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Management of severe polyuria in idiopathic Fanconi syndrome

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Abstract

Background

Polyuria is a common problem in patients with tubular diseases, especially for those with CKD and high-output Fanconi syndrome. There are currently no guidelines on how to treat debilitating polyuria, in children or adults, and vasopressin is usually not effective.

Case-diagnosis/treatment

A 13-year-old female with idiopathic Fanconi syndrome and an eGFR of 69 mL/min/1.73 m2 was severely affected by polyuria of 5 L per day (voiding at least 11 times during the day and up to 8 times at night), impacting her mood (measured by the RCADS-child) and academic performance at school. In the absence of guidelines and with literature discouraging the use of indomethacin in this condition, we attempted indomethacin treatment at a dose of 2 mg/kg divided in two doses with substantial success. Urine output dropped to 2.5L and this was accompanied by a substantial decrease of her sodium wasting from 24.6 to 7.7 mmol/kg/day. Over the course of 18 months, the patient’s eGFR dropped temporarily to 60 mL/min/1.73 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ decrease in her muscle when compared to age-matched peers with normal kidney function.

Conclusions

Indomethacin may be a safe and effective treatment option for polyuria in idiopathic Fanconi syndrome.

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Author information

Authors and Affiliations

  1. Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, 800 Commissioners Road East, E3-206, Ontario, N6A 5W9, London, Canada

    Guido Filler & Christopher William McIntyre

  2. Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, 800 Commissioners Road East, E3-206, London, Ontario, N6A 5W9, Canada

    Guido Filler & Yun Cong Zhang

  3. Pathology & Laboratory Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, 800 Commissioners Road East, E3-206, London, Ontario, N6A 5W9, Canada

    Guido Filler & Christopher William McIntyre

  4. Children’s Health Research Institute, University of Western Ontario, 800 Commissioners Road East, E3-206, London, Ontario, N6A 5W9, Canada

    Guido Filler, Rishika Geda & Christopher William McIntyre

  5. Lilibeth Caberto Kidney Clinical Research Unit, London, Ontario, Canada

    Guido Filler, Fabio Salerno & Christopher William McIntyre

  6. Medical Sciences, University of Western Ontario, London, Ontario, Canada

    Rishika Geda

  7. Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada

    Fabio Salerno & Christopher William McIntyre

  8. Department of Pediatrics, The University of North Carolina At Chapel Hill, Chapel Hill, NC, USA

    Maria E Díaz-González de Ferris

Authors
  1. Guido Filler
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  2. Rishika Geda
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  3. Fabio Salerno
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  4. Yun Cong Zhang
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  5. Maria E Díaz-González de Ferris
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  6. Christopher William McIntyre
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Contributions

Guido Filler conceived this project, wrote the drafts, collated the results, made multiple edits, collated all changes, added intellectual content, and approved the final version.

Rishika Geda conducted the literature review, provided major intellectual input into the design of the study, helped with the interpretation of the results, carefully edited and revised the various versions of the manuscript, and approved the final manuscript.

Fabio Salerno performed the sodium-23 (23Na) MRI study, provided major intellectual input into the analysis of the results, carefully edited and revised various versions of the manuscript, and approved the final manuscript.

Yun Cong Zhang provided major intellectual input into the design of the study, helped with the interpretation of the results, carefully edited and revised various versions of the manuscript, and approved the final manuscript.

Christopher William McIntyre provided major intellectual input into the design of the study, facilitated the sodium-23 (23Na) MRI, helped with the interpretation of the results, carefully edited and revised various versions of the manuscript, and approved the final manuscript.

Maria E Díaz-González de Ferris provided major intellectual input into the design of the study, helped with the interpretation of the results, carefully edited and revised various versions of the manuscript, and approved the final manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Guido Filler.

Ethics declarations

Ethics approval

Case reports are ethics-exempt in our institution; however, written informed consent about publication was obtained by the caregivers. The sodium MRI study received full approval from the Research Ethics Board.

Consent to participate

The authors declare that they have obtained consent to participate from the caregiver of the study.

Conflict of interest

The authors declare no competing interests.

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Key points

What is known about this subject Polyuria is a common problem in patients with tubular disorders and nocturia is highly disruptive, leading to a poor quality of life and negative mood outcomes. The mechanism of polyuria in Fanconi syndrome is thought to be caused by solute and water wasting in the tubules, especially sodium (Na+). Indomethacin therapy is an option for treatment of polyuria in children with infantile cystinosis, as it reduces polyuria by decreasing urinary solute delivery (especially Na +). In the past, this therapy was not recommended for the much rarer idiopathic Fanconi syndrome.

What this study adds We report the successful use of indomethacin in an adolescent female with idiopathic Fanconi syndrome associated with the loss of 0.385 Mb in chromosome region 3p12.2 (unknown significance). This patient had chronic kidney disease (CKD) stage II, debilitating nocturia and the need to void 11 times during the day and 8 times at night. The treatment was safe, did not lead to accelerated deterioration of kidney function, and resulted in a significant improvement in urinary frequency/volume, self-reported mood symptomatology (per the RCADS-Child survey), and academic performance. We also demonstrated a substantial reduction of Na+ wasting with indomethacin while the patient’s muscle Na+ concentration remained substantially depleted, suggesting no further role with Na+intake reduction.

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Filler, G., Geda, R., Salerno, F. et al. Management of severe polyuria in idiopathic Fanconi syndrome. Pediatr Nephrol 36, 3621–3626 (2021). https://doi.org/10.1007/s00467-021-05213-6

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  • DOI: https://doi.org/10.1007/s00467-021-05213-6

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