C3G Recurrence following Transplantation

Eculizumab in the treatment of C3G

NHS England have approved funding for the use of eculizumab in the treatment of recurrence of C3 glomerulopathy post-kidney transplant (NHS England: 16054/P).

All enquiries relating to this policy should be sent directly to atypical.hus@nhs.net

Cases can be discussed with the on-call consultant and clinical details summarised in our C3G checklist

Eligibility requires that all of the following criteria are met:

a)      A primary renal diagnosis of C3 glomerulopathy confirmed by renal biopsy including light microscopy, immunofluorescence and electron microscopy.

b)      Recurrent disease characterized on biopsy by an active glomerulonephritis with at least one cellular crescent.  Histopathology will be reviewed by a single centre with expertise in the pathology of C3 glomerulopathy. 

c)       Evidence of glomerular C9 deposition on transplant biopsy.

d)      Recurrent disease occurring at any time post-transplant.

e)      Evidence at the time of recurrence of a significant decline of transplant function (>20% decline in eGFR) within the previous three months. This criterion will not be necessary if the recurrence occurs immediately after transplantation when transplant function has not yet been established.

f)       No other cause for the decline in transplant function can be identified.

Criteria (b) and (c) require expert review of renal histology.

The single centre with expertise in the pathology of C3 glomerulopathy is the Imperial C3 glomerulopathy Centre, Imperial College Healthcare NHS Trust (C3Gimperial@nhs.net)

Details on when to send a set of slides to the expert pathologist are in the referral pathway.

Referral Pathway and Policy Implementation

The policy is implemented by an expert panel in liaison with the referring clinical team.

The panel comprise experts from Newcastle upon Tyne Hospitals NHS Foundation Trust (National Renal Complement Therapeutics Centre) and Imperial College Healthcare NHS Trust (Imperial C3 glomerulopathy Service, C3Gimperial@nhs.net).

What to do if you have identified a case of recurrent C3 glomerulopathy

A referral should contain sufficient clinical and pathological information to allow the expert panel to be confident that the starting criteria can be met.

Information should be sent to atypical.hus@nhs.net

The panel will review the information and then recommend that renal specimens are sent to the Imperial C3 glomerulopathy Service, Imperial College Healthcare NHS Trust.

This will provide expert pathology review and assessment of glomerular complement C9 deposition within the transplant.

Once pathological specimens have been received, the expert panel aims to issue a final decision within 5 working days.

What to do if your patient has been approved for eculizumab?

Protocols for vaccination and prophylactic antibiotics to reduce the risk of meningococcal infection and dosing of eculizumab are identical to those recommended for treatment of atypical HUS.

Approval is for a 4 month treatment course.

After this the expert panel will review clinical data with the referring clinical team to determine treatment outcome.

If there is loss of the graft function despite treatment, or if there is ongoing deterioration in graft function (eGFR) with no evidence of response to treatment, eculizumab is withdrawn.

If there is stabilisation of graft function (eGFR) or an improvement in graft function (eGFR), eculizumab is withdrawn, but may be reintroduced if there is subsequent deterioration in graft function and the initial starting eligibility criteria are fulfilled.

Eculizumab Dosage

The dose of Eculizumab for induction and maintenance is fixed for adults. For children and adolescents dose is adjusted according to body weight. Complete details of dosing schedules are available at: https://www.medicines.org.uk/EMC/medicine/19966/SPC/Soliris/

Dosing of Eculizumab

Adult dosing schedule

Paediatric dosing schedule - Patient body weight 40 kg or more:

Paediatric dosing schedule - Patient body weight 30 kg to less than 40 kg:

Paediatric dosing schedule - Patient body weight 20 kg to less than 30 kg:

Paediatric dosing schedule - Patient body weight 10 kg to less than 20 kg:

Paediatric dosing schedule - Patient body weight 5 kg to less than 10 kg:

Initial Dose (dose on day 0, 7, 21 and 28)

900 mg via 35 minute IV infusion then every 7 days for the first 4 doses, followed by 1200 mg for the fifth dose 7 days later.

9900 mg via 35 minute IV infusion then every 7 days for the first 4 doses, followed by 1200 mg for the fifth dose 7 days later.

600 mg via 35 minute IV infusion repeated after 7 days then followed by 900 mg for the third dose 7 days later.

600 mg via 35 minute IV infusion repeated after 7 days then followed by 600 mg for the third dose 7 days later.

600 mg via 35 minute IV infusion once, followed by 300 mg for the second dose 7 days later.

300 mg via 35 minute IV infusion once, followed by 300 mg for the second

Maintenance dose (fortnightly dose starting day 35)

1200 mg via 35 minute IV infusion every 14 days.

900 mg via 35 minute IV infusion every 14 days.

600 mg via 35 minute IV infusion every 14 days.

300 mg via 35 minute IV infusion every 14 days.

300 mg via 35 minute IV infusion every 21 days.

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Diagnostic Testing in C3G

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Treatment of C3G

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