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  • Review Article
  • Published:

Emerging risk factors and markers of chronic kidney disease progression

Nature Reviews Nephrology volume 5, pages 677–689 (2009)Cite this article

Abstract

Chronic kidney disease (CKD) is a common condition with an increasing prevalence. A number of comorbidities are associated with CKD and prognosis is poor, with many patients experiencing disease progression. Recognizing the factors associated with CKD progression enables high-risk patients to be identified and given more intensive treatment if necessary. The identification of new predictive markers might improve our understanding of the pathogenesis and progression of CKD. This Review discusses a number of emerging factors and markers for which epidemiological evidence from prospective studies indicates an association with progression of CKD. The following factors and markers are discussed: asymmetric dimethylarginine, factors involved in calcium–phosphate metabolism, adrenomedullin, A-type natriuretic peptide, N-terminal pro-brain natriuretic peptide, liver-type fatty acid binding protein, kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, apolipoprotein A-IV, adiponectin and some recently identified genetic polymorphisms. Additional epidemiological and experimental data are required before these markers can be broadly used for the prediction of CKD progression and before the risk factors can be considered as potential drug targets in clinical interventional trials.

Key Points

  • Chronic kidney disease (CKD) is a highly prevalent health problem with an increasing incidence and a strong tendency for progression

  • Few studies have searched for emerging risk factors or markers for progression of CKD

  • Available studies have identified markers related to nitric oxide synthesis, calcium–phosphate metabolism, natriuretic peptides, apolipoprotein A-IV, adiponectin and other parameters

  • Further epidemiological and experimental studies are required to determine whether these factors are involved in the pathogenesis of CKD progression or whether they are just markers of the risk for disease progression

  • Hypothesis-free approaches such as genome-wide association studies, metabolomic studies and other '-omics' technologies will identify new risk factors and markers of CKD progression in well-defined cohorts

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Figure 1: Risk factors and markers for the initiation and progression of chronic kidney disease.
Figure 2: The role of ADMA in the progression of kidney disease.
Figure 3: Receiver operating curves from the MMKD study for GFR measured by iohexol, ADMA, FGF23, apoA-IV and the natriuretic peptides ANP, NT-proBNP and adrenomedullin to predict progression of CKD.
Figure 4: Application of the concept of Mendelian randomization for identifying parameters causally related to progression of CKD, using adiponectin as an example.
Figure 5: The systems biology approach for identifying contributors to CKD, progression of CKD, cardiovascular outcomes and responses to drug treatment.

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Acknowledgements

The author would like to thank all collaborators of the Mild to Moderate Kidney Disease (MMKD) study who have continuously contributed to the investigation. In particular, he would like to thank Dr B. Kollerits for her contributions to the study. Funding from the Genomics of Lipid-associated Disorders (GOLD) of the Austrian Genome Research Programme (GEN-AU), and support from the German Ministry of Education and Research (BMBF) and the KfH - Stiftung Präventivmedizin to the German Chronic Kidney Disease (GCKD) study is greatly appreciated.

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  1. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

    Florian Kronenberg

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Kronenberg, F. Emerging risk factors and markers of chronic kidney disease progression. Nat Rev Nephrol 5, 677–689 (2009). https://doi.org/10.1038/nrneph.2009.173

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