Kidney Week

Abstract: FR-PO569

Urinary Plasmin(ogen), Blood Pressure, and Progression of Diabetic Kidney Disease

Session Information

• Hypertension: Clinical and Translational
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

• 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

• Ray, Evan C., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Evan C. Ray,

• Miller, Rachel G., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Rachel G. Miller,

• Demko, John E, University of California San Francisco, San Francisco, California, United States

John E Demko,

• Costacou, Tina, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Tina Costacou,

• Kinlough, Carol L., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Carol L. Kinlough,

• Allen, Casey, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Casey Allen,

• Unruh, Mark L., University of New Mexico, Los Ranchos, New Mexico, United States

Mark L. Unruh,

• Orchard, Trevor J., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Trevor J. Orchard,

• Kleyman, Thomas R., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Thomas R. Kleyman,

Background

Urinary plasmin and its precursor, plasminogen, are detectable in the urine of patients with diabetic or other proteinuric kidney diseases. Urinary plasmin(ogen) levels correlate with increased extracellular fluid volume and blood pressure and have been hypothesized to contribute to renal Na retention by activating the epithelial Na channel (ENaC) and to progression of chronic kidney disease through podocyte and tubular toxicity. We assessed whether urinary plasmin(ogen) levels predict subsequent increases in blood pressure or decline in kidney function in type 1 diabetes.

Methods

Individuals with childhood-onset type 1 diabetes were enrolled as part of the Pittsburgh Epidemiology of Diabetes Complications Study in 1986-1988 and followed prospectively for 25 years. The present nested-cohort study included 70 subjects chosen to represent a spectrum of baseline urinary protein levels. Clinical outcomes included 1) increased blood pressure over a two-year period, defined as any increase in systolic or diastolic blood pressure or addition of a new anti-hypertensive agent; 2) incident hypertension over the full 25 year study period, defined as new-onset blood pressure of 140/90 mmHg or hypertensive medication use; and 3) 50% decline in eGFR over the 25-year study period, calculated from baseline using the CKD-EPI formula. The predictive values of urinary plasmin(ogen) and albumin were compared.

Results

In those who experienced increased blood pressure, baseline plasmin(ogen) levels where higher, with a difference approaching significance (p = 0.08). Albumin did not differ (p = 0.43). Plasmin(ogen) predicted both incident hypertension (HR=2.05, p=0.001) and 50% decline in eGFR (HR=2.26, p<0.001), however adjusting for urinary albumin attenuated plasmin(ogen)’s 25-year predictive abilities (p= 0.95 and 0.45, respectively).

Conclusion

Over 2 years of follow-up, baseline urinary plasmin(ogen) was associated with an increase in blood pressure approaching significance, suggestive of a role in stimulating urinary Na retention. Over 25-years of follow-up, plasmin(ogen) predicted incident hypertension and 50% decline in eGFR, though not independently of albumin, suggesting that over the long-term, mechanisms non-specific to plasmin(ogen) contribute to hypertension and diabetic kidney disease progression.

Funding

• NIDDK Support