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Protective effect of N-acetylcysteine on progression to end-stage renal disease: Necessity for prospective clinical trial

  • Author Footnotes
    1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Lingya Dist., Kaohsiung City 802, Taipei, Taiwan, R.O.C.
    ,
    Author Footnotes
    2 Division of Nephrology, Department of Internal medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, R.O.C.
    Chen-Yi Liao
    Footnotes
    1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Lingya Dist., Kaohsiung City 802, Taipei, Taiwan, R.O.C.
    2 Division of Nephrology, Department of Internal medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, R.O.C.
    Affiliations
    Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan

    Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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  • Chi-Hsiang Chung
    Affiliations
    School of Public Health, National Defense Medical Center, Taipei, Taiwan

    Taiwanese Injury Prevention and Safety Promotion Association, Taiwan
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  • Chai-Chao Wu
    Affiliations
    Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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  • Fu-Huang Lin
    Affiliations
    School of Public Health, National Defense Medical Center, Taipei, Taiwan
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  • Chang-Huei Tsao
    Affiliations
    Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

    Department of Microbiology & Immunology, National Defense Medical Center, Taiwan
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  • Author Footnotes
    1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Lingya Dist., Kaohsiung City 802, Taipei, Taiwan, R.O.C.
    ,
    Author Footnotes
    2 Division of Nephrology, Department of Internal medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, R.O.C.
    Chih-Chiang Wang
    Correspondence
    Correspondence to: Chih-Chiang Wang, Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Lingya Dist., Kaohsiung City 802, Taipei, Taiwan, R.O.C.
    Footnotes
    1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Lingya Dist., Kaohsiung City 802, Taipei, Taiwan, R.O.C.
    2 Division of Nephrology, Department of Internal medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, R.O.C.
    Affiliations
    Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan

    Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
    Search for articles by this author
  • Author Footnotes
    3 School of Public Health, National Defense Medical Center, 4109R, No.161, Section 6, Min-Chuan East Road, Neihu District, Taipei City, 11490, Taiwan, R.O.C.
    Wu-Chien Chien
    Correspondence
    Correspondence to: Wu-Chien Chien, Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 7115R, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City 11490, Taiwan, R.O.C.
    Footnotes
    3 School of Public Health, National Defense Medical Center, 4109R, No.161, Section 6, Min-Chuan East Road, Neihu District, Taipei City, 11490, Taiwan, R.O.C.
    Affiliations
    School of Public Health, National Defense Medical Center, Taipei, Taiwan

    Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
    Search for articles by this author
  • Author Footnotes
    1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Lingya Dist., Kaohsiung City 802, Taipei, Taiwan, R.O.C.
    2 Division of Nephrology, Department of Internal medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, R.O.C.
    3 School of Public Health, National Defense Medical Center, 4109R, No.161, Section 6, Min-Chuan East Road, Neihu District, Taipei City, 11490, Taiwan, R.O.C.

      Highlights

      • NAC use was associated with reduced risk for progression to ESRDd.
      • Risk reduction was apparent in women, younger age, hypertension, the absence of diabetes mellitus and congestive heart failure.
      • The cumulative effect of NAC necessitate a prospective study.

      Abstract

      Background

      We aimed to evaluate the potential benefits of N-acetylcysteine (NAC) on the risk of chronic kidney disease (CKD) progression to dialysis-requiring end-stage renal disease (ESRDd).

      Methods

      In a population-based cohort study of 145,062 individuals, 123,608 CKD patients who were followed up for 10 years were included, and CKD patients treated with NAC (ICD-9-CM) were compared with those who were not treated. Using propensity score matching, we analyzed the predictors of CKD progression to ESRDd by Cox proportional hazards regression with adjustments for sex, age, and comorbidities, and evaluated the effect of NAC using cumulative defined daily dose (cDDD).

      Results

      NAC use was associated with a reduced risk for progression to ESRDd [hazard ratio (HR), 0.819; 95% confidence interval (CI), 0.781–0.965; P = 0.017]. Risk reduction was proportional to cDDD in NAC users compared with that in NAC non users (HR, 0.835, 0.811, and 0.799 for cDDD 91–180, 181–360, and >360, respectively; P for trend = 0.018). Risk reduction was apparent in women (P = 0.001) and in younger-aged patients of 18–29 years (P = 0.021) and 30–39 years (P = 0.033), in the presence of hypertension (P = 0.003), and in the absence of diabetes mellitus (P = 0.042) and congestive heart failure (P = 0.036).

      Conclusion

      NAC use was associated with a reduced risk for progression to ESRDd. These results, obtained from retrospective data, indicate that a prospective study is warranted.

      Keywords

      Abbreviations:

      CKD (chronic kidney disease), ESRD (end-stage kidney disease), NAC (N-acetylcysteine), COPD (chronic obstructive pulmonary disease), NHI (National Health Insurance), NHIRD (NHI Research Database), ICD-9-CM (International Classification of Disease, Ninth Revision, Clinical Modification), ESRDd (dialysis-requiring ESRD), CHF (congestive heart failure), CCI (Charlson comorbidity index), DDD (defined daily dose), cDDD (cumulative DDD), HR (hazard ratio), CI (confidence interval), ACEI (angiotensin-converting-enzyme inhibitor), ARB (angiotensin receptor blocker)
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