Page 960 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 68 Immunological Renal Diseases 927

A genetic predisposition to IgAN has been linked with poly- TABLE 68.2 Prevalence of antineutrophil
morphisms involving innate and adaptive immunities and the Cytoplasmic antibodies (anCas) in
alternative complement pathway. A “second hit” may be needed renal vasculitis
in predisposed individuals. Infections may play a role because
episodes of macroscopic bleeding often coincide with mucosal anCaS teSt POSItIvItY (%)
infections, including upper respiratory tract (synpharyngitic) P-anCas or C-anCas or
or GI infections.
type of renal vasculitis anti-Mpo anti-Pr3
Natural History Polyarteritis nodosa 10–20 10–20
Patients with IgAN who have low-grade proteinuria (<1 g/day) Microscopic polyangiitis 50–80 10–20
80–90
10–20
Granulomatosis with
have a good renal prognosis and usually have a low risk of progres- polyangiitis (Wegener
sion. However, it is recognized that at least one-third of patients granulomatosis)
34
with IgAN eventually progress to ESKD. Twenty years after Necrotizing and crescentic GN 50–80 10–20
apparent disease onset, the probability of renal failure is 25%,
and the probability of some renal dysfunction is 50%. Hyperten- MPO, myeloperoxidase; PR3, proteinase 3.
sion occurs frequently as the disease progresses and forebodes
a poor prognosis. Other clinical features that have been associated granulomatosis), eosinophilic granulomatosis with polyangiitis
with a poor prognosis include older age at disease onset, persistent (EGPA, formerly Churg-Strauss syndrome), and renal limited
proteinuria (>1 g/day), and persistent azotemia. vasculitis. As shown in Table 68.2, the patterns of ANCAs differ,
depending on the type of vasculitis.
Treatment Renal involvement is common in AAV but varies in type and
The most effective treatment of progressive IgAN remains severity. It occurs more frequently in MPA (90%) and in GPA
34
undefined and controversial. Angiotensin antagonists are recom- (80%) and less frequently in EGPA (45%). Clinically RPGN is
mended to achieve blood pressure control, to reduce proteinuria, a common manifestation of these renal vasculitides characterized
and to slow the rate of deterioration of renal function. There by the presence of hematuria, proteinuria, active urinary sedi-
are conflicting data about the value of fish oil dietary supplements ments, and renal failure.
(eicosanoids) in preventing renal progression in patients with
IgAN. The practice of tonsillectomy in IgAN has not been Pathology
confirmed. A large trial (STOP-IgA nephropathy) showed that The glomerular abnormalities are similar among the subtypes
immunosuppression (glucocorticoid monotherapy or a regimen of ANCA-associated glomerulonephritides (Fig. 68.11). The
that included prednisolone, cyclophosphamide, and azathioprine) glomerular lesions are characteristically focal and segmental in
did not have a significant beneficial effect on preservation of distribution, with fibrinoid necrosis and crescent formation.
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kidney function. However, a course of oral steroids may be Breaks in the GBM may be seen. There may be accompanying
considered in patients with high-grade proteinuria, and cytotoxic necrotizing arteritis. In contrast to immune complex–mediated
drugs are indicated in a small subset of patients with crescentic vasculitis, ANCA-associated vasculitis has little or no Ig deposition
rapidly progressive IgAN. The lack of effective therapy have in injured glomerular vessels, with minimal or negative staining
provided the impetus for several new phase II/III clinical trials by immunofluorescence, a so-called pauci-immune pattern.
testing novel therapies, such as B-cell activating factor (BAFF) Patients with large percentage of cellular crescents (>50%)
inhibition, proteasome inhibition, and B-cell inhibition. 34,35 typically present with severely reduced renal function but have
a good chance for recovery of renal function with treatment,
Renal Vasculitis Associated With Antineutrophil whereas those with a greater percentage of globally sclerotic
Cytoplasmic Antibodies glomeruli are less likely to recover renal function. 36

Treatment and Prognosis
KeY COnCePtS ANCA-associated renal vasculitis tends to be severe and fulminant,
Antineutrophil Cytoplasmic Antibodies (ANCAs)– making early detection critically important in management. Even
Associated Renal Vasculitis with early diagnosis, approximately one-third of patients will
progress to renal failure within 5 years. Relapsing courses are
• Renal vasculitis with glomerular involvement includes microscopic common in patients with microscopic polyangiitis, particularly
polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and necrotiz- GPA. This underscores the importance of prompt induction
ing crescentic glomerulonephritis (renal-limited vasculitis)
• Associated with ANCAs treatment followed by maintenance therapy. Glucocorticoids
• Rapidly progressive glomerulonephritis is common; early treatment are important in the early treatment of renal vasculitis.
includes pulse methylprednisolone, cyclophosphamide, rituximab, or Cyclophosphamide-based regimens are very effective in inducing
possibly plasma exchange remission in patients with AAVs. Most advocate daily oral
• Maintenance therapy: azathioprine, rituximab cyclophosphamide regimens, but intermittent pulse cyclophos-
phamide may be substituted to reduce the toxicity of extended
therapy. In patients with severe pulmonary hemorrhage or rapidly
ANCAs are associated with a distinct form of vasculitis that can progressive glomerulonephritis caused by renal vasculitis, pulse
affect many different types of vessels and any organ in the body. methylprednisolone, followed by prednisone and daily cyclo-
ANCA-associated vasculitis (AAV; Chapter 58) is categorized phosphamide, is clearly indicated. Adjunctive plasma exchange
into four main types: microscopic polyangiitis (MPA), granu- is commonly used in cases of aggressive pulmonary–renal
lomatosis with polyangiitis (GPA, formerly called Wegener syndrome. Rituximab has become a valuable alternative to