Acute Interstitial Nephritis with the Nephrotic Syndrome Following Recombinant Leukocyte A Interferon Therapy for Mycosis Fungoides

Averbuch, Steven D.; Austin, Howard A.; Sherwin, Stephen A.; Antonovych, Tatiana A.; Bunn, Paul A.; Longo, Dan L.

doi:10.1056/nejm198401053100107

Cited by 163 publications

(52 citation statements)

References 17 publications

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“…Given the generally poor outcome in patients with idiopathic collapsing FSGS (8 -12,14), the improvement after discontinuation of IFN-␣, -␤, and -␥ argues strongly in favor of its causative role in the development of collapsing FSGS in our cohort. This causative relationship is further strengthened by the reports of recurrent nephrotic syndrome after reintroduction of IFN (patient 9) (31,32). It is interesting to note that the mean duration of IFN therapy before the development of collapsing FSGS was 2.95 months for the eight patients who were treated with IFN-␣ (Tables 1 and 3).…”

Section: Discussionmentioning

confidence: 64%

“…All eight patients went into remission, including CR in six. Interestingly, IFN was subsequently reintroduced in three patients (31,32,37), followed by recurrence of nephrotic syndrome in two (31,32). Reports of FSGS after treatment with IFN have included FSGS of the usual type (FSGS NOS) (10 cases) and collapsing FSGS (three cases; Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, FSGS NOS has been reported to result from treatment with lithium (25), sirolimus (26), and more recently anabolic steroids (27). Although rare cases of collapsing FSGS also have been reported after treatment with IFN-␣ (28 -30), this therapeutic agent is more commonly associated with minimalchange disease (MCD) (31)(32)(33)(34)(35)(36)(37)(38) and FSGS NOS (39 -47). We report 11 additional cases of collapsing FSGS that developed during treatment with IFN, including six IFN-␣ (for hepatitis C virus [HCV] infection or melanoma), three IFN-␤ (for multiple sclerosis [MS]), and two IFN-␥ (for idiopathic pulmonary fibrosis).…”

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confidence: 99%

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Treatment with IFN-α, -β, or -γ Is Associated with Collapsing Focal Segmental Glomerulosclerosis

Markowitz¹,

Nasr²,

Stokes³

et al. 2010

Clinical Journal of the American Society of Nephrology

199

180

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Background and objectives: Treatment with IFN is rarely associated with nephrotic syndrome and renal biopsy findings of minimal-change disease or FSGS.Design, setting, participants, & measurements: We report 11 cases of collapsing FSGS that developed during treatment with IFN and improved after discontinuation of therapy.Results: The cohort consists of seven women and four men with a mean age of 48.2 yr. Ten of the 11 patients were black. Six patients were receiving IFN-␣ for hepatitis C virus infection (n ‫؍‬ 5) or malignant melanoma (n ‫؍‬ 1), three were receiving IFN-␤ for multiple sclerosis, and two were treated with IFN-␥ for idiopathic pulmonary fibrosis. After a mean and median duration of therapy of 4.0 and 12.6 months, respectively, patients presented with acute renal failure (mean creatinine 3.5 mg/dl) and nephrotic-range proteinuria (mean 24-hour urine protein 9.7 g). Renal biopsy revealed collapsing FSGS with extensive foot process effacement and many endothelial tubuloreticular inclusions. Follow-up was available for 10 patients, all of whom discontinued IFN. At a mean of 23.6 months, nine of 10 patients had improvement in renal function, including one with complete remission and two with partial remission. Among the seven patients with available data, mean proteinuria declined from 9.9 to 3.0 g/d. Four of the seven patients were treated with immunosuppression, and there was no detectable benefit.Conclusions: Collapsing FSGS may occur after treatment with IFN-␣, -␤, or -␥ and is typically accompanied by the ultrastructural finding of endothelial tubuloreticular inclusions. Optimal therapy includes discontinuation of IFN.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Treatment with IFN-α, -β, or -γ Is Associated with Collapsing Focal Segmental Glomerulosclerosis

Markowitz¹,

Nasr²,

Stokes³

et al. 2010

Clinical Journal of the American Society of Nephrology

199

180

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“…All three subtypes have been synthesized and used clinically against chronic active viral hepatitis [4], malignancies [5], or acquired immune deficiency syndrome (AIDS) [6]. However, side-effects, such as fever, myalgia, leucopenia, nephritis [7] and bronchiolitis obliterans organizing pneumonia (BOOP) [8] or pneumonitis [9][10][11][12] have been reported. The drug "Sho-saiko-to", a composite herbal preparation, has been popularly used for the treatment of chronic hepatitis in Japan [13], as it is reputed to protect liver cells against experimentally-induced damage in vitro, to enhance the induction of plaque-forming cells, to suppress the release of arachidonic acid and leukotriene B 4 production [14], and to enhance interferon production by human peripheral blood mononuclear cells [15].…”

Section: Case Studymentioning

confidence: 99%

Pneumonitis during interferon and/or herbal drug therapy in patients with chronic active hepatitis

Ishizaki¹,

Sasaki²,

Ameshima³

et al. 1996

Eur Respir J

108

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P Pn ne eu um mo on ni it ti is s d du ur ri in ng g i in nt te er rf fe er ro on n a an nd d/ /o or r h he er rb ba al l d dr ru ug g t th he er ra ap py y i in n p pa at ti ie en nt ts s w wi it th h c ch hr ro on ni ic c a ac ct ti iv ve e h he ep pa at ti it ti is s ABSTRACT: We report four cases of acute pneumonitis due either to interferon, or a herbal drug, " "Sho-saiko-to" ", or both in combination, in patients with chronic active hepatitis, focusing on its pathogenesis and response to prednisolone therapy. These cases shared common clinical features: fever, dry cough, dyspnoea, hypoxaemia, diffuse infiltrates both on chest radiography and chest computed tomography, restrictive pulmonary functional impairment, and alveolitis on examination of transbronchial lung biopsy, all of which suggest acute interstitial pneumonia. Furthermore, lymphocytosis was observed in association with the dominant CD8+ T-cell subset in bronchoalveolar lavage fluid. A lymphocyte stimulation test using peripheral blood was positive to interferon in one case and to Sho-saiko-to in another. All patients responded to oral prednisolone therapy. Peripheral soluble interleukin-2 receptor levels decreased in parallel with improvement in the clinical course. All patients were free of symptoms with a follow-up of 1-3 yrs.We conclude that interferon-and/or Sho-saiko-to-induced acute pneumonitis may be due to allergic-immunological mechanisms rather than toxicity, and that peripheral levels of soluble interleukin-2 receptor appear to be good markers of disease activity.

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“…The na ture of the antigen is not well established [3,14]. Tubulointerstitial abnormalities are uncommon [3], and only a few cases of clinically apparent interstitial nephritis in these patients have been reported [1,10,28].…”

Section: Introductionmentioning

confidence: 99%

Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer

Vlasveld

Kemenade

Boer

et al. 1993

Cancer Immunol Immunother

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Abstract.A patient with renal cell cancer developed acute renal failure due to biopsy-proven acute tubulo-interstitial nephritis (AIN) in the 6th week of continuous infusion of 9 x 106 IU n r 2 day-1 recombinant interleukin-2 (rIL-2). We investigated whether the AIN was the result of a cellu lar cytotoxic reaction induced by the rIL-2 treatment. The cytolytic activity of cryopreserved peripheral blood lym phocytes (PBL), isolated before and at the end of the rIL-2 treatment (at the time of AIN), was studied after 5 days of culture with or without rIL-2 or anti-CD28 and immobi lized anti-CD3 antibodies. The PBL isolated before and at the end of the rIL-2 treatment showed cytolytic activity towards a number of allogeneic targets. However, only the PBL isolated at the end of the rIL-2 treatment showed, when stimulated with rIL-2 in vitro, significant cytolytic activity against an autologous renal cell line cultured from the AIN biopsy specimen and against an allogeneic renal cell cancer cell line. These PBL displayed no enhanced killing capacity towards autologous PBL and the melano ma cell line M14. These observations suggest that the AIN may be the result of a cytotoxic lymphocyte-mediated reac tion induced by the rIL-2 treatment.

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Acute Interstitial Nephritis with the Nephrotic Syndrome Following Recombinant Leukocyte A Interferon Therapy for Mycosis Fungoides

Cited by 163 publications

References 17 publications

Treatment with IFN-α, -β, or -γ Is Associated with Collapsing Focal Segmental Glomerulosclerosis

Treatment with IFN-α, -β, or -γ Is Associated with Collapsing Focal Segmental Glomerulosclerosis

Pneumonitis during interferon and/or herbal drug therapy in patients with chronic active hepatitis

Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer

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