Disease severity correlates with thrombotic capacity in experimental nephrotic syndrome

Bryce A. Kerlin, Amanda P. Waller, Ruchika Sharma, Melinda A. Chanley, Marvin T. Nieman, William E. Smoyer

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Thrombotic disease, a major life-threatening complication of nephrotic syndrome, has been associated with proteinuria and hypoalbuminemia severity. However, it is not fully understood how disease severity correlates with severity of the acquired hypercoagulopathy of nephrotic syndrome. Without this knowledge, the utility of proteinuria and/or hypoalbuminemia as biomarkers of thrombotic risk remains limited. Here, we show that two well established ex vivo hypercoagulopathy assays, thrombin generation and rotational thromboelastometry, are highly correlated with proteinuria and hypoalbuminemia in the puromycin aminonucleoside and adriamycin rat models of nephrotic syndrome. Notably, in the puromycin aminonucleosidemodel, hyperfibrinogenemia and antithrombin deficiency were also correlated with proteinuria severity, consistentwith reports in human nephrotic syndrome. Importantly, although coagulation was not spontaneously activated in vivo with increasing proteinuria, vascular injury induced a more robust thrombotic response in nephrotic animals. In conclusion, hypercoagulopathy is highly correlated with nephrotic disease severity, but overt thrombosis may require an initiating insult, such as vascular injury. Our results suggest that proteinuria and/or hypoalbuminemia could be developed as clinicallymeaningful surrogate biomarkers of hypercoagulopathy to identify patients with nephrotic syndrome at highest risk for thrombotic disease and potentially target them for anticoagulant pharmacoprophylaxis.

Original languageEnglish (US)
Pages (from-to)3009-3019
Number of pages11
JournalJournal of the American Society of Nephrology
Issue number12
StatePublished - Dec 2015
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology


Dive into the research topics of 'Disease severity correlates with thrombotic capacity in experimental nephrotic syndrome'. Together they form a unique fingerprint.

Cite this