Kidney disease and risk of venous thromboembolism: a nationwide population‐based case‐control study

Abstract

Summary Background Chronic kidney disease is associated with hemostatic derangements, including both procoagulant activity and platelet dysfunction, which may influence the risk of venous thromboembolism. However, data associating kidney disease with risk of venous thromboembolism are sparse. Objectives We examined whether kidney disease is associated with increased risk of venous thromboembolism. Methods We conducted this nationwide case‐control study using data from medical databases. We included 128 096 patients with a hospital diagnosis of VTE in Denmark between 1980 and 2010 (54 473 had pulmonary embolism and 73 623 had deep venous thrombosis only) and 642 426 age‐ and gender‐matched population controls based on risk‐set sampling. We identified all previous hospital diagnoses of kidney disease, including nephrotic syndrome, glomerulonephritis without nephrotic syndrome, hypertensive nephropathy, chronic pyelonephritis/interstitial nephritis, polycystic kidney disease, diabetic nephropathy, or other kidney diseases. We used conditional logistic regression models to compute odds ratios (ORs) for venous thromboembolism with adjustment for potential confounders. Results Kidney disease was associated with an adjusted OR for venous thromboembolism ranging from 1.41 (95% CI, 1.22–1.63) for hypertensive nephropathy to 2.89 (95% CI, 2.26–3.69) for patients with nephrotic syndrome. The association was strongest within the first 3 months after a diagnosis of chronic kidney disease (adjusted OR for nephrotic syndrome = 23.23; 95% CI, 8.58–62.89), gradually declining thereafter. The risk, however, remained elevated for more than 5 years, especially in patients with nephrotic syndrome and glomerulonephritis. Conclusions Kidney diseases, in particular nephrotic syndrome and glomerulonephritis, were associated with an increased risk of venous thromboembolism.

Venous Thromboembolism in Primary Nephrotic Syndrome - Is the Risk High Enough to Justify Prophylactic Anticoagulation?

“…The incidence of VTE within the general population and in patients with CKD without NS is already established [10,11,12], and allows comparison of risk with these results. Patients with CKD 3 or 4 have been shown to have an incidence of VTE of 4.5 per 1,000 patient years, which is approximately twice that of the general population [11].…”

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

“…For example, thromboembolism may occur as the presenting manifestation of NS, but whether these patients have an underlying thrombotic predisposition remains unexplored. 8,17 Alternatively, hypercoagulopathy may fluctuate from the acute to chronic phase of disease. For example, albumin and coagulation factors are regulated by both similar and independent transcription factor pathways, and synthetic compensation for coagulation derangements may, thus, be in disequilibrium to albumin compensation.…”

“…3,7 In fact, compared with other kidney diseases, NS carries the highest risk of thrombosis, many episodes of which may be preventable. 8,9 The acquired blood coagulation derangements are believed to be a major contributor to NS-associated thrombotic risk. Although thrombosis could potentially be prevented with prophylactic anticoagulation, this approach remains controversial because of the treatment-associated risk of bleeding complications.…”

The emerging role of coagulation proteases in kidney disease

“…Thrombotic disease is a significant morbidity of renal diseases, especially in the settings of nephrotic syndrome and haemodialysis 78,79 . The likelihood of thrombosis is also heightened in other kidney diseases, including diabetic nephropathy, hypertensive nephropathy, glomerulonephritis, interstitial nephritis and polycystic kidney disease 78 .…”