Relationship of Pregnancy-Associated Plasma Protein-A to Renal Function and Dialysis Modalities

Abstract

Background: The aim of the study was to determine pregnancy-associated plasma protein-A (PAPP-A), which was recently described as a new marker of cardiovascular events, in patients with chronic renal insufficiency/failure and to find out its relationship to renal function and to prominent markers of oxidative stress (advanced oxidation protein products – AOPP) and inflammation (C-reactive protein – CRP). Methods: The studied group consisted of 36 chronic hemodialysis patients (HD), 10 patients treated with continuous ambulatory peritoneal dialysis (CAPD) and 38 patients with chronic renal insufficiency (CHRI) not yet dialyzed. PAPP-A was measured by Time Resolved Amplified Cryptate Emission technology. Determination of AOPP is based on a spectrophotometric method. Results: PAPP-A levels are statistically significantly elevated in the both groups of dialyzed patients in comparison with healthy subjects (27.0 ± 16.5 mIU/l in HD and 14.07 ± 6.73 mIU/l in CAPD vs. 8.22 ± 2.7 mIU/l in the control group, p < 0.0001 and p < 0.001, respectively, p < 0.05 HD vs. CAPD). The mean serum PAPP-A levels in the CHRI patients not yet dialyzed were not significantly higher in comparison with the control group (9.72 ±4.44 vs. 8.22 ± 2.7 mIU/l, n.s.). In the CHRI not dialyzed patients, we found a significant positive correlation between serum creatinine and PAPP-A levels (r = 0.68, p < 0.05). In comparison with controls, AOPP and CRP levels were significantly higher in HD patients [AOPP 155.0 ± 37.9 µmol/l, p < 0.0001 vs. controls, CRP 10.0 (4.6– 26.9) mg/l (median, interquartile range), p < 0.0001 vs. controls], CAPD patients [AOPP 118.5 ± 25.8 µmol/l, p < 0.0001 vs. controls, CRP 7.7 (2.0–18.8) mg/l, p < 0.01 vs. controls] and AOPP levels in chronic renal failure patients not yet dialyzed (98.5 ± 43.24 µmol/l, p < 0.01 vs. controls). The correlations between PAPP-A and AOPP (r = 0.49, p < 0.05) and PAPP-A and CRP (r = 0.48, p < 0.05) serum concentration were statistically significant in HD patients. In CAPD patients, neither a correlation between PAPP-A and AOPP nor a correlation between PAPP-A and CRP were found. Conclusion: We can conclude that serum PAPP-A levels sensitively reflect the changes in renal function, depend on dialysis modality, and may represent a novel marker associated with inflammation and oxidative stress in chronic renal failure patients.

Pregnancy-Associated Plasma Protein A and Soluble Receptor for Advanced Glycation End Products after Kidney Transplantation

“…PAPP-A has been demonstrated also in eroded and ruptured atherosclerotic plaques, and its serum levels were increased in patients with acute coronary syndromes [5] . It is elevated also in chronic hemodialysis patients [6,7] and might be associated with the mortality of these patients, as shown in our preliminary study [8] . Additionally, the pre-TX serum concentration of PAPP-A was recently demonstrated as a predictor of post-TX cardiovascular events and chronic allograft nephropathy [9] .…”

“…PAPP-A is linked to the inflammatory process and vice versa, and this relationship can also be observed in serum. A significant correlation was found between PAPP-A and Creactive protein in patients with acute coronary syndromes [5] as well as in hemodialysis patients, in whom PAPP-A was also associated with advanced oxidation protein products [7] , markers of both inflammation and oxidative stress. Additionally, herein we showed a possible association of PAPP-A serum levels with intragraft interstitial inflammation and vascular intimal thickening.…”

Future Biomarkers for Detection of Ischemia and Risk Stratification in Acute Coronary Syndrome

“…In a preliminary study, the release patterns of PAPP-A were highly variable, increasing early at 2 h after admission or late at 30 h after the onset of chest pain (54 ). Because preliminary findings showed that serum PAPP-A concentrations sensitively reflect changes in renal function, at least in dialyzed patients, and correlate with serum creatinine, the possible dependence of PAPP-A concentrations on renal function should be clarified (55 ).…”

Pregnancy-associated plasma protein A: spotlight on kidney diseases

“…In 2003, we fi rst described elevation of PAPP-A in patients with end-stage renal disease treated with hemodialysis (8) , and subsequently its relationship to renal function (9) and its possible prognostic role in long-term hemodialysis patients (10) . Elevation of PAPP-A measured by a different method with lower reference range was also confi rmed by Coskun et al (11) .…”

“…PAPP-A is signifi cantly elevated mainly in patients with end-stage renal disease with lower levels in patients treated with peritoneal dialysis than in patients treated with hemodialysis (9) . PAPP-A is detectable also in spent peritoneal dialysate but these concentrations are not related to serum levels.…”