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The role of urinary supersaturations for lithogenic salts in the progression of autosomal dominant polycystic kidney disease

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Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD) is associated with significant risk of forming kidney stones, especially those made of calcium oxalate and uric acid, compared with the general population. Since crystals are able to activate the inflammasome and lead to cell injury, crystalluria might worsen ADPKD natural history, acting as a third hit.

Methods

The Bern ADPKD registry is a prospective observational cohort study. Height-adjusted total kidney volume (ht-TKV) was measured at baseline and every 3 years. Twenty-four hour urinary solute excretions collected at baseline and eGFR measurements over time were included in this analysis. Twenty-four hour urinary supersaturations (SS) for calcium oxalate, calcium phosphate and uric acid were calculated using EQUIL-2. Linear regression models were used to assess linear and non-linear associations between slopes of ht-TKV and eGFR with SSs and 24 h urinary solute excretions.

Results

Seventy-seven participants (mean age 45.0 [SD 12.9] years, eGFR 76.4 [28.3] mL/min/1.73 m2) were included, with a median follow-up of 4 years. The median slopes of ht-TKV and eGFR were 3.9 percent/year and 2.9 mL/min/1.73 m2/year, respectively. SS for uric acid showed a direct, linear association (p value for linearity 0.035) with ht-TKV slope. When analyzing individual components, urinary uric acid, ammonium, magnesium and sulfate were all directly associated with ht-TKV slope. Urinary sulfate was also directly associated with eGFR slope.

Conclusions

Uric acid supersaturation and several other urinary components are identified as predictors of cyst growth in patients with ADPKD. Future studies with a dedicated design are needed to investigate the pathophysiological mechanisms underlying these associations.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by Otsuka (unrestricted research grant to DGF) and the Swiss National Science Foundation (grants: 33IC30_166785/1, NCCR TransCure and NCCR Kidney.CH). PMF received consultant fees and grant/other support from Allena Pharmaceuticals, Alnylam, Amgen, AstraZeneca, BioHealth Italia, Gilead, Otsuka Pharmaceuticals, Rocchetta, Vifor Fresenius, and royalties as an author for UpToDate. PMF and MB are members of the European Reference Network for Rare Kidney Diseases (ERKNet) – Project ID No 739532. DGF served as a consultant for Otsuka, Alnylam and Kyowa Kirin. DGF received additional unrestricted research grants from Abbvie and Boehringer Ingelheim and non-financial support from Sarstedt AG (biobank material). GG received consultant fees and grant/other support from Alexion, Alfa Sigma, Alnylam, AstraZeneca, Baxter, Roche Diagnostics, Vifor Pharma, and royalties as an author for UpToDate.

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Authors and Affiliations

  1. U.O.S. Terapia Conservativa Della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy

    Pietro Manuel Ferraro & Matteo Bargagli

  2. Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy

    Pietro Manuel Ferraro & Matteo Bargagli

  3. Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Matteo Bargagli, Nicolas Faller, Manuel A. Anderegg, Uyen Huynh-Do, Bruno Vogt & Daniel G. Fuster

  4. Division of Nephrology and Dialysis, Department of Medicine, University Hospital, Verona, Italy

    Giovanni Gambaro

Authors
  1. Pietro Manuel Ferraro
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  2. Matteo Bargagli
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  3. Nicolas Faller
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  4. Manuel A. Anderegg
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  5. Uyen Huynh-Do
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  6. Bruno Vogt
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  7. Giovanni Gambaro
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  8. Daniel G. Fuster
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Contributions

Data curation: DGF, MB, NF, MAA, UH, BV. Conceptualization: PMF, GG, DGF. Formal analysis: PMF. Visualization: PMF. Writing – original draft: PMF. Writing – review & editing: MB, NF, MAA, UH, BV, GG, DGF.

Corresponding author

Correspondence to Pietro Manuel Ferraro.

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Conflict of interest

The results presented in this paper have not been published previously in whole or part, except in abstract format.

Ethical approval and informed consent

Study approval and patient consent were obtained as required by national and local ethics committee regulations. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Supplementary file1 Flowchart of the study (PDF 32 KB)

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Ferraro, P.M., Bargagli, M., Faller, N. et al. The role of urinary supersaturations for lithogenic salts in the progression of autosomal dominant polycystic kidney disease. J Nephrol 36, 1011–1018 (2023). https://doi.org/10.1007/s40620-022-01540-5

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  • DOI: https://doi.org/10.1007/s40620-022-01540-5

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