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Renovascular disorder final shivaom
This document provides an overview of renovascular disorders. It begins by introducing how the kidneys rely on blood pressure and are vulnerable to vascular diseases. It then classifies renovascular disorders by anatomic location and describes several specific disorders in more detail, including thrombotic microangiopathies (like HUS and TTP), renal artery stenosis, ischemic renal disease, and others. It provides information on pathogenesis, clinical presentation, treatment, and prognosis for each.
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- 1. Renovascular Disorder A PRESENTATION BY: SHIVAOMCHAURASIA FIRST YEAR RESIDENT INTERNAL MEDICINE
- 2. INTRODUCTION: The Kidneysdepend on systemic blood pressure (SBP) to maintain adequate renal blood flow , adequate GFR, tubular function and overall salt and water balance. This explains the vulnerability of kidneys to diseases involving the renal vasculature. Vascular injury to kidneys is usually a manifestation of generalized vascular pathology.
- 3. Classification of RVDaccording to anatomic location of vasculopathy: Renal Arteries Thromboembolic occlusion Renal Artery Stenosis (RAS), and Ischemic renal disease Renal Arterioles and Microvasculature Atheroembolic Disease (cholesterol embolism syndrome CES) Thrombotic Microangiopathies: Hemolytic Uremic Syndrome (HUS) Thrombotic Thrombocytopenic Purpura (TTP) Scleroderma Sickle cell nephropathy Renal Veins Renal Vein Thrombosis (RVT)
- 4. Thrombotic Microangiopathies 1.Hemolytic Uremic Syndrome (HUS) 2.Thrombotic Thrombocytopenic Purpura (TTP) In both conditions, there is: Microangiopathic hemolytic Anemia (MAHA), with anemia, RBCs fragmentation, schistocytes, intravascular PLT clumping and hence thrombocytopenia Typical renal histological lesions include intraglomerular platelet and fibrin thrombi, with ischemia and arteriolar lesions
- 5. Hemolytic Uremic Syndrome(HUS) Commonest cause of AKI in children Children (< 4 years) ------> 90 % of cases It is loosely defined as presence of microangiopathic hemolytic angiopathy and renal impairment.
- 6. Forms of HUS 1. Typical, or Diarrhea-associated (D+ HUS): Onset is explosive, with AKI Most cases below 5 years Diarrohea, often bloody preceeds MAHA within 1 week in 80% cases Abdominal pain, cramping and vomiting frequent whereas fever is typically absent. Neurologic symptoms including dysphagia, hyperreflexia, blurred vision, memory deficit, encephalopathy, preservation and agraphia may often develop. SEIZURE and cerebral infarction may develop in severe cases.
- 7. PATHOGENESIS Shiga toxin(Stx1and Stx2) are referred as verotoxin. They are produced by E.coli and shigella dysenteriae Verotoxin-producing E.Coli O157:H7 (VTEC), with damage to the vascular endothelium(largely confined to kidneys) After entry into circulation Shiga toxin binds to glycolipid surface receptor globotriaosylceramide (gb3) which is richly expressed in renal vasculature. Upon entering into cell it induces inflammatory cytokines (IL-8), monocyte chemotactic protein 1 and stromal cell derived factor 1 and chemokines (cxcr4 and cxcr7) this action results in platelet aggregation and microangiopathic process.
- 8. 2. Atypical,or (D-HUS) : It results from complement deregulation, may be congenital or acquired Patient may have low C3 and a normal C4 characteristics of alternating pathway activation. Factor H deficiency most common defect. Factor H competes with Factor B to prevent formation of Cb3 A familial varient of aHUS -DEAP HUS ( Deficiency of CFHR plasma proteins and CFH AutoAb Positve) when autoantibody to factor H is formed. Older children and adults, most of them have no diarrhea Familial, associated with factor H deficiency which limit cleavage of unusual large von Willebrand; leading to continuing platelet activation Poorer prognosis, death in > 50 % of cases
- 9. Thrombotic Thrombocytopenic Purpura (TTP) Tradiationally, TTP is characterized by the pentad: MAHA, Thrombocytopenia, neurologic symptoms, fever and renal failure. Pathophysiology involves accumulation of ultra-large multimers of Von willebard factor as a result of absence or markedly decreased activity of plasma protease ADAMTS 13, These ultra large multimers forms clots and shear erythrocytes resulting in MAHA;TTP TTP is now defined as large MAHA associated with ADAMTS13 activity (less then 5-10%), however only absence of ADAMTS13 alone may not produce TTP; often triggering factors (infection, surgery, pancreatitis or pregnancy) is required to induce clinical TTP If untreated TTP has mortality rate exceeding 90 %, even with modern therapy 20 % die within 1st month from complication of microvascular thrombosis.
- 10. In idiopathicTTP, the formation of an autoantibody to ADAMTS13 (IgG or IgM) either increases its clearance or inhibits its activity. Upshaw-Schülman syndrome is a hereditary condition characterized by congenital deficiency of ADAMTS13. TTP in these patients can start within the first weeks of life but in some instances may not present until adulthood, especially during pregnancy. Both environmental and genetic factors are thought to influence the development of TTP. Plasma transfusion is an effective strategy for prevention and treatment. Drug-induced TMA is a recognized complication of treatment with some chemotherapeutic agents, immunosuppressive agents, and quinine.
- 11. HUS/TTP TREATMENT Treatmentshould be based on pathophysiology. Autoantibody-mediated TTP and DEAP HUS respond to the combination of plasma exchange and prednisone. In addition to removing the autoantibodies, plasma exchange with fresh-frozen plasma replaces ADAMTS13. Plasma infusion is usually sufficient to replace the ADAMTS13 in Upshaw-Schülman syndrome. Drug-induced TMA secondary to endothelial damage typically does not respond to plasma exchange and is treated primarily by discontinuing use of the agent and providing supportive care. Plasma infusion/exchange is effective in certain types of aHUS as it replaces complement-regulatory proteins.
- 12. RADIATION NEPHROPATHY Eitherlocal or total body irradiation can produce microangiopathic injury. The kidney is one of the most radiosensitive organs, and injury can result with as little as 4–5 Gy. Such injury is characterized by renal insufficiency, proteinuria, and hypertension usually developing ≥6 months after radiation exposure. Renal biopsy reveals classic TMA with damage to glomerular, tubular, and vascular cells, but systemic evidence of MAHA is uncommon. No specific therapy is available.
- 13. HIV RELATED TMA HIV-related TMA is a complication encountered mainly before widespread use of highly active antiretroviral therapy. It is seen in patients with advanced AIDS and low CD4+ T cell counts although it can be the first manifestation of HIV infection. The presence of MAHA, thrombocytopenia, and renal failure are suggestive, but renal biopsy is required for diagnosis since other renal diseases are also associated with HIV infection. The mechanism of injury is unclear, although HIV can induce apoptosis in endothelial cells. ADAMTS13 activity is not reduced in these patients. Cytomegalovirus co-infection may also be a risk factor. Effective antiviral therapy is key, while plasma exchange should be limited to patients who have evidence of TTP.
- 14. SCLERODERMA (PROGRESSIVE SYSTEMIC SCLEROSIS) Kidney involvement is common (up to 52%) in patients with widespread scleroderma, with 20% of cases resulting directly from scleroderma renal crisis. Other renal manifestations in scleroderma include transient (prerenal) or medication- related forms of acute kidney injury (e.g., associated with D-penicillamine, nonsteroidal anti-inflammatory drugs, or cyclosporine). Salt and water retention with microvascular injury can lead to pulmonary edema. Cardiac manifestations, including myocarditis, pericarditis, and arrhythmias, denote an especially poor prognosis.
- 15. Glomerulonephritis andvasculitis associated with antineutrophil cytoplasmic antibodies and systemic lupus erythematosus have been described in patients with scleroderma. Anti-U3-RNP may identify young patients at risk for scleroderma renal crisis. Anticentromere antibody, in contrast, is a negative predictor of this disorder. Because of the overlap between scleroderma renal crisis and other autoimmune disorders, a renal biopsy is recommended for patients with atypical renal involvement, especially if hypertension is absent. Scleroderma renal crisis occurs in 12% of patients with diffuse systemic sclerosis but in only 2% of those with limited systemic sclerosis Mild proteinuria is usually present ± HTN Sclerodermal renal crisis is most severe form characterized by- Accelerated HTN ( Ratinopathy and Encephalopathy may follow Htn) Rapid decline in renal function Nephrotic range proteinuria Hematuria
- 16. Systemic Sclerosis Pathology: Intimal proliferation of interlobular arteries, with deposition of mucoplysaccharides: Onion-Skin appearance Fibrinoid necrosis of afferent arterioles Treatment: Treatment with ACE inhibition is the first-line therapy unless contraindicated. The goal of therapy is to reduce systolic and diastolic blood pressure by 20 mmHg and 10 mmHg, respectively, every 24 h until blood pressure is normal. Additional antihypertensive therapy may be given once the dose of drug for ACE inhibition is maximized. Both ACE inhibitors and angiotensin II receptor antagonists are effective. Poor prognosis; Before the availability of angiotensin-converting enzyme (ACE) inhibitors, the mortality rate for scleroderma renal crisis was >90% at 1 month. Introduction of renin- angiotensin system blockade has lowered the mortality rate to 30% at 3 years. Nearly two-thirds of patients with scleroderma renal crisis may require dialysis support, with recovery of renal function in 50% (median time, 1 year). because of other organ involvement, especially restrictive cardiomyopathy
- 17. ANTIPHOSPHOLIPID SYNDROME Antiphospholipidsyndrome can be either primary or secondary to systemic lupus erythematosus and is mediated by antiphospholipid antibodies— mainly anticardiolipin antibodies , lupus anticoagulant, or anti-β-2 glycoprotein I antibodies (antiβ2GPI). TMA is commonly present in renal biopsies, although signs of MAHA and platelet consumption are usually absent. Hypertension is common. Treatment lifelong anticoagulation. Glucocorticoids may be beneficial in accelerated hypertension. Immunosuppression and plasma exchange may be helpful for catastrophic episodes of antiphospholipid syndrome but by themselves do not reduce recurrent thrombosis.
- 18. HELLP SYNDROME HELLP(hemolysis, elevated liver enzymes, low platelets) syndrome is a dangerous complication of pregnancy associated with microvascular injury. Occurring in 0.2–0.9% of all pregnancies and in 10–20% of women with severe preeclampsia, this syndrome carries a mortality rate of 7.4–34%. Most commonly developing in the third trimester, 10% of cases occur before week 27 and 30% post-partum. Renal failure occurs in half of patients with HELLP syndrome,.
- 19. Although renalfailure is common, the organ that defines this syndrome is the liver. Subcapsular hepatic hematomas sometimes produce spontaneous rupture of the liver and can be life-threatening. Neurologic complications such as cerebral infarction, cerebral and brainstem hemorrhage, and cerebral edema are other potentially life-threatening complications. Nonfatal complications include placental abruption, permanent vision loss due to Purtscher-like (hemorrhagic and vaso-occlusive vasculopathy) retinopathy, pulmonary edema, bleeding, and fetal demise. A history of MAHA before pregnancy is of diagnostic value. Serum levels of ADAMTS13 activity are reduced (by 30–60%) in HELLP syndrome but not to the levels seen in TTP (<5%). HELLP syndrome usually resolves spontaneously after delivery, although a small percentage of HELLP cases occur post-partum. Plasma exchange should be considered if hemolysis is refractory to glucocortcoids and/or delivery, especially if TTP has not been ruled out.
- 20. POEMS Syndrome POEMSsyndrome is a systemic disease characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. Peripheral neuropathy with severe motor sensory deficit is the hallmark of the disease. Another characteristic is that >95% of monoclonal light chain is of the lambda isotype. IgA also makes up about 50% of the monoclonal protein. Organomegaly can involve any organ and often presents as lymphadenopathy. In the kidney, the hypertrophy frequently is unilateral. Most patients present with mild to moderate renal impairment and low grade proteinuria. Progression to end stage renal ds may occur.
- 21. SICKLE CELL NEPHROPATHY Renal complications in sickle cell disease result from occlusion of the vasa recta in the renal medulla. The low partial pressure of oxygen and high osmolarity predispose to hemoglobin S polymerization and erythrocyte sickling. Sequelae include hyposthenuria, hematuria, and papillary necrosis (which can also occur in sickle trait). The kidney responds by increases in blood flow and glomerular filtration rate mediated by prostaglandins. Proteinuria is present in 20–30%, and nephrotic-range proteinuria is associated with progression to renal failure. Chronic kidney disease is present in 12–20% of patients. Despite the frequency of renal disease, hypertension is uncommon in patients with sickle cell disease.
- 22. MACROVASCULAR DISEASE: RenalArtery Stenosis Ischemic Renal Disease
- 23. Renal Artery Stenosis(RAS) and Ischemic Renal Disease: RAS Prevalence: 2-4 % in general population 30-40 % in accelerated HTN and renal insufficiency Causes: Atherosclerosis:(ARV D) 90 % Elderly Fibromuscular Dysplasia: 5-10 % Young Ischemic Renal Disease Atherosclerosis of 1 or both renal Artery Elderly male ± HTN Often with atherosclerotic PVD (68%) IHD (45%) CHF (33%) History of stroke (28%) Progressive loss of renal function
- 26. Atherosclerotic Reno-vascular disease: Itaccounts for >90% of all RVD, in patients > 55, or < 30 Years of age Lesions of RAS are 90% ostial (within the1st one cm of renal artery origin) It can be demonstrated in: >10% of patients undergoing coronary angiography >40% with peripheral vascular disease (PVD), with > 5 vessels involvement 30% with congestive cardiac failure (CCF), aged >70 years 15-20 % with ESRD It is increased with aging and is associated with common atherogenic risk factors: Hypertension Hypercholesterolemia Smoking Diabetes
- 27. Clinical Presentations: Hypertension(HTN), with Chronic Kidney Disease (CKD), a pro-atherogenic state make the incidental finding of ARVD, rather than being the cause of it.. Epi-gastric bruit Hypokalemia and metabolic alkalosis Flash pulmonary edema(5%): Sudden onset of acute heart failure in absence of myocardial ischemic event Commonly at night(due to posture-related redistribution of fluid or may be due to diurnal variations of vasoactive peptides) Mechanism may be due to reduced natriuretic ability, coupled with LVH and severe HTN in patients with severe bilateral RAS Acute Kidney Injury (AKI), due to arterial occlusion
- 28. Prognosis of ARVD: Renal outcome is determined by the presence of parenchymal disease giving the picture of ischemic nephropathy (intrarenal atheroma, or cholesterol embolization) The correlation between the severity of proximal lesions(degree of stenosis or occlusion) and renal function is poor. Poor prognosis (5-year survival<20 %)
- 31. Treatment of RAS: Conservative medical management: Cessation of smoking/weight loss/exercise Strict Control of HTN Lipid lowering agents Aspirin Revascularization, especially successful in significant RAS associated AKI, or with flash pulmonary edema: Percutaneous Transluminal Renal Angioplasty (PTRA), with stenting (PTRAS), in >95% of cases Surgical reconstruction: celiac, or mesenteric –to- Renal Bypass, in remainder of cases Balloon angioplasty: Uncontrolled HTN Success rate: 82-100 % Recurrence rate: 10 % (follow-up with duplex U/S)
- 32. Fibromuscular Dysplasia (FMD): It accounts for 10% of all RVD Most commonly in young women (20-35 Ys) The stenotic lesions are distal and appear like “string of beads”, at angiography Clinically, presented with severe HTN, but renal failure is unusual It is usually associated with other arterial lesions (carotid stenosis in 10% of cases) Revascularization cure the HTN and restores the kidney function completely; because the kidney beyond the FMD, is usually healthy Fibromuscular dysplasia of the renal artery, medial type (elastic tissue stain) The media shows marked fibrous thickening, and the lumen is stenotic
- 33. Atheroembolic RVD: Cholesterolembolisation syndrome (CES) is occurring in: Elderly patients with widespread atherosclerosis (almost exclusively) As complication of abdominal aorta/renal artery manipulation or surgery As a consequence of angiography Clinically: Renal insufficiency &/or HTN Livideo reticularis Evidence of embolisation in other organs: Cerebrovascular events, retinal artery occlusion, acute pancreatitis, ischemic bowels, gangrene of extremities Urine analysis: Cholesterol crystals (not usually present) Increased cellularity Proteinuria (mild) Eosinophiluria
- 35. Treatment of CES Control HTN (avoid hypotension) Adequate hydration Anticoagulants may delay healing of ulcerated atherosclerotic lesions Dialysis may be needed
- 36. Thromboembolic Occlusion of RenalArteries Causes: Intrinsic pathology in renal vessels:{In situ thrombosis} Post-traumatic.. Young patients (blunt trauma, deceleration injury,..) Atherosclerotic.. Old patients Dissection/Aneurysm/Arteriography Inflammatory: Takayasau, syphilis, systemic vasculitis, thrombangitis obliterans Embolization: {originating in distant vessels}; much more common (90%) and usually unilateral Tumor/Fat emboli Emboli from left heart (most common), as left mural thrombus following MI or AF, or bacterial endocarditis, septic/aseptic valvular vegetations.. Paradoxical emboli, passing through patent foramen ovale or ASD
- 37. Clinical Manifestations Of Thromboembolism Difficult to diagnose, require high index of suspicion Variable, depend on: extent/time course of occlusion and state of pre- existing renal circulation Acute renal thrombosis/infarction Sudden onset of flank pain/tenderness (absent in 55 %) Fever/nausea/vomiting Hematuria (microscopic) Deteriorated renal function: transient (unilateral), or severe (bilateral) Hypertension, usually transient (renin release in peri-infarction zone) Elevated TLC, AST, LDH, ALP (renal enzymes in infarction)
- 38. Clinical Manifestations Of Thromboembolism Gradual unilateral occlusion --> may go undetected Patients with RAS & established collateral circulation have no symptoms (little/no infarction) Thus, the spectrum of clinical manifestations lies between some extremes in different occasions: ARF Unexplained Progressive Azotemia (old patient ± refractory HTN) HTN + Azotemia (renal transplant)
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- 40. Clinical Manifestations ofRVT Depend on extent and rapidity of occlusion: 1. Acute: Nausea/vomiting Flank Pain Hematuria Leucocytosis Compromised renal functions Increased renal size on U/S 2. Chronic: Dramatic ↑ of proteinuria Tubular Dysfunction: Glucosuria, aminoaciduria, phosphaturia and impaired urinary acidification
- 41. Diagnosis of RVT Investigations: Doppler U/S: more sensitive then USG alone CT Angiogram- 100% sensitive Magnetic Resonance Angiography is another good option but is more expensive. Treatment: Anticoagulation Therapy and treatment of underlying cause Endovascular Thrombolysis may be considered in severe cases Occasionally, neprectomy may be undertaken for life-threatning complication Vena caval filters may be used to prevent migration of thrombi
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