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Abstract: FR-PO453

Soluble Urokinase Plasminogen Activator Receptor Predicts Kidney Function Decline and Mortality in Patients with Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Rotbain Curovic, Viktor, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Theilade, Simone, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Winther, Signe Abitz, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Tofte, Nete, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Eugen-Olsen, Jesper, Hvidovre Hospital, Copenhagen, Denmark
  • Persson, Frederik, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Hansen, Tine, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Jeppesen, Jørgen Lykke, University of Copenhagen, Copenhagen, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark
Background

Soluble urokinase plasminogen activator receptor (suPAR) is an important inflammatory biomarker. The predictive qualities of suPAR in relation to complications in patients with type 1 diabetes (T1D) are unknown. We investigated the prognostic ability of suPAR for the development of decline in renal function, end stage renal disease (ESRD), progression in albuminuric status and mortality in T1D.

Methods

667 patients with T1D and various degrees of diabetic kidney disease were included in a prospective study. suPAR was measured with commercial ELISA kits. Patients were traced through the National Death Register, the National Health Register and electronic laboratory records. Endpoints were: eGFR-decline ≥30%, development of ESRD, progression to higher albuminuric status and mortality. Follow-up ranged from 5.2 to 6.2 years. Results were adjusted for sex, age, LDL cholesterol, HbA1c, systolic blood pressure, BMI, smoking status, urinary albumin excretion rate, eGFR, prescribed renin-angiotensin-aldosterone system inhibitors, and CRP. Hazard ratio (HR) is shown per doubling of suPAR and presented with 95% confidence interval (CI). Relative integrated discrimination (rIDI) was calculated to assess predictive contribution of suPAR to known risk factors.

Results

Of 667 participants, 368 (55%) were male; mean±SD age was 55±13 years and eGFR 88±25 ml/min/1.73m2. Median (interquartile range) of suPAR was 3.4 (2.7-4.5) ng/ml. There were 93 cases of eGFR-decline ≥30%, 26 cases of ESRD, 36 cases of progression in albuminuria and 58 deaths. Adjusted HR (95% CI) for the respective endpoints were 2.96 (1.70-5.16, p<0.001), 2.99 (0.75-11.9; p=0.12), 1.41 (0.60-3.35; p=0.43) and 4.42 (2.05-8.62, p<0.001). rIDI analysis showed contribution of 18.6% (p=0.009) for eGFR-decline, 5.5% (p=0.29) for ESRD, 1.1% (p=0.68) for progression in albuminuria and 23.8% (p<0.001) for mortality.

Conclusion

Higher suPAR level is independently associated with an increased risk of eGFR-decline and mortality in patients with T1D. In addition, it is a sizeable contributor in the risk stratification of the same based on rIDI. Our results suggest that suPAR may have an important role in identifying T1D patients at early risk of kidney function decline and death.