Pregnancy‐associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy—a prospective follow‐up study

Astrup, Anne Sofie; Tarnow, Lise; Christiansen, Michael; Hansen, Peter Riis; Parving, Hans‐Henrik; Rossing, Peter

doi:10.1111/j.1464-5491.2007.02283.x

Cited by 10 publications

(13 citation statements)

References 30 publications

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“…In this way, PAPP-A can act as an autocrine/paracrine regulator of IGF action. A clinical study suggested prognostic value of circulating PAPP-A and increased all-cause mortality in type I diabetic patients with nephropathy (Astrup et al 2007). However, it is not known whether this increase in circulating PAPP-A reflected changes in the kidney.…”

Section: Discussionmentioning

confidence: 99%

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy

Mader

Resch

McLean

et al. 2013

Journal of Endocrinology

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We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old wild-type (WT) and PAPP-A knock-out (KO) mice. Renal histopathology was evaluated after four months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman’s capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration as diabetic WT mice indicating that these changes were predominantly age-related. However, thickened Bowman’s capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic PAPP-A KO mice had significantly reduced or no evidence of changes in Bowman’s capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT compared to PAPP-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy

Mader

Resch

McLean

et al. 2013

Journal of Endocrinology

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“…In type 1 diabetic patients with nephropathy, PAPP-A was associated with increased mortality in unadjusted analysis -however, after adjustment for traditional risk factors, the prognostic value of PAPP-A was no longer significant [24] . Concerning HD patients, to date only two studies evaluating the prognostic value of PAPP-A have been available, both of them with a lower number of patients and a markedly shorter follow-up period.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-Associated Plasma Protein A as an Independent Mortality Predictor in Long-Term Hemodialysis Patients

Kalousová¹,

Benáková²,

Kubêna³

et al. 2011

Kidney Blood Press Res

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Background/Aims: Pregnancy-associated plasma protein A (PAPP-A) is a biomarker related to vascular damage. The aim of the study was to focus on PAPP-A and related parameters and their relationship to the prognosis of long-term hemodialysis (HD) patients. Methods: This is a prospective observational cohort study which included 261 long-term HD patients followed up for 5 years and 66 healthy subjects. PAPP-A, placental growth factor (PlGF), matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-4 (IGFBP-4), and cardiac, nutritional and inflammatory parameters were measured at the beginning of the study and tested as predictors of mortality. Results: PAPP-A, PlGF, IGF-1, IGFBP-4 and MMP-2 were significantly increased in HD patients compared to controls (PAPP-A 27.6 ± 15.5 mIU/l in HD vs. 9.4 ± 2.5 mIU/l in controls, p < 0.001). Increased PAPP-A was a significant independent predictor of overall mortality and mortality due to infection in the multivariate Cox analysis [HR (95% CI): 1.237 (1.060–1.444), p = 0.007, and 1.416 (1.115–1.798), p = 0.004, per standard deviation, respectively]. PAPP-A was not related to cardiovascular mortality. Conclusion: Increased PAPP-A is a significant independent predictor of overall mortality and mortality due to infection but it was not related to cardiovascular mortality in this study.

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“…In diabetic patients, no difference in PAPP-A levels in DM1 or DM2 and healthy subjects was found (12) and another group did not fi nd its usefulness as a biomarker of carotid atherosclerosis in type 2 diabetics (13) . Conversely, PAPP-A was associated with increased mortality in type 1 diabetic patients with nephropathy but only in unadjusted analysis; after adjustment for traditional risk factors the prognostic value of PAPP-A was no longer signifi cant (14) . PAPP-A was signifi cantly elevated in allergic rhinitis (15) and in asthma and correlated with asthma severity (16) .…”

Section: History Of Papp-a In Laboratory Medicinementioning

confidence: 99%

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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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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Pregnancy‐associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy—a prospective follow‐up study

Abstract: We find PAPP-A to be associated with increased mortality in Type 1 diabetic patients with nephropathy in unadjusted analysis. After adjustment for traditional risk factors, the prognostic value of PAPP-A was no longer significant.

Cited by 10 publications

References 30 publications

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy

Pregnancy-Associated Plasma Protein A as an Independent Mortality Predictor in Long-Term Hemodialysis Patients

Pregnancy-associated plasma protein A: spotlight on kidney diseases

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