Serum levels of CMPF, a protein-bound uremic toxin, across different kidney replacement modalities

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Serum levels of CMPF, a protein-bound uremic toxin, across different kidney replacement modalities

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Co-author 1

Beatriz Akemi Kondo Van Spitzenbergen beatriz.van@pucpr.edu.br Pontifícia Universidade Católica do Paraná (PUCPR) PPGCS Curitiba Brazil -

Co-author 2

Rayane De Cássia Cagni Vicentin rayane.vicentin@pucpr.edu.br Pontifícia Universidade Católica do Paraná (PUCPR) PPGCS Curitiba Brazil -

Co-author 3

Nadja Grobe nadja.grobe@rriny.com Renal Research Institute RRI New York United States -

Co-author 4

Andrea N Moreno-Amaral andrea.moreno@pucpr.br Pontifícia Universidade Católica do Paraná (PUCPR) PPGCS Curitiba Brazil *

Co-author 5

Peter Kotanko kotanko.peter@yahoo.com Renal Research Institute RRI New York United States - Icahn School of Medicine at Mount Sinai School of Medicine New York United States

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Introduction

The protein-bound solute 2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid (CMPF), a metabolite derived from furan fatty acids, has been classified as a uremic toxin. Elevated CMPF levels have been reported in patients with chronic kidney disease (CKD), and emerging evidence suggests its potential impact on erythrocyte biology (Van Spitzenbergen, Nephrol Dial Transplant. 2025 Jun 30;40(7):1342-1349. doi: 10.1093/ndt/gfae275). This study aimed to quantify total serum CMPF levels in individuals with CKD undergoing different renal replacement therapy modalities.

Methods

Blood samples were obtained from healthy controls (CON n = 7), hemodialysis (HD n = 19), peritoneal dialysis (PD n = 26), and kidney transplant recipients (n = 13; POST 1–5 days, POST 1 month, POST 3 months). All participants provided written informed consent prior to sample and data collection. Samples were collected in citrate and SST gel tubes, aliquoted, and stored at −80 °C. Serum CMPF was extracted with ice-cold methanol and quantified by liquid chromatography–mass spectrometry (LC–MS). CMPF concentrations were compared across groups using appropriate statistical tests.

Results

CMPF serum levels were significantly higher in HD patients compared with CON (p < 0.05). Patients undergoing PD exhibited lower CMPF concentrations than those on HD, suggesting differential solute clearance between dialysis modalities. CMPF levels were reduced shortly after renal transplantation (1–5 days) compared with HD and remained lower at 1 month and 3 months post-transplantation (Figure 1).

Conclusion

CMPF accumulation is most pronounced in HD patients, likely due to the limited removal of this highly protein-bound solute. The lower CMPF level in PD patients may be related to residual kidney function and higher protein loss compared to HD. Although renal transplantation markedly decreases CMPF levels, it does not fully normalize them to control values, possibly related to impaired proximal tubular function of the graft. Whether different levels of CMPF are associated with different CKD-related metabolic and hematologic disturbances warrants further investigation.

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