of Health, Labor and Welfare 2018. Accessed 25 Aug 2020

  28. 28.

    Kohjimoto Y, Sasaki Y, Iguchi M, Matsumura N, Inagaki T, Hara I (2013) Association of metabolic syndrome traits and severity of kidney stones: results from a nationwide survey on urolithiasis in Japan. Am J Kidney Dis 61:923–929.

    Article  PubMed  Google Scholar 

  29. 29.

    Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J et al (2005) Definition and classification of chronic kidney disease: a position statement from Kidney Disease: improving Global Outcomes (KDIGO). Kidney Int 67:2089–2100.

    Article  PubMed  Google Scholar 

  30. 30.

    Curhan GC, Willett WC, Rimm EB, Stampfer MJ (1993) A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med 328:833–838.

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Ryosuke Ando.

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Ando, R., Nagaya, T., Suzuki, S. et al. Independent and interactive effects of kidney stone formation and conventional risk factors for chronic kidney disease: a follow-up study of Japanese men. Int Urol Nephrol (2021).

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  • Kidney stone
  • Chronic kidney disease
  • Conventional risk factors
  • Interaction