1. Nephrotic syndrome & Thromboembolic complications 신장내과 R3 김진숙 / Prof. 임천규 R3 김진숙 / Prof. 임천규

2. Nephrotic syndrome - definition Nephrotic syndrome Edema Hyper- lipidemia Hypo- albuminemi a Proteinuri a 3.5g/day/1.73m 2 body surface area

3. MCD, FSGS, MGN, MPGN … Nephrotic sydnrome Primary Secondary Nephrotic syndrome - causes Drug, Toxin, Allergy : Mercury, vaccine, pellicillamine, gold, NSAIDs, captopril, probenecid … Infection : HBV, HCV, HIV, leprosy, syphilis, Schistosomiasis Metabolic disease : Diabetic mellitus Autoimmune disease Collagen vascular disease Malignancy Genetic disease NEJM April 23, 1998 Volume 338 Number 17

4. Nephrotic syndrome - complications I nfection T hromboembolic complications A cute renal failure C ardiovascular complications H ypovolemic crisis A nemia H ormonal, mineral alterations

5. Thromboembolic complications in NS Clin J Am Soc Nephrol. 2012;7(1):43

6. Pathogenesis Platelet activation & aggregation - Hypoalbuminemia :↑availabilitiy of albumin-bound arachidonic acid  ↑TXA2 in Plt  stimulation Plt aggregation - Elevated LDL : lipid-lowering therapy reverses the spontaneous platelet hyperaggregability Thrombosis Research (2006) 118, 397— 407

7. Pathogenesis Activation of the coagulation system - Urinary loss > Increased synthesis : factor IX, X, XII, prothrombin, antithrombin, a2-antiplasmin - Urinary loss < Increased synthesis : factor V, VIII, von-Willebrand factor, fibrinogen, a2-macroglobulin accumulate Thrombosis Research (2006) 118, 397— 407

8. Pathogenesis Decreased endogenous anticoagulants - ↓ Inhibitors of endogenous anticoagulants : antithrombin III, protein S, protein C Decreased activity of fibrinolytic system - ↑plasminogen activator inhibitor (PAI-l) - ↓tissue plasminogen activator (t-PA) Thrombosis Research (2006) 118, 397— 407

9. Prothrombi c state

10. Clinical manifestations - vein Sites of venous thromboembolism - Renal vein thrombosis, Deep vein thrombosis, Pulmonary embolization, Cerebral venous thrombosis Risk of venous thrombosis - 8 times higher than general population (1.0 % per year) Renal vein thrombosis (6~60% of NS) - Young adults (mean age 20yrs) : acute phenomenon, classic symptoms (flank pain, macroscopic hematuria) - Older adults (mean age 38yrs) : chornoic phenomenon, extrarenal thromboembolism - Risk of thrombosis varies among the causes of NS Arch Intern Med. 1991;151(5):933 Thrombosis Research (2006) 118, 397- 407 Clin J Am Soc Nephrol. 2012;7(1):43

11. Clinical manifestations - artery Rarely been reported than venous thromboembolism Sites of arterial thromboembolism - Aortic, Renal, Femoral, Mesenteric, Cerebral & brachial sites Risk of arterial thrombosis - 8 times higher than general population (1.5 % per year) Venous thrombi : usually composed of fibrin and red cells Arterial thrombi : predominantly composed of platelets Surgery. 1993;114:618– 23 Arch Intern Med. 1991;151(5):933

12. M/53 sudden severe pain of the Left lower limb & facial edema Abdominal CT : Lt. common iliac a. occlusion Lt. peroneal n. paralysis  thrombectomy & fasciotomy Renal biopsy : MCD Nephrotic syndrome might be considered as a cause of acute arterial thrombosis

13. Risk factors

14. 1.02 % 1.48 %

15. Proportional-hazards analysis of association with the time to the first VTE and ATE among the total cohort

17. Management Prophylactic anticoagulation - Controvesial : lack of any large, prospective randomized trial - Patients with MGN : serum Alb. < 2.8g/dL - Patients with other cause of NS : serum Alb. < 2.0g/dL - Additional risk factors for thrombosis

18. Management Anticoagulation - An incidentally discovered RVT - Nonrenal thromboembolic event or acute RVT Thrombolytic therapy with or without catheter thrombectomy - Acute RVT Warfarin - 6 to 12 months, goal INR is 2.0 ~ 3.0