Necrotizing and crescentic glomerulonephritis with membranous nephropathy in a patient exposed to levamisole-adulterated cocaine

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Abstract

Levamisole is an antihelminthic agent widely used as an adulterant of illicit cocaine recently implicated as a cause of antineutrophil cytoplasmic antibody (ANCA)–associated microscopic polyangiitis in cocaine abusers. An isolated case of membranous nephropathy (MN) associated with levamisole exposure has also been reported. We report the first case, to our knowledge, of a patient with both microscopic polyangiitis manifest as a pauci-immune necrotizing and crescentic glomerulonephritis and concurrent MN in the setting of chronic cocaine abuse and presumed levamisole exposure, raising the hypothesis that levamisole was the causative agent in the development of this rare dual glomerulopathy.

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Most cited references 23

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Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease.

Tamara Isakova, John Niles, Catherine M McGrath … (2011)

Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. Cases were identified between March 2009 and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation. Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. We describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life-threatening complication of cocaine use.

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Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis.

G. Markowitz, M. Stokes, N Masani … (2009)

Only rare cases of concurrent membranous glomerulonephritis (MGN) and antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis (NCGN) have been reported. The authors report the clinical and pathologic findings in 14 patients with MGN and ANCA-associated NCGN. The cohort consisted of eight men and six women with a mean age of 58.7 yr. ANCA positivity was documented by indirect immunofluorescence or ELISA in all patients. Indirect immunofluorescence was positive in 13 patients (seven P-ANCA, five C-ANCA, one atypical ANCA). ELISA was positive in nine of 10 patients (five MPO-ANCA, three PR3-ANCA, one MPO- and PR3-ANCA). Clinical presentation included heavy proteinuria (mean 24-hr urine protein 6.5 g/d), hematuria, and acute renal failure (mean creatinine 4.4 mg/dl). Pathologic evaluation revealed MGN and NCGN, with crescents involving a mean of 32% of glomeruli. On ultrastructural evaluation, the majority of cases showed stage I or II membranous changes. Follow-up was available for 13 patients, 12 of whom were treated with steroids and cyclophosphamide. At a mean follow-up of 24.3 mo, five patients progressed to ESRD, seven had stabilization or improvement in renal function, and one had worsening renal function. Five patients, including three with ESRD, died during the follow-up period. The only independent predictor of progression to ESRD was serum creatinine at biopsy. MGN with ANCA-associated NCGN is a rare dual glomerulopathy seen in patients with heavy proteinuria, acute renal failure, and active urine sediment. Prognosis is variable, with 50% of patients reaching endpoints of ESRD or death.

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Drug-induced glomerular disease: immune-mediated injury.

Jonathan Hogan, Glen S Markowitz, Jai Radhakrishnan (2015)

Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Kidney J

Journal ID (iso-abbrev): Clin Kidney J

Journal ID (publisher-id): ckj

Journal ID (hwp): ndtplus

Title: Clinical Kidney Journal

Publisher: Oxford University Press

ISSN (Print): 2048-8505

ISSN (Electronic): 2048-8513

Publication date (Print): April 2016

Publication date (Electronic): 28 December 2015

Publication date PMC-release: 28 December 2015

Volume: 9

Issue: 2

Pages: 234-238

Affiliations

[1 ]Department of Medicine, Service of Nephrology, Azienda Ospedaliera Papa Giovanni XXIII , Bergamo, Italy

[2 ]Department of Medicine, Service of Nephrology, Aurora Kidney , Anchorage, AK, USA

[3 ]Department of Pathology, University of Washington Medical Center , Seattle, WA, USA

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Correspondence to: Camillo Carrara; E-mail: ca_mil_lo@ 123456yahoo.it

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Publisher ID: sfv141

DOI: 10.1093/ckj/sfv141

PMC ID: 4792616

PubMed ID: 26985374

SO-VID: 65eb8b48-404a-4eac-84cc-f81ddaa94c6a

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Necrotizing and crescentic glomerulonephritis with membranous nephropathy in a patient exposed to levamisole-adulterated cocaine

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Karger: Nephrology

Most cited references 23

Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease.

Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis.

Drug-induced glomerular disease: immune-mediated injury.

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