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Abstract: FR-PO443

Pre-ESRD Determinants of Post-ESRD Mortality in Patients with Type 1 Diabetes (T1D)

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Smiles, Adam, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Skupien, Jan, Jagiellonian University Medical College, Krakow, Poland
  • Doria, Alessandro, Joslin Diabetes Center - Harvard Medical School, Boston, Massachusetts, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

We reported that in T1D patients the patterns of estimated glomerular filtration rate decline (eGFR slopes) preceding the onset of ESRD were linear but varied greatly among individuals. The slopes could be grouped to fast, moderate and slow (Skupien et al. Diabetes Care). In this study we investigated in the same cohort whether post-ESRD mortality was influenced by the pre-ESRD eGFR slopes. In addition we sought whether plasma concentrations of 568 proteins during pre-ESRD period were associated with post-ESRD mortality.

Methods

A cohort of 206 T1D patients who developed ESRD while attending the Joslin Clinic were matched against the United States Renal Data System and National Death Index registries to ascertain dates of starting dialysis, renal transplant and mortality. Plasma samples obtained from these patients when they had had CKD stage 2-4 were assayed on the SOMAscan proteomics platform. Relative concentrations of 568 proteins were measured. Cox proportional hazard model for time to mortality was used, and proteins with a p value of <0.005 were selected.

Results

There were 75 deaths while on dialysis during 441 person-years (py) of follow-up (17.0 deaths/100 py) and 40 deaths after transplant during 1204 person-years (3.3 deaths/100 py). Total mortality was 115 deaths during 1644 person-years (7.0 deaths/100 py)
Patients with fast (< -10 ml/min/yr) and moderate (-5 -10 ml/min/yr) renal decline had a two times higher post-ESRD mortality than in those with slow (> -5 ml/min/yr) renal decline. This pattern was similar for mortality during time spent on dialysis and after receiving renal transplant (see Table). We identified 4 plasma proteins whose elevated level was associated with increasing risk of post-ESRD mortality: CCL3L1, CCL18, IL5RA, PRSS22 and 3 plasma proteins whose higher levels were associated with decreasing risk of post-ESRD mortality: VIP, IL11 and IFNL1.

Conclusion

Disease processes that determine post-ESRD mortality begin long before the onset of ESRD. The candidate proteins identified should be investigated further for their potential role as predictors and determinants of post-ESRD mortality.

Mortality Rates (Deaths/100 Person-Years)
Pre-ESRD eGFR slopeMortality during DialysisMortality after TransplantTotal Mortalityp value compared to Slow
Fast Decline18.34.68.70.0008
Moderate Decline18.34.07.40.014
Slow Decline13.30.63.9 

Funding

  • NIDDK Support