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Crescentic Glomerulonephritis

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Title: Crescentic Glomerulonephritis


1
Crescentic Glomerulonephritis
2
  • RPGN defined as any glomerular disease
    characterized by extensive crescents (usually
    gt50) as the principal histologic finding and by
    a rapid loss of renal function (usually a 50
    decline in the glomerular filtration rate GFR
    within 3 mo) as the clinical correlate.
  • Transient azotemia with oliguria is common in
    patients with acute glomerulonephritis

3
  • Some patients have acute glomerulonephritis and
    present with rapidly progressive renal failure
    that develops within weeks to months and displays
    little tendency for spontaneous or complete
    recovery.
  • Glomerular crescents can complicate any
    glomerulopathy, even noninflammatory
    glomerulopathy.
  • In patients with noninflammatory
    glomerulopathies, the crescents tend to be
    fibrotic rather than cellular.
  • Cellular crescents are a manifestation of a
    severe inflammatory process.

4
Classification
  • Idiopathic or primary crescentic
    glomerulonephritis is classified into the
    following types
  • Type I with linear deposits of immunoglobulin G
    (IgG) (antiglomerular basement membrane GBM
    disease)
  • Type II with granular deposits of immunoglobulin
    (immune-complex mediated)
  • Type III with few or no immune deposits
    (pauci-immune) - Antineutrophil cytoplasmic
    antibody (ANCA)associated (Renal-limited forms
    of ANCA-associated crescentic glomerulonephritis
    are thought to be related to small vessel
    vasculitis SVV with exclusive involvement of
    the glomerular capillaries.)
  • Type IV combinations of types I and III
  • Type V ANCA-negative renal vasculitis (5-10)

5
Pathophysiology
  • RPGN can develop in any of the following clinical
    settings
  • Complication of acute or subacute infectious
    process
  • Renal complication of multisystem disease
    Secondary forms comprise more than 40 of cases.
  • In association with use of certain drugs A
    review of published data on an association
    between hydrocarbon exposure and anti-GBM
    antibody-mediated disease suggests the
    possibility of a casual relationship.
  • Primary glomerular disease in which the kidney is
    the sole organ involved and in which extrarenal
    manifestations are caused by renal function
    disturbances

6
  • Acute RPGN is mediated by antibody or cellular
    immunity or by interaction of the two arms of the
    immune system.
  • Deposition of antibody along the basement
    membrane and/or glomerular deposition of
    preformed soluble immune complexes can result in
    glomerulonephritis.
  • Lymphocytes and macrophages, along with deposited
    antibody, are important in the production of
    proliferation and proteinuria.
  • The involved lymphocytes are identified as T
    cells most are helper T cells with some
    suppressor T cells.
  • Antibody- and cell-mediated immunity are together
    responsible for many lesions observed in patients
    with acute RPGN, and cell-mediated immunity
    without antibody may produce crescentic
    glomerulonephritis.

7
  • Crescents are defined as the presence of 2 or
    more layers of cells in the Bowman space.
  • The presence of crescents in glomeruli is a
    marker of severe injury.
  • The initiating event is the development of a
    physical disruption in the GBM.
  • The lesions are mediated by processes involving
    macrophages and cell-mediated immunity.
  • Following disruption of the glomerular capillary,
    circulating cells, inflammatory mediators, and
    plasma proteins pass through the capillary wall
    into the Bowman space.
  • Cells and mediators from the interstitium enter
    the Bowman space with disruption of the Bowman
    capsule, which leads to development of crescents

8
  • The major participants in crescent formation are
    coagulation proteins, macrophages, T cells,
    fibroblasts, and parietal epithelial cells.
    Activated macrophages contribute to the crescents
    by proliferating and releasing procoagulant
    tissue factor, interleukin-1 (IL-1) and tumor
    necrosis factor (TNF). T cells are not prominent
    components, but they play an important role in
    glomerular injury by antigen recognition and
    macrophage recruitment.
  • The reversibility of crescents correlates with
    relative predominance of cellular components.
    Whether crescents progress or resolve may depend
    upon the integrity of the Bowman capsule and
    resulting cellular composition of the crescent.
    Progression to fibrous crescents is more common
    when capsular rupture occurs and fibroblasts
    along with macrophages are prominent in the
    Bowman space. The presence of fibrous crescents
    usually correlates with glomerular sclerosis or
    irreversibility.

9
  • Mortality/Morbidity
  • Renal failure at presentation carries an
    increased risk for end-stage renal disease and
    death despite immunosuppressive therapy.1 Death
    or dialysis occurs in 73 of patients who are
    treated with conventional therapy and in 88 of
    patients if they are oligoanuric at time of
    presentation.
  • Race
  • No racial predilection exists.
  • Sex
  • For RPGN types I and III, a predilection for
    males exists.
  • Age
  • RPGN has a broad age distribution, as follows
  • RPGN type I generally occurs in young adults.
  • RPGN types II and III generally occur in older
    adults the peak incidence occurs in the fourth
    to sixth decades of life.

10
Clinical
  • History
  • Clinical and laboratory presentations of all
    types of acute RPGN are quite similar.
  • Some patients present with signs and symptoms of
    renal disease, for example, anemia, hematuria,
    fluid retention, oliguria, or even uremia.
  • Symptoms of weakness, nausea, and vomiting
    (indicative of azotemia) usually dominate the
    clinical picture.
  • Other patients present with signs and symptoms of
    their primary etiology (eg, Goodpasture syndrome,
    Wegener granulomatosis, systemic lupus
    erythematosus SLE).
  • Still others give a history of a flulike or viral
    prodrome. Vague aches and pains or frank
    arthritis, sinusitis, otitis, episcleritis, skin
    rash, neuritis, or encephalopathy are uncommon
    and are more common with a multisystem disease
    (suggesting secondary form).
  • Oliguria, abdominal or flank pain, and hemoptysis
    may occur (eg, Goodpasture syndrome).
  • Peripheral swelling may be present.
  • Fifteen percent of patients may be asymptomatic.

11
  • Physical
  • Blood pressure may be normal or slightly
    elevated.
  • Peripheral edema may be present in 10 of
    patients.
  • Pallor is common.
  • Skin rash A lesion suggesting leukocytoclastic
    vasculitis may be present.

12
Causes
  • Drugs
  • Penicillamine
  • Hydralazine (rare case reports)
  • Allopurinol (with vasculitis)
  • Rifampin (rare case reports)
  • Propylthiouracil, thiamazole, carbimazole,
    benzylthiouracil
  • Aminoguanidine
  • Primary glomerular disease
  • Idiopathic or primary crescentic
    glomerulonephritis
  • Type I with linear deposits of IgG (anti-GBM
    disease)
  • Type II with granular deposits of immunoglobulin
    (immune-complex mediated)
  • Type III with few or no immune deposits
    (pauci-immune) - ANCA-associated (renal-limited
    microscopic polyarteritis)
  • Type IV combinations of types I and IIIa
  • Type V ANCA-negative renal vasculitis (5-10)
  • Superimposed on another primary glomerular
    disease
  • Membranoproliferative glomerulonephritis (MPGN)
    type II
  • Membranous glomerulonephritis
  • Immunoglobulin A (IgA) nephropathy
  • Infectious diseases
  • Poststreptococcal glomerulonephritis (PSGN)
  • Infective endocarditis
  • Occult visceral sepsis
  • Hepatitis B infection (with vasculitis and/or
    cryoglobulinemia)
  • Multisystem diseases
  • SLE
  • Henoch-Schönlein purpura
  • Systemic necrotizing vasculitis (including
    Wegener granulomatosis)
  • Microscopic polyarteritis
  • Goodpasture syndrome
  • Essential mixed (IgG and immunoglobulin M IgM)
    cryoglobulinemia
  • Malignancy
  • Relapsing polychondritis
  • Rheumatoid vasculitis

13
Differential Diagnoses
  • Acute Renal Failure
  • Nephritis, Interstitial
  • Glomerulonephritis, Acute
  • Thrombotic Thrombocytopenic Purpura
  • Hemolytic-Uremic Syndrome
  • Hypertension
  • Hypertension, Malignant

14
Paradigm for the diagnosis of crescentic GN
15
Treatment Medication
  • Early and aggressive treatment is warranted to
    preserve renal function
  • A nephrologist should be involved early in the
    disease course
  • Renal diet Provide a low-salt, low-protein (0.8
    g/kg/d) diet, if renal dysfunction is present.
    Restrict potassium if the patient has
    hyperkalemia. Avoid malnutrition
  • No specific limitations are necessary other than
    limiting activity after renal biopsy

16
Medication - Principles of therapy
  • Supportive therapy involves control of infection,
    control of volume status (providing dialysis if
    required), and smoking cessation
  • Specific therapy is directed toward providing
    immunosuppressive therapy (eg, glucocorticoids,
    cyclophosphamide, azathioprine, mycophenolate
    MMF), plasma exchange (in patients presenting
    with life-threatening pulmonary hemorrhage or
    advanced renal failure, ie, creatinine level of
    gt500 µmol/L1 ), and anticoagulant agents

17
  • Recently, monoclonal antibodies (eg, infliximab,
    rituximab), alemtuzumab, pentoxifylline (reduces
    TNF), mizoribine (a purine synthesis inhibitor),
    and antithymocyte globulin have been used with
    encouraging results in a small number of
    patients, but controlled trials are needed
  • At present, the mainstay of therapy remains
    cyclophosphamide and steroids for induction of
    remission

18
Glucocorticoids
  • Pulses of intravenous methylprednisolone (5-20
    mg/kg) followed by high-dose oral prednisone (2
    mg/kg) daily or on alternate days for 2-3 months
    have shown improved 1-year renal survival rates
    of 40-70

19
  • Methylprednisolone
  • Potent anti-inflammatory steroid with greater
    anti-inflammatory potency and fewer tendencies to
    induce retention of salt and water than
    prednisolone
  • Adult 0.5-1 g (5-20 mg/kg) IV bolus qd for 3 d,
    followed by prednisone 2 mg/kg PO daily or on
    alternate days for 2-3 mo
  • Pediatric 30 mg/kg IV qd for 3 d, followed by
    prednisone 2 mg/kg PO qd
  • Prednisone
  • Decreases inflammation through multiple
    mechanisms. Reduced to its pharmacologically
    active form prednisolone.
  • When used on a long-term basis, alternate-day
    therapy may elicit fewer adverse effects than
    daily therapy
  • Adult 2 mg/kg PO qd for 2-3 mo then, taper dose
  • Pediatric Administer as in adults

20
Methylprednisolone
Prednisone
  • Interaction
  • Coadministration with digoxin may increase
    digitalis toxicity secondary to hypokalemia
    estrogens may increase levels of
    methylprednisolone phenobarbital, phenytoin, and
    rifampin may decrease levels of
    methylprednisolone (adjust dose) monitor
    patients for hypokalemia when taking medication
    concurrently with diuretics
  • Contraindication
  • Documented hypersensitivity viral, fungal, or
    tubercular skin infections
  • Interaction
  • Coadministration with estrogens may decrease
    clearance concurrent use with digoxin may cause
    digitalis toxicity secondary to hypokalemia
    phenobarbital, phenytoin, and rifampin may
    increase metabolism of glucocorticoids (consider
    increasing maintenance dose) monitor for
    hypokalemia with coadministration of diuretics
  • Contraindication
  • Documented hypersensitivity viral infection,
    peptic ulcer disease, hepatic dysfunction,
    connective-tissue infections, and fungal or
    tubercular skin infections GI disease

21
Methylprednisolone
Prednisone
  • Pregnancy
  • C - Fetal risk revealed in studies in animals but
    not established or not studied in humans may use
    if benefits outweigh risk to fetus
  • Precautions
  • Hyperglycemia, edema, osteonecrosis, peptic ulcer
    disease, hypokalemia, osteoporosis, euphoria,
    psychosis, growth suppression, myopathy, and
    infections are possible complications of
    glucocorticoid use may result in partial loss of
    hypertension control
  • Pregnancy
  • B - Fetal risk not confirmed in studies in humans
    but has been shown in some studies in animals
  • Precautions
  • Abrupt discontinuation of glucocorticoids may
    cause adrenal crisis hyperglycemia, edema,
    osteonecrosis, myopathy, peptic ulcer disease,
    hypokalemia, osteoporosis, euphoria, psychosis,
    myasthenia gravis, growth suppression, and
    infections may occur with glucocorticoid use

22
Immunosuppressive agents (cytotoxics)
  • Addition of cytotoxic agents to corticosteroids
    has yielded varying success in treating patients
    with crescentic glomerulonephritis.
  • Although pulse cyclophosphamide is often
    preferred in lupus nephritis, oral
    cyclophosphamide appears to have an advantage in
    Wegener granulomatosis.

23
  • Oral versus intravenous Recently completed,
    prospectively randomized Cyclophosphamide daily
    oral versus PulSed (CYCLOPS) trial has shown very
    little difference in time to remission and time
    to relapse between daily oral or intermittent
    intravenous cyclophosphamide for induction
    therapy

24
  • Cyclophosphamide 3 mg/kg/d for 12 weeks is a
    common recommendation, but the duration of
    therapy may be longer (4-6 mo) in patients with
    pauci-immune glomerulonephritis.
  • This therapy should be followed by the
    administration of azathioprine (1.5-2 mg/kg/d) or
    methotrexate (5-20 mg qwk as a single dose) until
    the patient is in remission for at least 6-12
    months.
  • The duration of azathioprine therapy to prevent
    further relapses is unknown, but it should be at
    least for 2 years

25
  • Continuing cyclophosphamide for longer than 6
    months is not necessary, as recently shown by
    Cyclophosphamide versus Azathioprine during
    Remission (CYCAZAREM) trial, where the time to
    relapse was identical whether the patient was
    given cyclophosphamide for less than 6 months or
    more than 6 months.
  • Recent evidence suggests that mycophenolate
    mofetil (CellCept) 0.75-1 g bid may also be
    effective in patients with pauci-immune
    vasculitis.

26
Cyclophosphamide
Azathioprine
  • Activated in the liver to its active metabolite,
    4-hydroxycyclophosphamide, which alkylates the
    target sites in susceptible cells in an
    all-or-nonetype reaction.
  • Adult 3 mg/kg PO qd for 12 wk
  • Pediatric 2 mg/kg/d PO qd
  • Mechanism by which azathioprine affects
    autoimmune diseases is unknown. Slow acting, and
    its effects may persist after discontinuation.
  • Adult 3 mg/kg PO qd for 12 wk
  • Pediatric 2 mg/kg/d PO qd

27
  • Allopurinol may increase risk of bleeding or
    infection and may enhance myelosuppressive
    effects of cyclophosphamide may potentiate
    doxorubicin-induced cardiotoxicity may reduce
    digoxin serum levels and antimicrobial effects of
    quinolones chloramphenicol may increase
    half-life of cyclophosphamide, while decreasing
    metabolite concentrations may increase effect of
    anticoagulants coadministration with high doses
    of phenobarbital may increase rate of metabolism
    and leukopenic activity of cyclophosphamide
    thiazide diuretics may prolong cyclophosphamide-in
    duced leukopenia and neuromuscular blockade by
    inhibiting cholinesterase activity
  • Toxicity increases with allopurinol concurrent
    use with ACE inhibitors may induce severe
    leukopenia may increase levels of methotrexate
    metabolites and decrease effects of
    anticoagulants, neuromuscular blockers, and
    cyclosporine

28
  • Contraindication
  • Documented hypersensitivity, severely depressed
    bone marrow function
  • Pregnancy
  • D - Fetal risk shown in humans use only if
    benefits outweigh risk to fetus
  • Precautions
  • Regularly examine hematologic profile
    (particularly neutrophils and platelets) to
    monitor for hematopoietic suppression regularly
    examine urine for RBCs, which may precede
    hemorrhagic cystitis young adults in
    reproductive age group should be advised about
    the risk of infertility, and appropriate steps
    should be taken to avoid this problem (either
    considering use of a sperm bank or use of
    leuprolide to suppress gonadotrophic function
    during the treatment course) malignancy of
    urinary bladder or lymphatic system may occur
  • Contraindication
  • Documented hypersensitivity
  • Pregnancy
  • D - Fetal risk shown in humans use only if
    benefits outweigh risk to fetus
  • Precautions
  • Increases risk of neoplasia caution with liver
    disease and renal impairment hematologic
    toxicities may occur

29
Antibiotics
  • Therapy must be comprehensive and should cover
    all likely pathogens in the context of this
    clinical setting.

30
Trimethoprim-sulfamethoxazole
  • Long-term treatment with TMP (160 mg) and SMX
    (800 mg) bid has been reported in a prospective,
    controlled, double-blind trial to sustain
    remission of Wegener granulomatosis.
  • The mechanism of this effect is not clear.
    Eradication of Staphylococcus aureus in the
    anterior nares of patients with Wegener
    granulomatosis has recently been reported to
    sustain remission of Wegener granulomatosis.
  • TMP-SMX is also helpful as Pneumocystis carinii
    pneumonia (PCP) prophylaxis in patients who are
    on corticosteroids and other immunosuppressive
    agents

31
  • Interactions
  • May increase PT when used with warfarin (perform
    coagulation tests, and adjust dose accordingly)
    coadministration with dapsone may increase blood
    levels of both drugs coadministration of
    diuretics increases incidence of thrombocytopenia
    purpura in elderly phenytoin levels may increase
    with coadministration may potentiate effects of
    methotrexate in bone marrow depression
    hypoglycemic response to sulfonylureas may
    increase with coadministration may increase
    levels of zidovudine
  • Adult
  • TMP 160 mg/SMX 800 mg PO q12h adjust dose per
    renal function CrCl gt25 mL/min No change CrCl
    15-25 mL/min Reduce dose by 50 CrCl lt15 mL/min
    Not recommended
  • Pediatric
  • lt2 months Do not administer gt2 months 5-10
    mg/kg/d PO tid/qid, based on TMP

32
  • Contraindications
  • Documented hypersensitivity megaloblastic anemia
    due to folate deficiency
  • Pregnancy
  • C - Fetal risk revealed in studies in animals but
    not established or not studied in humans may use
    if benefits outweigh risk to fetus
  • Precautions
  • Discontinue at first appearance of skin rash or
    sign of adverse reaction obtain CBC counts
    frequently discontinue therapy if significant
    hematologic changes occur goiter, diuresis, and
    hypoglycemia may occur with sulfonamides
    prolonged IV infusions or high doses may cause
    bone marrow depression (if signs occur,
    administer 5-15 mg/d leucovorin) caution in
    folate deficiency (eg, patients with chronic
    alcoholism, the elderly, patients receiving
    anticonvulsant therapy, or patients with
    malabsorption syndrome) hemolysis may occur in
    individuals with G-6-PD deficiency patients with
    AIDS may not tolerate or respond to TMP-SMX
    caution in renal or hepatic impairment (perform
    urinalyses and renal function tests during
    therapy) give fluids to prevent crystalluria and
    stone formation

33
Follow-up
Further Inpatient Care
  • Intensive plasma exchange Plasmapheresis (2-4 L
    of plasma qd or 3 times/wk), combined with
    glucocorticoids and cytotoxic agents, is
    beneficial in antiGBM-mediated disease, provided
    therapy is initiated before renal failure has
    progressed to require dialysis support.
  • Plasma exchange is also valuable as an adjunctive
    measure in patients with positive ANCA results
    who present with life-threatening pulmonary
    hemorrhage (ie, MEthylprednisolone versus Plasma
    EXchange MEPEX) or advanced renal failure

34
Further Inpatient Care
  • Plasma exchange increased the rate of renal
    recovery in ANCA-associated systemic vasculitis
    that presented with renal failure when compared
    with intravenous methylprednisolone however,
    patient survival and adverse event rates were
    similar in both groups
  • In the absence of any response within 3-5 weeks,
    acceptance of a diagnosis of end-stage renal
    disease is preferable to death secondary to
    iatrogenic causes

35
Further Inpatient Care
  • High-dose intravenous immunoglobulin has been
    reported to be successful in suppressing the
    activity of pauci-immune ANCA-positive
    vasculitis. The mechanism is not clear, but
    pooled normal immunoglobulin contains antibodies
    that neutralize ANCA and suppress complement
    activation through a nonspecific effect of the
    immunoglobulin heavy chains
  • Intravenous immunoglobulin may have a role in the
    temporary management of severe pauci-immune
    vasculitis when severe infection is present in
    patients in whom it is desirable to withhold
    cytotoxic agents and high-dose corticosteroids
    until the infection is controlled

36
Further Inpatient Care
  • In difficult to treat cases of ANCA-associated
    vasculitis, humanized monoclonal anti-CD52
    antibodies (alemtuzumab, CAMPATH-1H) that
    selectively deplete lymphocytes may be
    considered. In a recent study by Walsh et al,
    CAMPATH-1H induced remission in such a group of
    patients, but relapse and adverse events were
    common.3 Further study of CAMPATH-1H as an
    induction agent is warranted.

37
Further Outpatient Care
  • After induction of remission with oral
    cyclophosphamide and steroids, conversion to oral
    azathioprine (2 mg/kg/d) at 3 months appears to
    be safe and effective compared to continuation of
    cyclophosphamide for 1 year (if clinical signs of
    activity are minimal and preferably ANCA is
    negative).
  • The duration of maintenance therapy with
    azathioprine to prevent further relapses is
    unknown but should be at least for 2 years.
    Studies of longer periods of azathioprine
    maintenance (2 y vs 4 y) are in progress (eg,
    Randomized trial of prolonged REmission-MAINtenanc
    e therapy in systemic vasculitis REMAIN).

38
  • Monitor BUN, electrolyte, and serum creatinine
    levels in all patients.
  • Drug-responsive relapses may occur as late as 2-4
    years after remission.
  • RPGN may recur after renal transplantation. At
    present, after initiating dialysis, a waiting
    period of 3-6 months is recommended before
    considering renal transplantation.
  • No convincing evidence suggests that a bilateral
    nephrectomy performed before a renal
    transplantation reduces the risk of recurrent
    disease in patients with renal allografts

39
  • For patients who have achieved remission,
    evaluation at 2-month intervals is usually
    sufficient. The following testing is
    recommended  
  • Urinalysis with special emphasis on the presence
    of cellular casts BUN, electrolyte, and serum
    creatinine levels should be evaluated in all
    patients.
  • C-reactive protein or ESR (whichever correlates
    better with disease activity in a given patient)
  • ANCA (in ANCA-positive patients at 6- to 9-mo
    intervals) An increasing ANCA titer is often
    evidence of an impending relapse. A 4-fold or
    higher rise in ANCA titer may herald a relapse
    and require preemptive intervention.
  • Anti-GBM titers in patients with anti-GBM

40
Inpatient Outpatient Medications
  • Administer oral cyclophosphamide for 4-6 months,
    followed by azathioprine or methotrexate until
    the patient is in remission for 6 months to 1
    year.
  • Administer prednisone as a low-dose alternative
    for 6-9 months.
  • Administer trimethoprim-sulfamethoxazole 160/800
    mg bid (for Wegener granulomatosis) if renal
    function normal. Decrease the dose as guided by
    renal function. A lower dosage as PCP prophylaxis
    may be considered.

41
Transfer
  • Patients may need to be transferred to another
    center for the following
  • Plasmapheresis
  • Dialysis
  • Ventilatory support

42
Deterrence/Prevention
  • Because patients with pauci-immune vasculitis
    typically have a prodrome lasting for weeks to
    monthsduring which time they experience 1 or
    more vague symptoms (eg, intermittent fever,
    weight loss, anorexia, arthralgias, shortness of
    breath, hemoptysis, middle ear effusions,
    conjunctivitis, episcleritis, nasal septal
    perforation, saddle nose deformity)a high index
    of clinical awareness, early diagnosis, and
    treatment may prevent significant morbidity and
    mortality associated with this condition.

43
Prognosis
  • In general, the prognosis is poor and aggressive
    therapy is warranted. The chance of renal
    recovery exceeds the chance of dying in most
    cases. Intravenous methylprednisolone as
    an adjunctive therapy plus less than 18 normal
    glomeruli and severe tubular atrophy increased
    the chance of therapy-related death over the
    chance of dialysis independence. Plasma exchange
    treatment plus severe tubular atrophy and less
    than 2 normal glomeruli increased the chance of
    therapy-related death over that of dialysis
    independence.5
  • Fifty percent of patients require maintenance
    dialysis within 6 months of disease onset.
  • Spontaneous remission is uncommon, except among
    patients with infection as the basis for
    formation of antigen-antibody complexes, in whom
    removal of the antigen can take place.

44
  • Poor prognostic factors are as follows  
  • Large crescents in more than 80 of glomeruli
    (especially if fibrocellular or acellular)
  • Initial serum creatinine level of more than 500
    µmol/L or GFR of less than 5 mL/min at
    presentation
  • Oliguria
  • Presence of anti-GBM antibody
  • Age older than 60 years
  • Coexistence of HLA-DR2 and HLA-B7

45
Patient Education
  • Patients receiving immunosuppressive therapy
    should be educated about early signs of infection
    and advised to see their physician or health care
    worker at the early signs of infection in order
    to monitor WBC count.
  • Patients on a high dose of prednisone should be
    monitored for the development of diabetes and
    peptic ulcer disease and receive therapy to
    prevent steroid-induced osteoporosis.

46
Medicolegal Pitfalls
  • A high index of clinical awareness is important
    in order to make an early diagnosis in patients
    presenting with ill-defined fever, weight loss,
    anorexia, arthralgias, hemoptysis, middle ear
    effusions, deafness, nasal septal perforation,
    and saddle nose deformity.
  • Consider eradication of S aureus in anterior
    nares of patients with Wegener granulomatosis for
    sustained remission.
  • Be careful with immunosuppressive therapy (both
    cytotoxic agents and high-dose corticosteroids)
    in patients who may have active infection.
  • Ensuring that the patient has no active infection
    is important before starting immunosuppressive
    therapy in order to prevent significant morbidity
    and mortality associated with treatment of this
    disease.
  • Intravenous immunoglobulin may be useful to
    control disease activity when the patient has
    associated active infection and the need to hold
    immunosuppressive agents.

47
  • The adverse effects and toxicities of long-term
    corticosteroid and immunosuppressive therapy must
    be discussed with the patient.
  • With long-term steroid use, monitoring the
    patient for the development of diabetes, peptic
    ulcer disease, and osteoporosis is important, as
    is prescribing cytoprotective agents (to prevent
    peptic ulceration) and preventive therapy for
    steroid-induced osteoporosis.
  • In patients who are in the reproductive age
    group, discuss and document the effect on
    fertility of cytotoxic therapy. Patients should
    be counseled for sperm or egg preservation, or
    consideration should be given to leuprolide
    therapy to inhibit gametogenesis during treatment
    with cyclophosphamide therapy.
  • To prevent risk of hemorrhagic cystitis, patients
    on oral cyclophosphamide should be encouraged to
    drink plenty of fluids so that the metabolites of
    cyclophosphamide do not concentrate in the
    bladder.
  • The possibility of late malignancy associated
    with cytotoxic therapy should be discussed and
    documented in the patient's chart.
  • Failure to diagnose or empirically treat pending
    diagnosis, with a resulting rise of serum
    creatinine to unsalvageable levels (gt6 mg/dL or
    500 µmol/L), is a potential medicolegal pitfall.
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