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Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis
  1. Gabriella Moroni1,
  2. Mariele Gatto2,
  3. Francesco Tamborini1,
  4. Silvana Quaglini3,
  5. Francesca Radice4,5,
  6. Francesca Saccon2,
  7. Giulia Frontini1,
  8. Federico Alberici6,
  9. Lucia Sacchi3,
  10. Valentina Binda1,
  11. Barbara Trezzi4,5,
  12. Augusto Vaglio7,
  13. Piergiorgio Messa1,
  14. Renato Alberto Sinico4,5,
  15. Andrea Doria2
  1. 1 Nephrology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
  2. 2 Division of Rheumatology, Department of Medicine, DIMED, University of Padova, Padova, Italy
  3. 3 Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
  4. 4 Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy
  5. 5 Nephrology Unit, ASST-Monza, Ospedale San Gerardo, Milano, Italy
  6. 6 Nephrology Unit - Immunology Clinic, ASST Santo Paolo e Carlo - San Carlo Borromeo Hospital, Milano, Italy
  7. 7 Department of Biomedical Clinical and Experimental Sciences "Mario Serio", Meyer Children's Hospital, University of Florence, Firenze, Italy
  1. Correspondence to Dr Gabriella Moroni, Nephrological Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy; gabriella.moroni{at}policlinico.mi.it

Abstract

Objectives Short-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.

Methods We considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations: complete: proteinuria <0.5 g/24 hours, (near) normal estimated glomerular filtration rate (eGFR); partial: ≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; and no response: all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.

Results We studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97–18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (p<0.0001). CKD-free survival rates did not differ between complete and partial responders (p=0.067). Serum creatinine (HR: 1.485, 95% CI 1.276 to 1.625), eGFR (HR 0.967, 95% CI 0.957 to 0.977) and proteinuria at 12 months (HR 1.234, 95% CI 1.111 to 1.379) were associated with CKD, yet no reliable cut-offs were identified on the receiver operating characteristic curve. In multivariable analysis, no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), low C4 (HR 1.053, 95% CI 1.019 to 1.089) and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547) independently predicted CKD.

Conclusions Lack of EULAR/ERA-EDTA response at 12 months predicts CKD.

  • arterial hypertension
  • lupus nephritis
  • systemic lupus erythematosus
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Footnotes

  • RAS and AD are joint senior authors.

  • Handling editor Josef S Smolen

  • RAS and AD contributed equally.

  • Presented at The manuscript was based on a work presented at the EULAR conference in 2019 and was published as a conference abstract (number THU0685).

  • Contributors GM conceived and planned the study and took the lead in writing the manuscript. MG significantly contributed to drafting and revision of the paper. RAS and AD contributed substantially to data acquisition and interpretation, and to manuscript drafting. SQ and LS performed the statistical analysis. FT, GF, FS, FR, MG, BT, FA and VB helped in following patients and collected the data. PM, AV, AD and RAS critically revised the manuscript. All authors approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Ethics Committee of Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico di Milano, Italy (protocol number 505_2019bis) and of the other participating centres.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available for formal research purposes only upon request to the corresponding author.

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