{"id":205,"date":"2018-04-23T12:06:48","date_gmt":"2018-04-23T12:06:48","guid":{"rendered":"http:\/\/edren.org\/ren\/?page_id=205"},"modified":"2021-01-29T15:22:26","modified_gmt":"2021-01-29T15:22:26","slug":"sle","status":"publish","type":"page","link":"https:\/\/edren.org\/ren\/handbook\/unithdbk\/individual-kidney-diseases\/sle\/","title":{"rendered":"SLE"},"content":{"rendered":"
Acute severe disease<\/span><\/strong><\/h5>\n

Patients with impaired and usually deteriorating renal function with diffuse proliferative nephritis + crescents, or serious disease affecting other organs have been treated with cyclophosphamide-based regimes for many years, and these remain the standard therapy today. Daily cyclophosphamide may still be used in very severe disease, but pulsed regimens have largely substiduted in other circumstances. Alternatives to cyclophosphamide are being increasingly explored. Increasingly, pulsed regimens are being preferred to daily administration of cyclophosphamide.<\/p>\n

Oral cyclophosphamide regimen.<\/span><\/strong>\u00a0 Prednisolone at 1mg\/kg\/day and cyclophosphamide at 2mg\/kg\/day, rounded down to the nearest 50mg.\u00a0 This is usually 100 or 150mg\/day.\u00a0 (2.5mg\/kg\/day almost invariably results in leucopenia after 2-3 weeks treatment followed by stop-start treatment).\u00a0 Use less in over-55s.\u00a0 Cyclophosphamide is arbitrarily given for 12 weeks followed by a change to azathioprine at 2mg\/kg\/day (usual start dose = cyclophosphamide dose) or to MMF.\u00a0 Prednisolone is tapered but generally more slowly than in vasculitis once below 20-25mg\/day.<\/p>\n

Pulsed cyclophosphamide regimens<\/span><\/strong> are described in detail below.\u00a0 These reduce toxicity and cumulative dose.\u00a0 They also prolong the patient\u2019s exposure to cyclophosphamide, possibly an advantage in chronic\/relapsing disease.\u00a0 Note that doses should be adjusted to achieve lowering of wbc in severe disease.\u00a0 Dose interval may also be reduced.<\/p>\n

Mycophenolate Mofetil (MMF)<\/span><\/strong>\u00a0is being increasingly used and early trials have not shown that it is inferior to cyclophosphamide.\u00a0 However SLE is a disease with long evolution.\u00a0 MMF has the advantage of avoiding gonadal toxicity and probably has fewer severe side effects overall.\u00a0 The dose used in trials has been 3g\/day, which may not be well tolerated.\u00a0 In subacute setting usually start at 500mg BD and increase at intervals of a few days.<\/p>\n

Plasma exchange<\/span><\/strong>\u00a0may be used in patients with very severe disease, especially if apparently not responding to drug treatment.\u00a0 Possible indications might be dialysis-dependent disease, encephalopathy.<\/p>\n

Pulse methylprednisolone<\/span><\/strong>\u00a0\u2013 we hardly ever use this, as there is no evidence that it adds anything to the above regimens, which all include prednisolone 60mg\/kg\/d, and there are added risks of infection, effects on bone, and sometimes severely exacerbated hypertension.<\/p>\n

Maintenance after acute severe disease<\/span><\/strong><\/h5>\n

In general if patient goes into remission and extrarenal manifestations are controlled, prednisolone is gradually tapered to 10mg\/day by 6-9 months, and 5-7.5mg by 1 year.\u00a0 Azathioprine is generally substituted for cyclophosphamide (as for systemic vasculitis) at 3 months; MMF is now an alternative, but the minimum dose should be 1g BD.<\/p>\n

We generally taper and stop steroids and then aza\/MMF at 18-24 months except in patients with continuing active disease, or who have had several or particularly severe flares of disease.\u00a0 Any deterioration in renal function, especially if baseline function is good, is usually managed after repeat biopsy.\u00a0 Minor or extra-renal flares are often treated with increased steroids followed by slower reduction.<\/p>\n

Pulsed Cyclophosphamide Therapy<\/span><\/strong><\/h5>\n

(Note that this regimen is different from our current pulsed cyclophosphamide regimen for small vessel vasculitis)<\/a> 750mg\/m2 is given with Mesna at monthly intervals for 6 months; 500mg\/m2 if elderly or at increased risk of leucopaenia.\u00a0 If WBC nadir (10-14 days post dose) is much >5,000, next dose is increased by 250mg\/m2 to max 1g\/m2).\u00a0 Consider reducing by 10-15% if WBC <3,500 or neutrophils <1,500.\u00a0 Delay subsequent doses if neutropenia persists (neutrophils <2,000). Reductions for low GFR: see below. Shorten dose interval in severe disease.<\/p>\n

Prednisolone is usually increased at the start of this treatment and tapered as above.\u00a0 Three 2-monthly (or two 3-monthly) doses are given after the first 6 pulses.\u00a0 At one year most patients are converted to azathioprine\/ MMF and then managed as above.\u00a0 Conversion can be delayed until later, and cyclophosphamide pulses continued for longer in patients believed to be at high risk from recurrent disease.<\/p>\n

Haemorrhagic cystitis is very uncommon when cyclophosphamide is used in this way.\u00a0 Mesna may cause fixed drug eruptions.<\/p>\n

Protocol for pulsed cyclophosphamide<\/span><\/strong><\/h5>\n

First pulse<\/span><\/strong><\/p>\n\n\n\n\n\n\n\n\n
\n

\u00a0Time<\/span><\/strong><\/p>\n<\/td>\n

Protocol for IV pulsed cyclophosphamide<\/span><\/strong><\/td>\n<\/tr>\n
\n
\u00a00<\/span><\/strong><\/div>\n<\/td>\n
500ml N saline over 2h plus 500ml oral fluid.<\/td>\n<\/tr>\n
\n
1.5 h<\/span><\/strong><\/div>\n<\/td>\n
Ondansetron 8mg oral or granisetron 1mg oral, and dexamethasone 10mg orally if patient not taking prednisolone (unlikely)<\/td>\n<\/tr>\n
\n
2.0h<\/span><\/strong><\/div>\n<\/td>\n
Cyclophosphamide in 250mls N saline over 1h, 750 mg\/m2<\/sup> or 12 mg\/kg (see above).<\/p>\n

Mesna (20% of the cyclophosphamide dose) added to the same bag<\/td>\n<\/tr>\n

\n
3.0h<\/span><\/strong><\/div>\n<\/td>\n
Mesna (40%) orally at 4 and 8h after end of infusion.<\/p>\n

Ondansetron 8mg orally two more doses (not required if using granisetron)\u00a0 AND<\/i>\u00a0 Domperidone 20mg orally 6h prn for 3 days.<\/p>\n

Advise oral intake of 2.5-3 litres over next 24h.<\/td>\n<\/tr>\n

\n
10-14d<\/span><\/strong><\/div>\n<\/td>\n
Check wbc (outpatients or GP).<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

For IV cyclophosphamide\/MESNA, contact Pharmacy at least one day in advance so that it will be ready when the patient arrives.\u00a0 A detailed protocol will come from the Pharmacy with the drug.<\/p>\n

Patients should be cautioned to seek help if they become febrile or otherwise unwell during cytotoxic therapy of this type.<\/p>\n

Subsequent pulses<\/span><\/strong><\/p>\n