Drug-induced hemolytic uremic syndrome

Letters to Editor

Drug-induced hemolytic uremic syndrome Sir, Interferon (IFN) therapy is rarely associated with renal side effects.[1] Among histological findings detected, there are some reports with renal thrombotic microangiopathy (TMA).[2-5] We report here a case of interferon-induced hemolytic uremic syndrome (HUS). A 36-year-old Caucasian woman was admitted for acute renal failure and pulmonary edema. Three years ago, she was diagnosed with multiple sclerosis and received a course of prednisone for 2 months. Later she did not receive any other therapy. Blood pressure and results of renal function tests were always normal. Three months before the admission, because of new radiological findings in brain, the patient was started on IFN-b-1a treatment (22 µg thrice weekly); 7 days before the admission, she began to suffer from asthenia, gain in weight and dyspnea. IFN therapy was withdrawn. Up to admission, the patient received 35 doses of IFN. On admission, physical examination showed high blood pressure and severe pleural effusion without neurological or dermatological findings. We found laboratory features of microangiopathic hemolytic anemia. Immunological (Anti-Neutrophil Cytoplasm Antibodies, Anti-Nuclear Antibodies, Anti-doublestranded DNA antibodies, Anti-Extractable Nuclear Antigen Antibodies, anti-phospholipids-Antibodies) and microbiological laboratory tests were unremarkable. Renal biopsy disclosed signs of thrombotic microangiopathy; among 43 glomeruli, light microscopy revealed focal ischemic signs and mild mesangial cell proliferation; vessel narrowing with thrombi and thickening of arteriolar walls and intimal onion skin–like swelling; light interstitial lymphomonocytic infiltration; and focal tubular atrophy [Figures 1 and 2]. Immunofluorescence showed mesangial IgM, C1q and fibrinogen staining. A diagnosis of HUS was made. She was treated with transfusions, hemodialysis, plasma exchange and methylprednisolone i.v. followed by oral prednisone. Cardiac function improved, and hematological signs progressively disappeared but renal function didn’t recover. IFN-beta treatment was discontinued. Now she is on peritoneal dialysis. The mechanism for the development of TMA associated with IFN is not clear. Interferon, such as TNF, IL-1; and free radicals can participate in tissue injury and endothelial cell damage with the resulting deleterious effects. It can exert complex immunomodulatory effects on endothelial

cells with differential effects on various endothelial cell surface markers, including the major histocompatibility complex antigens and intracellular adhesion molecules. It can induce modulation of fibrinolytic response of endothelial cells through a prothrombotic way. The release of platelet-aggregating agents from the damaged endothelial cells is probably the final event, resulting in intraluminal thrombus formation and organ damage. In conclusion, in our patient the temporal association suggests a direct causal effect between IFN therapy and HUS.

Figure 1: Intralobular arteries have narrowed lumina due to marked intimal expansion; with edema, mucoid changes, myointimal hyperplasia and sclerosis. The glomerulus shows segmental mesangiolysis with coalescence of some capillary loops. Profiles of dilated tubular lumina contain fragmented erythrocytes. The interstitium appears widened by edema, and there are areas of sclerosis and inflammation (Masson trichrome stain)

Figure 2: Laminations in the fibrotic intima give the intralobular artery an “onion skin” pattern. The glomerulus on the left has prominent segmental mesangiolysis with formation of capillary microaneurysms. Degenerating red blood cell casts are present in some tubules. There are interstitial fibrosis and mild focal interstitial infiltration of mononuclear leukocytes (Masson trichrome stain)

Letters to Editor

G. Li Cavoli, A. Ferrantelli, C. Tortorici, L. Bono, C. Giammarresi, R. Passantino1, U. Rotolo

E, Nikeghbalian S, et al. Long term survival of living donor renal transplants: A single center study. Indian J Nephrol 2010;20:179-84.

Departments of Nephrology and Dialysis, 1Pathologic Anatomy, Civic and Di Cristina Hospital, Palermo, Italy Address for correspondence: Dr. Li Cavoli Gioacchino, via Francesco Cilea 43, 90144 Palermo, Italy. E-mail: [email protected]

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Website: www.indianjnephrol.org

References

DOI:

1.

10.4103/0971-4065.82378

Aravindan A, Yong J, Killingsworth M, Suranyi M, Wong J. Minimal change disease with interferon-beta therapy for relapsing remitting multiple sclerosis. NDT Plus 2010;3:132-4. 2. Magee CC. Renal thrombotic microangiopathy induced by interferon alpha. Nephrol Dial Transplant 2001;16:2111-2. 3. Badid C, McGregor B, Faivre JM, Guerard A, Juillard L, Fouque D, et al. Renal thrombotic microangiopathy induced by interferonalpha. Nephrol Dial Transplant 2001;16:846-8. 4. Vacher-Coponat H, Opris A, Daniel L, Harle JR, Veit V, Olmer M. Thrombotic microangiopathy in a patient with chronic myelocitic leukemia treated with alpha-interferon. Nephrol Dial Transplant 1999;14:2469-71. 5. Galesic K, Bozic B, Racic I, Scukanec-Spoljar M. Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myeloid leukemia. Nephrology (Carlton) 2006;11:49-52. Access this article online Quick Response Code:


Authors’ reply Sir, We would like to thank the author for his comments[1] on our article.[2] Unfortunately we did not follow our donors for more than 6 months after the operation. Most of the donors were lost to follow-up because of socioeconomic problems, and our analysis was not complete because of so much missing data. We will perform another study about the donors in the near future; and if the data are enough, it will be published as well. J. Hassanzadeh, A. A. Hashiani1, A. Rajaeefard, H. Salahi2, E. Khedmati3, F. Kakaei4

DOI: 10.4103/0971-4065.82377

Graft survival after living donor transplantation Sir, I am intrigued by the donor criterion mentioned by Hassanzadeh et al.,[1] accepting donors whose last preoperative serum creatinine was 1.4 mg/dL or lower. While the fate of the donor was not part of their original study, I would be interested to know if they have studied the renal function of the donors 10 years after donor nephrectomy. M. K. Mani Apollo Hospital, Chennai, India Address for correspondence: Dr. M. K. Mani, 1, Kasturirangan Road, Chennai, India. E-mail: [email protected]

References 1.

Department of Epidemiology, School of Health and Nutrition, Shiraz University of Medical Sciences, Shiraz, 1Faculty of Health, Arak University of Medical Sciences, Arak, 2Shiraz Organ Transplantation Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, 3Department of Social Welfare, University of Social Welfare and Rehabilitation Sciences, Tehran, 4Department of Surgery, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Address for correspondence: Mr. Amir Almasi Hashiani, School of Health, Arak University of Medical Sciences, Arak, Iran. E-mail: [email protected]

References 1. 2.

Mani MK. Graft survival after living donor transplantation. Indian J Nephrol 2011;21:145. Hassanzadeh J, Hashiani AA, Rajaeefard A, Salahi H, Khedmati E, Nikeghbalian S, et al. Long term survival of living donor renal transplants: A single center study. Indian J Nephrol 2010;20:179-84. Access this article online Quick Response Code:


Hassanzadeh J, Hashiani AA, Rajaeefard A, Salahi H, Khedmati

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April 2011 / Vol 21 / Issue 2

Indian Journal of Nephrology