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Pre-dialysis serum creatinine as an independent predictor of responsiveness to zinc supplementation among patients on hemodialysis

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Abstract

Background

To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD).

Methods

We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 μg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 μg/dL) and early response (serum zinc level ≥ 80 μg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis.

Results

Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = − 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24–11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation.

Conclusions

Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.

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References

  1. Imanishi M, Hori Y, Nagaoka M, Sugiura Y. Design of novel zinc finger proteins: towards artificial control of specific gene expression. Eur J Pharm Sci. 2001;13:91–7.

    Article  CAS  Google Scholar 

  2. McCall KA, Huang C, Fierke CA. Function and mechanism of zinc metalloenzymes. J Nutr. 1437S;130:1437S–S14461446.

    Article  CAS  Google Scholar 

  3. Zumkley H, Bertram HP, Lison A, Knoll O, Losse H. Aluminum, zinc and copper concentrations in plasma in chronic renal insufficiency. Clin Nephrol. 1979;12:18–211.

    CAS  PubMed  Google Scholar 

  4. Kobayashi H, Abe M, Okada K, et al. Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis. Nutrients. 2015;7:3783–95.

    Article  CAS  Google Scholar 

  5. Shiota J, Tagawa H, Izumi N, Higashikawa S, Kasahara H. Effect of zinc supplementation on bone formation in hemodialysis patients with normal or low turnover bone. Ren Fail. 2015;37:57–60.

    Article  CAS  Google Scholar 

  6. Bromley SM. Smell and taste disorders: a primary care approach. Am Fam Phys. 2000;61(427–36):438.

    Google Scholar 

  7. Prasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis. 2000;182(Suppl 1):S62–S6868.

    Article  CAS  Google Scholar 

  8. Yamaguchi M. Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem. 2010;338:241–54.

    Article  CAS  Google Scholar 

  9. Osawa M, Yamaguchi T, Nakamura Y, et al. Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis. Blood. 2002;100:2769–77.

    Article  CAS  Google Scholar 

  10. Okamoto T, Hatakeyama S, Konishi S, et al. Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: a single-center, open-label, prospective randomized study. Ther Apher Dial. 2019. https://doi.org/10.1111/1744-9987.13461.

    Article  PubMed  Google Scholar 

  11. Miller LV, Hambidge KM, Naake VL, et al. Size of the zinc pools that exchange rapidly with plasma zinc in humans: alternative techniques for measuring and relation to dietary zinc intake. J Nutr. 1994;124:268–76.

    Article  CAS  Google Scholar 

  12. Lowe NM, Fekete K, Decsi T. Methods of assessment of zinc status in humans: a systematic review. Am J Clin Nutr. 2051S;89:2040S–51S.

    Article  CAS  Google Scholar 

  13. Pinna K, Woodhouse LR, Sutherland B, Shames DM, King JC. Exchangeable zinc pool masses and turnover are maintained in healthy men with low zinc intakes. J Nutr. 2001;131:2288–94.

    Article  CAS  Google Scholar 

  14. Wastney ME, Aamodt RL, Rumble WF, Henkin RI. Kinetic analysis of zinc metabolism and its regulation in normal humans. Am J Physiol Integr Comp Physiol. 1986;251:R398–408.

    Article  CAS  Google Scholar 

  15. Canaud B, Granger Vallée A, Molinari N, et al. Creatinine index as a surrogate of lean body mass derived from urea Kt/V, pre-dialysis serum levels and anthropometric characteristics of haemodialysis patients. PLoS ONE. 2014;9:e93286.

    Article  Google Scholar 

  16. Tomita H. A proposal of the clinical standard value for diagnose of zinc deficiency by serum zinc value. Biomed Res Trace Elem. 2008;19(1):22–4.

    CAS  Google Scholar 

  17. Bouillanne O, Morineau G, Dupont C, et al. Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients. Am J Clin Nutr. 2005;82:777–83.

    Article  CAS  Google Scholar 

  18. Okamoto T, Tsutaya C, Hatakeyama S, et al. Low serum butyrylcholinesterase is independently related to low fetuin-A in patients on hemodialysis: a cross-sectional study. Int Urol Nephrol. 2018;50:1713–20.

    Article  CAS  Google Scholar 

  19. Okamoto T, Hatakeyama S, Kodama H, et al. The relationship between poor nutritional status and progression of aortic calcification in patients on maintenance hemodialysis. BMC Nephrol. 2018;19:1–8.

    Article  Google Scholar 

  20. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015;34:3661–799.

    Article  Google Scholar 

  21. Krebs NF. Overview of zinc absorption and excretion in the human gastrointestinal tract. J Nutr. 1374S;130:1374S–S13771377.

    Article  CAS  Google Scholar 

  22. Cousins RJ. Gastrointestinal factors influencing zinc absorption and homeostasis. Int J Vitam Nutr Res. 2010;80:243–8.

    Article  CAS  Google Scholar 

  23. Illing AC, Shawki A, Cunningham CL, Mackenzie B. Substrate profile and metal-ion selectivity of human divalent metal-ion transporter-1. J Biol Chem. 2012;287:30485–96.

    Article  CAS  Google Scholar 

  24. Gibson RS, Hess SY, Hotz C, Brown KH. Indicators of zinc status at the population level: a review of the evidence. Br J Nutr. 2008;99:S14–23.

    Article  CAS  Google Scholar 

  25. Lichten LA, Cousins RJ. Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr. 2009;29:153–76.

    Article  Google Scholar 

  26. Moreau-Gaudry X, Guebre-Egziabher F, Jean G, et al. Serum creatinine improves body mass index survival prediction in hemodialysis patients: a 1-year prospective cohort analysis from the ARNOS study. J Ren Nutr. 2011;21:369–75.

    Article  CAS  Google Scholar 

  27. Arase H, Yamada S, Yotsueda R, et al. Modified creatinine index and risk for cardiovascular events and all-cause mortality in patients undergoing hemodialysis: the Q-Cohort study. Atherosclerosis. 2018;275:115–23.

    Article  CAS  Google Scholar 

  28. Wang L-J, Wang M-Q, Hu R, et al. Effect of zinc supplementation on maintenance hemodialysis patients: a systematic review and meta-analysis of 15 randomized controlled trials. Biomed Res Int. 2017;2017:1–11.

    Google Scholar 

  29. Hsu J, Johansen KL, Hsu C-Y, Kaysen GA, Chertow GM. Higher serum creatinine concentrations in black patients with chronic kidney disease: beyond nutritional status and body composition. Clin J Am Soc Nephrol. 2008;3:992–7.

    Article  CAS  Google Scholar 

  30. Petrie L, Chesters JK, Franklin M. Inhibition of myoblast differentiation by lack of zinc. Biochem J. 1991;276(Pt 1):109–11.

    Article  CAS  Google Scholar 

  31. Tsuboi A, Watanabe M, Kazumi T, Fukuo K. Association of serum copper/zinc ratio with low-grade inflammation and low handgrip strength in elderly women. Biomed Res Trace Elem. 2013;24:163–9.

    CAS  Google Scholar 

  32. Park J-M, Lee J-H, Jang HM, et al. Survival in patients on hemodialysis: effect of gender according to body mass index and creatinine. PLoS ONE. 2018;13:e0196550.

    Article  Google Scholar 

  33. Watanabe Y, Kawanishi H, Suzuki K, et al. Japanese society for dialysis therapy clinical guideline for “maintenance hemodialysis: hemodialysis prescriptions”. Ther Apher Dial. 2015;19:67–92.

    Article  Google Scholar 

  34. Kim YJ, Jeon HJ, Kim YH, et al. Overhydration measured by bioimpedance analysis and the survival of patients on maintenance hemodialysis: a single-center study. Kidney Res Clin Pract. 2015;34:212–8.

    Article  Google Scholar 

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Acknowledgements

We thank all staffs of Oyokyo Kidney Institute Aomori Hospital for their invaluable help with data collection.

Funding

None.

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Authors and Affiliations

  1. Department of Urology, Oyokyo Kidney Research Institute Aomori Hospital, 101-1 Okabe, Ishie, Aomori, 038-0003, Japan

    Teppei Okamoto, Yoshimi Tanaka, Kengo Imanishi, Tooru Takashima & Fumitada Saitoh

  2. Department of Urology, Hirosaki University Graduate School of Medicine, 5 Zaifu-chou, Hirosaki, 036-8562, Japan

    Teppei Okamoto, Shingo Hatakeyama, Kyo Togashi, Tomoko Hamaya, Yoshimi Tanaka & Chikara Ohyama

  3. Department of Urology, Oyokyo Kidney Research Institute, 90, Yamazaki, Ozawa, Hirosaki, Japan

    Tadashi Suzuki

Authors
  1. Teppei Okamoto
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  2. Shingo Hatakeyama
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  3. Kyo Togashi
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  4. Tomoko Hamaya
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  5. Yoshimi Tanaka
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  6. Kengo Imanishi
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  7. Tooru Takashima
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  8. Fumitada Saitoh
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  9. Tadashi Suzuki
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  10. Chikara Ohyama
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Contributions

Conceptualization: TO; methodology: TO and SH; formal analysis and investigation: TO, writing—original draft preparation: TO; writing—review and editing: TO and SH; data acquisition and clinical follow-up: TO, KT, TH, YT, KI, TT, and FS; supervision: TS and CO.

Corresponding author

Correspondence to Teppei Okamoto.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study approved by the Ethics Committee of Hirosaki University Graduate School of Medicine (IRB number, Ken11H30001). The trial is registered in the UMIN Clinical Trials Registry UMIN000031200.

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Informed consent was obtained from all individual participants included in the study.

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10157_2020_1911_MOESM1_ESM.pptx

Figure S1. Correlation between pre-dialysis serum creatinine (SCre) and the creatinine index. Pearson’s correlation analysis revealed a strong positive correlation between pre-dialysis SCre and the creatinine index. Figure S2. Sex difference in pre-dialysis serum creatinine (SCre) and Δzinc. A Pre-dialysis SCre level in female patients was significantly lower than that in male patients (A). The Δzinc in patients with SCre ≥ 10 mg/dL were significantly lower overall than in those with SCre <10 mg/dL within male patients (B). No significant results were obtained within female patients (C). Figure S3. The change of pre-dialysis serum creatinine (SCre) during the study period. Repeated-measures analysis of variance (ANOVA) showed that there was a significant change in pre-dialysis SCre during the study (P = 0.008). On the post-hoc analysis, a pre-dialysis SCre at 3 months was significantly reduced compared with that in 1 month (P <0.001). P value adjustment by Bonferroni’s correction (PPTX 229 kb)

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Okamoto, T., Hatakeyama, S., Togashi, K. et al. Pre-dialysis serum creatinine as an independent predictor of responsiveness to zinc supplementation among patients on hemodialysis. Clin Exp Nephrol 24, 955–962 (2020). https://doi.org/10.1007/s10157-020-01911-x

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  • DOI: https://doi.org/10.1007/s10157-020-01911-x

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