Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (1998) 54, 193–202; doi:10.1046/j.1523-1755.1998.00982.x
Free pentosidine and neopterin as markers of progression rate in diabetic nephropathy
Miriam F Weiss, Roger A Rodby, Amy C Justice and Donald E Hricik the Collaborative Study Group1
Division of Nephrology, Department of Medicine, University Hospitals of Cleveland, Cleveland, Ohio; Division of Nephrology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Department of General Internal Medicine and Health Policy Research, Case Western Reserve University and the Cleveland Veteran's Administration Medical Center, Cleveland, Ohio, USA
Correspondence: Miriam F. Weiss, M.D., Division of Nephrology, Department of Medicine, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44124 USA. E-mail: maf3@po.cwru.edu
1The Collaborative Study Group.Clinical Coordinating Center. Rush Presbyterian St. Luke's Medical Center (Chicago, IL). Principal Investigator, Edmund J. Lewis; Project Coordinator and Director of Central Laboratory, Richard Rohde.Biostatistical Coordinating Center. George Washington University (Washington, D.C.). Principle Investigator, Raymond P. Bain; Co-Principal Investigators, J.K. Evans, T.R. Turlington, and P.K. Burrows.Collaborating Investigators and Clinics. J. Sheehan (Case Western Reserve University, Cleveland, OH); M. Pohl (Cleveland Clinic, Cleveland, OH); T. Berl (University of Colorado, Denver, CO); J. Lemann, Jr., S. Blumenthal, and S. Bresnahan (Medical College of Wisconsin, Milwaukee, WI); L. Hebert and N.S. Nahman, Jr. (Ohio State University, Columbus, OH); R. Rodby (Rush-Presbyterian/St. Luke's Medical Center, Chicago, IL); J. McGill (Washington University, St. Louis, MO); F. Whittier (Affiliated Hospitals of Canton, Canton, OH); D. Cattran (University of Toronto, Toronto, Ontario, Canada); J. Hano (Loyola Medical Center, Maywood, IL); L. Hunsicker (University of Iowa, Iowa City, IA); D. Maxwell (Indiana University, Indianapolis, IN); J. Porush and S. Spitalewitz (Brookdale Hospital Medical Center, Brooklyn, NY); K. Shapiro (Nyack Hospital, New York, NY); S. Adler (Harbor-UCLA Medical Center, Torrance, CA); N. Tolchin (Nephrology & Internal Medicine Specialists, P. C., Syracuse, NY); L. Svetkey (Duke Hypertension Center, Durham, NC); Z. Sharon and B. Rausenbaum (Atlanta Nephrology Referral Center, Decatur, GA); J. Breyer and G. Shulman (Vanderbilt University, Nashville, TN).
Received 8 December 1997; Revised 6 February 1998; Accepted 12 February 1998.
Abstract
Free pentosidine and neopterin as markers of progression rate in diabetic nephropathy.
Background
Patients with diabetic nephropathy experience a progressive and usually inexorable decline in renal function. The presence of the structurally defined advanced glycation end product (AGE) pentosidine on tissue and circulating proteins has been correlated with the severity of diabetic complications.
Methods
To delineate a role for this AGE in the progression of diabetic nephropathy, glycohemoglobin and free and protein-bound pentosidine were measured in baseline stored serum and urine from a subgroup of patients with diabetes mellitus and proteinuria originally followed by the Collaborative Study Group Trial. To delineate a potential role for an immune-activation response to AGEs, the inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP), and the monocyte activation marker neopterin were also measured at baseline. The patients chosen represented 67 subjects whose creatinine levels had "doubled" over the course of the study whether or not they later were treated with captopril, and 67 paired "non-doublers."
Results
Baseline disease activity, as manifested by glycohemoglobin, serum creatinine and degree of proteinuria was equal in the two groups, as was protein-bound pentosidine and the immune-markers IL-6 and CRP. At baseline the "doublers" as compared to the "non-doublers" had elevated serum levels of free pentosidine and neopterin. Baseline increases in these two parameters were also associated with an increased rate of "doubling" of serum creatinine by the proportional hazards method.
Conclusion
Differences in individual responsiveness to AGEs, as manifested by either the production of free pentosidine or its release from a protein-bound form, and by evidence of monocyte/macrophage activation, are associated with progression of diabetic nephropathy.
Keywords:
diabetic nephropathy, pentosidine, advanced glycation end products, neopterin, diabetic complications
