title: Relationship between declining glomerular filtration rate and measures of cardiac and vascular autonomic neuropathy.
abstract: OBJECTIVE
  Cardiac and vascular autonomic neuropathy contributes to increased morbidity and mortality in patients with chronic kidney disease. The aim of this study was to analyze the effects of a decline in glomerular filtration rate (GFR) on heart rate variability (HRV) and nocturnal blood pressure dipping.
  
  
  METHODS
  This cross-sectional study comprises 124 patients (46 women, 78 men; age 66 ± 14 years) with chronic kidney disease (CKD) 3-5, not on renal replacement therapy. GFR was measured with iohexol clearance, HRV with 24 h Holter electrocardiogram (ECG) and nocturnal dipping with 24 hour ambulatory blood pressure.
  
  
  RESULTS
  The GFR was 22.5 ± 8.5 mL/min per 1.73 m2. The main finding was a significant curvilinear association between the 24 h standard deviation of NN interval (24SDNN) in the HRV analysis and GFR (P = 0.01), logGFR (P = 0.006), diabetes mellitus (P = 0.05) and beta blocker treatment (0.03), respectively. The effect of diabetes mellitus on 24SDNN corresponded to a decline in GFR from 30 to 12 mL/min per 1.73 m2. There were significant curvilinear associations between systolic nocturnal dipping (P = 0.02) and diastolic nocturnal dipping (P = 0.05), respectively, and diabetes mellitus but not with GFR or logGFR.
  
  
  CONCLUSIONS
  In conclusion, cardiac sympathetic overdrive and decreased vagal control appear during CKD 4 and 5. The association with GFR is curvilinear. Diabetes mellitus was significantly associated with both cardiac and vascular autonomic neuropathy, as measured by heart rate variability and nocturnal blood pressure dipping, respectively. Knowing that arrhythmias, often due to sympathetic hyperactivity, are an important cause of sudden death in the dialysis population, this study contributes important knowledge on possible intervention thresholds.
authors.affiliation: Department of Nephrology, Institution of Clinical Sciences, Lund.
authors.forename: Naomi
authors.identifier: http://orcid.org/0000-0001-5284-4406
authors.initials: N
authors.lastname: Clyne
authors.affiliation: Department of Nephrology, Institution of Clinical Sciences, Lund.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hellberg
authors.affiliation: Sports Medicine Laboratory, School of Physical Education & Sport Sciences, Aristotle University of Thessaloniki, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kouidi
authors.affiliation: Sports Medicine Laboratory, School of Physical Education & Sport Sciences, Aristotle University of Thessaloniki, Greece.
authors.forename: Asterios
authors.initials: A
authors.lastname: Deligiannis
authors.affiliation: Department of Clinical Chemistry and Pharmacology, Institution of Laboratory Medicine, Lund University, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Höglund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002319:Cardiovascular System / Q000294:innervation*; D002940:Circadian Rhythm; D015716:Electrocardiography, Ambulatory; D005260:Female; D005919:Glomerular Filtration Rate; D006339:Heart Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D013548:Sweden; D013997:Time Factors; D055815:Young Adult
keywords: ambulatory blood pressure; autonomic neuropathy; chronic kidney disease; glomerular filtration rate; heart rate variability