ESPN 50th Annual Meeting

ESPN 2017


 
Improved outcomes with prompt management of anti-factor H (FH) associated atypical hemolytic uremic syndrome (aHUS) in children: Trends from nationwide database
PRIYANKA KHANDELWAL 1 ADITI SINHA 1 MAMTA PURASWANI 1 PANKAJ HARI 1 ARVIND BAGGA (for the HUS consortium) 1

1- ALL INDIA INSTITUTE OF MEDICAL SCIENCES
 
Introduction:

   Patients with anti-FH antibodies, comprising one-half of aHUS in children in India, are usually managed with plasma exchanges (PEX) and immunosuppressive agents. We report the characteristics of patients diagnosed in last 5-yr to those before 2012 to assess the impact of early diagnosis and protocolized therapy.

Material and methods:

   Of 684 patients in the nationwide database, 366 (53.5%) had anti-FH associated aHUS. In addition to intensive PEX over 4-6 weeks, induction therapy comprised of prednisolone and IV cyclophosphamide/ rituximab over 4-5 months, followed by maintenance with MMF/azathioprine for 2-yr. Clinical features and outcome were compared in patients presenting during 2005-12 (n=117) and 2012-17 (n=249). Adverse outcome was eGFR <30 mL/min/1.73 m2 or death.

Results:

   Anti-FH disease was diagnosed four-times more often in last 5-yr. Patients with anti-FH HUS were older, had severe illness and better outcomes than those without antibodies. Median decline of antibodies was 74%, 88% & 84% after 3, 5 & 7 PEX, respectively (P=0.08)titers were similar in those receiving IV cyclophosphamide or rituximab (generalized estimating equation, GEE; P=0.6). Combined PEX & induction immunosuppression was associated with improved long-term outcomes (HR 2.7; P=0.001); maintenance therapy reduced risk of relapses (HR=2.7; P=0.008). Patients presenting in last 5-yr showed less oliguria, seizures and hypertension, indicating benefits of early diagnosis and therapy (Table). Prompt PEX and immunosuppression enabled faster hematological & renal recovery. Adverse outcome at 3-months was decreased, with better 4-yr renal survival. Patients with relapse (n=27) had higher antibodies in remission than those who did not (n=91) during 5-yr follow up (GEE, P=0.015); titer >1300 AU/ml at 6-mo predicted relapses.

 

2005-12

N=117

2012-17

N=249

P

Age

8 (6-10)

7.5 (6-10)

0.9

Prodrome

69 (59%)

159 (64%)

<0.0001

Oligoanuria, days

10 (5-15)

5 (2-10)

<0.0001

Extrarenal symptoms

55 (47%)

139 (56%)

0.12

Stage 2 hypertension

82 (70%)

118 (47%)

<0.0001

C3, mg/dl

65 (48-85)

70 (54-87)

0.16

Anti-FH, AU/ml

2170 (950-7250)

3400 (1180-11706)

0.03

Days to PEX

 

19 (8-33)

 

12 (6-23)

 

0.026

Days to immunosuppression

 

34 (20-56)

 

22 (12-33)

 

0.001

Days to hematological remission

38 (23-55)

 

25 (17-36)

 

<0.0001

Duration of dialysis, days

31 (10-51)

11 (4-29)

<0.0001

Duration of PEX, days

36 (18-59)

28 (14-42)

0.006

CKD stage 2-3 @3-months

 

17 (16.5%)

 

24 (17.6%)

 

0.81

Adverse outcome @3-months

33 (32%)

24 (17.6%)

 

0.009

Adverse outcome @4-years

46 (39%)

65 (26%)

0.3

Median (IQR) or N (%)

Table | Clinical features and outcomes of anti-FH associated aHUS

 

 

 

Conclusions:

   Findings from this large nationwide database suggest that prompt recognition and specific therapy for anti-FH associated HUS, with PEX and immunosuppression, is associated with satisfactory outcomes without necessitating the use of complement inhibitors.