Long-term Effect of the Complement Inhibitor Eculizumab on Kidney Function in Patients with Paroxysmal Nocturnal Hemoglobinuria

Peter Hillmen (1) , Modupe Elebute (2) , Richard Kelly (1) , Alvaro Urbano-Ispizua (3) , Russell P Rother (4) , Gus Khursigara (5) , Chieh-Lin Fu (6) , Mitsuhiro Omine (7) , Paul Browne (8) , Wendell Rosse (9)

1 Department of Hematology
2 Department of Hematological Medicine
3 Department of Hematology
4 Alexion Pharmaceuticals
5 Alexion Pharmaceuticals
6 Dept. of Hematology Oncology
7 Division of Hematology, Internal medicine
8 Hematology
9 Hematology/Medicine

Paroxysmal nocturnal hemoglobinuria (PNH) is a debilitating and life-threatening disease in which lysis of PNH red blood cells frequently manifests with chronic hemolysis, anemia and thrombosis. Renal damage in PNH is associated with chronic hemosiderosis and/or microvascular thrombosis. We determined the incidence of renal dysfunction or damage, defined by stages of chronic kidney disease (CKD), in a large cohort of PNH patients, and evaluated the safety and efficacy of the complement inhibitor eculizumab in altering its progression. Renal dysfunction or damage was observed in 65% of the study population at baseline with 21% of patients with later stage CKD or kidney failure (GFR ≤ 60 mL/min/1.73 m2; stage 3, 4 or 5). Eculizumab treatment was safe and well-tolerated in patients with renal dysfunction or damage and resulted in the likelihood of improvement as defined as categorical reduction in CKD stage (P<0.001) compared to baseline and to placebo (P=0.04). Improvement in renal function was more commonly seen in patients with baseline CKD stage 1-2 (67.1% improvement, P<0.001) although improvement was also observed in patients with CKD stage 3-4 (p=0.05). Improvements occurred quickly and were sustained for at least 18 months of treatment. Patients categorized at CKD stage 3-5 did not worsen during treatment with eculizumab. Overall, 40 (21%) of 195 patients that demonstrated renal dysfunction or damage at baseline were no longer classified as such after 18 months of treatment. Administration of eculizumab to patients with renal dysfunction or damage was well tolerated and was usually associated with clinical improvement.

Mots clés: Medicine

Peter Hillmen, Modupe Elebute, Richard Kelly, Alvaro Urbano-Ispizua, Russell P Rother, et al.. Long-term Effect of the Complement Inhibitor Eculizumab on Kidney Function in Patients with Paroxysmal Nocturnal Hemoglobinuria. American Journal of Hematology, 2010, 85 (8), pp.553. ⟨10.1002/ajh.21757⟩. ⟨hal-00599451⟩