Urinary Plasmin(ogen) as a Prognostic Factor for Hypertension.

Area of Science:

• Nephrology
• Endocrinology
• Cardiovascular Medicine

Background:

• Plasmin and plasminogen are found in urine of patients with glomerular disease.
• Urinary plasmin(ogen) correlates with blood pressure and may influence renal sodium retention via ENaC activation.
• Type 1 diabetes patients often develop proteinuria and are susceptible to hypertension and cardiovascular complications.

Purpose of the Study:

• To investigate whether urinary plasminogen levels predict future blood pressure increases in type 1 diabetes.
• To determine if urinary plasminogen predicts incident hypertension or mortality in this cohort.
• To assess the long-term clinical outcomes associated with elevated urinary plasminogen.

Main Methods:

• A 25-year longitudinal nested-cohort study of 70 type 1 diabetes subjects from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study.
• Analysis of baseline urinary plasminogen/creatinine (uPl/Cr) and albumin/creatinine (uAlb/Cr) levels.
• Outcomes assessed included 2-year blood pressure increase, 25-year hypertension incidence, and all-cause/cardiovascular mortality using logistic and Cox regression.

Main Results:

• Higher baseline uPl/Cr levels were observed in subjects with a 2-year increase in blood pressure (P=0.04).
• Baseline uPl/Cr was significantly associated with increased 25-year hypertension incidence (HR=2.05, P=0.001), all-cause mortality (HR=2.05, P=0.01), and cardiovascular mortality (HR=3.30, P=0.005).
• These associations were not independent of urinary albumin/creatinine levels (uAlb/Cr).

Conclusions:

• This study provides the first long-term prospective data on clinical outcomes related to urinary plasminogen.
• Findings support a potential role for plasminogen in promoting elevated blood pressure.
• Distinguishing the specific effects of plasminogen from albuminuria remains a challenge.