Management and strategy plan: SLE with CKD

1. First, work out what kind of CKD this is

2. Treatment for every patient with SLE

• Hydroxychloroquine (HCQ) for life. The dose is ≤5 mg/kg/day of actual body weight. Reduce it at eGFR below 30 because toxicity risk rises, and screen the retina yearly. HCQ lowers flares, protects the kidney, reduces thrombosis, and improves survival.
• Minimise glucocorticoids. Aim for ≤5 mg/day of prednisone, or off, as soon as is safe.
• Control extra-renal disease (skin, joints, serositis) with the same steroid-sparing approach.
• Sun protection, stopping smoking, exercise, and vaccination (see section 6).

3. Active LN (class III or IV, with or without V)

1. Glucocorticoids + mycophenolic acid analogue (MPAA, e.g. mycophenolate mofetil) + belimumab.
2. Glucocorticoids + MPAA + a calcineurin inhibitor (CNI), preferably voclosporin. Use this only when eGFR is above about 45. The trials excluded lower eGFR, and CNIs cause haemodynamic nephrotoxicity.
3. Glucocorticoids + low-dose IV cyclophosphamide (Euro-Lupus: 500 mg every 2 weeks for 6 doses). Use this when adherence is a concern, or in a patient who can't take MPAA.
4. Dual therapy (glucocorticoids + MPAA) is acceptable when triple therapy isn't feasible.

• At least a 25% fall by 3 months.
• At least a 50% fall by 6 months.
• UPCR below 0.5 to 0.7 g/g by 12 months, extending to 24 months if the trend is improving.

4. Adjustments when CKD is already advanced

• eGFR below 30 with high chronicity and low activity: the benefit of intensive immunosuppression falls and infection risk rises. Treat only the active component, using lower-intensity regimens.
• CNIs: avoid at eGFR below about 45.
• Cyclophosphamide: reduce the dose for renal impairment.
• Azathioprine: reduce the dose, and check TPMT/NUDT15 status.
• MMF: usually fine, but watch for cytopenias and infection.
• Belimumab: no renal dose change.
• Avoid nephrotoxins: NSAIDs, aminoglycosides, and contrast unless essential.
• Reassess at 3 to 6 months. If there has been no response and the chronicity is high, stop escalating and move to supportive and conservative care.

5. CKD nephroprotection (applies to all)

• BP: target about <120 systolic (KDIGO 2021 CKD) if tolerated, and at least <130/80.
• RAAS blockade: an ACE inhibitor or ARB at maximum tolerated dose for proteinuria. Monitor potassium and creatinine. Stop if the patient is pregnant, planning pregnancy, or volume-depleted.
• SGLT2 inhibitor: reasonable at eGFR ≥20 once the lupus is quiet, because CKD trials show kidney benefit. The data in active LN are limited and genital infection risk is higher on immunosuppression. Specialist judgement is needed.
• Statin: SLE and CKD together carry high cardiovascular risk.
• Diet: sodium <2 g/day, protein about 0.8 g/kg/day, stop smoking, maintain weight.
• CKD complications: treat anaemia, CKD-mineral bone disease, metabolic acidosis, and hyperkalaemia as they arise.
• Bone health: calcium, vitamin D, and a bisphosphonate or alternative when on prolonged steroids and eGFR allows.

6. Safety, infection, and comorbidities

• Vaccines (non-live): influenza, COVID-19, pneumococcal, recombinant zoster, HBV, and HPV as indicated. Ideally give them before rituximab or intensive therapy.
• Screen for HBV, HCV, HIV, and TB before starting immunosuppression.
• PJP prophylaxis (TMP-SMX, dose-adjusted for eGFR) when on high-dose steroids plus a second agent.
• Antiphospholipid antibodies: test everyone. Treat thrombosis with warfarin. Avoid DOACs in triple-positive APS.
• Pregnancy: plan it when the disease has been quiet for at least 6 months. Stop MMF and cyclophosphamide, and switch to azathioprine (± a CNI). Continue HCQ and start low-dose aspirin.
• Contraception: avoid oestrogen in active disease or APS.
• Cancer screening: cervical screening and skin checks, especially after cyclophosphamide.

7. Refractory disease

• Confirm adherence and check drug levels (MPA AUC if available).
• Repeat the biopsy to distinguish active disease from scarring.
• Options: switch between cyclophosphamide and MPAA, add belimumab or a CNI, or give rituximab or obinutuzumab.
• CAR-T therapy is under trial. Anifrolumab has no established LN indication yet.

8. Kidney failure

• Transplant is preferred over long-term dialysis. Aim for quiescent lupus for about 6 months and check APS status first.
• Recurrence in the graft is uncommon (a few percent).
• Dialysis: continue HCQ and monitor serology. Extra-renal flares tend to ease on dialysis but infection risk rises.
• Do not stop immunosuppression abruptly after starting dialysis unless there is clear reason to.

9. Monitoring schedule

Practical summary

1. Classify the kidney problem: active, chronic, or other.
2. Give HCQ to everyone and use steroids sparingly.
3. For active class III/IV disease, use triple therapy (belimumab or voclosporin with MPAA and a short steroid course), or low-dose cyclophosphamide.
4. Maintain for at least 3 years.
5. Treat the CKD with ACEi/ARB, BP control, ± SGLT2i, and a statin.
6. Prevent infection, plan pregnancy, and check APS.
7. In advanced scarring, protect the kidney rather than escalate immunosuppression.
8. Prepare early for transplant.