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Apolipoprotein A-IV concentrations and cancer in a large cohort of chronic kidney disease patients: results from the GCKD study

  • Barbara Kollerits,
  • Simon Gruber,
  • Inga Steinbrenner,
  • Johannes P. Schwaiger,
  • Hansi Weissensteiner,
  • Sebastian Schönherr,
  • Lukas Forer,
  • Fruzsina Kotsis,
  • Ulla T. Schultheiss,
  • Heike Meiselbach,
  • Christoph Wanner,
  • Kai-Uwe Eckardt,
  • Florian Kronenberg,
  • Markus P. Schneider,
  • Mario Schiffer,
  • Hans-Ulrich Prokosch,
  • Barbara Bärthlein,
  • Andreas Beck,
  • André Reis,
  • Arif B. Ekici,
  • Susanne Becker,
  • Ulrike Alberth-Schmidt,
  • Anke Weigel,
  • Sabine Marschall,
  • Eugenia Schefler,
  • Gerd Walz,
  • Anna Köttgen,
  • Ulla T. Schultheiß,
  • Simone Meder,
  • Erna Mitsch,
  • Ursula Reinhard,
  • Jürgen Floege,
  • Turgay Saritas,
  • Alice Gross,
  • Elke Schaeffner,
  • Seema Baid-Agrawal,
  • Kerstin Theisen,
  • Hermann Haller,
  • Martin Zeier,
  • Claudia Sommerer,
  • Mehtap Aykac,
  • Gunter Wolf,
  • Martin Busch,
  • Andy Steiner,
  • Thomas Sitter,
  • Vera Krane,
  • Antje Börner-Klein,
  • Britta Bauer,
  • Peter Oefner,
  • Wolfram Gronwald,
  • Matthias Schmid,
  • Jennifer Nadal

摘要

Background

Chronic kidney disease (CKD) is highly connected to inflammation and oxidative stress. Both favour the development of cancer in CKD patients. Serum apolipoprotein A-IV (apoA-IV) concentrations are influenced by kidney function and are an early marker of kidney impairment. Besides others, it has antioxidant and anti-inflammatory properties. Proteomic studies and small case–control studies identified low apoA-IV as a biomarker for various forms of cancer; however, prospective studies are lacking. We therefore investigated whether serum apoA-IV is associated with cancer in the German Chronic Kidney Disease (GCKD) study.

Methods

These analyses include 5039 Caucasian patients from the prospective GCKD cohort study followed for 6.5 years. Main inclusion criteria were an eGFR of 30–60 mL/min/1.73m2 or an eGFR > 60 mL/min/1.73m2 in the presence of overt proteinuria.

Results

Mean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dL (median 27.6 mg/dL). 615 patients had a history of cancer before the enrolment into the study. ApoA-IV concentrations above the median were associated with a lower odds for a history of cancer (OR = 0.79, p = 0.02 when adjusted age, sex, smoking, diabetes, BMI, albuminuria, statin intake, and eGFRcreatinine). During follow-up 368 patients developed an incident cancer event and those with apoA-IV above the median had a lower risk (HR = 0.72, 95%CI 0.57–0.90, P = 0.004). Finally, 62 patients died from such an incident cancer event and each 10 mg/dL higher apoA-IV concentrations were associated with a lower risk for fatal cancer (HR = 0.62, 95%CI 0.44–0.88, P = 0.007).

Conclusions

Our data indicate an association of high apoA-IV concentrations with reduced frequencies of a history of cancer as well as incident fatal and non-fatal cancer events in a large cohort of patients with CKD.

Graphical Abstract