Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

Figures & data

Table 1 Laboratory test results during hospital admissions

Test item	First hospitalization		Second hospitalization
	At admission	At discharge (7th day)	At admission	At discharge (7th day)
Serum creatinine (μmol/L)	211	257	465	501
Serum urea (mmol/L)	13	13.9	13.9	25.6
Protein total (g/L)	59	54	64	62
Lactate dehydrogenase (IU/L)	923	287	285	194
Creatinine clearance (mL/min estimated with MDRD formula)	–	18	–	8
Hemoglobin (g/L)	80.3	112	96	103
Haptoglobin (g/L)	<0.1	0.35		1.14
Platelets (×10^9/L)	167	294	330	353
Schistocytes	Positive	Negative	Negative	Negative
C3 complement (g/L)	1.18	–	1.16	–
C4 complement (g/L)	0.29	–	0.28	–
Autoantibodies (*)	Negative	–	–	–

Notes:

* Autoantibodies included anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-GBM antibodies and anti-phospholipids. - indicates results not available.

Abbreviations: MDRD, modification of diet in renal disease; GBM, glomerular basement membrane.

Figure 1 Acute glomerular lesion.

Notes: There is global thickening of glomerular capillary walls caused by subendothelial expansion associated with focal mesangiolysis and a few capillary thrombosis (HES ×400 magnification).
Abbreviation: HES, hematoxylin, eosin, saffron.

Figure 2 Acute arteriolar lesion.

Notes: Mucoid intimal thickening with focal fibrinoid necrosis is responsible for occlusion of the lumen (HES ×400 magnification).
Abbreviation: HES, hematoxylin, eosin, saffron.

Figure 3 Severe chronic ischemic changes.

Notes: There is diffuse interstitial fibrosis with focal tubular atrophy. The three glomerular (on the left) show severe wrinkling of the basement membranes with sclerotic changes. The interlobular artery shows marked intimal fibrous thickening with resultant severe narrowing of the lumen (trichrome ×200 magnification).

Table 2 Summary of thrombotic microangiopathy case reports induced by interferon beta (IFNβ) therapy from literature review

Authors	Year	Age of patient	Indication of IFNβ-1a therapy	Duration of therapy	Clinical	Laboratory investigations	Treatment	Outcome
Ubara et al^Citation25	1998	66	HCV	44 days	HUS		Discontinuation of IFNβ	Remission
Herrera et al^Citation26	1999	N/A	MS	2 weeks	TTP		Discontinuation of IFNβ + plasmapheresis	Chronic kidney disease
Hansen et al^Citation23	2009	41	MS	Several years	Renal failure + SLE + APS	Antinuclear-antibodies and antiphospholipid positive	Discontinuation of IFNβ + plasmapheresis + steroids + mycophenolate mofetil	Chronic kidney disease
Broughton et al^Citation27	2011	53	MS	8 years	Renal failure + mild hypertension		Discontinuation of IFNβ + lisinopril	Chronic kidney disease
Olea et al^Citation28	2012	37	MS	5 months	Renal failure + severe hypertension		Discontinuation of IFNβ + steroids + enalapril + irbesartan	Remission

Abbreviations: APS, anti-phospholipid syndrome; SLE, systemic lupus erythematosus; HUS, hemolytic-uremic syndrome; MS, multiple sclerosis; TTP, thrombotic thrombocytopenic purpura; HCV, hepatitis C virus; N/A, not available.

Table 3 Summary of thrombotic microangiopathy notifications induced by interferon beta-1a (IFNβ) from French Pharmacovigilance Database

Year	Age	Duration of treatment	Disease	Clinical	Treatment	Laboratory investigations	Outcome
2006	47	1 year	MS	Proteinuria	Discontinuation of IFNβ		Remission
2007	58	5 years	MS	HUS + hypertension	Discontinuation of IFNβ + plasmapheresis + steroids		Chronic kidney disease
2008	55	6 years	MS	TTP	Discontinuation of IFNβ + plasmapheresis + steroids + rituximab	IgG anti-ADAMTS 13 positive	Remission
2009	66	1 year	MS	HUS + hypertension	Discontinuation of IFNβ + urapidil		Remission
2009	65	1 year	MS	Nephrotic syndrome	NA		NA
2010	38	10 years	MS	TTP	Discontinuation of IFNβ + plasmapheresis + steroids		NA
2011	44	3 years	MS	Renal failure + hypertension	Discontinuation of IFNβ + plasmapheresis	Antinuclear-antibodies positive	Chronic kidney disease
2012	52	>3 years	MS	HUS + hypertension	Discontinuation of IFNβ + plasmapheresis + nebivolol	Decreased activity of ADAMTS 13	Chronic kidney disease

Abbreviations: ADAMTS, A disintegrin and metalloproteinase with thrombospondin 1 motifs; Ig, immunoglobulin; NA, not available; HUS, hemolytic-uremic syndrome; MS, multiple sclerosis; TTP, thrombotic thrombocytopenic purpura.

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Herrera WG Balizet LB Harberts SW Occurrence of a TTP-like syndrome in two women receiving beta interferon therapy for relapsing multiple sclerosis [American Academy of Neurology 51st annual meeting. Toronto, Ontario, Canada. April 17–24, 1999. Abstracts] Neurology 1999 52 6 Suppl. 2 A135

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Broughton A Cosyns JP Jadoul M Thrombotic microangiopathy induced by long-term interferon-β therapy for multiple sclerosis: a case report Clin Nephrol 2011 76 5 396 400 22000560

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Olea T Díaz-Mancebo R Picazo ML Martínez-Ara J Robles A Selgas R Thrombotic microangiopathy associated with use of interferon-beta Int J Nephrol Renovasc Dis 2012 5 97 100 22815645

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