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Plasma pseudouridine levels reflect body size in children on hemodialysis

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Abstract

Background

Dialysis in children as well as adults is prescribed to achieve a target spKt/Vurea, where Vurea is the volume of distribution of urea. Waste solute production may however be more closely correlated with body surface area (BSA) than Vurea which rises in proportion with body weight. Plasma levels of waste solutes may thus be higher in smaller patients when targeting spKt/Vurea since they have higher BSA relative to body weight. This study measured levels of pseudouridine (PU), a novel marker solute whose production is closely proportional to BSA, to test whether prescription of dialysis to a target spKt/Vurea results in higher plasma levels of PU in smaller children.

Methods

PU and urea nitrogen (ureaN) were measured in plasma and dialysate at the midweek hemodialysis session in 20 pediatric patients, with BSA ranging from 0.65–1.87m2. Mathematical modeling was employed to estimate solute production rates and average plasma solute levels.

Results

The dialytic clearance (Kd) of PU was proportional to that of ureaN (average KdPU/KdUreaN 0.69 ± 0.13, r2 0.84, p < 0.001). Production of PU rose in proportion with BSA (r2 0.57, p < 0.001). The pretreatment plasma level of PU was significantly higher in smaller children (r2 0.20, p = 0.051) while the pretreatment level of ureaN did not vary with size.

Conclusions

Prescribing dialysis based on urea kinetics may leave uremic solutes at higher levels in small children. Measurement of a solute produced proportional to BSA may provide a better index of dialysis adequacy than measurement of urea.

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Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Acknowledgments

This work was supported by National Institutes of Health award R01 DK101674 to T.W.M. F.J.O’B. and L.L.G. were supported by fellowships from the Child Health Research Institute (CHRI) at Stanford. T.L.S. was supported by a Veterans Affairs Career Development Award (CX-001036-01A1). The authors thank the dialysis staffs of the Lucile Packard Children’s Hospital at Stanford and the UCSF Benioff Children’s Hospital for help with recruiting patients and collecting samples.

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Authors and Affiliations

  1. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Frank J. O’Brien

  2. Departments of Medicine, VA Palo Alto HCS and Stanford University, 3801 Miranda Ave, Palo Alto, CA, 94304, USA

    Tammy L. Sirich, Abigail Taussig, Natalie S. Plummer & Timothy W. Meyer

  3. Loma Linda University School of Medicine and VA Loma Linda HCS, Loma Linda, CA, USA

    Enrica Fung

  4. Department of Pediatrics, Stanford University, Palo Alto, CA, USA

    Lakshmi L. Ganesan & Scott M. Sutherland

  5. Department of Pediatrics, University of California, San Francisco, CA, USA

    Paul Brakeman

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  1. Frank J. O’Brien
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Correspondence to Timothy W. Meyer.

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The study was approved by the Institutional Review Boards of Stanford University and the University of California, San Francisco and was conducted in accordance with the Declaration of Helsinki. Consent was provided by subjects and/or their legally authorized representatives.

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O’Brien, F.J., Sirich, T.L., Taussig, A. et al. Plasma pseudouridine levels reflect body size in children on hemodialysis. Pediatr Nephrol 35, 305–312 (2020). https://doi.org/10.1007/s00467-019-04369-6

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