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Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease

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Abstract

Background

Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested.

Methods

Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%.

Results

MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45–5.17] vs. 4.2 [3.45–8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1–27.49] vs. 24.9 [16.23–39.4] pg/mL; p = 0.004) and IL-1β (21.33 [15.8–26.4] vs. 26.78 [18.22–35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09–1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09–9.87]; p = 0.035).

Conclusions

Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

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Acknowledgements

We thank all study participants who enrolled to the study

Funding

There is no funding to the study.

Author information

Authors and Affiliations

  1. Department of Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey

    Ismail Kocyigit, Eray Eroglu, Bulent Tokgoz, Murat Hayri Sipahioglu & Oktay Oymak

  2. Department of Internal Medicine, Erciyes University Medical Faculty, Kayseri, Turkey

    Fahir Ozturk, Ahmet Safa Kaynar & Mustafa Cetin

  3. Department of Endocrinology, Erciyes University Medical Faculty, Kayseri, Turkey

    Zuleyha Karaca

  4. Department of Genetics, Erciyes University Medical Faculty, Kayseri, Turkey

    Ruslan Bayramov

  5. Department of Biochemistry, Erciyes University Medical Faculty, Kayseri, Turkey

    Ahmet Sen

  6. Department of Nephrology, Istanbul Bilim University Medical Faculty, Istanbul, Turkey

    Tevfik Ecder

  7. Transplant Immunology Division, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

    Jonas Axelsson

  8. Department of Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden

    Jonas Axelsson

  9. Clinical Research Center, Lund University, Lund, Sweden

    Jonas Axelsson

Authors
  1. Ismail Kocyigit
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  2. Fahir Ozturk
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  7. Bulent Tokgoz
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  8. Murat Hayri Sipahioglu
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  9. Ruslan Bayramov
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  10. Ahmet Sen
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  11. Oktay Oymak
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  12. Tevfik Ecder
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Contributions

IK, EE, and FO conceived of the study and designed the protocol which was implemented by IK, JA, TE and EE. These authors also recruited the participants. BT, MHS, OO and ZK helped with the study design. AS set up and validated the inflammatory markers assay and helped to interpret the results. RB performed the tests for determining PKD mutation. IK, EE and FO coordinated the study. FO and MC collected the data of the study. IK, EE and ASK wrote the paper. JA reviewed the draft and provided expertise for revision. All authors participated in data analysis and interpretation, and also read and approved the final manuscript.

Corresponding author

Correspondence to Ismail Kocyigit.

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All authors declare that there is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Cite this article

Kocyigit, I., Ozturk, F., Eroglu, E. et al. Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease. Clin Exp Nephrol 23, 1130–1140 (2019). https://doi.org/10.1007/s10157-019-01748-z

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  • DOI: https://doi.org/10.1007/s10157-019-01748-z

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