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Lupus Nephritis (KDIGO 2021 Guidelines) - Dr. Gawad

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Lupus Nephritis (KDIGO 2021 Guidelines) - Dr. Gawad

- English version of this lecture is available at:
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- English version of this lecture is available at:
https://youtu.be/t7N2GSXhYwA
- Arabic version of this lecture is available at:
https://youtu.be/WzFZym9hDtQ
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
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Lupus Nephritis (KDIGO 2021 Guidelines) - Dr. Gawad

  1. 1. Lupus Nephritis KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases Mohammed Abdel Gawad MD Neph, ESENeph Lecturer of Nephrology, School of Medicine, New Giza University Nephrology Consultant, Alexandria Founder of NephroTube.com Co-chair of AFRAN Web/Media Committee ISN Education SoMe Team Member drgawad@gmail.com @Gawad_Nephro 29, June, 2022
  2. 2. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  3. 3. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  4. 4. LUPUS NEPHRITIS - DIAGNOSIS Practice Point 10.1.1: Approach to the diagnosis of kidney involvement in systemic lupus erythematosus (SLE).
  5. 5. LUPUS NEPHRITIS - DIAGNOSIS
  6. 6. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  7. 7. LUPUS NEPHRITIS – TREATMENT: CLASS I OR CLASS II LN Practice Point 10.2.2.1: Approach to immunosuppressive treatment for patients with Class I or Class II LN
  8. 8. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  9. 9. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B).
  10. 10. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B). Of likely importance to patients, the voclosporin regimen is significantly glucocorticoid sparing, and will hopefully reduce the glucocorticoid adverse events often seen during LN treatment.
  11. 11. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B).
  12. 12. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B).
  13. 13. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B).
  14. 14. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B). Biologics such as rituximab, which targets a B-cell surface marker, or belimumab, a monoclonal antibody to the B-cell growth and survival factor, B-cell activating factor (BAFF), are not included in the recommendation of first-line treatment. Biologics are, however, discussed in a practice point, noting that there are positive data from recent clinical trials demonstrating that biologics are effective in LN, and have favorable safety profiles. Despite these negative trials, rituximab enjoys considerable off-label use, and in uncontrolled but real-world patient settings, is frequently reported to be effective. At the same time, clinical trialists, having learned lessons from failed trials, designed new trials that have been successful.
  15. 15. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B). Regulatory approval from the US Food and Drug Administration of a biologic for LN came in December 2020 after the Efficacy and Safety of Belimumab in Patients with Active Lupus Nephritis (BLISS-LN) trial demonstrated that belimumab was more effective than placebo in achieving a primary efficacy renal response (PERR) at 2 years (43% vs. 32%; odds ratio 1.6; P ¼ 0.03) when added to background therapy of glucocorticoids plus either MMF or low-dose cyclophosphamide. The optimal use of belimumab in LN will become clear as its use increases, and the BLISS-LN data will be incorporated into the evidence review.
  16. 16. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Recommendation 10.2.3.1.1: We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus either low-dose intravenous cyclophosphamide or MPAA (1B). The combination of a glucocorticoid, MMF, and a CNI, the so-called “multitarget” regimen, shows good efficacy compared to cyclophosphamide. Because the multitarget regimen had not been studied in diverse lupus populations, it was not recommended as first-line treatment, but suggested as an alternative for MMF and cyclophosphamide.
  17. 17. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Practice Point 10.2.3.1.7: 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, but these alternatives may be associated with inferior efficacy, including increased rate of disease flares and/or increased incidence of drug toxicities.
  18. 18. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  19. 19. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: INITIAL THERAPY Practice Point 10.2.3.1.1: A regimen of reduced-dose glucocorticoids following a short course of methylprednisolone pulses may be considered during the initial treatment of active LN when both the kidney and extrarenal disease manifestations show satisfactory improvement. Practice Point 10.2.3.2.2: Glucocorticoids should be tapered to the lowest possible dose during maintenance, except when glucocorticoids are required for extrarenal lupus manifestations; discontinuation of glucocorticoids can be considered after patients have maintained a complete clinical renal response for ≥12 months.
  20. 20. LUPUS NEPHRITIS – TREATMENT: CLASS III OR CLASS IV LN: MAINTENANCE THERAPY Practice Point 10.2.3.2.4: If MPAA and azathioprine cannot be used for maintenance, CNIs or mizoribine should be considered. Practice Point 10.2.3.2.5: The total duration of initial immunosuppression plus combination maintenance immunosuppression for proliferative LN should not be <36 months.
  21. 21. • There are few high-quality data to support a specific duration of immunosuppression, although it is suggested that for patients who have achieved a complete kidney response and have no ongoing extrarenal SLE manifestations, the total duration of immunosuppression (initial plus maintenance) should not be <36 months. • These suggestions imply that patients who do not achieve a complete kidney remission, but only a partial remission, would need to be kept on immunosuppression indefinitely. However, repeat biopsy studies have shown that while persistent histologic activity is a risk factor for LN relapse, many patients who have achieved only a partial clinical remission have no remaining activity on kidney biopsy. Thus, a more focused use of repeat kidney biopsies may help in managing the duration of immunosuppression. • Protocol repeat biopsy studies have shown that clinical responses and histologic improvement of the kidneys may be discordant.
  22. 22. • The biomarkers used clinically for the evaluation of LN activity, such as complement levels and anti–double-stranded DNA titers, also have limitations. • Therefore, the Work Group suggested that if patients are improving, allowing 18–24 months to achieve a complete response is reasonable in the clinic and outside of the clinical trial setting. Importantly, many of the new trial designs are incorporating a longer timeline to assess clinical response.
  23. 23. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  24. 24. LUPUS NEPHRITIS – TREATMENT: CLASS V LN Practice Point 10.2.4.1: A suggested approach to the management of patients with pure Class V LN is described in the figure.
  25. 25. LUPUS NEPHRITIS – TREATMENT: CLASS V LN: MANAGEMENT OF UNSATISFACTORY RESPONSE TO TREATMENT Practice Point 10.2.4.2.1: An algorithmic approach to patients whose response to therapy is deemed unsatisfactory is provided in the figure.
  26. 26. LUPUS NEPHRITIS – TREATMENT: CLASS V LN: TREATMENT OF RELAPSE Practice Point 10.2.4.3.1: After a complete or partial remission has been achieved, LN relapse should be treated with the same initial therapy used to achieve the original response, or an alternative recommended first-line therapy.
  27. 27. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  28. 28. LUPUS NEPHRITIS – SPECIAL SITUATIONS: LN AND THROMBOTIC MICROANGIOPATHY Practice Point 10.3.1.1: Patients with LN and thrombotic microangiopathy (TMA) should be managed according to the underlying etiology of TMA, as shown in the figure.
  29. 29. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  30. 30. LUPUS NEPHRITIS – SPECIAL SITUATIONS: PREGNANCY Practice Point 10.3.2.1: 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 ≥6 months after LN becomes inactive. Practice Point 10.3.2.2: 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 10.3.2.3: Only glucocorticoids, hydroxychloroquine, azathioprine, and CNIs are considered safe immunosuppressive treatments during pregnancy.
  31. 31. Talk Outline • LN diagnosis • LN class I or II treatment • LN class III or IV treatment (induction) • LN class III or IV treatment (maintenance) • LN class V treatment • Special situations: LN and Thrombotic Microangiopathy • Special situations: Pregnancy • Special situations: Kidney failure
  32. 32. LUPUS NEPHRITIS – SPECIAL SITUATIONS: LN IN KIDNEY FAILURE Practice Point 10.3.4.1: Patients with LN who develop kidney failure may be treated with hemodialysis, peritoneal dialysis, or kidney transplantation; and kidney transplantation is preferred to long-term dialysis
  33. 33. Thank You drgawad@gmail.com twitter: @Gawad_Nephro Facebook: Doctor.Gawad www.NephroTube.com

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