RENAL

1
RENAL CARDIAC MANIFESTATIONS OF SLE

• Suhail Allaqaband, MD
• University of Wisconsin-Milwaukee Clinical Campus
• Sinai Samaritan Medical center
• Milwaukee, WI

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Systemic lupus erythematosus

• Patients with SLE are subject to a variety of
  symptoms, complaints, and inflammatory
  involvement that can affect virtually every organ
  
• The most common pattern is a mixture of
  constitutional complaints with skin,
  musculoskeletal, mild hematologic, and serologic
  involvement

3
CLINICAL CRITERIA FOR DIAGNOSIS

• Most physicians rely on the ARA revised Criteria
  for the Classification of SLE
• The diagnosis of SLE is made if four or more of
  the manifestations are present, either serially
  or simultaneously
• When tested against other rheumatic diseases,
  these criteria have a sensitivity and specificity
  of approximately 96 percent

4

• ARA Criteria for diagnosis of Systemic Lupus
  Erythematosus
• criterion definition
• malar rash fixed erythema, flap or raised, over
  the mainandevidence

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AUTOANTIBODIES

• The ANA test is the best screening test for SLE
  and should be performed whenever SLE is suspected
  
• The ANA is positive in significant titer (usually
  1160 or higher) in virtually all patients with
  SLE

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AUTOANTIBODIES

• dsDNA and Sm antibodies
• There are two autoantibodies that are highly
  specific for SLE
• anti-double-stranded DNA (dsDNA) antibodies
• anti-Sm antibodies
• Sensitivity 66 to 95 percent
• Specificity 75 to 100 percent
• Predictive value 89 to 100 percent

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Renal manifestations of SLE

• Renal involvement is common in SLE
• An abnormal urinalysis is present in
  approximately 50 of patients at the time of
  diagnosis and eventually develops in more than 75
  percent of cases
• The most frequently observed abnormality is
  proteinuria (80 percent) while approximately 40
  percent have hematuria and/or pyuria sometime
  during the course of their illness

8
Renal manifestations of SLE

• The total incidence of renal involvement among
  patients with SLE probably exceeds 90 percent
  since renal biopsy in patients without any
  clinical evidence of renal disease often reveals
  a focal or diffuse proliferative
  glomerulonephritis
• There are a number of different types of renal
  disease in SLE, with immune complex-mediated
  glomerular diseases being most common

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IMMUNE COMPLEX GLOMERULAR DISEASE

• Most patients with lupus nephritis have an immune
  complex-mediated glomerular disease
• The standard classification divides these
  disorders into five different patterns in which
  (type I) represents no disease
• Mesangial (type II)
• Focal proliferative (type III)
• Diffuse proliferative (type IV)
• Membranous (type V)

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Mesangial lupus nephritis (type II)

• Occurs in 10 to 20 of cases and represents the
  earliest and mildest form of glomerular
  involvement
• Presents clinically as microscopic hematuria
  and/or proteinuria hypertension is uncommon, and
  the nephrotic syndrome and renal insufficiency
  are virtually never seen
• The renal prognosis is excellent and no specific
  therapy is indicated unless the patient
  progresses to more advanced disease

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• Mesangial proliferative glomerulonephritis.
  Light micrograph of a mesangial
  glomerulonephritis showing segmental areas of
  increased mesangial matrix and cellularity
  (arrows). This finding alone can be seen in many
  diseases, including lupus nephritis and IgA
  nephropathy.

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Focal proliferative lupus nephritis (type III)

• Occurs in 10 to 20 of cases, but represents more
  advanced involvement than mesangial disease
• Hematuria and proteinuria are seen in almost all
  patients, some of whom also have the nephrotic
  syndrome, hypertension, and an elevated plasma
  creatinine concentration
• By definition, less than 50 percent of glomeruli
  are affected on light microscopy
• Electron microscopy shows immune deposits in the
  subendothelial space of the glomerular capillary
  wall as well as the mesangium

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Focal proliferative lupus nephritis (type III)

• The renal prognosis in focal proliferative lupus
  nephritis is variable
• Progressive renal dysfunction appears to be
  uncommon when less than 25 percent of the
  glomeruli are affected on light microscopy
• On the other hand, more widespread or severe
  involvement (40 to 50 percent of glomeruli
  affected, nephrotic range proteinuria, and/or
  hypertension) has a long-term prognosis that is
  similar to that of diffuse disease

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• Memberanoproliferative lupus nephritis. Light
  micrograph showing a memberanoproliferative
  pattern in lupus nephritis, characterized by
  areas of cellular proliferation (long arrows) and
  by thickening of the glomerular capillary wall
  (due to immune deposits) that may be prominent
  enough to form a wire-loop (short arrows).
  Although proliferative changes can be focal
  (affecting less than 50 of glomeruli), disease
  ofthis severity is usually diffuse.

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Diffuse proliferative lupus nephritis (type IV)

• The most common and most severe form of lupus
  nephritis affecting 40 to 60 of cases
• Hematuria and proteinuria are seen in almost all
  cases, and the nephrotic syndrome, hypertension,
  and renal insufficiency are all frequently seen
• Affected patients typically have significant
  hypocomplementemia and elevated anti-DNA levels,
  especially during active disease
• Immunosuppressive therapy is generally required
  to prevent progression of active diffuse
  proliferative lupus nephritis to ESRD

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Diffuse proliferative lupus nephritis. Kidney
biopsy from a patient with diffuse proliferative
lupus nephritis showing, on immunofluorescence
microscopy, massive lumpy bumpy deposits of IgG.
17
Membranous lupus (type V)

• Affects 10 to 20 percent of patients
• Patients typically present with nephrotic
  syndrome
• Microscopic hematuria and hypertension also may
  be seen at presentation, and the plasma
  creatinine concentration is usually normal or
  slightly elevated
• Membranous lupus is the one form of lupus
  nephritis that may present with no other clinical
  or serologic manifestations of SLE
• Most patients maintain a normal or near normal
  plasma creatinine concentration for five years or
  more and may not require immunosuppressive therapy

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Membranous lupus nephritis. Light micrograph of
membranous lupus nephritis. The changes are
similar to those in any form of membranous
nephropathy with diffuse thickening of the
glomerular capillary wall being the major
abnormality (short arrows). Focal areas of
mesangial expansion and hypercellularity (long
arrows) are the only findings suggestive of an
underlying disease such as lupus, although they
can also be seen in idiopathic membranous
nephropathy.
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Membranous lupus nephritis. Electron micrograph
of membranous lupus nephritis. The subepithelial
immune deposits (D) are characteristic of any
form of membranous nephropathy, but the
intraendothelial tubuloreticular structures
(arrow) strongly suggest underlying lupus. GBM
glomerular basement membrane EP epithelial
cell.
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Other Renal manifestations of SLE

• In addition to these glomerulopathies, there are
  three other less common forms of lupus renal
  disease
• interstitial nephritis
• vascular disease and
• renal disease infrequently associated with
  drug-induced lupus

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Tubulointerstitial nephritis

• Tubulointerstitial disease (interstitial
  infiltrate, tubular injury) is a common finding
  in lupus nephritis, almost always being seen with
  concurrent glomerular disease
• The severity of the tubulointerstitial
  involvement is an important prognostic sign,
  correlating positively with the presence of
  hypertension, an elevated plasma creatinine
  concentration, and a progressive course

22
Vascular disease

• Involvement of the renal vasculature is not
  uncommon in lupus nephritis and its presence can
  adversely affect the prognosis of the renal
  disease
• The most common problems are immune complex
  deposition, immunoglobulin microvascular casts, a
  thrombotic microangiopathy leading to a syndrome
  similar to TTP, and vasculitis
• Vascular immune deposits typically produce no
  inflammation, but fibrinoid necrosis with
  vascular narrowing can be seen in severe cases

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Vascular disease

• Other patients present with glomerular and
  vascular thrombi, often in association with
  antiphospholipid antibodies
• Renal involvement is characterized by fibrin
  thrombi in the small arteries and glomerular
  capillaries and, in some cases, in the larger
  renal artery branches
• These changes may occur as a primary disease or
  may be superimposed upon one of the immune
  complex forms of lupus nephritis
• Rarely, patients with lupus nephritis develop
  renal vein thrombosis

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Drug-induced lupus

• A variety of drugs can induce a lupus-like
  syndrome, particularly those that are acetylated
  in the liver, such as hydralazine, procainamide,
  and less often isoniazid
• Renal involvement is uncommon but a
  proliferative glomerulonephritis or the nephrotic
  syndrome can occur

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Cardiac manifestations of SLE

• Cardiac disease is common among patients with SLE
  as pericardial, myocardial, valvular, and
  coronary artery involvement can occur
• The incidence of these problems can be summarized
  as follows
• Cardiac abnormalities up to 55 percent
• Valvular disease up to 50 percent
• Pericardial disease, usually a clinically silent
  effusion up to 48 percent
• Myocardial dysfunction up to 78 percent

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VALVULAR DISEASE

• Systolic murmurs have been noted in 16 to 44
  percent of patients
• Structural valvular disease is most common but
  anemia, fever, tachycardia, and cardiomegaly can
  induce functional murmurs
• Diastolic murmurs have been noted in one to three
  percent of patients
• They often reflect aortic insufficiency, which
  occasionally requires valve replacement.

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VALVULAR DISEASE

• Mitral valve involvement is most common a mild
  to moderate regurgitant murmur may be heard but
  most patients remain asymptomatic
• Mitral valve prolapse appears to occur with
  increased frequency in lupus, occurring in 25
  percent of cases

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Verrucous endocarditis

• Libman-Sacks endocarditis is a not uncommon
  complication of SLE
• In one report of 74 patients, seven had verrucous
  lesions detected by TTE
• However, a higher frequency (43 percent) has been
  noted when more sensitive TEE is performed
• In addition, Libman-Sacks endocarditis is often
  associated with antiphospholipid antibodies
• Verrucous endocarditis is typically asymptomatic
• However, the verrucae can fragment and produce
  systemic emboli

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PERICARDIAL DISEASE

• Pericardial involvement is the second most common
  echocardiographic lesion in SLE, and is the most
  frequent cause of symptomatic cardiac disease
• Pericardial effusion occurs at some point in over
  one-half of patients, and a benign pericarditis
  may precede the clinical signs of lupus
• Pericardial disease is usually asymptomatic, and
  is generally diagnosed by echocardiography
  performed for some other reason

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PERICARDIAL DISEASE

• Symptomatic pericarditis typically presents with
  positional substernal chest pain with an audible
  rub on auscultation
• The pericardial fluid is a fibrinous exudate or
  transudate that may contain antinuclear
  antibodies, LE cells, low complement levels, and
  immune complexes
• The pericardium may reveal foci of inflammatory
  lesions with immune complexes

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PERICARDIAL DISEASE

• The course is benign in the large majority of
  patients with pericardial disease
• Symptomatic pericarditis often responds to an
  NSAID, especially indomethacin
• Patients who do not tolerate or respond to an
  NSAID can be treated with prednisone
• The most serious consequence is the development
  of purulent pericarditis in the immunosuppressed,
  debilitated patient
• Large effusions, suggestive of tamponade, and
  constrictive pericarditis are rare in SLE

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MYOCARDITIS

• Myocarditis is an uncommon, often asymptomatic
  manifestation of SLE with a prevalence of 8 to
  25
• It should be suspected if there is resting
  tachycardia disproportionate to body temp., EKG
  abnormalities and unexplained cardiomegaly
• Echocardiography may reveal abnormalities in both
  systolic and diastolic function of the left
  ventricle
• Acute myocarditis may accompany other
  manifestations of acute SLE, particularly
  pericarditis
• Myocarditis should be treated with prednisone
  plus usual therapy for congestive heart failure
  if present

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CONDUCTION ABNORMALITIES

• Conduction defects, which may represent a sequel
  of active or past pericarditis and/or myocarditis
  have been noted in 34 to 70 percent of patients
  with SLE
• Congenital heart block may be part of the
  neonatal lupus syndrome
• Many mothers of these infants have either SLE or
  Sjögren's syndrome, antibodies to Ro (SS-A)
  and/or La (SS-B), and are HLA-DR3 positive
• The anti-Ro and anti-La antibodies may induce
  autoimmune injury that prevents normal
  development of the conduction fibers
• It is recommended that anti-Ro antibody titers be
  measured early in pregnancy in women with SLE

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CORONARY ARTERY DISEASE

• Coronary artery disease has been recognized in 2
  to 16 of patients with SLE and can lead to acute
  myocardial infarction in young women
• Coronary disease, leading to angina, myocardial
  infarction, congestive heart failure, and death,
  is becoming an increasing problem, particularly
  in the young patient with long-standing SLE
  maintained on corticosteroids
• In one report, coronary disease (defined as
  angina, myocardial infarction, or sudden death)
  occurred in 8.3 percent of 229 patients and was
  responsible for 3 of 10 deaths

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CORONARY ARTERY DISEASE

• Patients with SLE should be made aware of the
  importance of risk factor reduction
• Patients with lupus should be advised to stop
  smoking, exercise, consider the use of hormone
  replacement therapy, and follow measures designed
  to improve lipid profiles
• Hydroxychloroquine should be used in preference
  to prednisone whenever possible and aspirin
  should be prescribed for its antiplatelet
  properties
• Symptomatic coronary artery disease should be
  treated as in patients without lupus

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VENOUS THROMBOSIS

• Thrombophlebitis has been reported in
  approximately 10 percent of patients with SLE
• It generally involves the lower extremity, but
  can also affect the renal veins and inferior vena
  cava
• Risk factors for venous thrombosis include
  antiphospholipid antibodies and the use of oral
  contraceptives, particularly in association with
  smoking cigarettes