Table 3The Effects of Smoking on Re

Table 3
The Effects of Smoking on Renal Function in Healthy Populations
The overall outcomes in the studies on renal function are conflicting. Only 5 studies with grade A or B in quality (27, 29, 31, 37, 38) detected a significant effect of smoking on the decline of renal function, which was also suggested in other 6 studies with grade C (12, 26, 28, 30, 32, 33). These studies were all conducted in community populations, some of those included many elderly persons (27, 28, 37, 38) or CKD patients (32, 33). Yamagata et al. (38) followed 124,000 inhabitants aged 40 years or older in a community in Japan for 10 years, excluding all those showing CKD signs beforehand, and observed that smoking caused a significant but only 10% increase in the risk for a declining GFR to the level of less than 60 ml/min/1.73m. On the other hand, 9 studies with any grade in quality even showed a higher GFR or Ccr in smokers than in non-smokers, especially those conducted in working populations (7, 17, 22, 25, 35, 36). A significantly lower risk of a low GFR was even observed in current smokers (17, 25). No difference was observed in age-related decline of GFR or Ccr among current and former smokers, and life-time non-smokers (7, 15). One study showed even a more modest decline of GFR in smokers than in non-smokers during a 5-year period (35).
In addition to the generally low LOE and quality of the literature, this article has some other limitations. The literature was collected only from the MEDLINE database, and some important articles may thus have been over-looked. The methods and manner of quality evaluation of the articles in this review have not been approved by experts other than us, which might have added some arbitrariness to the evaluation. But, in these specific circumstances, this review reveals some peculiar paradoxical findings of CKD signs in smokers in healthy populations, i.e., a persistently high appearance of proteinuria often accompanied with an elevated GFR.
5. Discussion
5.1. Significance of the Paradoxical CKD Signs in Smokers
Yoon et al. (25) in Korea has already pointed out the paradoxical CKD signs in a cross-sectional observation in 35,288 participants of a health screening program, and named “the different effect of smoking on GFR and proteinuria in a healthy population”. They mentioned that the association of smoking status with GFR was different between those showing a GFR of 50 ml/min/1.73m2 or above and those with a lower GFR. In those with the relatively high GFR, smokers showed a higher mean GFR than non-smokers, but an inverse association was observed in those with the low GFR, i.e., smokers have a lower GFR than non-smokers. From these findings and the limited appearance of proteinuria even in smokers, Yoon et al. proposed a hypothesis that most smokers from the general population do not show deteriorations of renal function even though they showed an elevated GFR, while only a small, especially susceptible subset of the population would show a lowered GFR and proteinuria. However, this hypothesis has not yet been confirmed.
Possible factors underlying the development of CKD in smokers were extensively discussed by Orth and Hallan (2) such as hypoxia, heavy metals in tobacco smoke, intrarenal vasoconstriction, oxidative stress and inflammatory process. Although the exact variable has remained uncertain, the intraglomerular hypertension caused by the intrarenal hemodynamic changes due to nicotine in cigarette smoke may be the most plausible reason. The high GFR in smokers may thus be a reflection of glomerular hyperfiltration following the intraglomerular hypertension and the early sign of renal damage like that observed in the early stage of diabetic nephropathy (39). If so, the high GFR in smokers may eventually decrease to a low level with continued smoking and cause proteinuria. However, this has not been confirmed either since longitudinal observations on GFR have so far failed to identify a more marked decline of GFR in smokers than in non-smokers (34, 35).
5.2. Advantages of Studies in Workplaces
The number of CKD patients is estimated to be 13 million or more in Japan, which is more than 10% of the national population. However, it has not been well recognized among healthcare experts, especially those engaged in preventing activities for life-style diseases at worksites. The population of Japan is aging rapidly and so is the workforce, and most workplaces are predicted to have as many as 30% or more workers aged 60 years or older in 2050. Since the renal toxic effects of smoking are more predominant in elderly persons, healthcare experts at worksites may face the far-ranging and profound impact of smoking-induced CKD in the near future.
The aging of the working population, on the other hand, may provide healthcare experts at worksites with a greater chance of observing the long-term annual changes in renal function in smokers throughout middle-age to the age of 70 years or longer. Therefore, workplaces may have special merits of revealing a more conspicuous decline of GFR in smokers once showing a higher GFR as compared to non-smokers from the data collected by the annual health check-ups mandated by the workplace. Healthcare experts at workplaces should pay more attention to smoking-induced CKD.
Acknowledgments
I am very grateful for the support and advice provided by Prof. Yuichi Yamada, Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine Ishikawa, Japan.
Footnotes
Implication for health policy/practice/research/medical education: Many previous studies in healthy populations showed a higher appearance of proteinuria with a higher GFR in smokers, and the underlying reasons for the paradoxical markers of CKD in smokers could be a focus for further studies.
Please cite this paper as: Noborisaka Y. Smoking and Chronic Kidney Disease (CKD) in Healthy Populations. Nephro-Urol Mon. 2013;5(1): 655-667. DOI: 10.5812/numonthly.3527
Authors’ Contributions: Yuka Noborisaka is the only author of the article.
Financial Disclosure: No finamcial support by any institution.
Funding/Support: This article is supported financially by KAKENHI, a Grant-in-Aid for Scientific Research (C), 2010, from the Japan Society for the Promotion of Science (JSPS).
References
1. Orth SR. Effects of smoking on systemic and intrarenal hemodynamics: influence on renal function. J Am Soc Nephrol. 2004;15(Suppl 1):S58–63. doi: 10.1097/01.ASN.0000093461.36097.D5. [PubMed] [Cross Ref]
2. Orth SR, Hallan SI. Smoking: a risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal patients--absence of evidence or evidence of absence? Clin J Am Soc Nephrol. 2008;3(1):226–36. doi: 10.2215/CJN.03740907. [PubMed] [Cross Ref]
3. Orth SR, Ritz E. The renal risks of smoking: an update. Curr Opin Nephrol Hypertens. 2002;11(5):483–8. doi: 10.1097/00041552-200209000-00002. [PubMed] [Cross Ref]
4. Orth SR, Ritz E, Schrier RW. The renal risks of smoking. Kidney Int. 1997;51(6):1669–77. doi: 10.1038/ki.1997.232. [PubMed] [Cross Ref]
5. Janssen WM, Hillege H, Pinto-Sietsma SJ, Bak AA, De Zeeuw D, de Jong PE. Low levels of urinary albumin excretion are associated with cardiovascular risk factors in the general population. Clin Chem Lab Med. 2000;38(11):1107–10. doi: 10.1515/CCLM.2000.165. [PubMed] [Cross Ref]
6. Jones-Burton C, Seliger SL, Scherer RW, Mishra SI, Vessal G, Brown J, et al. Cigarette smoking and incident chronic kidney disease: a systematic review. Am J Nephrol. 2007;27(4):342–51. doi: 10.1159/000103382. [PubMed] [Cross Ref]
7. Noborisaka Y, Ishizaki M, Nakata M, Yamada Y, Honda R, Yokoyama H, et al. Cigarette smoking, proteinuria, and renal function in middle-aged Japanese men from an occupational population. Environ Health Prev Med. 2012;17(2):147–56. doi: 10.1007/s12199-011-0234-x. [PMC free article] [PubMed] [Cross Ref]
8. Cho MK, Bero LA. Instruments for assessing the quality of drug studies published in the medical literature. JAMA. 1994;272(2):101–4. doi: 10.1001/jama.1994.03520020027007. [PubMed] [Cross Ref]
9. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3 Suppl):21–35. doi: 10.1016/S0749-3797(01)00261-6. [PubMed] [Cross Ref]
10. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461–70. [PubMed]
11. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [PubMed] [Cross Ref]
12. Briganti EM, Branley P, Chadban SJ, Shaw JE, McNeil JJ, Welborn TA, et al. Smoking is associated with renal impairment and proteinuria in the normal population: the AusDiab kidney study. Australian Diabetes, Obesity and Lifestyle Study. Am J Kidney Dis. 2002;40(4):704–12. doi: 10.1053/ajkd.2002.35677. [PubMed] [Cross Ref]
13. Cirillo M, Senigalliesi L, Laurenzi M, Alfieri R, Stamler J, Stamler R, et al. Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: The Gubbio Population Study. Arch Intern Med. 1998;158(17):1933–9. doi: 10.1001/archinte.158.17.1933. [PubMed] [Cross Ref]
14. Goetz FC, Jacobs DR, Jr., Chavers B, Roel J, Yelle M, Sprafka JM. Risk factors for kidney damage in the adult population of Wadena, Minnesota. A prospective study. Am J Epidemiol. 1997;145(2):91–102. doi: 10.1093/oxfordjournals.aje.a009091. [PubMed] [Cross Ref]
15. Halimi JM, Giraudeau B, Vol S, Caces E, Nivet H, Lebranchu Y, et al. Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population. Kidney Int.

النتائج (العربية) 1:

Table 3The Effects of Smoking on Renal Function in Healthy Populations The overall outcomes in the studies on renal function are conflicting. Only 5 studies with grade A or B in quality (27, 29, 31, 37, 38) detected a significant effect of smoking on the decline of renal function, which was also suggested in other 6 studies with grade C (12, 26, 28, 30, 32, 33). These studies were all conducted in community populations, some of those included many elderly persons (27, 28, 37, 38) or CKD patients (32, 33). Yamagata et al. (38) followed 124,000 inhabitants aged 40 years or older in a community in Japan for 10 years, excluding all those showing CKD signs beforehand, and observed that smoking caused a significant but only 10% increase in the risk for a declining GFR to the level of less than 60 ml/min/1.73m. On the other hand, 9 studies with any grade in quality even showed a higher GFR or Ccr in smokers than in non-smokers, especially those conducted in working populations (7, 17, 22, 25, 35, 36). A significantly lower risk of a low GFR was even observed in current smokers (17, 25). No difference was observed in age-related decline of GFR or Ccr among current and former smokers, and life-time non-smokers (7, 15). One study showed even a more modest decline of GFR in smokers than in non-smokers during a 5-year period (35).بالإضافة إلى لوي منخفضة بصفة عامة ونوعية للأدب، على هذه المقالة بعض القيود الأخرى. وجمعت في الأدب فقط من قاعدة بيانات MEDLINE، وبعض المواد الهامة وبالتالي يكون قد بدأ الإفراط. طريقة لتقييم نوعية المواد في هذا الاستعراض وأساليب لم تم بموافقة الخبراء خلاف لنا، وقد أضفت بعض التعسف في تقييم. ولكن، في هذه الظروف المحددة، يكشف هذا الاستعراض توقع بعض النتائج مفارقة غريبة من كد في المدخنين في صحة السكان، أي مظهر بروتينية غالباً ما يترافق مع GFR مرتفعة استمرار ارتفاع.5-مناقشة5-1-أهمية كد المفارقة يوقع في المدخنينYoon et al. (25) in Korea has already pointed out the paradoxical CKD signs in a cross-sectional observation in 35,288 participants of a health screening program, and named “the different effect of smoking on GFR and proteinuria in a healthy population”. They mentioned that the association of smoking status with GFR was different between those showing a GFR of 50 ml/min/1.73m2 or above and those with a lower GFR. In those with the relatively high GFR, smokers showed a higher mean GFR than non-smokers, but an inverse association was observed in those with the low GFR, i.e., smokers have a lower GFR than non-smokers. From these findings and the limited appearance of proteinuria even in smokers, Yoon et al. proposed a hypothesis that most smokers from the general population do not show deteriorations of renal function even though they showed an elevated GFR, while only a small, especially susceptible subset of the population would show a lowered GFR and proteinuria. However, this hypothesis has not yet been confirmed.Possible factors underlying the development of CKD in smokers were extensively discussed by Orth and Hallan (2) such as hypoxia, heavy metals in tobacco smoke, intrarenal vasoconstriction, oxidative stress and inflammatory process. Although the exact variable has remained uncertain, the intraglomerular hypertension caused by the intrarenal hemodynamic changes due to nicotine in cigarette smoke may be the most plausible reason. The high GFR in smokers may thus be a reflection of glomerular hyperfiltration following the intraglomerular hypertension and the early sign of renal damage like that observed in the early stage of diabetic nephropathy (39). If so, the high GFR in smokers may eventually decrease to a low level with continued smoking and cause proteinuria. However, this has not been confirmed either since longitudinal observations on GFR have so far failed to identify a more marked decline of GFR in smokers than in non-smokers (34, 35).5.2. Advantages of Studies in WorkplacesThe number of CKD patients is estimated to be 13 million or more in Japan, which is more than 10% of the national population. However, it has not been well recognized among healthcare experts, especially those engaged in preventing activities for life-style diseases at worksites. The population of Japan is aging rapidly and so is the workforce, and most workplaces are predicted to have as many as 30% or more workers aged 60 years or older in 2050. Since the renal toxic effects of smoking are more predominant in elderly persons, healthcare experts at worksites may face the far-ranging and profound impact of smoking-induced CKD in the near future.The aging of the working population, on the other hand, may provide healthcare experts at worksites with a greater chance of observing the long-term annual changes in renal function in smokers throughout middle-age to the age of 70 years or longer. Therefore, workplaces may have special merits of revealing a more conspicuous decline of GFR in smokers once showing a higher GFR as compared to non-smokers from the data collected by the annual health check-ups mandated by the workplace. Healthcare experts at workplaces should pay more attention to smoking-induced CKD.AcknowledgmentsI am very grateful for the support and advice provided by Prof. Yuichi Yamada, Department of Social and Environmental Medicine, Kanazawa Medical University School of Medicine Ishikawa, Japan.FootnotesImplication for health policy/practice/research/medical education: Many previous studies in healthy populations showed a higher appearance of proteinuria with a higher GFR in smokers, and the underlying reasons for the paradoxical markers of CKD in smokers could be a focus for further studies.Please cite this paper as: Noborisaka Y. Smoking and Chronic Kidney Disease (CKD) in Healthy Populations. Nephro-Urol Mon. 2013;5(1): 655-667. DOI: 10.5812/numonthly.3527Authors’ Contributions: Yuka Noborisaka is the only author of the article.Financial Disclosure: No finamcial support by any institution.Funding/Support: This article is supported financially by KAKENHI, a Grant-in-Aid for Scientific Research (C), 2010, from the Japan Society for the Promotion of Science (JSPS).References1. Orth SR. Effects of smoking on systemic and intrarenal hemodynamics: influence on renal function. J Am Soc Nephrol. 2004;15(Suppl 1):S58–63. doi: 10.1097/01.ASN.0000093461.36097.D5. [PubMed] [Cross Ref]2. Orth SR, Hallan SI. Smoking: a risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal patients--absence of evidence or evidence of absence? Clin J Am Soc Nephrol. 2008;3(1):226–36. doi: 10.2215/CJN.03740907. [PubMed] [Cross Ref]3. Orth SR, Ritz E. The renal risks of smoking: an update. Curr Opin Nephrol Hypertens. 2002;11(5):483–8. doi: 10.1097/00041552-200209000-00002. [PubMed] [Cross Ref]4. Orth SR, Ritz E, Schrier RW. The renal risks of smoking. Kidney Int. 1997;51(6):1669–77. doi: 10.1038/ki.1997.232. [PubMed] [Cross Ref]5. Janssen WM, Hillege H, Pinto-Sietsma SJ, Bak AA, De Zeeuw D, de Jong PE. Low levels of urinary albumin excretion are associated with cardiovascular risk factors in the general population. Clin Chem Lab Med. 2000;38(11):1107–10. doi: 10.1515/CCLM.2000.165. [PubMed] [Cross Ref]6. Jones-Burton C, Seliger SL, Scherer RW, Mishra SI, Vessal G, Brown J, et al. Cigarette smoking and incident chronic kidney disease: a systematic review. Am J Nephrol. 2007;27(4):342–51. doi: 10.1159/000103382. [PubMed] [Cross Ref]7. Noborisaka Y, Ishizaki M, Nakata M, Yamada Y, Honda R, Yokoyama H, et al. Cigarette smoking, proteinuria, and renal function in middle-aged Japanese men from an occupational population. Environ Health Prev Med. 2012;17(2):147–56. doi: 10.1007/s12199-011-0234-x. [PMC free article] [PubMed] [Cross Ref]8. Cho MK, Bero LA. Instruments for assessing the quality of drug studies published in the medical literature. JAMA. 1994;272(2):101–4. doi: 10.1001/jama.1994.03520020027007. [PubMed] [Cross Ref]9. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3 Suppl):21–35. doi: 10.1016/S0749-3797(01)00261-6. [PubMed] [Cross Ref]10. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461–70. [PubMed]11. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [PubMed] [Cross Ref]12. Briganti EM, Branley P, Chadban SJ, Shaw JE, McNeil JJ, Welborn TA, et al. Smoking is associated with renal impairment and proteinuria in the normal population: the AusDiab kidney study. Australian Diabetes, Obesity and Lifestyle Study. Am J Kidney Dis. 2002;40(4):704–12. doi: 10.1053/ajkd.2002.35677. [PubMed] [Cross Ref]13. Cirillo M, Senigalliesi L, Laurenzi M, Alfieri R, Stamler J, Stamler R, et al. Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: The Gubbio Population Study. Arch Intern Med. 1998;158(17):1933–9. doi: 10.1001/archinte.158.17.1933. [PubMed] [Cross Ref]14. Goetz FC, Jacobs DR, Jr., Chavers B, Roel J, Yelle M, Sprafka JM. Risk factors for kidney damage in the adult population of Wadena, Minnesota. A prospective study. Am J Epidemiol. 1997;145(2):91–102. doi: 10.1093/oxfordjournals.aje.a009091. [PubMed] [Cross Ref]15. Halimi JM, Giraudeau B, Vol S, Caces E, Nivet H, Lebranchu Y, et al. Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population. Kidney Int.

النتائج (العربية) 3:

الجدول 3 آثار التدخين على وظائف الكلى في السكان الأصحاء
فإن مجمل نتائج الدراسات على وظائف الكلى متضاربة.فقط 5 دراسات الصف أ أو ب في الجودة (27 و 29 و 31 و 37 و 38) اكتشاف أثر التدخين على انخفاض وظيفة الكلى، الذي اقترح أيضا في غيرها من 6 دراسات الصف الثالث (12 و 26 و 28 و 30 و 32 33).