Pauci-immune glomerulonephritis (ORPHA:93126)
A rare small vessel vasculitis associated with rapidly progressive glomerulonephritis (GN) and clinically characterized by renal manifestations such as urinary abnormalities (hematuria and/or proteinuria) and hypertension leading to renal failure within days or weeks, and distinguished by the absence of immune deposits on immunofluorescent microscopy. The disease can occur as a renal-limited disease or as a component of systemic necrotizing small-vessel vasculitis.
Epidemiology
Pauci-immune GN is the most common cause of rapidly progressive glomerulonephritis. The incidence of pauci-immune GN in the United States is estimated at 3.1/1,000,000, with significantly higher rates for Caucasians, males and individuals over 65. In the European population, the incidence is estimated between 1-2/100,000, with an increasing trend in recent years.
Clinical description
Patients with pauci-immune GN may present with different clinical pictures, and predominantly occurs in patients over 55 years of age, although rarely it may occur earlier. Most patients report a prodromal 'flu-like' illness preceding the overt vasculitic syndrome. Pauci-immune GN can occur as a renal-limited disease or as a component of systemic vasculitis. Systemic symptoms including fever, asthenia, arthralgias, weight loss, and myalgias can precede the renal presentation of the disease. Clinically, it is characterized by renal manifestations such as urinary abonormalities (hematuria and/or proteinuria) and hypertension leading to renal failure within days or weeks. It can also be associated with extrarenal manifestations depending on the disease process and may involve the upper and lower respiratory tract, nerves, skin, and musculoskeletal system. Risk factors for progression to end stage renal disease (ESRD) include increased initial serum creatinine or decreased estimated glomerular filtration rate (eGFR) at baseline, older age, presence of pulmonary hemorrhage, and dialysis-dependent acute kidney injury.
Diagnostic methods
The disease is associated with the presence of serum anti-neutrophil cytoplasmic antibodies (ANCAs) in a high percentage of subjects. Renal biopsy is essential for the diagnosis and subsequent management of pauci-immune GN, and is used to to determine the activity and chronicity of the renal lesions as well as the risk associated with immunotherapy of ANCA pauci-immune necrotizing glomerulonephritis. The histological hallmarks of the disease are the presence of extracapillary proliferation and segmental necrosis on light microscopy, and the absence of immune deposits on immunofluorescence microscopy. Immunologic classification is based on the presence or absence of circulating ANCAs, namely pauci-immune-GN with ANCAs and pauci-immune GN without ANCAs. Other laboratory data such as erythrocyte sedimentation rate, C-reactive protein (CRP) and urine test are not specific but can help with the diagnosis.
Differential diagnosis
Differential diagnosis includes other forms of crescentic GN.
Management and treatment
Conventional induction therapies for pauci-immune GN have been defined and include Cyclophosphamide (CYC) for at least 3 months, with a corticosteroid taper followed by maintenance immunosuppression for up to 2 years with azathioprine or mycophenolate mofetil. Clinical trials have shown that rituximab (RTX) is an effective induction therapy for pauci-immune ANCA-associated GN. Since preventing relapses and maintaining remission are critical to slowing chronic kidney disease (CKD) progression to ESRD in this group of patients, a number of trials have focused on repeat doses of RTX at 4/6 month intervals. As with other forms of CKD, patients with stable but decreased eGFR usually benefit from blood pressure control with long-term inhibition of RAAS axis to reduce glomerular hyperfiltration, a low-sodium diet, and moderate protein intake.
Prognosis
Despite the substantial progress in treatment, pauci-immune glomerulonephritis remain a group of diseases with significant morbidity and mortality related to the disease itself. Renal involvement is one of the most threatening aspects

                            Last update: 
                            June 2020


                            - Expert reviewer(s): 
                            Dr Roberta FENOGLIO | ERKNet* - Pr Dario ROCCATELLO | ERKNet*


                                * European Reference Network