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Prevalence, phenotypic characteristics and prognostic role of apparent treatment resistant hypertension in the German Chronic Kidney Disease (GCKD) study

Journal of Human Hypertension volume 37, pages 345–353 (2023)Cite this article

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Abstract

Treatment resistant hypertension (TRH) appears of particular relevance in patients with chronic kidney disease (CKD). However, causes and consequences of TRH in CKD patients remain incompletely understood. Therefore, we analyzed the prevalence of apparent TRH (aTRH), and phenotypic characteristics and prognosis associated with aTRH among participants of the German Chronic Kidney Disease (GCKD) study. As insufficient medication adherence has been shown to be a frequent cause of pseudoresistance, we also assessed treatment adherence. Study participants were classified as having aTRH, controlled hypertension and uncontrolled hypertension based on study visit blood pressure and self-reported medication intake. Drug adherence was assessed by comparing self-reported antihypertensive medication with detectable urinary drug metabolites measured by mass spectroscopy. Out of 4901 individuals included in this study, 38% were classified as having aTRH. Male sex, older age, lower estimated glomerular filtration rate (eGFR), higher body mass index (BMI), higher urine albumin-to-creatinine ratio (UACR) and presence of diabetes mellitus were independently associated with higher prevalence of aTRH in a multivariable adjusted regression model. Patients classified as aTRH had higher risk for major adverse cardiovascular events and worsening of kidney disease compared to patients with no aTRH after multivariate adjustment for potential confounders. There was a high agreement between self-reported medication and detectable urinary drug metabolites. In conclusion, in a cohort of Caucasian patients with moderately severe CKD, aTRH was highly prevalent and, in most cases, likely not caused by low medication adherence. Furthermore, aTRH was linked to cardio-renal endpoints, emphasizing the need for improved management.

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Fig. 1: Comparison of the proportion of self-reported drug use across patient groups.
Fig. 2: Visual comparison of cumulative incidence rates across groups for selected time-to-event endpoints.
Fig. 3: Hazard ratios for comparison between patients classified as aTRH vs. patients classified as non-aTRH patients.
Fig. 4: Comparison of Cohen’s kappa (agreement between self-reported and metabolite-detectable medication) across patients with controlled, uncontrolled hypertension and patients classified as aTRH.

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Data availability

GCKD data is not publicly available. The code for this analysis is available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful for the willingness of the patients to participate in the GCKD study. The enormous effort of the study personnel of the various regional centers is highly appreciated. We thank the large number of nephrologists who provide routine care for the patients and collaborate with the GCKD study. The work of AK was supported by grant 3598/5-1 from the German Research Foundation (DFG). FK was supported by the Else Kroener Fresenius Foundation (NAKSYS) and by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (grant 01ZX1912B). The GCKD study was/is funded by grants from the Federal Ministry of Education and Research (BMBF, grant number 01ER0804) and the KfH Foundation for Preventive Medicine and corporate sponsors.

Author information

Authors and Affiliations

  1. Bayer AG, Research & Early Development, Disease Understanding and Precision Biomarkers, Division Pharmaceuticals, Wuppertal, Germany

    Johanna Mielke, Holger Trucks-Jansen, Claudia Schurmann & Daniel F. Freitag

  2. Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center—University of Freiburg, Freiburg, Germany

    Fruzsina Kotsis & Anna Köttgen

  3. Department of Medicine IV – Nephrology and Primary Care, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany

    Fruzsina Kotsis

  4. Department of Nephrology and Hypertension, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

    Markus P. Schneider & Kai-Uwe Eckardt

  5. Department of Nephrology and Hypertension, Klinikum Nürnberg, Paracelsus Medical University, Nürnberg, Germany

    Markus P. Schneider

  6. Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Kai-Uwe Eckardt

  7. Bayer AG, Research & Early Development, Precision Nephrology, Division Pharmaceuticals, Wuppertal, Germany

    Frank Eitner & Michael S. Becker

  8. Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center—University of Freiburg, Freiburg, Germany

    Fruzsina Kotsis & Anna Köttgen

  9. Department of Medicine IV – Nephrology and Primary Care, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany

    Fruzsina Kotsis

  10. Department of Nephrology and Hypertension, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

    Markus P. Schneider & Kai-Uwe Eckardt

  11. Department of Nephrology and Hypertension, Klinikum Nürnberg, Paracelsus Medical University, Nürnberg, Germany

    Markus P. Schneider

  12. Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Kai-Uwe Eckardt

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  1. Johanna Mielke
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Consortia

GCKD Investigators

  • Fruzsina Kotsis
  • , Anna Köttgen
  • , Markus P. Schneider
  •  & Kai-Uwe Eckardt

Contributions

Design of this study: JM, MSB. Recruitment, management and conduct of cohort study: FK, AK, MPS, KUE. Bioinformatics and statistical analysis: JM, CS. Wrote the manuscript: JM, MSB, HT-J. Edited, critically read and approved the manuscript: JM, HT-J, CS, FK, AK, MPS, KUE, DFF, FE, MSB.

Corresponding author

Correspondence to Michael S. Becker.

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Competing interests

JM, HT-J, CS, DFF, FE, MSB are employees from Bayer AG. For the remaining authors no conflicts of interest were declared.

Ethical approval

The study was approved by the local ethics committee, registered in the German national registry for clinical studies (DRKS00003971) and was conducted according to the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained from all patients prior to enrollment.

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Mielke, J., Trucks-Jansen, H., Schurmann, C. et al. Prevalence, phenotypic characteristics and prognostic role of apparent treatment resistant hypertension in the German Chronic Kidney Disease (GCKD) study. J Hum Hypertens 37, 345–353 (2023). https://doi.org/10.1038/s41371-022-00701-0

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