Protein C assays in uremia

Sørensen, Per; Knudsen, Flemming; Nielsen, Arne Høj; Dyerberg, Jørn

doi:10.1016/0049-3848(89)90088-1

Cited by 24 publications

(14 citation statements)

References 22 publications

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“…45 In this regard, the observed reduction in renal PC expression may result in an increase in the local procoagulant potential of the kidney, leading to a predisposition to renal microthrombosis and in the development of renal injuries under these pathological conditions. Interestingly, PC activity has been reported to decrease in patients with chronic renal insufficiency 46 and uremia, 47 possibly because of the presence of an inhibitor. Although these observations are consistent with the possibility that the observed reduction in PC expression could contribute to the development of several types of human renal disease, other reports show increased PC antigen in nephrotic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Extrahepatic Expression and Regulation of Protein C in the Mouse

Yamamoto

Loskutoff

1998

The American Journal of Pathology

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Activated protein C (APC) acts as an anticoagulant by inhibiting coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C (PC) synthesis, the demonstration that other components of this system are produced extrahepatically raises the possibility that PC itself is synthesized in other tissues. We therefore used quantitative reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemistry to screen various murine tissues for PC expression. Relatively high levels of PC mRNA were detected in the kidney (35% of liver) and testis (22% of liver). PC mRNA and antigen were demonstrated in tubular epithelial cells in the renal cortex, in spermatogenic cells in the testis, and in epithelial cells in the epididymis. Low but significant levels of PC mRNA were detected in the epididymis (1.7% of the level in liver), brain (1.1% of liver), and lung (0.8% of liver). PC antigen was demonstrated in bronchial epithelial cells in the lung, in pyramidal neurons in the cerebrum, and in Purkinje cells in the cerebellum. The extrahepatic expression of PC mRNA (ie, in the kidney) was significantly decreased in mice with renal disease (eg, in MRL lpr/lpr mice with autoimmune lupus nephritis, in db/db mice with diabetic nephropathy, and in endotoxin-treated mice with acute renal injury). The decreased renal expression of PC may contribute to the increased procoagulant potential of the kidney during septic and inflammatory processes and to the progression of kidney disease associated with these conditions.

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Section: Discussionmentioning

confidence: 99%

Extrahepatic Expression and Regulation of Protein C in the Mouse

Yamamoto

Loskutoff

1998

The American Journal of Pathology

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“…The data imply that ongoing control of fibrinolytic activity is a natural requirement of the kidney milieu. Any pathological process that alters the fibrinolytic balance could potentially have deleterious effects on the kidney function, as it is known that plasma levels of the zymogen of another target protease of PCI, protein C, are significantly decreased in patients with chronic renal insufficiency and uremia (34,35). In view of data showing that uPA has a direct mitogenic effect on primary cultures of renal cells (33), the role of its regulator, PCI, needs to be evaluated in the progression of renal cancer.…”

Section: Resultsmentioning

confidence: 99%

Protein C inhibitor is expressed in tubular cells of human kidney.

Radtke¹,

Fernández²,

Greengard³

et al. 1994

J. Clin. Invest.

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“…In addition, protein C levels may not perfectly correlate with activated protein C levels, a more direct measure of anticoagulant activity. Indeed, patients with diabetes and those undergoing hemodialysis may exhibit normal or higher protein C levels but lower activated protein C levels or thrombomodulin-induced anticoagulant activity (43,44).…”

Section: Discussionmentioning

confidence: 99%

Hemostatic Factors, APOL1 Risk Variants, and the Risk of ESRD in the Atherosclerosis Risk in Communities Study

Tin

Grams

Maruthur

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Hemostatic factors have been associated with kidney function decline, and evidence suggests stronger effects among African Americans. The presence of APOL1 renal risk variants, common in African Americans, might partly underlie this risk difference.Design, setting, participants, & measurements A total of 13,337 participants in the Atherosclerosis Risk in Communities study were followed from 1987-1989 until 2010. Participants were categorized into three groups by ancestry and APOL1 risk status: European Americans (n=10,206), African Americans with zero or one APOL1 risk allele (n=2,733), and African Americans with two APOL1 risk alleles (n=398). ESRD events were ascertained through linkage to the US Renal Data System. Cox regression was used to estimate the risk for ESRD associated with hemostatic factors (factor VIIc, factor VIIIc, fibrinogen, von Willebrand factor, protein C, and antithrombin III).Results There were 232 cases of ESRD over 21.5 years (European Americans, 119; African Americans with zero or one APOL1 risk allele, 94; African Americans with two APOL1 risk alleles, 19). In unadjusted and adjusted analysis of the overall population, higher levels of all hemostatic factors, except antithrombin III, were significantly associated with ESRD (all P,0.05). Factor VIIc had the strongest association (per one interquartile range; adjusted hazard ratio, 1.46; 95% confidence interval, 1.21 to 1.76). With the exception of fibrinogen, the risk associated with each hemostatic factor was stronger in African Americans with two APOL1 risk alleles compared with the other two groups. Statistically significant interactions were seen for factor VIIIc and protein C (interaction between those with two APOL1 risk allele and the other two groups: P,0.02 for factor VIIIc and ,0.04 for protein C).Conclusions Higher levels of factor VIIc, VIIIc, fibrinogen, von Willebrand factor, and protein C were associated with ESRD risk, with a significantly stronger association of factor VIIIc and protein C in African Americans with two APOL1 risk alleles.

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Protein C assays in uremia

Cited by 24 publications

References 22 publications

Extrahepatic Expression and Regulation of Protein C in the Mouse

Extrahepatic Expression and Regulation of Protein C in the Mouse

Protein C inhibitor is expressed in tubular cells of human kidney.

Hemostatic Factors, APOL1 Risk Variants, and the Risk of ESRD in the Atherosclerosis Risk in Communities Study

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