How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule

Wen-Sheng Liu; Shih-Shin Liang; Mei-Mei Cheng; Ming-Tsan Wu; Szu-Yuan Li; Tien-Tien Cheng; Tsung-Yun Liu; Ching-Yao Tsai; Yen-Ting Lai; Chien-Hung Lin; Hsiang-Tsui Wang; Han-Hsing Tsou

doi:10.1002/tox.24248

How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule

Environ Toxicol. 2024 Apr 4. doi: 10.1002/tox.24248. Online ahead of print.

Authors

Wen-Sheng Liu^{1

2

3

4

5}, Shih-Shin Liang^{6

7}, Mei-Mei Cheng⁸, Ming-Tsan Wu⁹, Szu-Yuan Li^{2

10}, Tien-Tien Cheng⁴, Tsung-Yun Liu⁴, Ching-Yao Tsai^{11

12

13}, Yen-Ting Lai^{14

15

16}, Chien-Hung Lin^{2

3

17}, Hsiang-Tsui Wang¹⁸, Han-Hsing Tsou^{4

19}

Affiliations

¹ Division of Nephrology, Department of Medicine, Taipei City Hospital, Taipei, Taiwan.
² School of Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
³ College of Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan.
⁴ Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
⁵ Department of Special Education, University of Taipei, Taipei, Taiwan.
⁶ Institute of Biomedical Science, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁷ Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁸ Division of nephrology, Department of internal medicine, West Garden Hospital, Taipei, Taiwan.
⁹ Department of internal medicine, Fu-Ling clinic, New Taipei City, Taiwan.
¹⁰ Division of Nephrology, and Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹¹ Institute of Public Health, Department of Public Health, College of Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
¹² Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan.
¹³ Department of Business Administration, Fu Jen Catholic University, New Taipei City, Taiwan.
¹⁴ Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei, Taiwan.
¹⁵ Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
¹⁶ Department of Nursing, College of Medical Technology and Nursing, Yuanpei University of Medical Technology, Hsinchu, Taiwan.
¹⁷ Division of Pediatric Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁸ Department of Pharmacology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
¹⁹ Kim Forest Enterprise Co., Ltd., New Taipei City, Taiwan.

PMID: 38572829
DOI: 10.1002/tox.24248

Abstract

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, while PFOA increased in responders. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

Keywords: acrolein; activated charcoal; chronic kidney disease (CKD); indoxyl sulfate; oral toxin adsorbents; per‐and poly‐fluoroalkyl substances (PFAS); p‐cresol.

Grants and funding

TPCH-112-21/Taipei City Hospital