1. Renal vein thrombosis Nephrology discussion Dr. Coetser Prof. Van Rensburg and dr. Rossouw

2. Our case

3. Epidemiology RVT is seen in 10-50% of patients with nephrotic syndrome ◦RVT seen in 20-60% of membranous nephropathy ◦Also associated with:  Minimal change glomerulonephritis  Membranoproliferative glomerulonephritis  Focal segmental glomerulosclerosis Other associations: ◦Renal malignancy ◦External compression from e.g. lymphnodes, aneurysms ◦Oral contraceptive use and pregnancy ◦Hypovolaemia secondary to severe dehydration ◦Inherited procoagulant disorders  Antiphospholipid syndrome, factor V Leiden ◦Trauma, including kidney bx

4. Pathogenesis of RVT in the nephrotic syndrome Hypercoagulability ◦Decreased levels of antithrombin III and plasminogen ◦Hyperfibrinogenaemia ◦Increased platelet activation ◦Fibrinogen moieties circulating ◦Inhibition of plasminogen activation Tendency to thrombose in renal vein ◦Loss of fluid over glomerulus causes increased haematocrit in post-glomerular venous circulation

5. Clinical presentation Complete venous obstruction causes swelling of the kidney, compromising arterial blood flow and leading to a haemorrhagic infarct Thrombosis can be unilateral or bilateral, can extend into the inferior vena cava Acute RVT ◦Asymptomatic ◦Flank pain ◦Microscopic or macroscopic haematuria ◦Nausea and vomiting Chronic RVT ◦Asymptomatic, usually presents with pulmonary embolism

6. Diagnosis Gold standard is selective renal venography Other options: ◦CT abdomen with contrast ◦MRI ◦Doppler ultrasonography Blood tests: ◦Rise in urea and creatinine if bilateral ◦Rise in LDH

7. Inferior cavography Thrombus extending from the left renal vein into the inferior vena cava

8. Contrast CT abdomen A thrombus extends from the left renal vein to the inferior vena cava. Note that the left renal vein runs retroaortic.

9. MRI Left renal vein thrombosis in a patient with renal cell carcinoma.

10. Screening Not recommended to routinely screen for RVT in all patients with nephrotic syndrome: ◦No proven benefit in diagnosing occult disease ◦A patient with a negative test can develop RVT at a later stage, meaning that sequential tests need to be done Not recommended to look for RVT in patients presenting with embolic phenomenon, e.g. pulmonary embolism ◦Difficult to prove that embolism originated in renal vein ◦In situ pulmonary thrombosis could occur in nephrotic syndrome ◦Both nephrotic patients presenting with thromboembolism and those with RVT need anticoagulation therapy

11. Prophylaxis for RVT Not routinely recommended in nephrotic syndrome Authors of UpToDate recommend prophylaxis in: ◦Severe proteinuria >10g/day ◦Albumin <20g/L ◦Another risk factor for venous thromboembolism, e.g. orthopaedic or gynaecological surgery, immobilization etc.

12. Treatment of RVT Anticoagulation Can be used alone if: ◦Normal renal function ◦No flank pain ◦No other evidence of thromboembolism Unfractionated or low molecular weight heparin, followed by warfarin for minimum of 6-12 months Recommended to continue as long is nephrotic syndrome persists

13. Treatment of RVT Fibrinolysis Systemic fibrinolysis is not recommended due to the complication of haemorrhage and increased mortality (14-49% mortality) Local fibrinolysis very effective in reports: ◦7 patients received local thrombolysis for 22h following catheter thrombectomy. All had restoration of renal venous flow, improvement in creatinine and no recurrence of RVT in the 2 year follow-up ◦No haemorrhagic complication reported No particular agent proven to be superior at present

14. Treatment of RVT Indications for fibrinolysis Acute bilateral RVT and acute renal failure Extension of thrombus into inferior vena cava Acute renal failure Massic thrombus with high risk of systemic embolization Pulmonary embolism present Severe flank pain

15. Treatment of RVT Contraindications to fibrinolysis History of haemorrhagic stroke Active intracranial neoplasm Recent (< 2 months) intracranial surgery or trauma ABSOLUTE Active or recent internal bleeding in prior 6 months Bleeding diathesis Uncontrolled severe hypertension (systolic BP >200 mmHg or diastolic BP >110 mmHg) Nonhaemorrhagic stroke within prior 2 months RELATIVE Surgery within the previous 10 days Thrombocytopenia (<100,000 platelets per mm3) Post-partum thrombolysis haemorrhagic risk is highest in first 8h following delivery. No clear guidelines exist as only a few case reports have been described.

16. Treatment of RVT Catheter thrombectomy Technique described in 7 patients: ◦Treated initially with heparin to keep PTT 2-2,5x normal ◦Percutaneous access via right femoral vein ◦Catheter guided into thrombosed renal vein ◦Direct renal venogram obtained ◦Mechanical thrombectomy done with AngioJet or Helix Clot Buster ◦Residual thrombosis treated with local fibrinolysis (alteplase or urokinase) ◦Any remaining stenosis treated with balloon venoplasty ◦Heparin infusion reinitiated, followed by chronic anticoagulation with warfarin

17. Treatment of RVT Surgery Surgical thrombectomy only indicated in acute bilateral RVT with acute renal failure which can not be treated with local fibrinolysis or catheter thrombectomy

18. Bibliography Fauci, AS, Braunwald, E. Harrison’s principles of internal medicine, 17 th edition, 2008. 1815. Hyun, S et al. Catheter-directed thrombectomy and thrombolysis for acute renal vein thrombosis. Journal of vascular interventional radiology, 2006. 17:815-822 Radhakrishnan, J. Renal vein thrombosis and hypercoagulable state in nephrotic syndrome. UpToDate v17.3 Saddiqi, A et al. Renal vein thrombosis. http://emedicine.medscape.com/article/382686-overview http://emedicine.medscape.com/article/382686-overview Tapson, VF. Fibrinolytic (thrombolytic) therapy in pulmonary embolism and deep vein thrombosis. UpToDate v17.3. Waldemar, E et al. Clinical characteristics and long-term follow-up of patients with renal vein thrombosis. American journal of kidney diseases, 2008. 51:224-232.