In honor of Lupus Awareness Month this guidelines side-by-side highlights a component of lupus, lupus nephritis.
Lupus nephritis (LN) is a complication of systemic lupus erythematosus (SLE) that occurs in up to 60% of patients at some point during their lifetime. The goal of treating lupus nephritis is to preserve kidney function and decrease morbidity and mortality.
This Guidelines Side-by-Side compares the latest clinical practice guidelines from the American College of Rheumatology (ACR) and Kidney Disease Improving Global Outcomes (KDIGO). The recommendations made are meant to guide clinical practice, taking into consideration the unique desires and needs of individual patients.
The full guidelines can be viewed below:
- Lupus Nephritis Screening and Treatment Recommendations and Good Practice Statements
- Published by ACR on November 2024
- KDIGO 2024 Clinical Practice Guideline for the management of LUPUS NEPHRITIS
- Published by KIDIGO January 2024
Titles of Comparison
| Details | 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis | KDIGO 2024 Clinical Practice Guideline for The Management of Lupus Nephritis |
|---|---|---|
| Authoring Organization | American College of Rheumatology | Kidney Disease Improving Global Outcomes |
| Publication Date | (Summary) November 2024 | January 2024 |
| Includes Graded Recommendations | Yes | Yes |
| Uses GRADE | Unclear | Yes |
| Comments | Recommendations are made for screening, treatment, and management. Recommendations for adult and pediatric patients | Recommendations are made for treatment, also includes "practice points" |
| Guideline Summary | - | Management of Lupus Nephritis |
Key Takeaways
Both the ACR and KDIGO guidelines agree on the importance of early diagnosis and treatment of lupus nephritis to preserve kidney function.
The ACR has shifted treatment recommendations to triple immunosuppressive regimens with lower doses of glucocorticoids, and preference for mycophenolic acid analog (MPAA) regimens over cyclophosphamide (CYC) regimens.
KDIGO recommends double or triple immunosuppressive regimens for initial therapy, agreeing with the ACR that lower doses of glucocorticoids can be used with equal efficacy and less toxicity.
Both societies are in agreement that kidney transplant is preferred for renal replacement therapy in patients with LN who have end stage kidney disease (ESKD).
To review these and other recommendations made by the ACR and KDIGO, take a look at the table below.
Recommendation Comparison
| Topic | ACR | KDIGO |
|---|---|---|
| Screening | Strong recommendation for screening for proteinuria at least every 6-12 months, or when flares occur | Practice point: Testing for kidney involvement as part of regular surveillance or for suspicion of disease flare |
| Kidney Biopsy | Good practice statement (GPS): Prompt kidney biopsy should be performed in people with systemic lupus erythematosus (SLE) when LN is suspected Conditional recommendation for kidney biopsy in patients with proteinuria >0.5 g/g and/or impaired kidney function not otherwise explained Conditional recommendation for repeat kidney biopsy in patients with treated LN in remission who have a suspected LN flare or patients with 6 months or more of appropriate treatment and ongoing worsening of proteinuria, hematuria, and/or decreased kidney function | Practice point: Consider kidney biopsy if there is evidence of decreasing GFR or 24 hour proteinuria is at least 500 mg/d |
| Treatment of Class I or II LN | Not addressed | Practice Point: Consider immunosuppressive treatments for low-level proteinuria. Consider maintenance combination therapy with low-dose glucocorticoid and another immunosuppressive agent with nephrotic syndrome |
| Treatment of Active LN Class III/IV or V(General) | GPS: Prompt glucocorticoid treatment should be administered for suspected LN to suppress acute inflammation while awaiting a kidney biopsy and histopathology results GPS: Dosage of LN medications should be adjusted in people with decreased GFR at initiation of therapy and periodically GPS: Adjunctive treatment with systemic anticoagulation for people with LN and significant risk factors for thrombosis (e.g., low serum albumin in context of severe proteinuria) should be discussed with nephrology | Practice point: IV cyclophosphamide can be used for initial therapy if a patient has difficulty adhering to an oral regimen |
| Treatment of Active/New Onset/Flare of Class III/IV or V | Strong recommendation for starting and/or continuing hydroxychloroquine (HCQ) Conditional recommendation for renin-angiotensin-aldosterone system inhibitors (RAAS-I) as add-on therapy for patients with any elevation in proteinuria | Recommendation for patients with SLE including patients with LN to be treated with HCQ |
| Conditional recommendation for pulse IV glucocorticoids 250 - 1000 mg methylprednisolone daily for 1-3 days, followed by oral glucocorticoid of no more than 0.5 mg/kg/day (max 40 mg/day) with a taper to a target dose of no more than 5mg/kg/day by 6 months | Practice point: Consider a reduce-dose glucocorticoid regimen after a short course of methylprednisolone pulses during initial treatment of active LN when kidney and extrarenal disease shows satisfactory improvement | |
| Treatment of Active/New Onset/Flare of Class III/IV (With/Without Class V) | Conditional recommendations for triple immunosuppressive regimen consisting of pulse IV glucocorticoids 250-1000 mg methylprednisolone daily for 1-3 days, followed by oral glucocorticoid of 0.5 mg/kg/day or less (max 40mg/day) with taper plus - MPAA plus belimumab or - MPAA plus calcineurin inhibitor (CNI) or - Euro Lupus Nephritis Trial (ELNT) low-dose CYC plus belimumab (MPAA substituted for CYC after CYC course complete) | Recommends initial treatment with glucocorticoids plus any one of the following: - MPAA - Low-dose IV CYC - Belimumab and either MPAA or low-dose IV CYC - MPAA and CNI when kidney function is not severely impaired (eGFR 45 ml/min per 1.73 m or less) Practice point: Glucocorticoids should be tapered to the lowest possible dose during maintenance, except when glucocorticoids are required for extra-renal lupus manifestations; discontinuation of glucocorticoids can be considered after patients have maintained a complete clinical renal response for at least 12 months |
| Conditional recommendation for MPAA-based regimens over CYC-based regimens | Practice point: MPAA regimen preferred for initial therapy in patients at high risk of infertility | |
| Conditional recommendation for triple immunosuppressive regimen that contains MPAA plus CNI for patient with proteinuria 3g/g or more | Practice point: Initial therapy with an immunosuppressive regimen that includes a CNI (voclosporin, tacrolimus, or cyclosporine) may be preferred in patients with relatively preserved kidney function and nephrotic range proteinuria who cannot tolerate standard dose MPAA or cannot use cyclophosphamide-based regimens | |
| Conditional recommendation for triple immunosuppressive regimen that contains belimumab for patients with extra-renal manifestations | Practice point: Triple immunosuppressive regimen of belimumab with glucocorticoids and either MPAA or reduced-dose cyclophosphamide may be preferred in patients with repeated kidney flares or at high risk for progression to kidney failure | |
| Conditional recommendation for patients on a CYC regimen for ELNT low-dose CYC over high-dose monthly pulse IV regimen and Strong recommendation ELNT low-dose CYC over daily oral CYC regimen | Not addressed | |
| Conditional recommendation for patients who have undergone triple immunosuppressive therapy and achieved complete renal response to continue the same regimen. Conditional recommendation for patients who have undergone triple immunosuppressive therapy and achieved a partial renal response to individualize therapy depending on clinical factors that include the trajectory of response | Practice point: Patients treated with triple immunosuppressive regimens that include belimumab or a CNI in addition to standard immunosuppressive therapy can continue with a triple immunosuppressive regimen as maintenance therapy | |
| Conditional recommendation for patients who have undergone dual immunosuppressive therapy (glucocorticoids plus either CYC or MPAA) and achieved a complete renal response to continue therapy with MPAA | Recommendation for maintenance with MPAA after completion of initial therapy Practice point: Azathioprine is an alternative to MPAA after completion of initial therapy in patients who do not tolerate MPAA, who do not have access to MPAA, or who are considering pregnancy Practice point: : If MPAA and azathioprine cannot be used for maintenance, CNIs or mizoribine or leflunomide can be considered Practice point: Other therapies, such as azathioprine or leflunomide combined with glucocorticoids, may be considered in lieu of the recommended initial drugs for proliferative LN in situations of patient intolerance, lack of availability, and/or excessive cost of standard drugs | |
| Conditional recommendation for patients who have undergone dual immunosuppressive therapy (glucocorticoids plus either CYC or MPAA) and achieved a partial renal response, escalate therapy to a triple immunosuppressive regimen | Not addressed | |
| Not addressed | Practice point: dose of mycophenolate mofetil (MMF) in the early maintenance phase is approximately 750–1000 mg twice daily, and for mycophenolic acid (MPA), approximately 540–720 mg twice daily | |
| Treatment of Pure Class V LN(Active/New Onset/Flare) | Conditional recommendations for triple immunosuppressive regimen with proteinuria of 1 g/g or more. Regimen consisting of: - Pulse IV glucocorticoids 250-1000 mg methylprednisolone daily for 1-3 days, followed by oral glucocorticoid of 0.5 mg/kg/day or less (max 40 mg/day) with taper and - MPAA plus calcineurin inhibitor (CNI) Conditional recommendation for treatment with glucocorticoids and/or immunosuppressive therapy (MPAA, azathioprine, CNI) in patients with proteinuria less than 1 g/g | Practice point: Monitor proteinuria, renin-angiotensin system blockage and blood pressure control, immunosuppressive treatment, and HCQ depending on degree of proteinuria and complications |
| Duration of Treatment | Conditional recommendation for total duration of therapy of at least 3-5 years for patients with LN class III/IV or V who have complete renal response after treatment with any triple or dual immunosuppressive therapy | Practice point: The total duration of initial immunosuppression plus combination maintenance immunosuppression for proliferative LN should be at least 36 months |
| Treatment of Nonresponsive or Refractory LN | GPS: Medication dose and patient adherence should be assessed as an important first step in evaluating inadequate response or refractory LN, as insufficient treatment is an important cause of non-response Conditional recommendation to escalate treatment for patients with inadequate renal response: - For initial dual therapy, escalate to triple therapy - For initial triple therapy, change to an alternative triple therapy or consider addition of anti-CD20 agents (rituximab or obinutuzumab) Conditional recommendation to escalate therapy for patients with refractory LN: - Addition of anti-CD20 agents (rituximab or obinutuzumab) or - Combination therapy with three non-glucocorticoid immunosuppressives or - Referral for investigational therapy | Practice point: For patients with unsatisfactory response to therapy: - Verify adherence - Ensure adequate dose of immunosuppressive medications with plasma drug levels - Repeat kidney biopsy if concern for chronicity or other diagnosis Consider switching treatment regimen - Consider the following for patients refractory to first line treatment regimens: - Adding rituximab or other biologic - Extended course of IV pulse cyclophosphamide or - Enrollment in clinical trials. Practice point: New biologic and non-biologic therapies are being developed and may be an option in the future |
| Treatment of LN Relapse | Not addressed | Practice point: After complete or partial remission, LN relapse should be treated with the same initial therapy used to achieve the original response, or an alternative recommended therapy |
| Other Lupus Kidney Disease | GPS: Alternative etiologies of kidney dysfunction in people with SLE should be carefully excluded, including non inflammatory etiologies such as hypertensive, diabetic, and medication-induced nephropathy | Not addressed |
| Adjunctive and Non-Immunologic Treatment | GPS: Adjunctive and non-immunologic therapies and practices should be initiated in addition to appropriate immunosuppressive therapy to improve overall kidney health. Management of cardiovascular health, bone health, infection risk, and reproductive concerns should be addressed | Practice point: Adjunctive therapies to manage LN and decrease complications of the disease or its treatment should be considered for all patients Practice point: Lifestyle modifications, screening and vaccination for infectious diseases, supplements, when appropriate to improve bone density, use of sunscreen and limiting UV exposure, evaluation for premature ovarian failure and contraception, evaluation for malignancy risk and minimize the lifetime exposure to cyclophosphamide to less than 36 g |
| Pediatric Considerations | GPS: In children with childhood-onset SLE (cSLE) and LN, glucocorticoid regimens should be reduced to pediatric appropriate doses for children, as reduction of cumulative glucocorticoid dosing is critically important given the early age of onset in cSLE and attendant comorbidities GPS: In children with cSLE and LN, clinicians should monitor for delayed pubertal onset and decreased growth velocity that can result from disease activity and glucocorticoid treatment and consider referral to pediatric endocrinology if indicated GPS: For children with cSLE, a structured, intentional transition from pediatric to adult rheumatology care is indicated to avoid poor outcomes during this vulnerable period | Practice point: Treat pediatric patients with LN using immunosuppression regimens similar to those used in adults, but consider issues relevant to this population, such as dose adjustment, growth, fertility, and psychosocial factors, when devising the therapy plan |
| Considerations for Older Adults | GPS: For older people with LN, medication number, type, and dosage should be regularly assessed, given the risks of polypharmacy and age-related decline in GFR in this population | Not addressed |
| Considerations in Pregnancy | Not addressed | Practice point: Patients with active LN should be counseled to avoid pregnancy while the disease is active or when treatment with potentially teratogenic drugs is ongoing, and for at least 6 months after LN becomes inactive Practice point: To reduce the risk of pregnancy complications, hydroxychloroquine should be continued during pregnancy, and low-dose aspirin should be started before 16 weeks of gestation Practice point: Glucocorticoids, HCQ, azathioprine, tacrolimus, and cyclosporine are considered safe immunosuppressive treatments during pregnancy |
| Considerations for patients with LN and Thrombotic Microangiopathy (TMA) | Not addressed | Practice point: Patients with LN and TMA should be managed according to the underlying etiology of TMA |
| Monitoring | Strong recommendation for quantifying proteinuria at least every 3 months in patients who have not achieved complete renal response Strong recommendation for quantifying proteinuria every 3 to 6 months in patients with sustained complete renal response GPS: In people with LN, serum complement levels and anti-dsDNA antibody concentrations should be checked at every clinic visit but not more frequently than monthly | Not addressed |
| Renal Replacement Therapies | GPS: Decisions for initiation and type of dialysis and timing for kidney transplant require close collaboration with nephrology Strong recommendation for kidney transplant over dialysis in patients with LN and end stage kidney disease (ESKD) Conditional recommendation for preemptive kidney transplant for patients with LN nearing ESKD Conditional recommendation for proceeding with kidney transplant without complete clinical or serological remission if there is no other major organ involvement | Practice point: Patients with LN who develop kidney failure may be treated with hemodialysis, peritoneal dialysis, or kidney transplantation; and kidney transplantation is preferred over long-term dialysis |
| Strong recommendation for regular follow up with Rheumatology in patients with LN on dialysis or after kidney transplantation | Not addressed |
This concludes our Guidelines Side-by-Side for Lupus Nephritis. Don’t forget to sign up for alerts to stay informed on the latest published guidelines and articles.
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