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Long-term changes in albuminuria: underlying causes and future mortality risk in a 20-year prospective cohort the Nord-Trøndelag Health (HUNT) Study

Romundstad, Solfrid; Hatlen, Gudrun; Hallan, Stein I.

doi: 10.1097/HJH.0000000000001035

Objective: Knowledge on how changing risk factors influence the progression of albuminuria over time is still limited. Furthermore, large population-based cohorts are needed to study the association between albuminuria change and mortality risk in nondiabetic study participants.

Methods: We evaluated changes of albuminuria in 6282 nondiabetic individuals from the Norwegian population-based Nord-Trøndelag Health study. Using three albumin/creatinine ratios (ACR), we studied the influence of cardiovascular risk factors on ACR change from baseline to follow-up 11 years later. We evaluated the next 8-year mortality risk by using flexible parametric methods to identify nonlinear main effects and their two-way interactions.

Results: Mean albuminuria increased significantly over 11 years (1.82–3.02 mg/mmol, P < 0.0001), but two-thirds of individuals had stable levels (ΔACR −1.40 to 1.40 mg/mmol). Higher age, ACR, and SBP as well as smoking and lower glomerular filtration rate at baseline were associated with increasing albuminuria. Study participants in the upper quartile of the increasing group had mean adjusted hazard ratio 1.31 (P = 0.004) for all-cause mortality compared with those with stable ACR. Those with decreasing ACR also had increased mortality, but the risk was strongly attenuated when adjusting for comorbidity. It also decreased the first 3 years before increasing. There was a strong interaction between baseline ACR and ΔACR. Increasing albuminuria had strongest effect on mortality in study participants with moderately increased baseline values.

Conclusion: Both increasing and decreasing albuminuria are significant independent predictors of mortality in nondiabetic individuals, but must be interpreted in light of baseline values. Cutoffs and clinical usefulness in nondiabetic study participants should be further investigated.

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aDepartment of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim

bDepartment of Internal Medicine, Levanger Hospital, Health Trust Nord-Trøndelag, Levanger

cDepartment of Nephrology

dDepartment of Emergency, Clinic of Emergency Medicine and Prehospital Care, St. Olav University Hospital, Trondheim, Norway

Correspondence to Solfrid Romundstad, PhD, Department Internal Medicine, Levanger Hospital, Health Trust Nord-Trøndelag, Kirkegt. 2, NO-7600 Levanger, Norway. Tel: + 47 99032610; e-mail:

Abbreviations: ACR, albumin/creatinine ratio; CVD, cardiovascular disease; GFR, glomerular filtration rate; HUNT, the Nord-Trøndelag Health Study; RCV, reference change value; UAE, urine albumin excretion

Received 10 November, 2015

Revised 17 April, 2016

Accepted 10 June, 2016

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