Renal disease in small-vessel vasculitis
ABSTRACTGlomerulonephritis (GN) is a common manifestation of the antineutrophil cytoplasmic antibody–associated systemic vasculitides (AASV), which include granulomatosis with polyangiitis and microscopic polyangiitis. The level of renal involvement at presentation is highly predictive of survival and should be assessed early so that kidney function can be preserved. AASV patients with urinary sediment but normal function have a twofold greater risk of death than those with no renal involvement. Those with impaired renal function at diagnosis have a fivefold greater risk of death. Renal vasculitis is most prevalent in older patients, who have more severe disease and poorer prognoses. Renal biopsy not only establishes diagnosis but provides information on severity of renal-function impairment and prognosis. Induction of remission with cyclophosphamide is standard treatment. For patients with crescentic, rapidly progressive GN, adjunctive plasma exchange can promote renal recovery. Renal failure occurs in one-fourth of AASV patients after 3 to 4 years; 60% of patients receiving dialysis for acute GN can recover independent renal function. Renal transplant patients with vasculitis fare as well as renal transplant patients without vasculitis. Lastly, renal vasculitis is an independent risk factor for cardiovascular events.
Necrotizing glomerulonephritis (GN) is the classical renal manifestation of the small-vessel vasculitides, which include granulomatosis with polyangiitis (GPA [Wegener’s granulomatosis]), microscopic polyangiitis (MPA), and eosinophilic GPA (Churg-Strauss syndrome). MPA is pauci-immune (lacks antibody depositions) and causes focal segmental necrotizing GN. Other small-vessel vasculitides are Henoch-SchÖnlein purpura, which features nephritis from immunoglobulin A–dominant immune deposits, and essential cryoglobulinemic vasculitis, in which cryoglobulin immune deposits lead to membranoproliferative GN.1
Renal involvement occurs in 25% to 75% of patients with antineutrophil cytoplasmic antibody (ANCA)–associated systemic vasculitis (AASV), with the higher percentage reflecting patients who first present to a nephrologist rather than a rheumatologist. Roughly 35% are dialysis-dependent, mainly those who are elderly or proteinase-3– or myeloperoxidase-ANCA–positive. In duc tion of remission through immunosuppression allows 50% to 60% of dialysis-dependent patients to recover independent renal function.2,3
PROGNOSTIC SIGNIFICANCE OF RENAL INVOLVEMENT
Patients should be assessed at the earliest opportunity for renal involvement as it is highly predictive of survival. Diagnosis allows immunosuppressive treatment to be started early, when kidney function may still be preserved.
Reinhold-Keller et al3 examined survival by level of renal involvement at diagnosis in 155 patients with GPA who were followed for a median of 7 years. Survival in those with normal renal function, but with nephritic urinary sediment at diagnosis, declined over time compared with patients who had no renal involvement at diagnosis, with a more than twofold greater risk of death (hazard ratio [HR], 2.41; 95% confidence interval [CI] 0.53–11.06). Patients who had impaired renal function at diagnosis had a fivefold greater risk of death (HR, 5.42; 95% CI 1.76–16.68).
Maximum serum creatinine in the first month of treatment is also highly predictive of survival. An outcome analysis followed 80 patients with AASV and renal involvement for a median of 46.7 months.4 Patients were divided equally into groups by maximum serum creatinine levels after the first month of treatment: less than 299 μmol/L, 299 to 582 μmol/L, and greater than 582 μmol/L. All patients were treated for induction of remission with cyclophosphamide and oral corticosteroids. Survival was significantly worse in patients who had the highest maximum serum creatinine in the first month (P = .025).
Pooled prospective data from four European Vasculitis Study Group (EUVAS) trials of 535 patients with AASV and follow-up of 5.2 years found a mortality ratio of 2.6 (95% CI, 2.2–3.1) compared with matched subjects from the general population.5 Stage 5 chronic kidney disease (glomerular filtration rate < 15 mL/min) was a significant negative prognostic determinant of survival in these trials.
A DISEASE OF AGING
Renal vasculitis is most prevalent in people aged 50 years and older and often occurs in those aged 70 years and older.6 Because the very old may not have extrarenal symptoms, it is necessary to maintain a high index of suspicion for AASV and measure urinary sediment and renal function in this age group.
Older patients also present with more severe renal disease and have a poorer prognosis. Harper and Savage compared presentation and outcomes of patients aged 65 years and older with renal AASV with those of patients younger than 65 years.7 Older patients had more severe renal failure than did younger patients (serum creatinine 657 vs 470 μmol/L, respectively; P < .001), and this did not appear to be associated with delayed diagnosis. Survival was worse in those with serum creatinine levels greater than 400 μmol/L irrespective of age; however, when comparing younger and older groups with similar renal insufficiency, older patients were more likely to progress to end-stage renal failure (P = .039), survival was worse (P = .016), and death occurred earlier.7
HISTOPATHOLOGIC CLASSIFICATION
An international working group of renal pathologists8 developed pathologic classifications for rapidly progressive GN caused by AASV: focal (≥ 50% normal glomeruli), crescentic (≥ 50% glomeruli with cellular crescents), mixed (no predominant glomerular feature), and sclerotic (≥ 50% globally sclerotic glomeruli). These correspond to the order of severity of renal-function impairment. A study of 100 biopsies from patients with ANCA-associated GN found that the classifications at presentation closely correlated with outcomes.8
Patients with sclerotic GN had the worst renal function initially, with little improvement at 5 years; hence, immunosuppression is of little value if the kidney is more than 50% sclerotic. Patients with focal disease who had good renal function initially were found to retain good function after 5 years of treatment. Patients in the crescentic class present with rapidly progressive GN and very poor renal function. However, they were found to improve considerably after 5 years and had good recovery (P = .001). Presenting disease manifestations within the kidney are of diagnostic as well as prognostic value.
