Plasma Prekallikrein

A Risk Marker for Hypertension and Nephropathy in Type 1 Diabetes

  1. Ayad A. Jaffa1,
  2. Ramon Durazo-Arvizu2,
  3. Deyi Zheng2,
  4. Daniel T. Lackland2,
  5. Sujata Srikanth3,
  6. W. Timothy Garvey14,
  7. Alvin H. Schmaier3 and
  8. the DCCT/EDIC Study Group5
  1. 1Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
  2. 2Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, South Carolina
  3. 3Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan
  4. 4Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina
  5. 5NDIC/EDIC, Bethesda, Maryland

    Abstract

    The relevance and significance of the plasma kallikrein/kinin system as a risk factor for the development of vascular complications in diabetic patients was explored in a cross-sectional study. We measured the circulating levels of plasma prekallikrein (PK) activity, factor XII, and high−molecular weight kininogen in the plasma of 636 type 1 diabetic patients from the Diabetes Control and Complications Trial/Epidemiology and Diabetes Intervention and Complications Study cohort. The findings demonstrated that type 1 diabetic patients with blood pressure ≥140/90 mmHg have increased PK levels compared with type 1 diabetic patients with blood pressure <140/90 (1.53 ± 0.07 vs. 1.27 ± 0.02 units/ml; P < 0.0001). Regression analysis also determined that plasma PK levels positively and significantly correlated with diastolic (DBP) and systolic blood pressures (SBP) as continuous variables (r = 0.17 and 0.18, respectively; P < 0.0001). In multivariate regression analysis, the semipartial r2 value for PK was 2.93% for SBP and 2.92% for DBP (P < 0.0001). A positive correlation between plasma PK levels and the urinary albumin excretion rate (AER) was also observed (r = 0.16, P < 0.0001). In categorical analysis, patients with macroalbuminuria had a significantly higher level of plasma PK than normoalbuminuric patients (1.45 ± 0.08 vs. 1.27 ± 0.02 units/ml; P < 0.01), whereas microalbuminuric patients had an intermediate PK value (1.38 ± 0.05 units/ml; P = NS). Among patients in the microalbuminuric subgroup, we observed a positive and independent correlation between PK and AER in univariate and multivariate regression analysis (r = 0.27, P < 0.03; n = 63). We concluded that in type 1 diabetes, 1) PK levels are elevated in association with increased blood pressure; 2) PK levels are independently correlated with AER and are categorically elevated in patients with macroalbuminuria; and 3) although the positive correlation between PK and AER within the subgroups of patients with microalbuminuria suggest that PK could be a marker for progressive nephropathy, longitudinal studies will be necessary to address this issue.

    Footnotes

    • Address correspondence and reprint requests to Ayad a Jaffa, Ph.D., Department of Medicine, Endocrinology-Diabetes-Medical Genetics, Medical University of South Carolina, 114 Doughty St., P.O. Box 250776, Charleston, SC 29425. E-mail: jaffaa{at}musc.edu.

      Received for publication 10 December 2002 and accepted in revised form 10 February 2003.

      ACEI, ACE inhibitor therapy; AER, albumin excretion rate; APTT; BK, bradykinin; BP, blood pressure; CI, confidence interval; DBP, diastolic BP; DCCT, Diabetes Control and Complications Trial; EDIC, Epidemiology and Diabetes Intervention and Complications; GFR, glomerular filtration rate; HK, high−molecular weight kininogen; KKS, kallikrein/kinin system; MUSC, Medical University of South Carolina; OR, odds ratio; PK, prekallikrein; RPF, renal plasma flow; RVR, renal vascular resistance; SBP, systolic BP.

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