Abstract
Background
Although venous thromboembolism is a well-known complication of nephrotic syndrome,
the long-term absolute and relative risks of arterial thromboembolism, venous thromboembolism,
and bleeding in adults with nephrotic syndrome remain unclarified.
Methods
In this matched cohort study, we identified every adult with first-time recorded nephrotic
syndrome from admissions, outpatient clinics, or emergency department visits in Denmark
during 1995-2018. Each patient was matched by age and sex with 10 individuals from
the general population. We estimated the 10-year cumulative risks of recorded arterial
thromboembolism, venous thromboembolism, and bleeding accounting for the competing
risk of death. Using Cox models, we computed crude and adjusted hazard ratios (HRs)
of the outcomes in patients with nephrotic syndrome versus comparators.
Results
Among 3967 adults with first-time nephrotic syndrome, the 1-year risk of arterial
thromboembolism was 4.2% (95% confidence interval [CI] 3.6-4.8), of venous thromboembolism
was 2.8% (95% CI 2.3-3.3), and of bleeding was 5.2% (95% CI 4.5-5.9). The 10-year
risk of arterial thromboembolism was 14.0% (95% CI 12.8-15.2), of venous thromboembolism
7.7% (95% CI 6.8-8.6), and of bleeding 17.0% (95% CI 15.7-18.3), with highest risks
of ischemic stroke (8.1%), myocardial infarction (6.0%), and gastrointestinal bleeding
(8.2%). During the first year, patients with nephrotic syndrome had increased rates
of both arterial thromboembolism (adjusted HR [HRadj] = 3.11 [95% CI 2.60-3.73]), venous thromboembolism (HRadj = 7.11 [5.49-9.19]), and bleeding (HRadj = 4.02 [3.40-4.75]) compared with the general population comparators after adjusting
for confounders.
Conclusion
Adults with nephrotic syndrome have a high risk of arterial thromboembolism, venous
thromboembolism, and bleeding compared with the general population. The mechanisms
and consequences of this needs to be clarified.
Keywords
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Article Info
Publication History
Published online: December 30, 2021
Footnotes
Funding: The study was generously supported by a grant from the Independent Research Fund Denmark (grant number 0134-00407B), The Danish Kidney Association, The Danish Society of Nephrology, The Oticon Foundation, and The Hede Nielsen Family Foundation.
Conflicts of Interest: DN is on the steering group for 2 GlaxoSmithKline-funded studies of kidney function in sub-Saharan Africa unrelated to this article. SVV, HB, BD, HTS, CFC report none. The Department of Clinical Epidemiology, Department of Biomedicine, and Department of Renal Medicine, however, are involved in studies with funding from various companies as research grants to (and administered by) Aarhus University or Aarhus University Hospital. None of these studies are related to the current study.
Authorship: SVV, BD, HTS, and CFC had access to the raw data, and HB and DN had access to aggregate results but no raw data due to legislation regarding data access. All authors had a role in writing this manuscript.
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