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Revista Brasileira de Reumatologia

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Sumário

Original articles • Rev. Bras. Reumatol. 55 (1) • Jan-Feb 2015 • https://doi.org/10.1016/j.rbr.2014.09.008 copy

Consensus of the Brazilian Society of Rheumatology for the diagnosis, management and treatment of lupus nephritis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Objective

To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil.

Method

Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology.

Results and conclusions

(1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. (2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. (3) Risks and benefits of treatment should be shared with the patient and his/her family. (4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. (5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). (6) Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers are recommended as antiproteinuric agents for all patients (unless contraindicated). (7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including corticosteroids and an immunosuppressive agent, even though histological confirmation is not possible. (8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient could achieve and maintain a sustained and complete remission. (9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision.

Systemic lupus erythematous; Lupus nephritis; Therapeutics; Brazil; Consensus

Recommendations	Agreement
Indications for renal biopsy
Perform a renal biopsy whenever possible and when indicated.	a) 1.0
Elevation of serum creatinine with no apparent cause and potentially associated with SLE.	a) 1.0
Isolated proteinuria >1.0 g/24 h (or R P/C >1.0).	a) 1.0
Proteinuria ≥ 0.5 g/24 h associated with glomerular dysmorphic hematuria and/or cellular casts.	a) 1.0
Note: changes must be confirmed with a second test.	a) 1.0
Inference of histological class
Possibility to make some inference based on clinical and laboratory criteria.	a) 0.54 b) 0.46
Creatinine elevation (with no other cause) associated with proteinuria >0.5 g/24 h or R P/C >0.5 and recent HBP and/or active urinary sediment: consider as proliferative GN (class III or IV), especially if accompanied by low blood levels of complement and anti-ds-DNA AB.	a) 0.9 b) 0.1
Proteinuria >2 g/h or R P/C >2, with no activity in urinary sediment or hypertension, and mostly without anti-ds-DNA AB and normal complement levels, suggestive of membranous GN (class V). However, we cannot exclude proliferative lesion.	a) 0.9 b) 0.1
Proteinuria <1 g/24 h or R P/C <1 with normal creatinine and without HBP suggests mesangial GN (class II). However, we cannot exclude initial-stage proliferative or membranous GN.	a) 1.0
Also consider the possibility of other causes of renal injury at all stages of evolution of LN (APSN, renal vein thrombosis, TIN, ATN, diabetic nephropathy, hypertensive nephropathy and/or nephropathy secondary to infection).
Care for immunosuppressed patients
Vaccine update.	a) 1.0
Avoid live virus vaccines.	a) 1.0
Tuberculosis (latent or disease) screening.	a) 1.0
Continuous evaluation for infections throughout the period of immunosuppression.	a) 1.0
Share risks and benefits of treatment with patient and his/her family.	a) 1.0
Guidance on contraception (avoiding estrogens), and risks of pregnancy during treatment.	a) 1.0
Empirical antiparasitic treatment.	a) 1.0
Consider prophylaxis for Pneumocystis jirovecii in cases of previous infection or in patients with lymphopenia <500 mm³.	a) 1.0
Prescribe hydroxychloroquine for patients, unless contraindicated.	a) 1.0
Obtain an informed and free consent form (IFCF).	a) 1.0
Response criteria
The treatment efficacy evaluation should be made with objective criteria of response.	a) 1.0
Complete remission: proteinuria <0.5 g/24 h or R P/C <0.5 and normal GFR; or reduction ≤10% of previous value for the patient or ULN of method (if the first is not available) and a normal urinalysis.	a) 1.0
Partial remission: reduction >50% of initial proteinuria with a value <3.0 g/24 h or R P/C <3.0, normal GFR or reduction ≤10% of the previous value of the patient, or ULN of method (if the first is not available) and a normal urinalysis.	a) 0.9 b) 0.1

Recommendations	Agreement
Adjuvant measures for all histologic classes
The use of hydroxychloroquine (preferably) or chloroquine is recommended for all patients (unless contraindicated) during induction and maintenance phases.	a) 1.0
ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated).	a) 1.0
Prevent and treat risk factors for cardiovascular disease: physical inactivity, dyslipidemia (LDL <100 mg/dL), diabetes, obesity, HBP (BP <130 × 80 mmHg) and smoking.	a) 1.0
Encourage a diet rich in calcium and consider supplementation, when necessary.	a) 1.0
Consider supplementation of vitamin D (25 (OH) (if vitamin D serum levels >30 ng/mL).	a) 1.0
Avoid nephrotoxic drugs, especially non-steroidal anti-inflammatory agents.	a) 1.0
Protocol for induction and maintenance in mesangial GN (classes I and II)
For patients with persistent proteinuria ≥1.0 g/24 h or R P/C ≥1.0: induction and maintenance of remission, consider AZA or MMF.	a) 1.0
Protocol for induction in proliferative GN (classes III and IV)
Target to be achieved in six months is RC.	a) 1.0
The identification of clinical and/or laboratory signs suggestive of proliferative GN should indicate an immediate specific therapy, including CS and an immunosuppressant agent, even in cases when histological confirmation is not possible.	a) 1.0
The treatment should begin with MP pulse therapy [0.5–1.0 g IV (or 10–30 mg/kg/day in PSLE patients) for 3 days]. Doses of prednisone between 0.5 and 1.0 mg/kg/day for 3–4 weeks, with subsequent reduction and with the goal of achieving a dose of 5–10 mg/day for 6 months.	a) 0.9 b) 0.1
In conjunction with CS, include CY IV 0.5–1.0 g/m² BSA monthly for 6 months, or CY IV 0.5 g every 15 days for 3 months, or MMF (2–3 g/day).	a) 0.9 b) 0.1
In patients with severity criteria, consider CY as a first option, taking into account its availability, absorption and tolerance to medication and treatment adherence.	a) 0.9 b) 0.1
Lack of response or worsening of renal disease after 3 months of an appropriate therapy suggests the need to consider an early change of the induction protocol.	a) 1.0
After 6 months of treatment at this stage, if CR or PR were not achieved, the patient should be considered as refractory to induction; in this case, a new therapy with MP and replacement of CY by MMF, or of MMF by CY, are recommended.	a) 1.0
Protocol for maintaining proliferative GN (classes III and IV)
AZA or MMF are indicated for patients who have achieved CR or PR in the induction phase.	a) 1.0
These medications must be used for at least 36 months, but they can be kept for longer periods. Their suspension should only be performed after achieving and maintaining a complete and continuous remission.	a) 1.0
The doses of corticosteroids should be reduced progressively and, if possible, discontinued, ideally after achieving and maintaining a complete and sustained remission.	a) 0.9 b) 0.1

Recommendations	Agreement
Protocol for induction in membranous GN (class V)
CR or PR are the targets to be achieved in six months.	a) 1.0
Immunosuppressants are recommended for all patients, because they are more effective than CS as monotherapy.	a) 1.0
Attention should be given to the exclusion of thromboses, including into renal veins, which are frequently present with positivity for aPl.	a) 1.0
The treatment should begin with MP pulse therapy [0.5–1.0 g IV (or 10–30 mg/kg/day in PSLE patients) for 3 days] followed by prednisone (0.5–1.0 mg/kg/day) for 3–4 weeks, with subsequent reduction and with the goal to achieve a dose of 5–10 mg/day within six months.	a) 1.0
In conjunction with CS, CY IV 0.5–1.0 g/m² BSA monthly for 6 months, or CY IV 0.5 g every 15 days for 3 months, or MMF (2–3 g/day) and AZA (2 mg/day) should be included.	a) 0.9 b) 0.1
Lack of response after 3 months of an appropriate therapy indicates the need to consider an early change of induction protocol.	a) 0.9 b) 0.1
After 6 months of induction treatment, if CR or PR have not been achieved, LN is considered refractory, and a new induction therapy with MP and an exchange of the immunosuppressive agent (CY, MMF or AZA) are recommended.	a) 1.0
Protocol for maintenance in membranous GN (class V)
The modification of the treatment regimen for that of the maintenance phase depends on achieving CR or PR.	a) 1.0
AZA or MMF are indicated for patients who have achieved CR or PR in the induction phase.	a) 1.0
For patients who have not achieved a favorable response with AZA or MMF, switching to one another, or the substitution by a calcineurin inhibitor or rituximab, should be considered.	a) 1.0
These medications must be used for at least 36 months, but they can be kept for longer periods. Their suspension should only be performed after achieving and maintaining a complete and continuous remission.	a) 1.0
The doses of corticosteroids should be reduced progressively and, if possible, discontinued, ideally after achieving and maintaining a complete and sustained remission.	a) 0.9 b) 0.1

Recommendations	Agreement
Refractory LN
LN should be considered refractory when CR or PR is not achieved after 12 months of an appropriate treatment.	a) 1.0
Consider a new kidney biopsy to assist in identifying the cause of refractoriness and in therapeutic decision.	a) 0.9 b) 0.1
Rituximab is indicated, including cases with renal insufficiency.	a) 1.0
Tacrolimus (alone or in combination with MMF) may be used as an alternative.	a) 1.0
APSN associated to LN
Search aPl in patients with LN, due to the possibility of an association with APSN.	a) 1.0
Maintain control of risk factors associated with vasoocclusive events in patients with aPl.	a) 1.0
In patients with APSN, maintain INR close to 3 and consider the concomitant use of antiplatelet agents.	a) 1.0
LN and pregnancy
SLE female patients should be advised not to become pregnant until disease remission for at least six months and with a normal renal function.	a) 1.0
Pregnancy should be planned, including discontinuation of teratogenic medications (ARB, CY, coumarin, ACE inhibitors, leflunomide, MMF and MTX).	a) 0.75 b) 0.25
Monitoring should be done by a multidisciplinary team throughout pregnancy and puerperium.	a) 0.9 b) 0.1
HCLQ should be used throughout pregnancy.	a) 1.0
CS and AZA can be used during pregnancy.	a) 1.0
LN in PSLE patients
The treatment of nephritis in PSLE patients is similar to that of adults, with dose adjustment of drugs (AZA = 2.0–3.0 mg/kg/day, MP = 20–30; MMF = 30 mg/kg/day or 600 mg/m2 BSA/day); reinforce adherence at every visit.	a) 1.0
LN and ERF
Maintain the treatment by a rheumatologist even after RRT, including the use of HCLQ with adjustment of its doses.	a) 1.0
Extrarenal recurrences can be treated with CS, AZA and MMF (with adjusted doses).	a) 1.0
Consider renal transplantation in patients with ERF (living or cadaver donor).	a) 1.0
Special consideration should be given to patients with aPl, because of the risk of thrombosis in arteriovenous fistula and vasoocclusive lesions with potential graft loss.	a) 1.0

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E-mail: sbre@terra.com.br

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