Pregnancy-associated plasma protein A in dialysis patients

Pregnancy-associated plasma protein A (PAPP-A) is a biomarker routinely used in screening for Down syndrome in the fi rst trimester of pregnancy. It is also present in very small amounts in men and non-pregnant women. PAPP-A is a key regulator of local insulin-like growth factor (IGF) bioavailability -IGFs are essential for normal body size during fetal development, but they are associated with aging and agerelated diseases. Measurement of circulating PAPP-A can provide valuable information not only in pregnant women (chromosomal anomalies and adverse pregnancy outcomes) but also in patients with coronary artery disease (contribution to diagnosis, prognostic value) and in patients with kidney diseases. PAPP-A is associated with renal function and proteinuria, is increased mainly in dialysis patients and decreases after kidney transplantation. It is an independent mortality predictor of hemodialysis patients and indicator of adverse outcome of transplanted patients. PAPP-A levels can be infl uenced by various chemicals and drugs, among them mainly heparin. Various assays for PAPP-A exist and the type of assay used in a study should be considered. This article reviews the data summarizing basic information about PAPP-A with a particular focus on the signifi cance of PAPP-A in renal diseases.

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“…Elevation of PAPP-A measured by a different method with lower reference range was also confi rmed by Coskun et al (11) .…”

Section: History Of Papp-a In Laboratory Medicinesupporting

confidence: 65%

“…PAPP-A levels are three-fold higher than in healthy controls, however 100 -1000-fold lower than in the fi rst trimester of pregnancy. Elevation of PAPP-A in hemodialysis patients measured by a different method giving lower values was confi rmed Coskun et al (11) .…”

Section: Clinical and Laboratory Studies In Patients With Kidney Disementioning

confidence: 62%

Pregnancy-associated plasma protein A: spotlight on kidney diseases

Kalousová

Tesař

Muravská

et al. 2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…PAPP-A levels correlated with dialysis vintage, and this is consistent with previous reports [9]. In the HD setting, PAPP-A may be a marker for cumulative exposure to the pro-inflammatory, pro-atherosclerotic uraemic milieu, and this is supported by evidence that PAPP-A levels are high in patients immediately following renal transplant, with serial decline in PAPP-A levels reflective of restoration of renal function and normalisation of biochemical and physiological parameters [17,20].…”

Section: Discussionsupporting

confidence: 93%

“…Until recently, assays for PAPP-A have measured total (complexed plus free) PAPP-A (tPAPP-A), and the current cardiorenal literature describes the associations of tPAPP-A. tPAPP-A levels in acute coronary syndromes predict adverse cardiovascular outcomes [8], and tPAPP-A has been demonstrated to associate with dialysis vintage [9] and mortality in HD patients [10,11]. However, it has been recently established by Qin et al [12] that fPAPP-A is released in acute coronary syndromes, and cPAPP-A is detected only in negligible amounts (this, however, is in contrast to pregnancy where cPAPP-A predominates).…”

Section: Introductionmentioning

confidence: 99%

Elevated Serum Free Pregnancy-Associated Plasma Protein-A Independently Predicts Mortality in Haemodialysis Patients but Is Not Associated with Recurrent Haemodialysis-Induced Ischaemic Myocardial Injury

Jefferies¹,

Tertti²,

Wittfooth³

et al. 2015

Nephron

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Background/Aims: Pregnancy-associated plasma protein-A (PAPP-A) is a putative marker of atheroma instability and ischaemic myocardial stress prior to necrosis. Total PAPP-A (tPAPP-A) levels in acute coronary syndromes predict adverse outcomes. However, free PAPP-A (fPAPP-A) predominates in the circulation. Ischaemic haemodialysis (HD)-induced cardiac injury (myocardial stunning) is common and is associated with markers of myocardial necrosis, inflammation, cardiovascular events and mortality. Coronary plaque instability in pathophysiology of HD-induced myocardial stunning has not been studied. We aimed to investigate the relationship of fPAPP-A with stunning and mortality. Methods: 130 prevalent patients from two HD centres (Finland and UK) were studied. Pre-HD free, complexed and total PAPP-A were measured by immunoassay. A subset of 62 patients underwent echocardiography to assess HD-induced myocardial stunning. The mean duration of follow-up was 407 ± 98 days. Results: fPAPP-A was elevated (median: 3.45 mIU/l) and correlated with dialysis vintage (r = 0.391, p < 0.001), cardiac troponin T (cTnT; r = 0.29, p = 0.001) and cardiac troponin I (cTnI; r = 0.22, p = 0.01). PAPP-A was not related to stunning. Dialysis vintage and cTnT independently predicted Ln fPAPP-A (model R = 0.463). fPAPP-A, cTnT and age independently predicted death (Nagelkerke R² = 0.362). Conclusions: fPAPP-A, a novel predictor of HD-related mortality, demonstrates better prognostic power than tPAPP-A. Coronary plaque instability may contribute to sub-lethal myocardial injury, but may not be critical in pathogenesis of HD-induced ischaemic cardiac injury.

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“…The main pathophysiologic mechanism underlying the high mortality of ESRD is premature atherosclerosis and chronic inflammation [2]. A large number of biomolecules have been shown to predict the atherosclerotic and inflammatory process in ESRD [3,4,5,6]. Adipose tissue produces a variety of proteins called adipokines.…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Omentin in End-Stage Renal Disease Patients

Alçelik

Tosun²,

Özlü³

et al. 2012

Kidney Blood Press Res

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Introduction: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients. Therefore, evaluation and prevention of cardiovascular diseases in end-stage renal disease (ESRD) patients are very important. The plasma level of omentin was found to be associated with different conditions such as insulin resistance. It is one of the novel adipokines synthesized mainly in the visceral adipose tissue. In this study, we aimed to investigate the level of omentin in patients with ESRD receiving hemodialysis. Methods: The study population consisted of 59 adult chronic hemodialysis patients (30 women and 29 men) and age-matched control subjects were selected from apparently healthy subjects (28 participants; 14 women and 14 men). Blood samples were obtained before the dialysis session. Omentin concentrations were determined by using enzyme-linked immunosorbent assay. Results: Plasma levels of omentin were found to be markedly higher in ESRD patients (606.6 ± 313.0 ng/ml) than in the control group (357.5 ± 147.4 ng/ml; p < 0.0001). Also, serum omentin levels were found to be correlated with creatinine (r = 0.333, p = 0.002). Conclusions: Omentin levels were found to be elevated in patients with ESRD receiving hemodialysis. To the best of our knowledge, this is the first clinical study that demonstrated the association between omentin and ESRD.

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Pregnancy-associated plasma protein A in dialysis patients

Abstract: PAPP-A levels are elevated in acute coronary syndromes and are closely related to inflammation and oxidative stress. We conclude that PAPP-A levels are increased in dialysis patients and may reflect a greater degree of chronic inflammation than osteodystrophy in uremic patients.

Cited by 23 publications

References 19 publications

Pregnancy-associated plasma protein A: spotlight on kidney diseases

Pregnancy-associated plasma protein A: spotlight on kidney diseases

Elevated Serum Free Pregnancy-Associated Plasma Protein-A Independently Predicts Mortality in Haemodialysis Patients but Is Not Associated with Recurrent Haemodialysis-Induced Ischaemic Myocardial Injury

Serum Levels of Omentin in End-Stage Renal Disease Patients

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