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A. Classification of Disease navigator

  1. Large Vessel Disease
    1. Renal Artery Stenosis (RAS) - atherosclerotic and fibromuscular dysplasia (FMD)
    2. Renal Infarctions - atheroembolic, dissection
    3. Renal Artery Thrombosis [1]
    4. Renovascular disease in children - often with abnormalities of other blood vesels [2]
  2. Small Vessel Disease
    1. Atheroembolism / Cholesterol Emboli Syndrome [3]
    2. Scleroderma (PSS)
    3. Malignant Hypertension / Chronic Hypertension (HTN)
    4. Hemolytic-Uremic Syndrome (HUS)
    5. Thrombotic Thrombocytopenic Purpura (TTP)
    6. Acute Cortical Necrosis
    7. Antiphospholipid Antibody Syndrome (APLS) [4]
  3. Vasomotor Disorders
    1. Hepatorenal Syndrome
    2. Hypercalcemia
    3. Sepsis
    4. ACE Inhibitors
    5. NSAIDs (including COX-2 specific agents) [5]
    6. Cyclosporine
    7. Contrast Agents

B. Renal Artery Atherosclerosis navigator

  1. Most common cause (90%) of RAS, usually in elderly patients
  2. Presents as renal dysfunction and/or hypertension (HTN)
  3. Patients with renal stenosis and nephrotic proteinuria often have arterial thromboses [1]
  4. Detection ,
    1. Duplex ultrasonography is sensitive and specific (98% each) and safe
    2. Magnetic resonance angiography (MRA) and computed tomographic (CT) angiography preferred in patients with possible RAS and hypertension [6]
    3. Captopril-renal scans are fairly sensitive at detecting asymmetric renal blood flow
    4. MRA and CT angiography are superior to captopril-renal scans [6]
  5. Overview of Treatments
    1. HTN usually poorly sensitive to ACE inhibitors
    2. Calcium channel blockers and/or ß1-selective adrenergic blockers are recommended
    3. Restoration of renal blood flow is critical for long term success
    4. Standard percutaneous angioplasty (with stenting for ostial lesions) is used [7]
    5. Balloon angioplasty and drug therapy equally effective in treating HTN associated with RAS [8]
    6. Balloon angioplasty may prevent reduce renal dysfunction compared with drug therapy alone [8]

C. Renal Artery Thromboembolismnavigator

  1. Atheroembolic disease may be responsible for 5-10% of ARF in hospital
  2. Diffuse atherosclerosis with fracture of atheromata and acute occlusion
  3. Nephrotic proteinuria often have renal arterial (or venous) thromboses [1]
  4. Risk Factors
    1. Hypercoagulable states
    2. Antiphospholipid Syndrome [4,9]
  5. Treatment
    1. Open occluded artery
    2. Balloon angioplasty ± stenting is recommended
    3. Heparin anticoagulation followed by warfarin therapy

D. Cholesterol Emboli Syndrome [3] navigator

  1. Fragments of cholesterol plaques break off and circulate
  2. These plaques are highly inflammatory
    1. Lodge in and inflame microvasculature
    2. Produce vasculitis-like reaction
  3. Usually occurs in setting of mechanical instrumentation such as cardiac angioplasty
  4. Peripheral and urinary eosinophilia with rapidly progressive renal failure

E. Fibromusclar Dysplasia (FMD) [2] navigator

  1. Usually presents as HTN in children or young persons
    1. Usual medial fibroplasia
    2. Intimal fibroplasia less frequent
  2. Characteristics
    1. Patients are typically women age 15-50 with HTN
    2. Familial cases in 10-60%
    3. Bilateral in >65% of cases
    4. HTN associated with intrarenal disease alone in 44% and intrarenal / main artery RAS in 31%
    5. Concomitant stenoses of other arteries typical (up to 55% of cases)
    6. Extra- and intracranial cerebrovascular disease also observed
  3. Associations
    1. Non-Syndromic: idiopathic, no associations
    2. Syndromic: Neurofibromatosis I, Tuberous sclerosis, WIlliams' Syndrome, Marfan's Syndrome
    3. Vasculitis: Takayasu's Arteritis, Polyarteritis Nodosa, Kawasaki Disease, others
    4. Extrinsic Compression: neuroblastoma, Wilms' tumor, other tumors
    5. Miscellaneous: radiation, umbilical artery catheterization, trauma, congenital rubella
    6. Transplant renal artery stenosis
  4. Angiography or Magnetic Resonance Angiogram shows aneurysms and narrowing (stenosis)
  5. Patients will often present with infarctions of kidney, gut, and/or liver
  6. Surgical Repair and/or angioplasty ± drug therapy required to correct HTN
  7. Treatments aimed at reducing restonisis in angioplasty may have some efficacy
  8. Drugs blocking renin-angiotensin axis generally contraindicated in children with FMD

F. Ischemic Nephropathynavigator

  1. Obstruction of renal blood flow leading to ischemia and renal excretory dysfunction
  2. Occurs when effective perfusion pressure across kidneys fall to <70-80 mm Hg
  3. Pathogenesis
    1. Poorly understood
    2. Reduction in nitric oxide production
    3. Increased production endothelin
    4. Activation of renin-angiotensin system
  4. May present as acute (ARF) or chronic (CRF) progressive renal failure
  5. Renal artery stenosis, usually atherosclerotic without HTN, is most common cause
  6. ARF may follow initiation of therapy with ACE inhibitor
  7. Kidneys are often asymmetric in ischemic nephropathy
  8. Revascularization is recommended in most cases

G. Vasculitis navigator

  1. Polyarteritis nodosa (PAN) - renal arteries
  2. Wegener's Granulomatosis - arterioles usually affected
  3. Hypersensitivity Angiitis - small vessel disease
  4. Cryoglobulinemia - small vessel disease
  5. Henoch-Schnlein Purpura (HSP) - small vessel
  6. Vasculitis associated with systemic lupus erythematosus (unusual)

H. Hypertension navigator

  1. Chronic HTN leads to vascular thickening, necrosis, fibrosis
  2. Pathology shows focal glomerular sclerosis
  3. Proteinuria is most common finding
  4. Presence of proteinuria early in pregnancy in women with chronic HTN is a 3 fold risk factor for premature (<35 weeks) birth and to have small for gestational age babies [10]

I. Small Vessel Diseasenavigator

  1. HUS / TTP
    1. Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP)
    2. These are likely related syndromes with endothelial damage
    3. Hemolytic anemia, thrombus formation, and thrombocytopenia are common
    4. Renal dysfunction due to small vessel obstruction is common
  2. Progressive Systemic Sclerosis (PSS, scleroderma)
    1. Idiopathic fibrosis and stenosis of vessels, skin, gut, heart, other organs
    2. Most patients develop vascular lesions but few progress to renal failure
    3. Scleroderma Renal Crisis - usually middle aged women, mean 7 years of disease
    4. Renal crisis includes new azotemia, severe HTN, possible hematuria
    5. Ultrasound should be performed to rule out obstructive contribution
    6. Urinalysis usually shows proteinuria; red cells and/or red cell fragments may be present
    7. Renal biopsy may be done in atypical cases
  3. Heroin Nephropathy
  4. Preeclampsia
  5. Sickle Cell Anemia

J. Sickle Cell Nephropathy navigator

  1. Pathology
    1. Membranoproliferative Glomerulonephritis
    2. Focal Segmental Glomerulosclerosis (FSGS)
    3. Hypertensive Microvascular Changes (FSGS with glomerular enlargement)
    4. Immune Complex Deposition
    5. Glomerular hyperfiltration appears to be major problem
  2. Genesis
    1. ~25% of Sickle Cell patients have proteinuria
    2. Hematuria
    3. Progression to Nephrotic syndrome, Chronic renal failure
    4. Increased incidence of Urinary tract infections
    5. Hyposthenuria
    6. Renal artery and Renal vein thrombosis
  3. Treatment
    1. Enalapril 5-10mg po qd decreases proteinuria in 6 months and over long term
    2. ACE Inhibitors likely protect kidney by decreasing glomerular filtration pressures
    3. Effects of 6 months of enalapril occasionally last even after drug is stopped
    4. Captopril reduces microalbuminuria >50% in normotensive sickle cell patients [14]

K. Drug Effects [11]navigator

  1. Mainly affect renal perfusion pressure
    1. Perfusion pressure depends on afferent arteriolar dilatation first
    2. Efferent arteriole must be relatively constricted to maintain trans-glomerular pressure
  2. NSAIDs (Non-steroidal Anti-inflammatory Drugs) [11,12]
    1. Prostaglandins may be important in maintaining afferent arteriolar dilatation
    2. This is mainly true in diseases with reduced renal perfusion (including CHF, nephrotic)
    3. NSAIDs inhibit prostaglandin synthesis and predispose to reduced renal perfusion
    4. Mainly intermediate and long acting NSAIDs associated with renal dysfunction
    5. This leads to reduced glomerular filtration rates (GFR)
    6. Synergistic interaction with ACE inhibitors may reduce GFR and lead to azotemia
    7. However, combination of NSAIDs with ACE inhibitors or diuretics did not appear to increase risk of renal dysfunction
  3. Angiotensin II Blockade
    1. Angiotensin II is main vasoconstrictor of the efferent arteriole
    2. Blockade of angiotensin II production (with ACE inhibitors) or antiogensin II receptors with ARB allows efferent dilatation
    3. Efferent arteriolar dilatation leads to reduced trans-glomerular pressure
    4. This leads to a drop in the GFR
    5. In addition, ACE inhibitors and ARB lead to reduced aldosterone synthesis
    6. With reduced GFR and reduced aldosterone, hyperkalemia may be induced
    7. Renin inhibitor is now available with unknown effects
  4. Cyclosporine and Radiocontrast Agents
    1. Cause afferent arteriolar constriction
    2. May exacerbate amphotericin B induced nephropathy [13]
    3. Clearly additive with other renal insults [11]

References navigator

  1. Halimi JM, Ribstein J, Du Cailar G, Mimram A. 2000. Am J Med. 108(2):120 abstract
  2. Tullus K, Brennan E, Hamilton G, et al. 2008. Lancet. 371(9622):1453 abstract
  3. Spring MW, Hartley B, Scoble JE, Viberti GC. 1998. Lancet. 352(9132):956 (Case Report) abstract
  4. Coggins CH and McCluskey RT. 2001. NEJM. 344(15):1152 (Case Record)
  5. Swan SK, Rudy DW, Lasseter KC, et al. 2000. Ann Intern Med. 133(1):1 abstract
  6. Vasbinder GB, Nelemans PJ, Kessels AG, et al. 2001. Ann Intern Med. 135(6):401 abstract
  7. Van de Ven PJ, Kaatee R, Beutler JJ, et al. 1999. Lancet. 353(9149):282 abstract
  8. Van Jarrsveld BC, Krinjen P, Pieterman H, et al. 2000. NEJM. 342(14):1007 abstract
  9. Rennke HG and Laposata M. 1999. NEJM. 340(24):1900 (Case Record)
  10. Sibai BM, Lindheimer M, Hauth J, et al. 1998. NEJM. 339(10):667 abstract
  11. Abuelo JG. 2007. NEJM. 357(8):797 abstract
  12. Sturmer T, Erb A, Keller F, et al. 2001. Am J Med. 111(7):521 abstract
  13. Harbarth S, Pestotnik SL, Lloyd JF, et al. 2001. Am J Med. 111(7):528 abstract
  14. Foucan L, Bourhis V, Bangou J, et al. 1998. Am J Med. 104(4):339 abstract