International Survey on Diagnosis and Management of C3 Glomerulopathy (C3G) and atypical Haemolytic Uremic Syndrome (aHUS)

Please answer according to your knowledge of routine practice at your centre. If the information is unavailable or outside your scope, select “Don’t know” or “Not applicable.”

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1. Please enter your name

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2. Please enter your affiliation

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3. In case of publication, would you like to be in the author list?

Yes

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4. Country

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5. Type of centre

University hospital

Tertiary referral centre

Regional hospital

Other (please specify)

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6. Type of patient

Paediatric-only

Adult-only

Mixed adult and paediatric

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7. Type of professional completing the survey

Nephrologist

Paediatrician

Internal Medicine physician

Haematologist

Other (please specify)

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8. Approximate number of HUS cases managed per year

5–10

>10

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9. Approximate number of C3G cases managed per year

5–10

>10

SECTION 2: DIAGNOSTIC WORKUP

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10. Is ADAMTS13 activity testing available for suspected thrombotic microangiopathy (TMA) at your centre?

Yes, performed on-site

Yes, sent to a reference laboratory

Don’t know / Not Applicable

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11. What is the typical turnaround time for ADAMTS13 activity results?

Less than 24 hours

24-48 hours

3-5 days

>5 days

Don't know / Not applicable

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12. How is Shiga toxin or STEC infection assessed at your centre? (Select all that apply)

Stool or rectal swab culture

PCR for VTEC virulence genes in stool

Other (please specify)

Don't know / Not applicable

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13. Do you have access to complement testing for suspected aHUS or C3G beyond C3 and C4 levels?

Yes

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14. If yes, where is complement testing performed?

On-site at our centre

External reference laboratory (national)

External reference laboratory (international)

Don’t know/ Not applicable

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15. Which complement components/autoantibodies are routinely assessed? (Select all that apply)

C3, C4 levels

C3 breakdown products

CH50

AH50

Factor H levels

Factor I levels

Factor B levels

Soluble C5b-9

C5b-9 endothelial deposition

MCP (CD46) expression on neutrophils

Nephritic factors

Anti-Factor H antibodies

Anti-Factor B antibodies

Don't know / not applicable

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16. Typical turnaround time for complete complement components / autoantibodies results

<3 days

3-7 days

1-2 weeks

>2 weeks

Don't know / not applicable

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17. Do you perform genetic testing in patients with suspected or confirmed atypical HUS?

Routinely

Selectively

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18. Do you perform genetic testing in patients with suspected or confirmed C3G?

Routinely

Selectively

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19. Where is genetic testing performed?

On-site at our centre

External reference laboratory (national)

External reference laboratory (international)

Don’t know / Not applicable

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20. Which genes are routinely included in genetic testing (Select all that apply)

CFH

CFI

MCP (CD46)

CFB

ADAMTS13

THBD

DGKE

MMACHC

Don't know / not applicable

Other (please specify)

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21. Does your genetic testing detect copy number variations or genomic rearrangements in the CFH-CFHR gene cluster?

Yes

Don’t know / not applicable

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22. Does your reference genetic laboratory report complement risk haplotypes (e.g., MCP, CFH), and is this information used in clinical decision-making?

Yes, reported and used clinically

Reported but not used clinically

Not reported

Don't know / Not applicable

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23. Typical turnaround time for genetic results:

<2 weeks

2-4 weeks

1-3 months

>3 months

Don't know / Not applicable

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24. Which of the following techniques are available and routinely used in your centre for the pathologic evaluation and diagnosis of C3G? (Select all that apply)

Light microscopy

Immunofluorescence (IF) on frozen sections

Immunohistochemistry

IF on pronase-digested paraffin sections for light chain deposits

Electron microscopy

C4d staining

𝛌 / k staining

Don't know / not applicable

Other (please specify)

SECTION 3. TREATMENT STRATEGIES

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25. Is eculizumab available at your centre?

Yes

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26. Are there institutional or national approval requirements for eculizumab?

Yes (please specify below)

Don't know/ Not applicable

Institutional or national approval requirements for eculizumab:

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27. Are biosimilar complement inhibitors available at your centre?

Yes

Other (please specify)

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28. Is ravulizumab available at your centre?

Yes

Other (please specify)

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29. If yes, in which scenarios is ravulizumab preferred over eculizumab? (Select all that apply)

Used first line

Maintenance therapy in patients with confirmed primary (complement-mediated) aHUS

Paediatric patients

Adherence / logistical reasons

None

Don't know / Not applicable

Other (please specify)

Regarding treatment stategies in aHUS:

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30. If eculizumab is NOT available at your centre, how are patients with suspected aHUS managed?

Plasma exchange is used as a first-line therapy

Supportive care only

Patients are transferred to another centre with access to eculizumab

Don't know / Not applicable

Other (please specify)

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31. If eculizumab is available in your centre, under what conditions can it be initiated in the setting of aHUS?

Based on clinical judgement at presentation before ADAMTS13 activity results

Only after ADAMTS13 activity excludes TTP

Don't know / Not Applicable

Other (please specify)

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32. Indications for starting eculizumab for treatment of aHUS at your centre (Select all that apply):

Suspected primary (complement-mediated) atypical HUS, before genetic confirmation

Suspected secondary atypical HUS, before genetic study results

Confirmed primary (complement-mediated) atypical HUS

Confirmed secondary atypical HUS (please specify below)

Relapsing disease or post-transplant recurrence

Don't know / Not applicable

Other (please specify other indications)

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33. Regarding eculizumab use in STEC-HUS, which statement best reflects your centre's approach?

Eculizumab is not used, STEC-HUS is managed with supportive care only

Eculizumab may be considered as rescue therapy in severe cases

Eculizumab is used when complement-mediated TMA cannot be excluded

Eculizumab is used routinely in severe STEC-HUS

Don't know / Not applicable

Regarding treatment strategies in C3G:

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34. What is your centre's usual first-line therapy for C3G?

Corticosteroids in monotherapy

Corticosteroids and mycophenolate mofetil (MMF)

Complement inhibition

Supportive care only

Don't know / Not applicable

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35. If complement inhibition is used, do you have a choice of agent? (Select all that apply)

Eculizumab

Pegcetacoplan

Iptacopan

None

Other (please specify)

SECTION 4: FOLLOW-UP AND MONITORING

Question Title

36. What tests do you use to monitor complement blockade in patients receiving C5 inhibitors? (Select all that apply)

CH50

AP100

AH50

Eculizumab levels

Free C5

sC5b-9

C5b9 endothelial deposits

None of the above

Don't know / Not applicable

Other (please specify)

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37. In pregnant patients receiving eculizumab, do you monitor drug levels and/or complement activity to guide dosing?

Yes

Don’t know / Not applicable

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38. In native (non-transplant) aHUS, when do you stop treatment with eculizumab
(Select all that apply):

If patient has no pathogenic complement variants in genetic testing

If patient remains on dialysis after 3-6 months, regardless of genetic testing results

In the presence of a pathogenic complement mutation, after 3-6 months, in case of response to treatment with an eGFR>30

If clear secondary cause subsequently identified

If a patient has biallelic mutations in DGKE and no complement mutations

If a patient has biallelic mutations in MMACHC and no complement
mutations

Other (please specify)

SECTION 5: KIDNEY TRANSPLANTATION

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39. Are patients with aHUS transplanted at your centre?

Yes

Don’t know / Not applicable

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40. Are patients with C3G transplanted at your centre?

Yes

Don’t know / Not applicable

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41. Is genetic testing mandatory before transplant for STEC-HUS?

Yes

Don’t know

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42. Is genetic testing mandatory prior to kidney transplantation in patients with a history of aHUS?

Yes

Don’t know / Not applicable

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43. Is genetic testing mandatory prior to kidney transplantation in patients with a history of C3G?

Yes

Don’t know / Not applicable

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44. In which situations do you use prophylactic complement inhibition at
transplantation in patients with aHUS? (Select all that apply)

Routinely

In the presence pathogenic defects in complement genes or FH autoantibodies

In patients with negative genetic study but loss of previous graft

Never

Don't know / Not applicable

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45. Do you use prophylactic complement inhibition at transplantation in patients with C3G? (Please select one answer only)

Yes, routinely

Yes, selectively

Don't know / Not applicable

International Survey on Diagnosis and Management of C3 Glomerulopathy (C3G) and atypical Haemolytic Uremic Syndrome (aHUS)

Question Title

* 1. Please enter your name

Question Title

* 2. Please enter your affiliation

Question Title

* 3. In case of publication, would you like to be in the author list?

Question Title

* 4. Country

Question Title

* 5. Type of centre

Question Title

* 6. Type of patient

Question Title

* 7. Type of professional completing the survey

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* 8. Approximate number of HUS cases managed per year

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* 9. Approximate number of C3G cases managed per year

Question Title

* 10. Is ADAMTS13 activity testing available for suspected thrombotic microangiopathy (TMA) at your centre?

Question Title

* 11. What is the typical turnaround time for ADAMTS13 activity results?

Question Title

* 12. How is Shiga toxin or STEC infection assessed at your centre? (Select all that apply)

Question Title

* 13. Do you have access to complement testing for suspected aHUS or C3G beyond C3 and C4 levels?

Question Title

* 14. If yes, where is complement testing performed?

Question Title

* 15. Which complement components/autoantibodies are routinely assessed? (Select all that apply)

Question Title

* 16. Typical turnaround time for complete complement components / autoantibodies results

Question Title

* 17. Do you perform genetic testing in patients with suspected or confirmed atypical HUS?

Question Title

* 18. Do you perform genetic testing in patients with suspected or confirmed C3G?

Question Title

* 19. Where is genetic testing performed?

Question Title

* 20. Which genes are routinely included in genetic testing (Select all that apply)

Question Title

* 21. Does your genetic testing detect copy number variations or genomic rearrangements in the CFH-CFHR gene cluster?

Question Title

* 22. Does your reference genetic laboratory report complement risk haplotypes (e.g., MCP, CFH), and is this information used in clinical decision-making?

Question Title

* 23. Typical turnaround time for genetic results:

Question Title

* 24. Which of the following techniques are available and routinely used in your centre for the pathologic evaluation and diagnosis of C3G? (Select all that apply)

Question Title

* 25. Is eculizumab available at your centre?

Question Title

* 26. Are there institutional or national approval requirements for eculizumab?

Question Title

* 27. Are biosimilar complement inhibitors available at your centre?

Question Title

* 28. Is ravulizumab available at your centre?

Question Title

* 29. If yes, in which scenarios is ravulizumab preferred over eculizumab? (Select all that apply)

Question Title

* 30. If eculizumab is NOT available at your centre, how are patients with suspected aHUS managed?

Question Title

* 31. If eculizumab is available in your centre, under what conditions can it be initiated in the setting of aHUS?

Question Title

* 32. Indications for starting eculizumab for treatment of aHUS at your centre (Select all that apply):

Question Title

* 33. Regarding eculizumab use in STEC-HUS, which statement best reflects your centre's approach?

Question Title

* 34. What is your centre's usual first-line therapy for C3G?

Question Title

* 35. If complement inhibition is used, do you have a choice of agent? (Select all that apply)

Question Title

* 36. What tests do you use to monitor complement blockade in patients receiving C5 inhibitors? (Select all that apply)

Question Title

* 37. In pregnant patients receiving eculizumab, do you monitor drug levels and/or complement activity to guide dosing?

Question Title

* 38. In native (non-transplant) aHUS, when do you stop treatment with eculizumab(Select all that apply):

Question Title

* 39. Are patients with aHUS transplanted at your centre?

Question Title

1. Please enter your name

2. Please enter your affiliation

3. In case of publication, would you like to be in the author list?

4. Country

5. Type of centre

6. Type of patient

7. Type of professional completing the survey

8. Approximate number of HUS cases managed per year

9. Approximate number of C3G cases managed per year

10. Is ADAMTS13 activity testing available for suspected thrombotic microangiopathy (TMA) at your centre?

11. What is the typical turnaround time for ADAMTS13 activity results?

12. How is Shiga toxin or STEC infection assessed at your centre? (Select all that apply)

13. Do you have access to complement testing for suspected aHUS or C3G beyond C3 and C4 levels?

14. If yes, where is complement testing performed?

15. Which complement components/autoantibodies are routinely assessed? (Select all that apply)

16. Typical turnaround time for complete complement components / autoantibodies results

17. Do you perform genetic testing in patients with suspected or confirmed atypical HUS?

18. Do you perform genetic testing in patients with suspected or confirmed C3G?

19. Where is genetic testing performed?

20. Which genes are routinely included in genetic testing (Select all that apply)

21. Does your genetic testing detect copy number variations or genomic rearrangements in the CFH-CFHR gene cluster?

22. Does your reference genetic laboratory report complement risk haplotypes (e.g., MCP, CFH), and is this information used in clinical decision-making?

23. Typical turnaround time for genetic results:

24. Which of the following techniques are available and routinely used in your centre for the pathologic evaluation and diagnosis of C3G? (Select all that apply)

25. Is eculizumab available at your centre?

26. Are there institutional or national approval requirements for eculizumab?

27. Are biosimilar complement inhibitors available at your centre?

28. Is ravulizumab available at your centre?

29. If yes, in which scenarios is ravulizumab preferred over eculizumab? (Select all that apply)

30. If eculizumab is NOT available at your centre, how are patients with suspected aHUS managed?

31. If eculizumab is available in your centre, under what conditions can it be initiated in the setting of aHUS?

32. Indications for starting eculizumab for treatment of aHUS at your centre (Select all that apply):

33. Regarding eculizumab use in STEC-HUS, which statement best reflects your centre's approach?

34. What is your centre's usual first-line therapy for C3G?

35. If complement inhibition is used, do you have a choice of agent? (Select all that apply)

36. What tests do you use to monitor complement blockade in patients receiving C5 inhibitors? (Select all that apply)

37. In pregnant patients receiving eculizumab, do you monitor drug levels and/or complement activity to guide dosing?

38. In native (non-transplant) aHUS, when do you stop treatment with eculizumab
(Select all that apply):

39. Are patients with aHUS transplanted at your centre?

40. Are patients with C3G transplanted at your centre?

41. Is genetic testing mandatory before transplant for STEC-HUS?

42. Is genetic testing mandatory prior to kidney transplantation in patients with a history of aHUS?

43. Is genetic testing mandatory prior to kidney transplantation in patients with a history of C3G?

44. In which situations do you use prophylactic complement inhibition at
transplantation in patients with aHUS? (Select all that apply)

45. Do you use prophylactic complement inhibition at transplantation in patients with C3G? (Please select one answer only)