Lupus Nephritis in Spain: Symptoms, Causes & Treatment | aihealz
Nephrologysevere
Lupus Nephritis.Care & specialists in Spain
In Spain, lupus Nephritis is managed by nephrologists. Lupus nephritis is glomerular injury caused by systemic lupus erythematosus, affecting roughly 40-60% of adults and 60-80% of children with SLE within 5 years of diagnosis. Immune complexes containing anti-double-stranded DNA antibody and nuclear antigens deposit in the glomerulus, triggering complement activation, mesangial proliferation, and capillary wall injury.
Lupus nephritis (ICD-10: M32.14, N08) is glomerular injury secondary to systemic lupus erythematosus, caused by deposition of circulating immune complexes containing anti-nuclear and anti-DNA antibodies in the kidney. The disease is histologically heterogeneous and is classified by the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) system into six classes: class I (minimal mesangial), class II (mesangial proliferative), class III (focal, less than 50% of glomeruli involved), class IV (diffuse, 50% or more of glomeruli involved, the most severe proliferative form), class V (membranous), and class VI (advanced sclerosing, more than 90% globally sclerosed). Classes III and IV are subclassified as active (A), chronic (C), or both, and class V may coexist with III or IV. Immunofluorescence typically shows a 'full-house' pattern (IgG, IgA, IgM, C3, and C1q) — a feature highly suggestive of lupus when present.
key facts
Prevalence
Lupus nephritis develops in 40-60% of adults and 60-80% of children with SLE, with annual incidence of overt nephritis around 0.4-0.7 per 100,000 in Western populations
Demographics
Female:male ratio 9:1; higher prevalence and severity in Black, Hispanic, Asian, and Indigenous populations
Avg. age
Median age at lupus nephritis onset 25-35 years; pediatric SLE often develops nephritis within the first year
Global cases
Roughly 1.5-3 million people worldwide; lupus nephritis is the leading cause of end-stage kidney disease attributable to autoimmune disease
Specialist
Nephrology
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How you might notice it
The key symptoms of Lupus Nephritis are: Foamy urine and ankle swelling reflecting proteinuria above 0.5-3.5 g/day, the most common presenting feature., Cola-coloured or visibly bloody urine during severe class III or IV flares, with dysmorphic red blood cells and red cell casts on microscopy., Bilateral lower extremity oedema, periorbital swelling, and weight gain from nephrotic syndrome in class V or mixed disease., New or worsening hypertension, often resistant to single-agent therapy, in 30-50% of patients at presentation., Fatigue, malaise, and reduced exercise tolerance from anemia of chronic disease, uremia, or active lupus., Malar (butterfly) rash, photosensitive cutaneous lupus, oral ulcers, alopecia, and arthralgia signalling concurrent systemic lupus activity., Pleuritic chest pain and serositis with pleural or pericardial effusions during severe SLE flares..
01Foamy urine and ankle swelling reflecting proteinuria above 0.5-3.5 g/day, the most common presenting feature.
02Cola-coloured or visibly bloody urine during severe class III or IV flares, with dysmorphic red blood cells and red cell casts on microscopy.
03Bilateral lower extremity oedema, periorbital swelling, and weight gain from nephrotic syndrome in class V or mixed disease.
04New or worsening hypertension, often resistant to single-agent therapy, in 30-50% of patients at presentation.
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How it’s diagnosed
diagnosis
Diagnosis begins with routine SLE surveillance — urinalysis, urine protein-to-creatinine ratio, blood pressure, serum creatinine, complement (C3 and C4), and anti-dsDNA at every clinic visit. Suspected lupus nephritis is defined by KDIGO 2024 and ACR criteria as proteinuria above 0.5 g/day (or urine protein-to-creatinine ratio above 500 mg/g) and/or active urinary sediment (red cells, red cell casts) in a patient meeting SLE classification criteria. A kidney biopsy is recommended in nearly all patients with proteinuria above 0.5 g/day to confirm the diagnosis, define the ISN/RPS class, score activity and chronicity, and exclude alternative or coexisting disease (lupus podocytopathy, APOL1 nephropathy, thrombotic microangiopathy). Light microscopy assesses glomerular and tubulointerstitial changes; immunofluorescence usually shows the characteristic full-house pattern (IgG, IgA, IgM, C3, C1q); electron microscopy localises deposits (mesangial, subendothelial, subepithelial). Class III, IV, V, and mixed lesions carry distinct treatment implications. Adjunctive investigations include antiphospholipid antibody screen (anticardiolipin, anti-beta-2-glycoprotein-I, lupus anticoagulant), thrombotic microangiopathy markers (haptoglobin, LDH, blood film), and viral hepatitis screen before immunosuppression. The activity and chronicity indices (NIH or modified) guide intensity of induction therapy.
Key tests
01
Urinalysis with phase-contrast microscopyDetects active urinary sediment — dysmorphic red blood cells, red cell casts, leukocyte casts
02
Urine protein-to-creatinine ratio and 24-hour urine collectionQuantifies proteinuria, the major driver of nephron loss and a key trial endpoint
03
Serum creatinine and estimated GFRQuantifies kidney function and monitors response to therapy
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Treatment & cost
medical treatments
✓Hydroxychloroquine 5 mg/kg/day (max 400 mg)
✓Mycophenolate mofetil 2-3 g/day in divided doses
✓Cyclophosphamide (Euro-Lupus low-dose IV: 500 mg every 2 weeks for 6 doses, or NIH regimen 0.5-1 g/m2 monthly for 6 months)
✓Belimumab 10 mg/kg IV monthly after weekly loading (or 200 mg subcutaneous weekly)
surgical options
Kidney transplantation5-year graft survival 80-85% for living-donor and 70-75% for deceased-donor; recurrence of lupus nephritis in the graft 2-10%
Arteriovenous fistula creation for haemodialysis accessPrimary patency 60-70% at 12 months; maturation rate above 80% in non-diabetic patients
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Causes & risk factors
known causes
Systemic lupus erythematosus
Lupus nephritis is the kidney manifestation of SLE, an autoimmune disease driven by autoantibodies against nuclear antigens (dsDNA, histones, nucleosomes, Sm, Ro). Immune complexes deposit in the kidney mesangium, subendothelium, and subepithelium, activating complement and recruiting inflammatory cells.
Anti-double-stranded DNA antibodies
Anti-dsDNA antibodies are present in 60-80% of patients with active lupus nephritis. They bind nucleosomes deposited in the glomerular basement membrane, fix complement, and amplify glomerular injury. Rising titres predict renal flares.
Complement system activation and consumption
Immune complexes activate the classical complement pathway, consuming C3 and C4. Low complement levels at SLE diagnosis carry a 2-3 fold higher risk of nephritis development within 5 years.
Genetic susceptibility
HLA-DR2, HLA-DR3, and complement deficiencies (C1q, C2, C4) confer the strongest genetic risk. Genome-wide studies have identified over 100 SLE susceptibility loci including STAT4, IRF5, and ITGAM.
Hormonal and environmental triggers
Estrogens, ultraviolet light, smoking, Epstein-Barr virus infection, and silica exposure precipitate lupus and renal flares. The 9:1 female predominance and pregnancy-associated flares reflect the role of sex hormones.
Drug-induced lupus with renal involvement
Hydralazine, procainamide, anti-TNF biologics, and minocycline can cause lupus-like disease, occasionally with mild nephritis. The disease typically remits within 6 months of stopping the offending drug.
risk factors
Confirmed diagnosis of systemic lupus erythematosus
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Living with it
01Maintain lifelong hydroxychloroquine 5 mg/kg/day in all SLE patients to halve flare risk and improve renal outcomes.
02Use broad-spectrum sun protection (SPF 50+) and avoid tanning beds — UV exposure precipitates SLE and lupus nephritis flares.
04Plan pregnancy when nephritis has been quiescent for at least 6 months on safe medications (hydroxychloroquine, azathioprine, tacrolimus, low-dose steroids).
05Vaccinate against influenza, pneumococcus, SARS-CoV-2, HPV, and shingles before immunosuppression where possible.
06Screen all SLE patients with urinalysis, urine protein-to-creatinine ratio, blood pressure, complement, and anti-dsDNA at every clinic visit.
recommended foods
•Mediterranean-style diet rich in vegetables, fruits, whole grains, fish, and olive oil
•Vitamin-D-rich foods (oily fish, fortified dairy, egg yolks) plus supplementation to keep 25-OH-vitamin-D above 30 ng/mL
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When to seek help
why see a nephrology
Lupus nephritis is managed jointly by nephrology and rheumatology. Early specialist referral allows timely biopsy, ISN/RPS classification, and induction therapy — delays beyond 3 months from proteinuria onset are associated with worse renal survival. Refractory or rapidly progressive disease, pregnancy, and end-stage kidney disease should be managed at tertiary centres.
01End-stage kidney disease requiring dialysis or transplantation in 10-30% within 10-15 years; monitor eGFR every 3 months during active disease.
02Treatment-related infections (pneumonia, varicella zoster, opportunistic pathogens including Pneumocystis jirovecii) — vaccinate and provide prophylactic trimethoprim-sulfamethoxazole when on high-dose immunosuppression.
03Cardiovascular disease (coronary disease, stroke, peripheral vascular disease) — risk doubled to tripled compared with the general population; aggressive risk-factor control needed.
04Steroid toxicity: osteoporosis, avascular necrosis (especially femoral head), diabetes, cataract, weight gain — minimised by lower-dose protocols and bone-protective therapy.
05Premature gonadal failure with high-dose cyclophosphamide; preserved by Euro-Lupus regimen and GnRH agonist co-therapy.
Class I — Minimal mesangial lupus nephritisNormal light microscopy with mesangial immune deposits on immunofluorescence and electron microscopy. Asymptomatic; no specific treatment beyond SLE control.
Class II — Mesangial proliferative lupus nephritisPure mesangial hypercellularity. Microscopic hematuria and low-grade proteinuria; renal prognosis excellent with hydroxychloroquine and treatment of the underlying lupus.
Class III — Focal lupus nephritis (A, A/C, C)Subendothelial deposits with proliferation in under 50% of glomeruli. Active lesions cause hematuria, proteinuria, and falling eGFR; requires immunosuppressive induction.
Class IV — Diffuse lupus nephritis (S/G, A/C)Subendothelial deposits and proliferation in 50% or more of glomeruli — the commonest and most severe proliferative form. Frequent nephrotic syndrome, hypertension, and acute kidney injury.
Class V — Membranous lupus nephritisSubepithelial immune deposits causing thickened glomerular capillary walls. Presents with nephrotic-range proteinuria; may coexist with class III or IV (mixed class V/III or V/IV).
Class VI — Advanced sclerosing lupus nephritisMore than 90% of glomeruli globally sclerosed. Represents end-stage disease; immunosuppression no longer beneficial and renal replacement therapy is the focus.
Living with Lupus Nephritis
Timeline
Proteinuria begins to fall within 4-8 weeks of starting induction therapy. Complete renal response (proteinuria under 0.5 g/g and normal creatinine) is achieved by 6-12 months in 25-45% with mycophenolate plus glucocorticoids and 40-50% when belimumab or voclosporin is added. Maintenance therapy continues for at least 3-5 years; relapses occur in 20-40% over 5 years and are managed with reinduction.
Lifestyle
01Take hydroxychloroquine every day even when feeling well — adherence is the strongest modifiable predictor of remission.
02Use SPF 50+ broad-spectrum sunscreen daily on exposed skin.
03Stop smoking and limit alcohol to under 14 units per week.
04Maintain a healthy body mass index of 18.5-24.9 kg/m2 and treat obesity with diet, exercise, and weight-loss medications where appropriate.
05Restrict sodium to under 2 g/day during active nephritis and oedematous states.
06Discuss reliable contraception with the rheumatology team while on teratogenic medications (mycophenolate, cyclophosphamide).
Daily management
01Take hydroxychloroquine, mycophenolate or azathioprine, and prednisolone at the same time each day.
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Complementary approaches
Multitarget therapy (mycophenolate plus tacrolimus plus prednisolone)Used in some Asian centres for refractory or mixed class V/IV disease. Provides simultaneous T- and B-cell suppression and is supported by Chinese RCT data (Liu et al. 2015).
Vitamin D supplementation (1,000-2,000 IU/day)Most SLE patients are vitamin D deficient. Supplementation improves disease activity scores in some small RCTs and is supported by EULAR adjunctive recommendations.
Choosing a doctor
Choose a nephrologist with a percutaneous biopsy programme and a rheumatologist experienced in SLE classification and biologic therapy. For pregnant or pregnancy-planning patients, identify a high-risk obstetric unit experienced in lupus nephritis. Ask whether the centre uses lower-dose glucocorticoid protocols and has access to belimumab and voclosporin.
Lupus Research Alliance →Research foundation funding SLE and lupus nephritis trials, with patient-focused educational resources.
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Frequently asked
What is lupus nephritis?▾▴
Lupus nephritis is kidney inflammation caused by systemic lupus erythematosus. Immune complexes containing antibodies against the patient's own DNA deposit in the kidney filters, triggering inflammation and scarring. It causes blood and protein in the urine, high blood pressure, and reduced kidney function.
What percentage of lupus patients get lupus nephritis?▾▴
Around 40-60% of adults and 60-80% of children with systemic lupus erythematosus develop lupus nephritis, usually within 5 years of SLE diagnosis. Lupus nephritis is more common and more severe in Black, Hispanic, Asian, and Indigenous populations.
What are the symptoms of lupus nephritis?▾▴
Symptoms include foamy urine from heavy protein loss, ankle and facial swelling, cola-coloured urine during severe flares, fatigue, weight gain, and new or worsening high blood pressure. Many patients are detected by routine urinalysis before symptoms develop.
How is lupus nephritis diagnosed?▾▴
Diagnosis requires proteinuria above 0.5 g/day or active urinary sediment in a patient with SLE, confirmed by a kidney biopsy showing characteristic immune-complex deposits. Supporting tests include serum creatinine, complement C3/C4, anti-double-stranded DNA, and antiphospholipid antibodies.
Is lupus nephritis curable?▾▴
Lupus nephritis is not curable but is highly controllable. With modern induction-maintenance therapy, 80-90% achieve at least partial renal response. Sustained remission can last decades, but flares occur in 20-40% over 5 years and require careful long-term follow-up.
What is the life expectancy with lupus nephritis?▾▴
Five-year renal survival is now above 90% and 10-year survival is 80-85% with modern treatment. Cardiovascular disease and infection are the leading causes of premature death. Patients who achieve complete renal response at 12 months have near-normal long-term renal survival.
What classes of lupus nephritis are there?▾▴
The 2018 ISN/RPS classification recognises six classes: I (minimal mesangial), II (mesangial proliferative), III (focal), IV (diffuse, most severe), V (membranous), and VI (advanced sclerosing). Classes III, IV, and mixed III/V or IV/V drive immunosuppressive treatment decisions.
Do I need a kidney biopsy?▾▴
Yes, in nearly all patients with proteinuria above 0.5 g/day or active urinary sediment. The biopsy defines the ISN/RPS class, scores activity and chronicity, and rules out alternative diagnoses. Treatment intensity and prognosis depend on biopsy findings.
What is the role of hydroxychloroquine?▾▴
Hydroxychloroquine (5 mg/kg/day, max 400 mg) is recommended for every patient with SLE regardless of nephritis activity. It halves flare risk, improves response to induction therapy, and reduces cardiovascular events. Annual ophthalmology screening starts after 5 years of treatment.
What is voclosporin?▾▴
Voclosporin is a calcineurin inhibitor FDA-approved in 2021 for active lupus nephritis. Added to mycophenolate and steroids, it produced complete renal response in 41% versus 23% on standard therapy at one year in the AURORA trial, with benefit maintained at 30 months.
Can pregnancy be safe with lupus nephritis?▾▴
Yes, when planned. Conception should be timed for at least 6 months of quiescent nephritis on pregnancy-safe drugs (hydroxychloroquine, azathioprine, tacrolimus, low-dose steroids). Mycophenolate and cyclophosphamide are teratogenic and must be stopped 3 months before conception.
Is lupus nephritis hereditary?▾▴
Lupus nephritis itself is not directly inherited, but susceptibility to SLE has a strong genetic component. First-degree relatives of SLE patients have a 5-15% risk of developing the disease. Genetic risk is highest in those of West African, Hispanic, and Asian ancestry.
What is the best diet for lupus nephritis?▾▴
A Mediterranean-style diet with adequate fruits, vegetables, whole grains, fish, and olive oil supports cardiovascular and renal health. Limit sodium to under 2 g/day during active nephritis. Avoid alfalfa sprouts, which can trigger lupus flares.
Does lupus nephritis cause kidney failure?▾▴
Approximately 10-30% of lupus nephritis patients progress to end-stage kidney disease within 10-15 years, especially class IV/V with high chronicity index, hypertension, or Black ancestry. Modern induction-maintenance therapy reduces this risk and delays progression.
What is the role of belimumab?▾▴
Belimumab is a monoclonal antibody against B-cell activating factor (BAFF), approved as add-on therapy for active lupus nephritis. In the BLISS-LN trial it increased complete renal response from 32% to 43% at 2 years and reduced renal-related events by 49%.
Can men get lupus nephritis?▾▴
Yes. Although SLE is 9 times more common in women, men can develop lupus and lupus nephritis. Male patients often have more severe disease, with higher rates of nephritis at diagnosis, faster progression to kidney failure, and more cardiovascular comorbidity.
Will I need kidney dialysis or a transplant?▾▴
Most patients on modern therapy do not need dialysis or transplant. Around 10-30% progress to end-stage kidney disease in the long term. Transplantation is the preferred option once dialysis is needed, with excellent outcomes and low (2-10%) recurrence of lupus nephritis in the graft.
How often should I see my nephrologist?▾▴
During active induction therapy, plan monthly visits with blood and urine tests. Once in remission, visits every 3 months for the first 2 years, then every 6 months long-term. Pregnant patients need monthly multidisciplinary review.
What infections are most common during treatment?▾▴
Common infections include bacterial pneumonia, urinary tract infection, varicella zoster, and opportunistic pathogens such as Pneumocystis jirovecii. Vaccinate against influenza, pneumococcus, and SARS-CoV-2 before immunosuppression, and use prophylactic trimethoprim-sulfamethoxazole during high-dose induction.
What blood pressure target is recommended?▾▴
Most guidelines recommend a target under 130/80 mmHg, with under 120/80 mmHg preferred in proteinuric disease. ACE inhibitors or angiotensin receptor blockers are first-line. SGLT2 inhibitors are added once nephritis is stable, providing additional kidney protection.
Can lupus nephritis come back after remission?▾▴
Yes. Renal flares occur in 20-40% of patients within 5 years, often after stopping hydroxychloroquine, missed mycophenolate, infection, pregnancy, or sun exposure. Most flares respond to reinduction; close monitoring with urine protein and serology detects relapse early.
07Pleuritic chest pain and serositis with pleural or pericardial effusions during severe SLE flares.
08Reduced urine output, nausea, pruritus, and asterixis in patients reaching advanced chronic kidney disease.
early warning signs
•New proteinuria on dipstick or urine protein-to-creatinine ratio above 200 mg/g in a known SLE patient
•Persistent microscopic hematuria with dysmorphic red blood cells on phase-contrast microscopy
•Falling complement (C3 or C4) and rising anti-double-stranded DNA titres on routine SLE monitoring
•New hypertension developing under age 40 in a patient with known SLE or a positive antinuclear antibody
•Pregnancy planning or early pregnancy in a woman with known SLE — pre-conception kidney assessment is essential
● emergency signs
•Rapidly rising serum creatinine, oliguria, and active urinary sediment — possible rapidly progressive crescentic lupus nephritis
•Hypertensive emergency with headache, seizures, or visual change
•Heavy hematuria with passage of clots or severe flank pain (rare but reported with renal vein thrombosis in nephrotic SLE)
•Severe pulmonary symptoms with hypoxia in a patient with lupus nephritis — exclude diffuse alveolar haemorrhage or pulmonary embolism
•New focal neurology, seizures, or psychosis in a patient on immunosuppression — exclude CNS lupus, infection, or PRES
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Serum complement C3 and C4 with anti-dsDNA antibodyMarkers of disease activity; falling complement and rising anti-dsDNA predict flares
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Percutaneous kidney biopsy with ISN/RPS classificationConfirms diagnosis, defines class (I-VI), and grades activity/chronicity
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Antiphospholipid antibody screenIdentifies coexisting antiphospholipid syndrome and thrombotic risk
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Renal ultrasoundExcludes obstruction, confirms two normally sized kidneys, screens for renal vein thrombosis in nephrotic syndrome
Outlook
Prognosis has improved substantially over the past 50 years. Five-year renal survival is now above 90% and 10-year survival 80-85% with modern induction-maintenance regimens. Complete renal response (proteinuria under 0.5 g/day, normal creatinine) at 6-12 months is the strongest predictor of long-term outcome — patients in complete response have under 5% risk of ESKD at 10 years, versus 30-40% in patients with no response. Class IV disease, mixed class IV/V, high chronicity index, hypertension, Black ancestry, and male sex predict worse outcomes. Cardiovascular disease, infection, and ESKD account for most premature deaths. Pregnancy outcomes are good when nephritis has been quiescent for at least 6 months pre-conception. Approximately 10-30% of patients still progress to ESKD within 10-15 years, but kidney transplantation offers excellent results with under 10% recurrence and 5-year graft survival above 80%.
non-modifiable
All cases of lupus nephritis occur in patients with SLE. 40-60% of adults and 60-80% of children with SLE develop kidney involvement within 5 years.
Female sexnon-modifiable
9:1 female:male predominance in adults. Disease in men is often more severe with higher rates of nephritis and end-stage kidney disease.
Black, Hispanic, Asian, or Indigenous ancestrynon-modifiable
Lupus nephritis prevalence is 2-3 times higher and progression to kidney failure 2-4 times faster than in White populations. APOL1 high-risk variants worsen outcomes in patients of West African ancestry.
High anti-dsDNA antibody titrenon-modifiable
Persistently elevated anti-dsDNA titre confers a 5-10 fold higher risk of nephritis flare within 12 months. Routine monitoring guides preemptive escalation.
Persistently low complement (C3/C4)non-modifiable
Low C3 and C4 are markers of active immune complex disease and a 2-3 fold higher risk of nephritis flare.
Hypertension and obesitymodifiable
Both accelerate proteinuria and eGFR loss in established nephritis. Weight reduction and blood pressure control under 130/80 mmHg are part of standard care.
Pregnancy without pre-conception planningmodifiable
Pregnancy doubles the risk of lupus flare and is high-risk in active nephritis. Pre-pregnancy planning with quiescent disease for at least 6 months on safe medications reduces flares and adverse outcomes.
Non-adherence to hydroxychloroquinemodifiable
Hydroxychloroquine reduces flare risk by 50% and improves renal outcomes. Stopping the drug is the single most common modifiable risk factor for nephritis flare.
•Low-sodium intake under 2 g/day during active nephritis
•Adequate calcium (1,000-1,200 mg/day) to offset steroid-induced bone loss
foods to avoid
•Excess sodium and processed foods that worsen oedema and hypertension
•Alfalfa sprouts, which contain L-canavanine and can precipitate lupus flares
•High-sugar, high-saturated-fat diets that worsen steroid-induced metabolic syndrome
•Grapefruit and grapefruit juice while on tacrolimus or voclosporin — they raise drug levels
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Thrombotic events in patients with coexisting antiphospholipid syndrome — anticoagulation may be required.
choosing the right hospital
01Joint nephrology-rheumatology clinic for lupus patients
02On-site kidney biopsy programme with renal pathology and electron microscopy
03Access to belimumab, voclosporin, mycophenolate, cyclophosphamide, and rituximab
04Multidisciplinary high-risk pregnancy service
05Kidney transplant and dialysis programmes
Essential facilities
Tertiary nephrology centres with biopsy and transplant programmesLupus clinics with combined nephrology-rheumatology inputRenal pathology with full immunofluorescence and electron microscopyHigh-risk pregnancy unitsKidney transplant and dialysis units
Apply broad-spectrum sunscreen daily and reapply every 2 hours during outdoor activity.
03Check home blood pressure twice weekly and report sustained readings above 130/80 mmHg.
04Self-monitor for new oedema, foamy urine, rashes, joint pain, and unexplained fevers.
06Use reliable contraception while on mycophenolate or cyclophosphamide.
Exercise
Aerobic exercise at moderate intensity (150 minutes per week) reduces fatigue and improves cardiovascular outcomes in SLE. Add two resistance sessions to offset steroid-induced muscle loss and osteoporosis. Avoid extreme exertion during active flares. Patients with eGFR under 30 mL/min/1.73 m2 should adjust intensity and discuss exercise plans with their renal team.