Anti-neutrophil cytoplasmic antibody associated glomerulonephritis complicating treatment with hydralazine

Abstract

Hydralazine, a widely used therapy for hypertension and heart failure, can elicit autoimmune disease, including anti-neutrophil cytoplasmic antibody associated glomerulonephritis (ANCA-GN). We identified 80 cases of ANCA-GN complicating treatment with hydralazine, accounting for 4.3% (80/1858 biopsies) of ANCA-GN diagnosed between 2006 and 2019. Over three-fourths of patients were on hydralazine for at least one year, with mean daily dose of approximately 250 mg/day. ANCA testing revealed p-ANCA/myeloperoxidase-ANCA seropositivity in 98%, including 39% with dual p-ANCA/myeloperoxidase-ANCA and cANCA/anti-protinase 3-ANCA positivity, often accompanied by anti-nuclear antibody (89%), anti-histone antibody (98%), and hypocomplementemia (58%). Kidney biopsy revealed necrotizing and crescentic glomerulonephritis, similar to primary ANCA-GN, but significantly less frequently pauci-immune (77 vs. 100%) and more commonly associated with mesangial hypercellularity (30 vs. 5%), electron dense deposits (62 vs. 20%), and endothelial tubuloreticular inclusions (11 vs. 0%); all significant differences. On follow-up, 42 of 51 patients received induction immunosuppression: 19 reached the combined end-points of kidney failure or death and 32 had mean creatinine of 1.49 mg/dL at last follow-up. Thus, hydralazine-associated ANCA-GN often exhibits overlapping clinical and pathologic features of mild immune complex glomerulonephritis resembling lupus nephritis. With discontinuation of hydralazine and immunosuppression, outcomes are similar to primary ANCA-GN. Hydralazine, a widely used therapy for hypertension and heart failure, can elicit autoimmune disease, including anti-neutrophil cytoplasmic antibody associated glomerulonephritis (ANCA-GN). We identified 80 cases of ANCA-GN complicating treatment with hydralazine, accounting for 4.3% (80/1858 biopsies) of ANCA-GN diagnosed between 2006 and 2019. Over three-fourths of patients were on hydralazine for at least one year, with mean daily dose of approximately 250 mg/day. ANCA testing revealed p-ANCA/myeloperoxidase-ANCA seropositivity in 98%, including 39% with dual p-ANCA/myeloperoxidase-ANCA and cANCA/anti-protinase 3-ANCA positivity, often accompanied by anti-nuclear antibody (89%), anti-histone antibody (98%), and hypocomplementemia (58%). Kidney biopsy revealed necrotizing and crescentic glomerulonephritis, similar to primary ANCA-GN, but significantly less frequently pauci-immune (77 vs. 100%) and more commonly associated with mesangial hypercellularity (30 vs. 5%), electron dense deposits (62 vs. 20%), and endothelial tubuloreticular inclusions (11 vs. 0%); all significant differences. On follow-up, 42 of 51 patients received induction immunosuppression: 19 reached the combined end-points of kidney failure or death and 32 had mean creatinine of 1.49 mg/dL at last follow-up. Thus, hydralazine-associated ANCA-GN often exhibits overlapping clinical and pathologic features of mild immune complex glomerulonephritis resembling lupus nephritis. With discontinuation of hydralazine and immunosuppression, outcomes are similar to primary ANCA-GN. Treatment with or exposure to certain drugs can elicit the generation of autoantibodies and clinical autoimmune disease affecting the kidneys, including immune complex–mediated or pauci-immune glomerulonephritis (GN) and membranous glomerulopathy.1Hogan J.J. Markowitz G.S. Radhakrishnan J. Drug-induced glomerular disease: immune-mediated injury.Clin J Am Soc Nephrol. 2015; 10: 1300-1310Crossref PubMed Scopus (46) Google Scholar Clinical awareness of drug-induced autoimmune disease is important given the need to discontinue the offending agent in the management of these conditions. Drugs associated with anti–neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) include propylthiouracil, cocaine adulterated with levamisole, tumor necrosis factor-α inhibitors, and hydralazine.1Hogan J.J. Markowitz G.S. Radhakrishnan J. Drug-induced glomerular disease: immune-mediated injury.Clin J Am Soc Nephrol. 2015; 10: 1300-1310Crossref PubMed Scopus (46) Google Scholar, 2Stokes M.B. Foster K. Markowitz G.S. et al.Development of glomerulonephritis during anti-TNF-alpha therapy for rheumatoid arthritis.Nephrol Dial Transplant. 2005; 20: 1400-1406Crossref PubMed Scopus (187) Google Scholar, 3Pendergraft W.F. Niles J.L. Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis.Curr Opin Rheumatol. 2014; 26: 42-49Crossref PubMed Scopus (88) Google ScholarEditor’s NoteThis study is perhaps the largest and most detailed investigation of the clinical and kidney histopathologic features of anti–neutrophil cytoplasmic antibody–associated vasculitis (AAV) occurring in the setting of hydralazine use. Hydralazine has also been associated with lupus-like syndromes, and several of the patients described here seemed to have features of both AAV and lupus. Hydralazine affects DNA methylation and B-cell tolerance, and fosters NETosis, all of which could contribute to induction of autoimmunity in susceptible patients. Given the array of effective, and possibly less toxic, anti-hypertensive medications available today, the Editorial Board wondered whether hydralazine was used very much anymore. An informal poll among nephrology colleagues showed considerable variation in use worldwide. In Canada, the Unites States, and Australia, it is used frequently, and often by cardiologists when renin-angiotensin system blockers are contraindicated. It is rarely used in Mexico, Argentina, mainland China, Hong Kong, Singapore, and Japan. In India, hydralazine is used mainly by cardiologists for congestive heart failure in patients with chronic kidney disease. It is not used in France, the Czech Republic, or Germany, and only rarely in the Netherlands, United Kingdom, and Russia. We suspect that cases of hydralazine-associated AAV will continue to be found, maybe more so in patients with cardiovascular disease, and it will be important for nephrologists to keep this in mind as we consult for our cardiology colleagues. This study is perhaps the largest and most detailed investigation of the clinical and kidney histopathologic features of anti–neutrophil cytoplasmic antibody–associated vasculitis (AAV) occurring in the setting of hydralazine use. Hydralazine has also been associated with lupus-like syndromes, and several of the patients described here seemed to have features of both AAV and lupus. Hydralazine affects DNA methylation and B-cell tolerance, and fosters NETosis, all of which could contribute to induction of autoimmunity in susceptible patients. Given the array of effective, and possibly less toxic, anti-hypertensive medications available today, the Editorial Board wondered whether hydralazine was used very much anymore. An informal poll among nephrology colleagues showed considerable variation in use worldwide. In Canada, the Unites States, and Australia, it is used frequently, and often by cardiologists when renin-angiotensin system blockers are contraindicated. It is rarely used in Mexico, Argentina, mainland China, Hong Kong, Singapore, and Japan. In India, hydralazine is used mainly by cardiologists for congestive heart failure in patients with chronic kidney disease. It is not used in France, the Czech Republic, or Germany, and only rarely in the Netherlands, United Kingdom, and Russia. We suspect that cases of hydralazine-associated AAV will continue to be found, maybe more so in patients with cardiovascular disease, and it will be important for nephrologists to keep this in mind as we consult for our cardiology colleagues. Hydralazine, an arterial vasodilator, is widely used as an anti-hypertensive agent and in the management of heart failure. Drug-induced autoimmunity, including drug-induced AAV and drug-induced lupus, is a long-recognized potential complication of hydralazine use. Drug-induced lupus occurs in 5% to 10% of patients receiving hydralazine, and is characterized by the development of anti-nuclear autoantibodies (ANAs) and anti-histone antibodies and symptoms that include myalgias, fever, and serositis.4Hess E. Drug-related lupus.N Engl J Med. 1988; 318: 1460-1462Crossref PubMed Scopus (171) Google Scholar Renal involvement is uncommon.5Yokogawa N. Vivino F.B. Hydralazine-induced autoimmune disease: comparison to idiopathic lupus and ANCA-positive vasculitis.Mod Rheumatol. 2009; 19: 338-347Crossref PubMed Google Scholar AAV appears to be a rare complication, with <100 cases reported to date.6Kumar B. Strouse J. Swee M. et al.Hydralazine-associated vasculitis: overlapping features of drug-induced lupus and vasculitis.Semin Arthritis Rheum. 2018; 48: 283-287Crossref PubMed Scopus (16) Google Scholar However, the true incidence of AAV is unknown. In one series, 10 of 30 patients with AAV and the highest titers of anti-myeloperoxidase (MPO) antibodies had been exposed to hydralazine.7Choi H.K. Merkel P.A. Walker A.M. Niles J.L. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.Arthritis Rheum. 2000; 43: 405-413Crossref PubMed Scopus (282) Google Scholar Hydralazine-induced lupus and AAV may show considerable overlap.6Kumar B. Strouse J. Swee M. et al.Hydralazine-associated vasculitis: overlapping features of drug-induced lupus and vasculitis.Semin Arthritis Rheum. 2018; 48: 283-287Crossref PubMed Scopus (16) Google Scholar The clinical course of hydralazine-associated AAV is dominated by rapidly progressive GN. Extrarenal disease, including pulmonary involvement, is rare. In addition to high-titer MPO-ANCA, serologic evaluation typically reveals positive ANA and anti-histone autoantibodies and hypocomplementemia.7Choi H.K. Merkel P.A. Walker A.M. Niles J.L. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.Arthritis Rheum. 2000; 43: 405-413Crossref PubMed Scopus (282) Google Scholar Descriptions of biopsy-proven hydralazine-associated ANCA-GN are largely limited to case reports and small case series, most of which reveal pauci-immune necrotizing and crescentic GN.5Yokogawa N. Vivino F.B. Hydralazine-induced autoimmune disease: comparison to idiopathic lupus and ANCA-positive vasculitis.Mod Rheumatol. 2009; 19: 338-347Crossref PubMed Google Scholar However, systematic and detailed descriptions of histologic, immunofluorescence (IF), and ultrastructural findings, as well as comparisons to primary ANCA-GN and reports on long-term follow-up, are lacking. Herein, we report 80 patients diagnosed with ANCA-GN while on hydralazine, the largest kidney biopsy series to date, providing detailed descriptions of clinical-pathologic findings and long-term follow-up. We also compare key clinical and pathologic features with a control group of primary ANCA-GN. All native kidney biopsies with a diagnosis of ANCA-associated GN accessioned at the Columbia University Renal Pathology Laboratory from 2006 to 2019 were reviewed for a history of treatment with hydralazine preceding renal biopsy. Inclusion criteria included: (i) predominant light microscopic findings of necrotizing and crescentic GN; (ii) ANCA seropositivity; and (iii) a history of treatment with hydralazine. Exclusion criteria included a known history of AAV, systemic lupus erythematosus, or other autoimmune/connective tissue disease before treatment with hydralazine, commencement of treatment with hydralazine only at the time of initial presentation with acute kidney injury, and known exposure to other drugs associated with AAV (including propylthiouracil, cocaine, or anti–tumor necrosis factor-α therapy). Seventy-five consecutive biopsies from 2016 showing primary ANCA-GN, in the absence of a documented history of treatment with hydralazine, were utilized as a comparison group of select initial clinical and demographic features as well as pathologic findings. Biopsies from patients with documented exposure to hydralazine, propylthiouracil, cocaine, or anti–tumor necrosis factor-α therapy were excluded from the comparison group, as were biopsies with overlapping serologic or IF evidence of anti–glomerular basement membrane nephritis. All kidney biopsies were processed according to standard techniques for light microscopy, IF, and electron microscopy and were interpreted by 1 of 6 renal pathologists. For IF, 3-μm frozen sections were stained with fluorescein isothiocyanate–conjugated rabbit anti-human IgG, IgM, IgA, C3, C1q, and κ and λ light chain (Dako). The submitting nephrologists provided the following information: patient demographics, medical history, systemic findings of extrarenal AAV, duration of hydralazine use, daily dose of hydralazine at time of kidney biopsy, requirement for renal replacement therapy at presentation, serum creatinine at presentation, urine protein-to-creatinine ratio or 24-hour urine protein level, presence of hematuria (>5 cells/high-power field), anti-nuclear antibody, anti-histone antibodies, double-stranded DNA antibodies, serum complements, anti-neutrophil cytoplasmic antibodies, lupus anticoagulant, and anti-cardiolipin antibodies. In addition, follow-up information regarding serum creatinine, repeated serologic testing, and type of treatment was obtained. The following pathologic parameters were collected: (i) predominant light microscopic pattern of glomerular injury; (ii) number of total and globally sclerotic glomeruli; (iii) percentage of glomeruli with cellular or fibrocellular crescents; (iv) percentage glomeruli with fibrous crescents; (v) percentage of cortex with interstitial fibrosis and tubular atrophy; (vi) degree of interstitial inflammation (scale, 0–3; none indicates 0; mild (0%–25%), 1; moderate (26%–50%). 2; or severe (>50%), 3); (vii) degree of vascular sclerosis (scale, 0–3); (viii) presence of coexisting disease process; (ix) intensity of IF staining (scale, 0–3+); (x) presence and location of electron-dense deposits; and (xi) presence or absence of endothelial tubuloreticular inclusions. Histopathologic classifications were assigned according to the scheme described by Berden et al.8Berden A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google Scholar was as staining of intensity for all immune on an intensity from to for patients were with mean for and percentage for We initial clinical and biopsy parameters between patients with hydralazine-associated ANCA GN and a comparison group with primary ANCA-associated GN a for and the for were This study was by the Board of Columbia University We identified 80 patients kidney biopsy-proven ANCA-GN, all of were hydralazine before presentation, accounting for 4.3% (80/1858 biopsies) of all ANCA-GN diagnosed between 2006 and 2019 in our Clinical at the time of biopsy are provided in The mean was and of patients were The as and of hydralazine use before kidney biopsy was available for patients in the of time was in to in and in of hydralazine at the time of kidney biopsy were available from 30 with mean at biopsy of 80 patients with hydralazine-associated and clinical and creatinine, or ANA or or ANCA of hydralazine anti-nuclear anti–neutrophil cytoplasmic double-stranded are given as mean or in a anti-nuclear anti–neutrophil cytoplasmic double-stranded are given as mean or serum creatinine at the time of biopsy was patients were at was or by 24-hour or urine protein-to-creatinine ANA and double-stranded DNA antibody were in of and of of antibody was in all patients of was in of of including with and with and with and anti-cardiolipin antibodies were in of 10 and of All patients were ANCA patients were positive for antibody were dual ANCA and were positive for antibody All patients had testing for anti–glomerular basement membrane the time of kidney biopsy, patients had documented clinical evidence of pulmonary involvement (including with had and had clinical evidence of involvement by In all 80 biopsies A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google the light microscopic pattern of was necrotizing and crescentic GN with mean percentage sclerosis of mean percentage of glomeruli with of and mean percentage of glomeruli with fibrous of The mean percentage of of was to the classification by Berden et A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google Scholar were sclerotic were were crescentic and were A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google The mean percentage of glomeruli with necrosis was glomeruli with cellular or fibrocellular hypercellularity was documented in biopsies and membranous features were rare. The degree of interstitial fibrosis and tubular was mild in biopsies moderate in biopsies and severe in biopsies The mean degree of interstitial fibrosis and tubular was mean interstitial inflammation was and mean was was in only biopsies of necrotizing and crescentic GN were on of in biopsies of 80 with hydralazine-associated microscopy with cellular or fibrocellular with fibrous inflammation positive positive positive positive positive microscopy With immune ANCA A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google anti–neutrophil cytoplasmic interstitial fibrosis and tubular atrophy; tubuloreticular are given as mean or in a anti–neutrophil cytoplasmic interstitial fibrosis and tubular atrophy; tubuloreticular are given as mean or IF, biopsies were as of which showed to intensity mesangial staining for at least one immune including of of of of or of The biopsies showed intensity staining (scale, for at least one immune including of mean of mean of mean of mean or of mean were or of the 80 biopsies showed staining or glomerular basement membrane staining for of anti–glomerular basement membrane nephritis. biopsies staining for and the vascular none of which were as microscopy was in of which had electron-dense deposits were most of and from to of and of deposits were less and were the pauci-immune electron microscopy was in and showed immune deposits in tubuloreticular inclusions were in biopsies We clinical and pathologic features of hydralazine-associated ANCA-GN with consecutive biopsies from a diagnosed as primary ANCA-GN. were significant in and with primary ANCA-GN, patients with hydralazine-associated ANCA-GN had a significantly of ANA vs. and hypocomplementemia vs. were more to be dual ANCA positive vs. and were less to be positive for only antibody vs. with primary ANCA-GN, hydralazine-associated ANCA-GN was more often and less often sclerotic according to the Berden et classification A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google Scholar hypercellularity was more in patients on hydralazine vs. and membranous features were but also more this not vs. and vs. Biopsies from patients on hydralazine were less frequently pauci-immune by IF vs. and were more to have electron-dense deposits on electron microscopy vs. were also more in patients hydralazine vs. the patients with hydralazine-associated ANCA-GN, we the biopsy findings between patients with pauci-immune IF with with IF IF biopsies had similar of ANA vs. dual ANCA vs. and hypocomplementemia vs. with biopsies that criteria for However, the cases of mesangial hypercellularity vs. the pauci-immune GN GN creatinine, or or ANCA with cellular or fibrocellular with fibrous inflammation by by A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google anti-nuclear anti–neutrophil cytoplasmic electron IF, interstitial fibrosis and tubular atrophy; tubuloreticular are given as mean or in a anti-nuclear anti–neutrophil cytoplasmic electron IF, interstitial fibrosis and tubular atrophy; tubuloreticular are given as mean or was available from 51 patients with duration of Hydralazine was in all patients. received induction including in in in in and in among the 42 patients received immunosuppression, received received received both and received of the patients received including in 6 and in the of follow-up, patients to kidney disease and including 6 reached before Thus, 19 of 51 patients reached the combined of death or the 32 the mean serum creatinine at of follow-up was 1.49 On repeated testing, which discontinuation of treatment with hydralazine, of patients with available had positive ANA and of patients had of 30 patients ANCA positive at time of last follow-up, with of follow-up of including with antibody and with dual ANCA patients not receiving induction immunosuppression, reached the combined of death or The patients had a creatinine of all of which had biopsies as Berden course in 51 of 80 with available follow-up or of follow-up, at creatinine and not 6 patients reached before or kidney 6 patients reached before in a kidney We report the largest series of hydralazine-associated ANCA-GN, including clinical presentation, kidney biopsy findings, and clinical follow-up. cases for 4.3% of all ANCA-GN diagnosed in our the study with hydralazine-associated ANCA-GN had a mean of were most often and with rapidly progressive GN. Extrarenal involvement was with evidence of pulmonary involvement in of patients. the of ANCA-GN, patients with hydralazine-associated ANCA-GN were frequently ANA positive and ANCA testing revealed seropositivity in 98%, including 39% with dual and was rare antibody positivity, typically associated with drug-induced lupus, was et described a similar serologic in hydralazine-associated AAV, including ANA positive and with hypocomplementemia.7Choi H.K. Merkel P.A. Walker A.M. Niles J.L. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.Arthritis Rheum. 2000; 43: 405-413Crossref PubMed Scopus (282) Google Scholar Thus, in the setting of ANCA-GN, dual ANCA positivity, or ANA or anti-histone antibody for a drug-induced with medications for potential exposure to hydralazine. The of anti-histone antibodies in hydralazine-associated ANCA-GN with lupus. In all the light microscopic findings were necrotizing and crescentic GN. with the of ANCA-GN, these biopsies were less frequently pauci-immune vs. and had more mesangial hypercellularity vs. electron-dense deposits vs. and endothelial tubuloreticular inclusions vs. In the of the other positive autoimmune these findings ANCA-GN with features of of Pathology lupus nephritis. cases also mild to lupus or membranous to lupus In all the degree of necrosis and was of to (i) the degree of and (ii) the of immune in of a for ANCA in all We have similar findings in rare patients not receiving hydralazine, but with lupus and biopsy findings of necrosis and et and crescentic lupus with antineutrophil cytoplasmic antibody J Am Soc Nephrol. PubMed Scopus (88) Google Scholar In addition to hydralazine, 42 of 51 patients received induction immunosuppression, including and were similar to primary ANCA-GN, with of patients the combined of or For in the death from or in approximately of M. Merkel P.A. et and in severe ANCA-associated Engl J Med. PubMed Scopus Google Scholar and in the which ANCA-GN patients with severe as the cases in our at 1 et in ANCA-associated renal Engl J Med. 2010; PubMed Scopus Google Scholar In the of of outcomes were with mean serum creatinine at of follow-up of 1.49 The in most patients may be by the of biopsies as by the Berden A.E. Ferrario F. Hagen E.C. et al.Histopathologic classification of ANCA-associated glomerulonephritis.J Am Soc Nephrol. 2010; 21: PubMed Scopus Google Scholar outcomes have been reported in series of B. Strouse J. Swee M. et al.Hydralazine-associated vasculitis: overlapping features of drug-induced lupus and vasculitis.Semin Arthritis Rheum. 2018; 48: 283-287Crossref PubMed Scopus (16) Google K. et ANCA associated vasculitis (AAV) with a case report with Scholar with the high of ANCA discontinuation of hydralazine in our series, the of in the management of hydralazine-associated ANCA-GN. three-fourths of patients in our series were on hydralazine for at least 1 year, with mean daily dose of approximately 250 at the time of biopsy. identified reports of hydralazine AAV, with hydralazine dose from to and treatment duration from 1 to M. J. Hydralazine-induced ANCA-positive pauci-immune a case report and 2009; PubMed Scopus Google Scholar In series of treatment from to with of to at time of B. Strouse J. Swee M. et al.Hydralazine-associated vasculitis: overlapping features of drug-induced lupus and vasculitis.Semin Arthritis Rheum. 2018; 48: 283-287Crossref PubMed Scopus (16) Google Scholar are on the of of and may be as a of of In patients with ANCA the and and are as a of in with patients in and ANCA glomerulonephritis and J Am Soc Nephrol. PubMed Scopus Google Scholar is at the and in of ANCA vasculitis patients to of and failure of to which is for J. et for of in with ANCA 2010; PubMed Scopus Google Scholar Hydralazine a of as a DNA methylation that DNA N. DNA as therapy for PubMed Scopus Google Scholar This could AAV by of and of drug could also disease among of W.F. Niles J.L. Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis.Curr Opin Rheumatol. 2014; 26: 42-49Crossref PubMed Scopus (88) Google Scholar Hydralazine is by the which is with approximately of the hydralazine which may to as et hydralazine J Nephrol. PubMed Scopus Google Scholar our not the of disease, it is that ANCA seropositivity following drug in a significant percentage of our and similar to primary ANCA-GN, patients with hydralazine-associated ANCA-GN to from is to the for hydralazine-associated ANCA-GN. This study has several on hydralazine exposure were only available from a of patients and on patient or but not by to of we could not report or and antibody We also be that cases of ANCA-GN in our were not associated with hydralazine but that this information was not to of the of the study of could not be only of 51 received the of therapy could not be The use of therapy and outcomes in this that of hydralazine and a limited induction course of may in patients. In our the largest series of hydralazine-associated ANCA-GN. typically with rapidly progressive similar to primary ANCA-GN. Extrarenal involvement is typically show a serologic of drug-induced lupus and AAV with primary ANCA-GN, a percentage of and dual ANCA with ANCA-GN, hydralazine-associated ANCA GN is more often and less often features of mild immune complex GN resembling lupus were also more which may as a to the drug-induced of disease. With discontinuation of hydralazine and immunosuppression, outcomes are similar to ANCA-GN. are to for the development of ANCA-GN, for this drug-induced complication when hydralazine, at All the The to the nephrologists for providing clinical and for to in the of patients. ANCA glomerulonephritis the disease 2019 are globally on a rare are We report a case of anti–neutrophil cytoplasmic antibody (ANCA) glomerulonephritis receiving the

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