Renal Vasculitis: Definition, Diagnosis, and Management
Renal vasculitis is a group of diseases characterized by necrotizing inflammation of small blood vessels in the kidneys, typically presenting as rapidly progressive glomerulonephritis with hematuria, proteinuria, and declining kidney function. 1
Definition and Classification
Renal vasculitis is primarily a manifestation of small-vessel vasculitis affecting the kidney's arterioles, capillaries, and venules. The main types include:
Pauci-immune small-vessel vasculitides, which are typically associated with antineutrophil cytoplasmic antibodies (ANCA) and include:
- Granulomatosis with polyangiitis (GPA, formerly Wegener's)
- Microscopic polyangiitis (MPA)
- Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss) 1
The kidney lesion is characterized by pauci-immune focal and segmental necrotizing and crescentic glomerulonephritis (NCGN) 1
Pathophysiology and Clinical Features
About 90% of patients with small-vessel vasculitis affecting the kidneys have ANCA, directed primarily against myeloperoxidase (MPO) or proteinase 3 (PR3) neutrophil proteins 1
Clinical manifestations include:
- Microscopic hematuria with dysmorphic red blood cells and red cell casts
- Moderate proteinuria (1-3 g/day)
- Rapidly declining glomerular filtration rate (GFR) over days to weeks 1
Renal vasculitis may occur with or without extrarenal manifestations affecting:
- Upper and lower respiratory tract
- Skin
- Eyes
- Nervous system 1
Pulmonary-renal syndrome (simultaneous kidney injury and alveolar hemorrhage) occurs in approximately 10% of patients with ANCA-associated vasculitis and is associated with increased mortality 1
Diagnosis
Diagnosis relies on a combination of:
- Clinical findings
- Laboratory tests (C-reactive protein, complete blood count, kidney parameters, urine sediment)
- ANCA serology (MPO-ANCA or PR3-ANCA)
- Kidney biopsy 1
High-quality antigen-specific immunoassays are the preferred screening method for MPO- and PR3-ANCA 1
Kidney biopsy remains the gold standard for diagnosis with a diagnostic yield as high as 91.5% in GPA 1
In patients with rapidly deteriorating kidney function and positive ANCA serology, treatment should not be delayed while waiting for biopsy results 1
Treatment
Induction Therapy
Standard induction therapy consists of high-dose glucocorticoids combined with either:
Plasma exchange should be considered in patients with:
Pulse cyclophosphamide has equivalent remission rates to continuous cyclophosphamide but carries an increased risk of relapse 2, 3
Maintenance Therapy
After achieving remission, maintenance therapy should be continued for at least 24 months 4
Effective maintenance agents include:
For azathioprine maintenance: start at 1.5-2 mg/kg/day for 18-24 months, then decrease to 1 mg/kg/day until 4 years after diagnosis, then taper by 25 mg every 3 months 1
Glucocorticoids should be continued at 5-7.5 mg/day for 2 years and then slowly reduced by 1 mg every 2 months 1
Management of Relapse and Refractory Disease
Patients with relapsing disease should be reinduced, preferably with rituximab 1
Refractory disease can be treated by:
- Increasing glucocorticoids (intravenous or oral)
- Adding rituximab if cyclophosphamide was used initially, or vice versa
- Considering plasma exchange 1
Prognosis
Patient survival and risk of end-stage renal disease are closely associated with renal function at presentation 4
Prognostic factors include:
MPA (and/or P-ANCA positive patients) typically have higher chronic damage than GPA (and/or C-ANCA positive patients) 5
Without treatment, necrotizing and crescentic glomerulonephritis has an unfavorable course leading to end-stage renal disease within weeks to months 5