Plasma Pentosidine Levels Measured by a Newly Developed Method Using ELISA in Patients with Chronic Renal Failure

The plasma pentosidine levels in patients with renal disease were measured by a simple method which was established for plasma and urinary pentosidine determinations. The method, which can be completed within a few hours, involves pretreating plasma with proteolytic enzyme (pronase) and measuring the concentration of pentosidine in the sample by ELISA using antipentosidine antibodies. The prepared antibodies showed no cross-reaction with the raw materials for pentosidine synthesis or with compounds having similar structures. SDS-PAGE indicated that the antibodies had a high purity. The reaction of the antibodies and keyhole limpet hemocyanin-pentosidine in the competitive ELISA system was inhibited by free pentosidine. Excellent standard curves for pentosidine determination were obtained. In actual measurements of clinical samples from patients, a good correlation (r = 0.9356) was obtained between the values measured by ELISA and HPLC. The plasma pentosidine level in patients with renal disease correlated significantly with plasma creatinine, urea nitrogen, β2-microglobulin, and creatinine clearance, indicating its usefulness in evaluating the severity of renal disease. A significant elevation in plasma pentosidine levels was observed in mild renal dysfunction, whereas no significant increases in creatinine and urea nitrogen levels were detected, suggesting that the plasma pentosidine level is useful in the early diagnosis of beginning renal failure. In patients with chronic renal failure, no difference in plasma pentosidine levels was observed between diabetic nephropathy and chronic glomerulonephritis, while a significant correlation was observed with phosphatidylcholine hydroperoxide, suggesting the possibility that the plasma pentosidine level reflects injury due to oxidation. From these results, the quantitative measurement method developed by us is judged to be a superior innovation for measuring pentosidine in body fluids. The plasma pentosidine level may be useful for the early diagnosis of mild renal failure and to estimate the degree of the severity of renal diseases.

[1]  V. Monnier,et al.  Pentosidine Formation in Skin Correlates With Severity of Complications in Individuals With Long-Standing IDDM , 1992, Diabetes.

[2]  K. Fujimoto,et al.  Presence of phosphatidylcholine hydroperoxide in human plasma. , 1988, Journal of biochemistry.

[3]  A. Cupisti,et al.  Ultrasonic Tissue Characterization of the Carotid Artery in Chronic Renal Failure Patients , 2002, Nephron.

[4]  M. Nangaku,et al.  Increased pentosidine, an advanced glycation end product, in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with inflammatory markers. , 1998, Biochemical and biophysical research communications.

[5]  C. Ponticelli,et al.  Calcium and Phosphate Plasma Levels in Dialysis Patients after Dietary Ca-P Overload , 2002, Nephron.

[6]  T. Lyons,et al.  Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus. , 1993, The Journal of clinical investigation.

[7]  Satoko Honda,et al.  Decreased CD4 Lymphocyte Count as a Marker Predicting High Mortality Rate in Managing ANCA Related Rapidly Progressive Glomerulonephritis , 2002, Nephron.

[8]  J. Baynes,et al.  Glycation, Glycoxidation, and Cross-Linking of Collagen by Glucose: Kinetics, Mechanisms, and Inhibition of Late Stages of the Maillard Reaction , 1994, Diabetes.

[9]  T. Miyata,et al.  A sensitive and specific ELISA for plasma pentosidine. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[10]  S. Rodriguez-Segade,et al.  Increased concentrations of serum pentosidine in rheumatoid arthritis. , 1998, Clinical chemistry.

[11]  T. Miyata,et al.  Autoxidation products of both carbohydrates and lipids are increased in uremic plasma: is there oxidative stress in uremia? , 1998, Kidney international.

[12]  V. Monnier,et al.  ELISA of pentosidine, an advanced glycation end product, in biological specimens. , 1994, Clinical chemistry.

[13]  H. Nihei,et al.  Therapeutic effect of a newly developed antioxidative agent (OPC-15161) on experimental immune complex nephritis. , 1997, Nephron.

[14]  T. Miyata,et al.  Implication of altered redox regulation by antioxidant enzymes in the increased plasma pentosidine, an advanced glycation end product, in uremia. , 1998, Biochemical and biophysical research communications.

[15]  Masaaki Takahashi,et al.  The Relationship between Pentosidine and Hemodialysis- Related Connective Tissue Disorders , 1998, Nephron.

[16]  Hideto Takahashi,et al.  Prognosis of Asymptomatic Hematuria and/or Proteinuria in Men , 2002, Nephron.

[17]  Y. Wada,et al.  Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure. , 1997, Kidney international.

[18]  B. Rutkowski,et al.  High Plasma Adenine Concentration in Chronic Renal Failure and Its Relation to Erythrocyte ATP , 2002, Nephron.

[19]  H. Nihei,et al.  Mechanism of elevated local oxidant stress in early anti-glomerular basement membrane nephritis: an evaluation of oxidant production and superoxide dismutase expression. , 1996, Nihon Jinzo Gakkai shi.

[20]  F. Woude,et al.  Graft Immunogenicity Revisited: Relevance of Tissue-Specific Immunity, Brain Death and Donor Pretreatment , 2002 .

[21]  T. Kato,et al.  Increased serum levels of pentosidine, but not carboxymethyl lysine, in type 2 diabetes without obvious diabetic nephropathy. , 1999, Diabetes care.

[22]  T. Miyazawa.  Determination of phospholipid hydroperoxides in human blood plasma by a chemiluminescence-HPLC assay. , 1989, Free radical biology & medicine.

[23]  V. Monnier,et al.  Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. , 1989, The Journal of biological chemistry.

[24]  T. Miyata,et al.  Carbonyl stress in the pathogenesis of diabetic nephropathy. , 1999, Internal medicine.

[25]  K. Kushida,et al.  Quantification of the cross-link pentosidine in serum from normal and uremic subjects. , 1993, Clinical chemistry.

[26]  P. Jungers,et al.  Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. , 1998, Journal of immunology.

[27]  L. L. Moore,et al.  Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy. , 1993, The Journal of clinical investigation.

[28]  V. Monnier,et al.  Chromatographic Quantitation of Plasma and Erythrocyte Pentosidine in Diabetic and Uremic Subjects , 1992, Diabetes.

[29]  V. Monnier,et al.  End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. , 1990, The Journal of clinical investigation.

[30]  C van Ypersele de Strihou,et al.  Alterations in nonenzymatic biochemistry in uremia: origin and significance of "carbonyl stress" in long-term uremic complications. , 1999, Kidney international.

[31]  R. W. Wright,et al.  Enhancement by N-hydroxysulfosuccinimide of water-soluble carbodiimide-mediated coupling reactions. , 1986, Analytical biochemistry.

[32]  T. Lyons,et al.  Accumulation of Maillard Reaction Products in Skin Collagen in Diabetes and Aging a , 1992, Annals of the New York Academy of Sciences.