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Abstract

Pregnancy-associated plasma protein A (PAPP-A) and soluble receptor for advanced glycation end products (sRAGE) are new markers related to vascular damage. Thirty-one patients who had undergone kidney transplantation (TX) in the year 2005 under tacrolimus-based immunosuppression were included in this prospective single-center study. PAPP-A and sRAGE were determined before TX and 2 and 6 weeks and 3 months after TX. The results were correlated with the 3-month protocol kidney graft biopsy findings. Both PAPP-A and sRAGE decreased after TX (mean values in serum: PAPP-A 20.8, 13.7, 12.1, and 10.7 mIU/l, respectively, before and 2 and 6 weeks and 3 months after TX, p < 0.001; sRAGE 4,403.4, 2,512.7, 1,909.0, and 1,817.6 pg/ml, respectively, before and 2 and 6 weeks and 3 months after TX, p < 0.001) and were correlated with the graft function (PAPP-A vs. modification of diet in renal disease formula r = -0.52, p < 0.001; sRAGE vs. modification of diet in renal disease formula r = -0.54, p < 0.001). Additionally, the PAPP-A levels correlated with interstitial inflammation (r = 0.57, p < 0.05) and vascular intimal thickening (r = 0.47, p < 0.05), while sRAGE correlated with arteriolar hyalinosis (r = 0.49, p < 0.05). Our study demonstrates the role of the kidney in the metabolism and/or the removal of PAPP-A and sRAGE. After successful TX, these substances decrease, and, on the contrary, early chronic vascular changes in the kidney TX are associated with elevation of their serum levels. Copyright 2007 S. Karger AG, Basel.

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Prediction of Creatinine Clearance from Serum Creatinine

Donald W Cockcroft, Henry Gault (1976)

A formula has been developed to predict creatinine clearance (C cr ) from serum creatinine (S cr ) in adult males: Ccr = (140 – age) (wt kg)/72 × S cr (mg/100ml) (15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18–92. Values for C cr were predicted by this formula and four other methods and the results compared with the means of two 24-hour C cr’s measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr·s of 0.83; on average, the difference between predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.

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The Banff 97 working classification of renal allograft pathology.

L C Racusen, K Solez, R B Colvin … (1999)

Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions.

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The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A.

John Hays, Claus Oxvig, Cheryl Conover … (1999)

Proteolytic cleavage of the six known insulin-like growth factor binding proteins (IGFBPs) is a powerful means of rapid structure and function modification of these important growth-regulatory proteins. Intact IGFBP-4 is a potent inhibitor of IGF action in vitro, and cleavage of IGFBP-4 has been shown to abolish its ability to inhibit IGF stimulatory effects in a variety of systems, suggesting that IGFBP-4 proteolysis acts as a positive regulator of IGF bioavailability. Here we report the isolation of an IGF-dependent IGFBP-4-specific protease from human fibroblast-conditioned media and its identification by mass spectrometry microsequencing as pregnancy-associated plasma protein-A (PAPP-A), a protein of unknown function found in high concentrations in the maternal circulation during pregnancy. Antibodies raised against PAPP-A both inhibited and immunodepleted IGFBP-4 protease activity in human fibroblast-conditioned media. Moreover, PAPP-A purified from pregnancy sera had IGF-dependent IGFBP-4 protease activity. PAPP-A mRNA was expressed by the human fibroblasts and osteoblasts, and PAPP-A protein was secreted into the culture medium. In conclusion, we have identified an IGF-dependent IGFBP protease and at the same time assigned a function to PAPP-A. This represents an unanticipated union of two areas of research that were not linked in any way before this report.

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PubMed ID:: 17237617

DOI:: 10.1159/000098811

ScienceOpen disciplines: Chemistry

Keywords: Biological Markers,blood,Female,Humans,Kidney,physiopathology,Kidney Transplantation,Male,Middle Aged,Pregnancy-Associated Plasma Protein-A,metabolism,Prospective Studies,Receptors, Immunologic,Solubility

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Pregnancy-associated plasma protein a and soluble receptor for advanced glycation end products after kidney transplantation.

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Karger: Nephrology

Most cited references 21

Prediction of Creatinine Clearance from Serum Creatinine

The Banff 97 working classification of renal allograft pathology.

The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A.

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