Per-protocol Repeat Kidney Biopsy in Incident Cases of Lupus Nephritis

NCT04449991 | Recruiting

• 1 other identifier: REBIOLUP
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 1

Brief Summary

Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Among people living with SLE, 35-60% will develop LN during the course of the disease. This complication is one of the factors that contribute to deterioration of the renal function. Some centres perform kidney biopsies after completion of treatment for an episode of LN as a part of the treatment evaluation. The term "repeat biopsy" is often used to describe these biopsies. Several studies have reported that repeat kidney biopsies show activity at the level of tissue, even in patients with normal routine blood and urine markers. The investigators strongly believe that this information is important, and should be taken into consideration during decision of treatment. To provide evidence for this, the investigators have designed a collaborative project within the frame of the Lupus Nephritis Trials Network. With this research project, the investigators want to contribute to an increased proportion of patients with LN who achieve remission (inactivity) of LN, and a reduced proportion of patients who worsen in renal function in the long term. Patients with SLE who develop a first episode of LN will be asked to participate in this project, and will receive treatment according to current guidelines. Half of the patients will undergo a repeat biopsy 12 months later, and half of the patients will not. The selection of patients who will undergo or not undergo repeat biopsy will be random. Patients with high disease activity at the level of kidney tissue will receive more intense immunosuppressive treatment. Patients who have not undergone repeat biopsy will continue to be treated according to standard routine. The investigators will compare the results of treatment between the group of patients who underwent and the group of patients who did not undergo repeat biopsy, with regard to (i) complete disease inactivity at month 24 and (ii) renal function at month 60 from treatment initiation. The investigators expect that significantly greater proportions of patients in the repeat biopsy group will have inactive disease at month 24 and adequate levels of renal function at month 60. This will provide support for performing repeat biopsies as a part of the treatment evaluation, in order to optimise the therapeutic management and improve the long-term prognosis of patients with LN.

Conditions

Lupus Nephritis

Keywords

systemic lupus erythematosus; lupus nephritis; kidney biopsy; renal function impairment; long-term prognosis; electron microscopy

Outcome Measures

Primary Outcomes (1)

• Complete Renal Response (CRR) at month 24 from baseline

  UPCR ≤ 0.5 g/g in two consecutive first-morning void urine specimens and no increase in serum creatinine by ≥ 25% from baseline.

  Month 24 from baseline

Secondary Outcomes (5)

• Renal function impairment at month 60

  Month 60 from baseline

• Renal relapse (proteinuric flare)

  Between month 12 and month 60 from baseline

• Reabsorption of immune deposits in repeat kidney biopsies

  Month 12 from baseline

• End-stage kidney disease (ESKD)

  Between month 12 and month 60 from baseline

• Mortality rate

  Between month 12 and month 60 from baseline

Study Arms (2)

Intervention arm: Repeat kidney biopsy at M12

EXPERIMENTAL

Patients will undergo repeat kidney biopsy at month 12 from baseline.

Procedure: Repeat kidney biopsy

Control arm: No repeat kidney biopsy

NO INTERVENTION

Patients will not undergo repeat kidney biopsy at month 12 from baseline.

Interventions

Repeat kidney biopsy PROCEDURE

Intensification of immunosuppression if NIH AI \> 3

Intervention arm: Repeat kidney biopsy at M12

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fulfilment of the EULAR/ACR classification criteria of SLE.
• years of age or above.
• Incident biopsy-proven proliferative or membranous LN, or combinations thereof (with UPCR ≥ 1 g/g), i.e. 2003 ISN/RPS class III (A or A/C) ± V, class IV (A or A/C) ± V, or class V.
• Consent to the possibility of a repeat kidney biopsy at month 12 from baseline.
• Initiation of the following treatment regimens:
• intravenous pulses of methylprednisolone (total dose of 500-3000 mg);
• oral prednisone or equivalent 0.3-0.5 mg/kg/day with tapering;
• hydroxychloroquine unless contraindicated;
• angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs);
• either one of mycophenolate mofetil (MMF) equivalent dose 2-3 g/day, or IV cyclophosphamide (CYC) according to the Euro-Lupus regimen;
• the NIH protocol for IV CYC (0.5-0.75 g/m2 monthly for six months) could be considered in severe cases;
• add-on therapies (e.g. calcineurin inhibitors, biologics) to the above two regimens are optional.

You may not qualify if:

• Antiphospholipid syndrome nephropathy (APSN).
• Medical contraindications to kidney biopsy, e.g. thrombocytopenia \< 50,000/μL, uncontrolled hypertension or end-stage kidney disease (ESKD).
• Anticipated non-adherence to therapy.
• Medical conditions interfering with outcome evaluations.
• Inability to read and/or sign the informed consent form.

Sponsors & Collaborators

• Karolinska Institutet: lead
• Université Catholique de Louvain: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, 17676, Sweden

RECRUITING

Related Publications (4)

• Newman LB, Anderson EE, Waggover MD, Schulman CC. The relationship of blood urea nitrogen and serum uric acid: a computerized analysis. Acta Urol Belg. 1972 Oct;40(4):784-7. No abstract available.

  PMID: 4654096 BACKGROUND

• Robertson DR. The ultimobranchila body in Rana pipiens. VII. Cellular responses in denervated glands in autoplastic transplants. Z Zellforsch Mikrosk Anat. 1968;90(2):273-88. No abstract available.

  PMID: 5724342 BACKGROUND

• Pineiro GJ, Arrizabalaga P, Sole M, Abellana RM, Espinosa G, Cervera R. Repeated Renal Biopsy - A Predictive Tool to Assess the Probability of Renal Flare in Lupus Nephritis. Am J Nephrol. 2016;44(6):439-446. doi: 10.1159/000452229. Epub 2016 Oct 28.

  PMID: 27788504 BACKGROUND

• Parodis I, Adamichou C, Aydin S, Gomez A, Demoulin N, Weinmann-Menke J, Houssiau FA, Tamirou F. Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis. Rheumatology (Oxford). 2020 Nov 1;59(11):3424-3434. doi: 10.1093/rheumatology/keaa129.

  PMID: 32353879 BACKGROUND

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Ioannis Parodis, MD PhD

  Karolinska Institutet

  STUDY CHAIR

• Farah Tamirou, MD PhD

  Université Catholique de Louvain

  STUDY CHAIR

• Julia Weinmann-Menke, MD PhD

  Johannes Gutenberg University Mainz

  STUDY CHAIR

• Hans-Joachim Anders, Professor

  Ludwig-Maximilians - University of Munich

  STUDY CHAIR

• Brad H Rovin, Professor

  Ohio State University

  STUDY CHAIR

• Frédéric A Houssiau, Professor

  Université Catholique de Louvain

  STUDY CHAIR

Central Study Contacts

Ioannis Parodis, MD PhD | Associate Professor

CONTACT

+46722321322; ioannis.parodis@ki.se

Farah Tamirou, MD PhD

CONTACT

+32487586016; farah.tamirou@uclouvain.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: At baseline, patients will be randomised 1:1 to either undergo or not undergo a per-protocol repeat kidney biopsy at month 12 from baseline.

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: June 29, 2020
• Study Start: January 5, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Starting ten years after the baseline visit of the last study participant recruited.
• Access Criteria: The REBIOLUP steering committee will review all proposals and provide IPD to investigators upon reasonable request, however highly depending on the research questions to be addressed.

Locations

SE (1)