Clinical and Pathological Features of Renal Involvement in Propylthiouracil-Associated ANCA-Positive Vasculitis

doi:10.1053/j.ajkd.2007.01.021

American Journal of Kidney Diseases

Volume 49, Issue 5, May 2007, Pages 607-614

https://doi.org/10.1053/j.ajkd.2007.01.021 Get rights and content

Background

The kidney is one of the organs affected in patients with propylthiouracil (PTU)-associated antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. We present a series of Chinese patients with renal involvement in PTU-associated ANCA-positive vasculitis and describe their clinical and pathological characteristics.

Methods

Clinical and pathological data from patients with PTU-associated ANCA-positive vasculitis with renal involvement, diagnosed in Peking University First Hospital, were collected and analyzed retrospectively.

Results

Nineteen patients with PTU-associated ANCA-positive vasculitis were treated at Peking University First Hospital between December 1999 and December 2005, and 15 of them had renal involvement. Of the 15 patients, 13 were female and 2 were male, with an average age of 26.3 ± 11.8 years. All 15 patients were perinuclear ANCA positive with specificities to myeloperoxidase (15 of 15), cathepsin G (9 of 15), human leukocyte elastase (8 of 15), lactoferrin (7 of 15), azurocidin (5 of 15), and proteinase 3 (4 of 15). Duration of PTU administration was 43.0 ± 31.2 months. All 15 patients had clinical markers of renal involvement, including hematuria (100%), proteinuria (100%), and renal function abnormality (47%). All 15 patients underwent percutaneous renal biopsy. Ten patients had necrotizing crescentic glomerulonephritis, and 7 of these 10 patients had immune complex deposition. Three patients had minimal involvement, 2 patients had immunoglobulin A nephropathy, and 2 patients had membranous nephropathy. PTU treatment was discontinued in all 15 patients. All except 2 patients with minimal renal involvement received immunosuppressive treatment. Eleven of 15 patients achieved complete clinical remission.

Conclusion

Renal involvement in our case series of patients with PTU-associated ANCA-positive vasculitis was heterogeneous, and nearly half our patients had renal immune complex deposition.

Section snippets

Patient Selection

Clinical and laboratory data and kidney biopsy results of patients with PTU-associated ANCA-positive vasculitis with renal involvement who were diagnosed in Peking University First Hospital from December 1999 to December 2005 were reviewed retrospectively. PTU-associated ANCA-positive vasculitis was defined by the following characteristics: (1) signs and symptoms of vasculitis were related closely to PTU administration and regressed with its discontinuation, (2) positive serum ANCA result

Demographic Features of Patients With PTU-Associated ANCA-Positive Vasculitis

There were 19 patients with PTU-associated ANCA-positive vasculitis and 15 patients (80%) with renal involvement (Table 1). They were administered PTU for Graves disease. Duration of PTU administration was 43.0 ± 31.2 months (1.5 to 96 months). Of 15 patients with renal involvement, 13 were female and 2 were male, with an average age of 26.3 ± 11.8 years (11 to 57 years). Sera from all 15 patients were perinuclear ANCA positive, but cytoplasmic ANCA was not detected in any patient. Sera from

Discussion

ANCA can be shown at some time in about 6% to 63% of patients treated with PTU, but at most, full-blown vasculitis will be diagnosed in 20% of individuals administered PTU and with PTU-associated ANCA.18, 19, 20, 21 Clinical and pathological characteristics of renal involvement and renal outcome in patients with PTU-associated ANCA-positive vasculitis are not well described.

Renal involvement in patients with PTU-associated ANCA-positive vasculitis as reported in the literature ranged from 58%

References (35)

K.M. Dolman et al.
Vasculitis and anti-neutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy
Lancet
(1993)
M.H. Zhao et al.
Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis
Kidney Int
(2006)
P.A. Merkel
Drug-induced vasculitis
Rheum Dis Clin North Am
(2001)
H.A. Hauer et al.
Renal histology in ANCA-associated vasculitis: Differences between diagnostic and serologic subgroups
Kidney Int
(2002)
H.A. Hauer et al.
Determinants of outcome in ANCA-associated glomerulonephritis: A prospective clinico-histopathological analysis of 96 patients
Kidney Int
(2002)
M. Chen et al.
Characteristics of Chinese patients with Wegener’s granulomatosis with anti-myeloperoxidase autoantibodies
Kidney Int
(2005)
J. Savige et al.
Antineutrophil cytoplasmic antibodies and associated diseases: A review of the clinical and laboratory features
Kidney Int
(2000)
C.O. Savage
ANCA-associated renal vasculitis
Kidney Int
(2001)
M. Tanemoto et al.
Myeloperoxidase-antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis complicating the course of Graves’ disease: Report of three adult cases
Am J Kidney Dis
(1995)
Y. Gao et al.
Anti-myeloperoxidase IgG subclass distribution and avidity in sera from patients with propylthiouracil-induced antineutrophil cytoplasmic antibodies associated vasculitis
Clin Immunol
(2005)

J.C. Jennette et al.

Nomenclature of systemic vasculities: Proposal of an international consensus conference

Arthritis Rheum

(1994)

R.A. Sinico et al.

Prevalence and clinical significance of anti-neutrophil cytoplasmic antibodies in Churg-Strauss syndrome

Arthritis Rheum

(2005)

H.K. Choi et al.

Drug-associated anti-neutrophil cytoplasmic antibody-positive vasculitis: Prevalence among patients with high titers of anti-myeloperoxidase antibodies

Arthritis Rheum

(2000)

F. Mikiya et al.

Clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment

J Am Soc Nephrol

(2002)

A.S. Levey et al.

A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation

Ann Intern Med

(1999)

R.A. Luqmani et al.

Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis

QJM

(1994)

G.G. Hunder et al.

The American College of Rheumatology 1990 criteria for the classification of vasculitis

Arthritis Rheum

(1990)

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: Originally published online as doi:10.1053/j.ajkd.2007.01.021 on March 1, 2007.

: Support: National Natural Science Fund (No. 30500459) and a grant from the Chinese 985 Project (985-2-033-39). Potential conflicts of interest: None.

View full text

Original InvestigationPathogenesis and Treatment of Kidney DiseaseClinical and Pathological Features of Renal Involvement in Propylthiouracil-Associated ANCA-Positive Vasculitis

Background

Methods

Results

Conclusion

Section snippets

Patient Selection

Demographic Features of Patients With PTU-Associated ANCA-Positive Vasculitis

Discussion

Lancet

Kidney Int

Rheum Dis Clin North Am

Kidney Int

Kidney Int

Kidney Int

Kidney Int

Kidney Int

Am J Kidney Dis

Clin Immunol

Nomenclature of systemic vasculities: Proposal of an international consensus conference

Arthritis Rheum

Prevalence and clinical significance of anti-neutrophil cytoplasmic antibodies in Churg-Strauss syndrome

Arthritis Rheum

Drug-associated anti-neutrophil cytoplasmic antibody-positive vasculitis: Prevalence among patients with high titers of anti-myeloperoxidase antibodies

Arthritis Rheum

Clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment

J Am Soc Nephrol

A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation

Ann Intern Med

Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis

QJM

The American College of Rheumatology 1990 criteria for the classification of vasculitis

Arthritis Rheum

Original Investigation
Pathogenesis and Treatment of Kidney Disease
Clinical and Pathological Features of Renal Involvement in Propylthiouracil-Associated ANCA-Positive Vasculitis