Plasmatherapy in Cases of Ahus with Complete Deficiency of CFH

Supplementary Table 1

Plasmatherapy in cases of aHUS with complete deficiency of CFH

Case / Complement Profile / Plasmatherapy / Outcome
[follow up (mths)]
8 mths male 44 / CH50 13 µ/ml
(25–45),
AP50 4·5 µ/ml
(12–26)
C3 0·12 g/l
(0·75–1·75)
Factor B 35%
(70–150),
Properdin 60%
(60–130)
C5, 6, 7, 8, 9 levels normal
Factor I levels normal
C3 nephritic factor absent
Free C3d in plasma / None given / Normal renal function (7m)
19 yrs female 49 / CH50 54%
NHP (77–122), AP50 37% (75–125)
C3 19 mg/dl
(72–135)
Factor B 17 mg/dl (22–48)
Properdin 115% (82–119)
C5 40% (67–133)
C8 100% (67–133)
Factor I levels normal
C3 nephritic factor absent
6M
4F
Median age
(1-20 wks) 46 / Full complement profile measured in 4 cases:
C3 12, 0, 14, 0% (45–91)
Factor B 18, 14, 57, 118% (36–86)
Properdin 24, 54, 46, 90% (39–69)
C5 34, 25, 52, 61% (41–103)
C9 4, 18, 96, 89% (36–64)
Factor I levels normal / FFP 10mls/kg daily during relapses and weekly in between (9/10 patients)
IVIG (2 patients)
Death during first episode (2 patients) / ESRD (5 patients) despite FFP 10mls/kg daily during relapses and weekly during remission
Death (8 patients)
7mth 45, 31 / During remission:
CH50 < 10%
NHP (70–130)
C3 < 3 mg/dl
(65–110)
Factor B < 12 mg/dl (16–40)
Factor I levels normal
C3 nephritic factor absent / Long-term weekly FFP infusions / Remission
11 mth 45 / During remission:
CH50 12%
NHP (70–130)
C3 < 3 mg/dl
(65–110)
Factor B < 12 mg/dl (16–40)
Factor I levels normal
C3 nephritic factor absent
22 days female 35 / Persistently low C3 / Improved with FFP infusions, relapses frequently followed infections
8 mth male 30 / C3 0.26
(0.75 to 1.40) mg/mL
Elevated C3d
181 mU/L
(normal <40 mU/L)
Factor H <1 μg/mL (288 to 631) μg/mL / FFP 20ml/kg
Every 2 weeks / Prevention of further deterioration in renal function

Supplementary Table 2

Plasmatherapy in cases of aHUS with functional deficiency of CFH

Case / Complement Profile / Plasmatherapy / Outcome
(f-up)
6mth female 57 / Not reported / PE with FFP as replacement
FFP infusions 2/wk / ESRD
(8yr)
33 yrs male 55 / Factor H 275
(450-600) mg/l
Normal factor B, I and properdin levels / PE (40mls/kg daily x 1week)
Tapered to weekly x 3mths
FFP (15mls/kg) weekly x 1 mth / CrCl 53ml/min (1yr)
3mth male 56 / Low C3 0.23 g/l,
Elevated C3d 63 mg/l
Low Factor H 85 mg/ml / PE weekly x 4mths
FFP (20mls/kg) (3yr) / GFR
50ml/min/1.73m2
1 yr 29 / Normal Factor H levels / FFP (30mls/kg x 2/week)
PE 40-45mls/kg weekly or every 4-5 weeks with FFP infusions in between
(1 yr) / GFR
50ml/min/1.73m2
4yr Twin I 28, 29
4.5yr Twin II
3 yrs 28 / Normal Factor H levels
Normal Factor H levels
Normal Factor H levels
Normal C3 levels / PE (40ml/kg/day x 10 days)
FFP 10ml/kg daily (during relapses)
Pre-Transplant PE
Post-Transplant PE
(daily for 7 days)
2 Recurrences Post-Transplant (PE daily)
PE 40ml/kg/day x 21 days
Recurrences: PE 40ml/kg daily x 10 days
Maintenance: PE 40mls/kg every 2 wks
(3.6yrs)
None following to initial presentation as immediate ESRF
None pre-first transplant
Prophylactic PE Pre-Second Transplant: PE X1 Pre-transplant
PE daily Post-Transplant
Tapered to PE weekly x 2mths
Further tapered to PE every 2 weeks / ESRD at 4 mths
Recurrent HUS post-transplantation
Creatinine 127umol/l
(10 yrs)
Normal renal function (6yrs)
Immediate ESRF
Recurrence post-first transplant
Transplantectomy
Recurrence post second transplant
Transplantectomy d75 due to late initiation of daily PE

Supplementary Table 3

Outcome of CFH-autoantibody associated aHUS with CFHR1 and CFHR3 Deficiency

Case / Complement Profile / Plasmatherapy / Outcome
9 yr female 9, 39 / C3 0.51 g/l
(0.68-1.38) g/l
C4 0.23 g/l
(0.18-0.6) g/l
Factor H 0.57 g/l
(0.35-0.59) g/l
Factor I 62 g/l
(38-58) mg/l / PE with FFP / ESRD without recurrence in renal allograft
5yr male 9
11yr male 9
8yr female 9
4yr female 9
10yr female 9
8yr male 9
6yr male 9
1yr male 9
9yr female 9
5yr male 9
4yr female 9
9yr female 9 / C3 0.61 g/l
(0.68-1.38) g/l
C4 0.1 g/l
(0.18-0.6) g/l
Factor H 0.37 g/l
(0.35-0.59) g/l
Factor I 39g/l
(38-58) mg/l
C3 0.57 g/l
(0.68-1.38) g/l
C4 0.15 g/l
(0.18-0.6) g/l
Factor H 0.44 g/l
(0.35-0.59) g/l
Factor I 70g/l
(38-58) mg/l
C3 0.86 g/l
(0.68-1.38) g/l
C4 0.25 g/l
(0.18-0.6) g/l
Factor H 0.49 g/l
(0.35-0.59) g/l
Factor I 58 g/l
(38-58) mg/l
C3 0.89 g/l
(0.68-1.38) g/l
C4 0.3 g/l
(0.18-0.6) g/l
Factor H 0.52 g/l
(0.35-0.59) g/l
Factor I 41 g/l
(38-58) mg/l
C3 0.92 g/l
(0.68-1.38) g/l
C4 0.2 g/l
(0.18-0.6) g/l
Factor H 0.29 g/l
(0.35-0.59) g/l
C3 1.08 g/l
(0.68-1.38) g/l
C4 0.36 g/l
(0.18-0.6) g/l
Factor H 0.5 g/l
(0.35-0.59) g/l
Factor I 74 g/l
(38-58) mg/l
C3 0.77 g/l
(0.68-1.38) g/l
C4 0.28 g/l
(0.18-0.6) g/l
Factor H 0.56 g/l
(0.35-0.59) g/l
Factor I 77 g/l
(38-58) mg/l
C3 1.59 g/l
(0.68-1.38) g/l
C4 0.38 g/l
(0.18-0.6) g/l
Factor H 0.67 g/l
(0.35-0.59) g/l
Factor I 75 g/l
(38-58) mg/l
Factor H 0.63 g/l
(0.35-0.59) g/l
C3 1.06 g/l
(0.68-1.38) g/l
C4 0.13 g/l
(0.18-0.6) g/l
Factor H 0.45 g/l
(0.35-0.59) g/l
Factor I 68 g/l
(38-58) mg/l
C3 0.85 g/l
(0.68-1.38) g/l
C4 0.24 g/l
(0.18-0.6) g/l / PE x 2 /week
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
PE x 1 every 2 weeks
Not reported
Not reported / Recovered renal function
Recovered renal function
ESRD
ESRD
ESRD
No recurrence in renal allograft
ESRD
ESRD
No recurrence in renal allograft
Recovered renal function
Recovered renal function
Recovered renal function
Recovered renal function
Recovered renal function
10 yr male 60
6.8  yr female 60
5yr male 60 / Low C3
High C3d
Not reported / PE (initial response)
PE & FFP (no response)
MMF (no response)
Rituximab (no response)
Cyclophosphamide (no response)
Immunoadsorption (no response)
PE
Prednisolone
MMF
PE & FFP / ESRD
Recovered renal function
CrCl 35-50 ml/min/1.73m2
5yr 87
4yr 87
4yr 87
6yr 87
8yr 87
3yr 87
7yr 87 / C3 55.7
(77-135) mg/dl
C4 8.85
(14-47) mg/dl
C3 86.2
(77-135) mg/dl
C4 28.4
(14-47) mg/dl
C3 117
(77-135) mg/dl
C4 16.6
(14-47) mg/dl
C3 66.7
(77-135) mg/dl
C4 16.7
(14-47) mg/dl
C3 58.5
(77-135) mg/dl
C4 19.6
(14-47) mg/dl
C3 81.3
(77-135) mg/dl
C4 40.6
(14-47) mg/dl
C3 58.5
(77-135) mg/dl
C4 19.6
(14-47) mg/dl / PE
PE
None
PE & PI
PE
None
PE with albumin / Recovered renal function
Recovered renal function
ESRD
Recovered renal function
Recovered renal function
ESRD
Death
7yr 61
9yr 61
10yr 61 / C3 0.54
(0.7-1.5) g/l
C4 0.26
(0.1-0.35) g/l
Factor B 0.16
(0.09-0.32) g/l
Factor H 60
(65-140) %
Factor I 104
(70-130) %
C3 0.42
(0.7-1.5) g/l
C4 0.33
(0.1-0.35) g/l
Factor B 0.13
(0.09-0.32) g/l
Factor H 73
(65-140) %
Factor I 72
(70-130) %
C3 0.68
(0.7-1.5) g/l
C4 0.23
(0.1-0.35) g/l
Factor B 0.21
(0.09-0.32) g/l
Factor H 58
(65-140) %
Factor I 115
(70-130) % / PE & PI
Pred/Aza/IVIG
PE & PI
Pred
PI / eGFR 54 ml/min/1.73m2
eGFR 57 ml/min/1.73m2
eGFR 112
ml/min/1.73m2
10 yr female 62 / C3 460 mg/l
(660-1250)
C4 130 mg/l
(93-380)
Factor B 68 mg/l
(90-320)
Factor H 91%
(65-140)
Normal ADAMTS13 / Pred/AZA/Rituximab
PE / ESRD
No recurrence in renal allograft

Supplementary Table 4

Plasmatherapy in cases of aHUS with complete or functional deficiency of CFI

Case / Complement Profile / Plasmatherapy / Outcome
0.5yr 65, 66
28 yr 65, 66 / C3 1150 mg/l
(660-1275) mg/l
Factor B 206 mg/l
(42-78) mg/l
Factor I 76 mg/l
(42-78) mg/l
C3 (p.Lys155Gln)
C3 694 mg/l
(660-1275) mg/l
Factor B 118 mg/l
(42-78) mg/l
Factor I 82 mg/l
(42-78) mg/l
DEL CFHR1 / Not reported
Not reported / Death
ESRD
18 yr 65
30 yr 65
39 yr 65
32 yr 65
31 yr 65
0.04 yr 65
22 yr 65
2 yr 65 / C3 857 mg/l
(660-1275) mg/l
Factor B 139 mg/l
(42-78) mg/l
Factor I 44 mg/l
(42-78) mg/l
C3 704 mg/l
(660-1275) mg/l
Factor B 107 mg/l
(42-78) mg/l
Factor I 40 mg/l
(42-78) mg/l
C3 583 mg/l
(660-1275) mg/l
Factor B 80 mg/l
(42-78) mg/l
Factor I 23 mg/l
(42-78) mg/l
C3 891 mg/l
(660-1275) mg/l
Factor B 104 mg/l
(42-78) mg/l
Factor I 28 mg/l
(42-78) mg/l
C3 545 mg/l
(660-1275) mg/l
Factor B 72 mg/l
(42-78) mg/l
Factor I 24 mg/l
(42-78) mg/l
Del CFHR1
C3 777 mg/l
(660-1275) mg/l
Factor B 129 mg/l
(42-78) mg/l
Factor I 40 mg/l
(42-78) mg/l
C3 738 mg/l
(660-1275) mg/l
Factor B 128 mg/l
(42-78) mg/l
Factor I 20 mg/l
(42-78) mg/l
C3 915 mg/l
(660-1275) mg/l
Factor B 176 mg/l
(42-78) mg/l
Factor I 67 mg/l
(42-78) mg/l
MCP (R69W) / Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported
Not reported / Relapses (2, 3 and 8 months)
ESRD (2 yrs)
ESRD (12 yrs)
No relapse (4 yr)
ESRD (18 mths)
ESRD
No relapse at 6 yrs
No relapse at 5 yrs
Two relapses (5, 7yrs) and lost from follow up
22 yr male 84 / C3 87.6 mg/l
(77-210) mg/l
C4 29.2 mg/l
(14-47) mg/l
Factor H 223.9 mg/l
(46.6 – 278.4) mg/l
Factor B 176 mg/l
(42-78) mg/l
Factor I 53%
(75-115)%
MCP 73%
(91-109)% / PE and FFP
Dialysis dependent (5m) / Renal function recovered and was dialysis free for 13 years
Peri-transplantation FFP
No HUS recurrence in renal allograft
26 yr female 82 / C3 58 mg/dL
(88 - 201 mg/dL)
C4 20 mg/dL
(16 - 47 mg/dL). ADAMTS13 activity 97% (normal range, ≥67%)
ADAMTS13 inhibitor <0.4 units (normal range, ≤0.4 units) / PE (initially daily; alternate days) / Recurrence in live-related renal transplant (1mth)
No response to PE nor FFP
Transplantectomy
28 yr female 63
47 yr female 63 / C3 781 mg/l
(660-1250) mg/l
C4 273 mg/l
(93-320) mg/l
Factor H 515 mg/l
(338-682) mg/l
Factor B 86 mg/l
(90-320) mg/l
Factor I 34 mg/l
(42-78) mg/l
MCP 763 (MFI)
(600-1500) MFI
C3 692 mg/l
(660-1250) mg/l
C4 203 mg/l
(93-320) mg/l
Factor H 510 mg/l
(338-682) mg/l
Factor B 80 mg/l
(90-320) mg/l
Factor I 32 mg/l
(42-78) mg/l
MCP 1201 (MFI)
(600-1500) MFI / PE & FFP for de novo TMA(690 days) in renal allograft (primary disease IgAN)
PE & FFP for de novo TMA(10 days) in renal allograft (primary disease nephroangiosclerosis) / No graft loss after one year
Graft loss after one year
17 mth female 66
6mth male 66
32 yr male 66 / C3 0.49
(0.77-1.38) g/l
Factor B 75
(59-154) %
C4 0.2
(0.12-0.33) mg/l
Factor H 79
(69-154)%
Factor I 91
(60-152)%
C1q 121
(76-136)%
C3d 11.5
(< 5 mg/l)
C4BP 95
(58-102)%
C3 0.59
(0.77-1.38) g/l
Factor B 100
(59-154) %
C4 0.12
(0.12-0.33) mg/l
Factor H 142
(69-154)%
Factor I 127
(60-152)%
C3 0.65
(0.77-1.38) g/l
Factor B 150
(59-154) %
C4 0.28
(0.12-0.33) mg/l
Factor H 118
(69-154)%
Factor I 107
(60-152)% / PE weekly
Post Transplant PE: recurrence
(no response)
PE (no response)
PE (no response) / ESRD
Posttransplant recurrence
Transplantectomy after 10 mths; platelets normalized
On dialysis
ESRD (7mths)
ESRD
Posttransplant recurrence at 11 mths
(no response to PE)
Transplantectomy after 12 mths
15mth female 63, 79, 81 / Normal Factor H levels
Normal Factor I levels
Loss of C3b cofactor activity
Increased C3d
Low C3
Alternative pathway 26% (pre plasma infusion) and 40% (post plasma infusion) / Plasma infusion
(20mls/kg) / Failed first transplant due to recurrence
Failed second transplant due to recurrence
Third transplant: recurrence of HUS
25 yrs 11
3yrs 11
9 mths 11
31 yrs 11, 79
3 yrs 11
26 yrs male 79 / Low C3
Normal C3
Factor I 98%
Normal C3
Factor I 77%
Normal C3
Normal C4
CH50 75%
(70-130%)
C3 990
(660-1250) mg/l
Factor B 123
(90-320) mg/l
Normal C4 256
(93-320) mg/l
H ag 107 (70-130)%
Factor I 36%
(70-130)%
Not available / Plasmatherapy: complete or partial remission (3/6)
Partial response to PE following second transplant
PE (no response)
Transplant recurrence
(no response) / ESRD
ESRD
ESRD
(within 7mths)
First transplant: immediate recurrence
(allograft loss)
Second transplant
ESRD
Recurrence in first transplant after 11yrs
No recurrence in second transplant
(2 years)
57 yr female 85
41 yr female 85 / C3 96 (77 – 210) mg/l
C4 42 (14-47) mg/l
Factor H 30
(12-56) mg/dl
Factor I 53
(75-115) %
MCP 62 (91-109) %
C3 84
(77 – 210) mg/l
C4 27 (14-47) mg/l
Factor H 30
(12-56) mg/dl
Factor I 46
(75-115) %
MCP 56
(91-109) % / PE (initial response)
No response following relapse (PE & FFP)
Not documented / ESRD
ESRD
0.16 yr 12
0 yr female 12
0.08 yr male 12 / C3 1000 mg/l
Factor B 190 mg/l
Factor I 112 mg/l
C3 1030 mg/l
Factor I 43 mg/l
C3 410 mg/l
Factor B 67 mg/l / Not documented
FFP / No ESRD