Limits...
Can eculizumab be discontinued in aHUS?: Case report and review of the literature.

Sahutoglu T, Basturk T, Sakaci T, Koc Y, Ahbap E, Sevinc M, Kara E, Akgol C, Caglayan FB, Unsal A, Daha MR - Medicine (Baltimore) (2016)

Bottom Line: One of our aHUS cases with a novel complement factor H mutation, who developed unusual laboratory findings (thrombocytopenia and mild creatinine elevation without other features of TMA) following discontinuation of eculizumab was presented.Limited experience suggests that the risk of recurrence of TMA following discontinuation of eculizumab is relatively low for patients with MCP mutations, homozygous CFHR3/R1 deletions, anti-CFH antibodies, CFI mutations, and no identifiable mutations, whereas there is a major risk for patients with CFH mutations.Early detection of TMA recurrence and prompt retreatment with eculizumab seem to be efficient in controlling of TMA and restoration of kidney functions.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Nephrology, Sisli Hamidiye Etfal Educational and Research Hospital, Istanbul bDepartment of Internal Medicine, Recep Tayyip Erdogan University, Rize, Turkey cDepartment of Nephrology, C3-P, Leiden University Medical Center, Leiden, The Netherlands.

ABSTRACT

Background: The management of atypical hemolytic uremic syndrome (aHUS) has evolved into better control of thrombotic microangiopathy (TMA) and recovery of renal functions since the recent introduction of the terminal complement cascade blocker, eculizumab, into clinical use. Better characterization of genotype-phenotype relations has become possible with genetic and clinical studies. However, these advances brought up some important issues, such as the possibility and timing of discontinuation of eculizumab and strategy of follow-up that need to be enlightened.

Case summary: One of our aHUS cases with a novel complement factor H mutation, who developed unusual laboratory findings (thrombocytopenia and mild creatinine elevation without other features of TMA) following discontinuation of eculizumab was presented. Literature and case reports relevant to discontinuation of eculizumab in aHUS patients were reviewed.

Conclusion: Limited experience suggests that the risk of recurrence of TMA following discontinuation of eculizumab is relatively low for patients with MCP mutations, homozygous CFHR3/R1 deletions, anti-CFH antibodies, CFI mutations, and no identifiable mutations, whereas there is a major risk for patients with CFH mutations. Early detection of TMA recurrence and prompt retreatment with eculizumab seem to be efficient in controlling of TMA and restoration of kidney functions.

No MeSH data available.


Related in: MedlinePlus

(A) Creatinine levels decrease initially with plasma exchange and hemodialysis, but rise again under plasma exchange treatment. Treatment with eculizumab induces steady decline in creatinine levels and later allows to discontinue hemodialysis. (B) Thrombocyte counts and lactate dehydrogenase (LDH) levels change initially toward normal ranges, but return to abnormal levels under plasma exchange and hemodialysis. Treatment with eculizumab results in consistent normalization of both thrombocyte counts and LDL levels. (C) The course of LDH levels and thrombocyte count during off treatment follow-up shows that thrombocyte counts drop and remain <150,000 cells/μL since the 7th month of discontinuation of eculizumab, whetreas LDH levels remain mostly just below the upper limit of normal. (D) Creatinine levels during off treatment follow-up swing around 1.6 mg/dL, which is 0.25 mg/dL higher than the nadir level of 1.35 mg/dL under eculizumab treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4979790&req=5

Figure 1: (A) Creatinine levels decrease initially with plasma exchange and hemodialysis, but rise again under plasma exchange treatment. Treatment with eculizumab induces steady decline in creatinine levels and later allows to discontinue hemodialysis. (B) Thrombocyte counts and lactate dehydrogenase (LDH) levels change initially toward normal ranges, but return to abnormal levels under plasma exchange and hemodialysis. Treatment with eculizumab results in consistent normalization of both thrombocyte counts and LDL levels. (C) The course of LDH levels and thrombocyte count during off treatment follow-up shows that thrombocyte counts drop and remain <150,000 cells/μL since the 7th month of discontinuation of eculizumab, whetreas LDH levels remain mostly just below the upper limit of normal. (D) Creatinine levels during off treatment follow-up swing around 1.6 mg/dL, which is 0.25 mg/dL higher than the nadir level of 1.35 mg/dL under eculizumab treatment.

Mentions: Daily plasma exchange using 40 mL/kg fresh frozen plasma and on-demand hemodialysis were started. Markers of thrombotic microangiopathy did not consistently normalize during 22 sessions of plasma exchange; therefore, PE was replaced by eculizumab within 2 weeks of vaccination against Neisseria meningitides (900 mg/week for 4 weeks, 1200 mg every other week from the 5th week on). Thrombocytopenia and elevated LDH normalized within 1 month along with gradual improvement in renal functions and the need for dialysis was eliminated within 2 months of eculizumab treatment (Fig. 1 A, B). Eculizumab was discontinued after 1 year of treatment, during which creatinine nadir was 1.35 mg/dL, and the patient was set to follow-up. Thrombocytes dropped and remained below the lower limit of normal from the 7th month (January 6, 2015) of follow-up on, but LDH levels remained around the upper limit of normal (Fig. 1 C). Multiple peripheral blood films, serum haptoglobin levels, and reticulocyte counts were found normal, except for thrombocytopenia, since detection of thrombocytopenia. Levels of creatinine slightly increased but remained <2 mg/dL except for a few occasions, whereas the levels of proteinuria remained <0.5 g/day (385 mg/day at last visit) (Fig. 1 D). Informed consent was obtained from the patient.


Can eculizumab be discontinued in aHUS?: Case report and review of the literature.

Sahutoglu T, Basturk T, Sakaci T, Koc Y, Ahbap E, Sevinc M, Kara E, Akgol C, Caglayan FB, Unsal A, Daha MR - Medicine (Baltimore) (2016)

(A) Creatinine levels decrease initially with plasma exchange and hemodialysis, but rise again under plasma exchange treatment. Treatment with eculizumab induces steady decline in creatinine levels and later allows to discontinue hemodialysis. (B) Thrombocyte counts and lactate dehydrogenase (LDH) levels change initially toward normal ranges, but return to abnormal levels under plasma exchange and hemodialysis. Treatment with eculizumab results in consistent normalization of both thrombocyte counts and LDL levels. (C) The course of LDH levels and thrombocyte count during off treatment follow-up shows that thrombocyte counts drop and remain <150,000 cells/μL since the 7th month of discontinuation of eculizumab, whetreas LDH levels remain mostly just below the upper limit of normal. (D) Creatinine levels during off treatment follow-up swing around 1.6 mg/dL, which is 0.25 mg/dL higher than the nadir level of 1.35 mg/dL under eculizumab treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979790&req=5

Figure 1: (A) Creatinine levels decrease initially with plasma exchange and hemodialysis, but rise again under plasma exchange treatment. Treatment with eculizumab induces steady decline in creatinine levels and later allows to discontinue hemodialysis. (B) Thrombocyte counts and lactate dehydrogenase (LDH) levels change initially toward normal ranges, but return to abnormal levels under plasma exchange and hemodialysis. Treatment with eculizumab results in consistent normalization of both thrombocyte counts and LDL levels. (C) The course of LDH levels and thrombocyte count during off treatment follow-up shows that thrombocyte counts drop and remain <150,000 cells/μL since the 7th month of discontinuation of eculizumab, whetreas LDH levels remain mostly just below the upper limit of normal. (D) Creatinine levels during off treatment follow-up swing around 1.6 mg/dL, which is 0.25 mg/dL higher than the nadir level of 1.35 mg/dL under eculizumab treatment.
Mentions: Daily plasma exchange using 40 mL/kg fresh frozen plasma and on-demand hemodialysis were started. Markers of thrombotic microangiopathy did not consistently normalize during 22 sessions of plasma exchange; therefore, PE was replaced by eculizumab within 2 weeks of vaccination against Neisseria meningitides (900 mg/week for 4 weeks, 1200 mg every other week from the 5th week on). Thrombocytopenia and elevated LDH normalized within 1 month along with gradual improvement in renal functions and the need for dialysis was eliminated within 2 months of eculizumab treatment (Fig. 1 A, B). Eculizumab was discontinued after 1 year of treatment, during which creatinine nadir was 1.35 mg/dL, and the patient was set to follow-up. Thrombocytes dropped and remained below the lower limit of normal from the 7th month (January 6, 2015) of follow-up on, but LDH levels remained around the upper limit of normal (Fig. 1 C). Multiple peripheral blood films, serum haptoglobin levels, and reticulocyte counts were found normal, except for thrombocytopenia, since detection of thrombocytopenia. Levels of creatinine slightly increased but remained <2 mg/dL except for a few occasions, whereas the levels of proteinuria remained <0.5 g/day (385 mg/day at last visit) (Fig. 1 D). Informed consent was obtained from the patient.

Bottom Line: One of our aHUS cases with a novel complement factor H mutation, who developed unusual laboratory findings (thrombocytopenia and mild creatinine elevation without other features of TMA) following discontinuation of eculizumab was presented.Limited experience suggests that the risk of recurrence of TMA following discontinuation of eculizumab is relatively low for patients with MCP mutations, homozygous CFHR3/R1 deletions, anti-CFH antibodies, CFI mutations, and no identifiable mutations, whereas there is a major risk for patients with CFH mutations.Early detection of TMA recurrence and prompt retreatment with eculizumab seem to be efficient in controlling of TMA and restoration of kidney functions.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Nephrology, Sisli Hamidiye Etfal Educational and Research Hospital, Istanbul bDepartment of Internal Medicine, Recep Tayyip Erdogan University, Rize, Turkey cDepartment of Nephrology, C3-P, Leiden University Medical Center, Leiden, The Netherlands.

ABSTRACT

Background: The management of atypical hemolytic uremic syndrome (aHUS) has evolved into better control of thrombotic microangiopathy (TMA) and recovery of renal functions since the recent introduction of the terminal complement cascade blocker, eculizumab, into clinical use. Better characterization of genotype-phenotype relations has become possible with genetic and clinical studies. However, these advances brought up some important issues, such as the possibility and timing of discontinuation of eculizumab and strategy of follow-up that need to be enlightened.

Case summary: One of our aHUS cases with a novel complement factor H mutation, who developed unusual laboratory findings (thrombocytopenia and mild creatinine elevation without other features of TMA) following discontinuation of eculizumab was presented. Literature and case reports relevant to discontinuation of eculizumab in aHUS patients were reviewed.

Conclusion: Limited experience suggests that the risk of recurrence of TMA following discontinuation of eculizumab is relatively low for patients with MCP mutations, homozygous CFHR3/R1 deletions, anti-CFH antibodies, CFI mutations, and no identifiable mutations, whereas there is a major risk for patients with CFH mutations. Early detection of TMA recurrence and prompt retreatment with eculizumab seem to be efficient in controlling of TMA and restoration of kidney functions.

No MeSH data available.


Related in: MedlinePlus