Settembre Ottobre 2024 - Articoli originali

Risk Factors for Stroke in Patients with Nephrotic Syndrome: Experience from Two Centers in Poland

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Michael Kitlinski

DOI: 10.69097/41-05-2024-10

Michael Kitlinski1,3, Zbigniew Heleniak MD PhD1, Aleksander Och1, Piotr Tylicki1, Justyna Fercho MD2, Tomasz Liberek MD PhD1, Tomasz Stompór MD PhD4, Tomasz Szmuda MD PhD2, Alicja Dębska-Ślizień MD PhD1

1 Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland
2 Department of Neurosurgery, Medical University of Gdansk, Poland
3 Department of Translational Medicine, Clinical Research Centre, Lund Univeristy, Malmö, Sweden
4 Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury in Olsztyn, 10-516 Olsztyn, Poland

Corresponing author:
Michael Kitlinski
Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, 80-210 Gdansk
Marii Skłodowskiej-Curie 3a, 80-210 Gdańsk, Poland
Tel: +46 722 41 48 41
email: michael.kitlinski@gumed.edu.pl

 

Abstract

Objective. Patients with nephrotic syndrome (NS) have an increased risk of developing acute ischemic stroke (aIS) and intracranial hemorrhage (ICH). However, the informations on the risk factors for these outcomes are unknown. The aim of this study was therefore to determine the risk factors for stroke among patients with NS.
Methods. A multicentric retrospective cohort of patients who developed aIS or ICH, following a diagnosis of NS between 2010 and 2021 was assembled. NS patients who did not develop stroke at follow-up were assembled as non-matched controls from the same study period. Cox regression yielding a hazard ratio (HR) with a 95% confidence interval was applied to investigate the potential risk factors for stroke among patients with NS. A meta-analysis on the current litterature was also performed.
Results. With a mean follow-up of 6 years, a total of 45 patients with NS were included of which 14 were diagnosed with aIS and 4 with ICH at follow-up. Significant risk factors for stroke in patients with NS were diabetes mellitus (DM) (HR 2.85, 95%CI 1.10-7.49; p-value = 0.03), diabetic nephropathy (HR 2.74, 95% CI 1.06-7.07; p-value = 0.038) smoking (HR 8.29, 95% CI 2.20-31.2; p-value = 0.002), prior arterial thromboembolic events (ATEs) (HR 2.86, 95% CI 1.09-7.53: p-value = 0.03) and age > 55 years old (HR 4.84, 95% CI 1.48-15.8; p-value = 0.009). Administration of low molecular weight heparin (LMWH) (HR 0.88, 95% CI 0.22-3.43; p-value = 0.848) did not affect the risk-estimates for developing stroke in patients with NS. Meta-analysis including 1091 patients revealed prior ATEs, diabetes, hypertension and smoking to be risk factors for ATEs among patients with NS.
Conclusion. In this study we found older age, DM, prior ATEs and smoking to increase the risk of developing stroke in patients with NS, while notably LMWH had no protective effects. Our findings may serve as an aid for physicians in managing and identifying high-risk patients for stroke in this subpopulation.

Keywords: Nephrotic syndrome, Stroke, Thromboembolism, Risk factors

Ci spiace, ma questo articolo è disponibile soltanto in inglese.

Introduction

Nephrotic syndrome (NS), which present with clinical features such as heavy proteinuria, edema, and hyperlipidemia, is associated with a widely known increased risk of developing thromboembolic events (TEs). Although multifactorial, thrombogenesis in the setting of NS is hypothesized to be mainly due to a hemostatic shift into a hypercoagulable state. With the nephrotic-range proteinuria many important anti-coagulatory proteins (antithrombin and protein S) with a similar molecular size of albumin are excreted into the urine, leading to a compensatory hepatic synthesis of lipids and pro-thrombotic proteins (fibrinogen, factor V and VII) [1]. Depending on the underlying glomerulopathy and degree of diagnostic evaluation, the reported incidence of venous thromboembolic events (VTEs) in patients with NS can vary between 2% to 37% [2]. The association between arterial thromboembolic events (ATEs) and NS on the other hand has been questionable in the past, however, newly aggregated data clearly suggest an increased risk of ATEs in patients with NS [3], in particular a 1.8-fold increased risk of acute ischemic stroke (aIS) [4]. In comparison, same study reports a 2.6-fold increased risk of VTEs. 

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