Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus nephritis cohort
Abstract
OBJECTIVE: There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We used data from the Euro-Lupus Nephritis Trial to evaluate the performance of proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as predictors of good long-term renal outcome. METHODS: Patients from the Euro-Lupus Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6, or 12 months and with a minimum of 7 years of followup were included (n = 76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as a serum Cr value ≤1.0 mg/dl) at 7 years. Receiver operating characteristic curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters. Sensitivity and specificity were calculated for the parameters alone and in combination. RESULTS: A proteinuria value of <0.8 gm/day at 12 months after randomization was the single best predictor of good long-term renal function (sensitivity 81% and specificity 78%). The addition of serum Cr to proteinuria as a composite predictor did not improve the performance of the outcome measure; addition of urinary RBCs as a predictor significantly decreased the sensitivity to 47%. CONCLUSION: This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome in patients with lupus nephritis. Inclusion of urinary RBCs as part of a composite outcome measure actually undermined the predictive value of the trial data. We therefore suggest that urinary RBCs should not be included as a component of clinical trial response criteria in lupus nephritis.
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In monitoring renal response, reduction of urinary protein following treatment is more important than residual haematuria.
“In monitoring renal response, reduction of UPr (to less than 0.8 g/day) following treatment is more important than residual haematuria.”
From 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus (2019) · cites this paper as [21]
Cites
Rovin, B. H., Furie, R. A., Latinis, K. M., Looney, R. J., Fervenza, F. C., Sánchez‐Guerrero, J., Maciuca, R. D., Zhang, D., Garg, J. P., Brunetta, P. G., et al. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34359 · Cited by 1,467 · see citing works
Self-citationHahn, B. H., McMahon, M. A., Wilkinson, A. H., Wallace, W. D., Daikh, D., FitzGerald, J. D., Karpouzas, G. A., Merrill, J. T., Wallace, D. J., Yazdany, J., et al. (2012) · Arthritis Care & Research · doi:10.1002/acr.21664 · Cited by 1,464 · see citing works
Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis
Appel, G. B., Contreras, G. N., Dooley, M. A., Ginzler, E. M., Isenberg, D. A., Jayne, D. R. W., Leishi, L., Mysler, E., Accent]nchez-Guerrero, J. S. A., Solomons, N., et al. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008101028 · Cited by 1,121 · see citing works
Houssiau, F., Vasconcelos, C., D’Cruz, D. P., Sebastiani, G. D., Garrido, E. D. R., Danieli, M. G., Abramowicz, D., Blockmans, D., Mathieu, A., Di̇reskeneli̇, H., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10461 · Cited by 1,074 · see citing works
Self-citationA readers' guide to the interpretation of diagnostic test properties: clinical example of sepsis
Fischer, J. E., Bachmann, L. M., & Jaeschke, R. (2003) · Intensive Care Medicine · doi:10.1007/s00134-003-1761-8 · Cited by 890 · see citing works
Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis
Dooley, M. A., Jayne, D. R. W., Ginzler, E. M., Isenberg, D. A., Olsen, N. J., Wofsy, D., Eitner, F., Appel, G. B., Contreras, G. N., Lisk, L., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1014460 · Cited by 645 · see citing works
Houssiau, F., Vasconcelos, C., D’Cruz, D. P., Sebastiani, G. D., Garrido, E. D. R., Danieli, M. G., Abramowicz, D., Blockmans, D., Cauli, A., Di̇reskeneli̇, H., et al. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.102533 · Cited by 540 · see citing works
Self-citationHoussiau, F., D’Cruz, D. P., Sangle, S. R., Remy, P., Vasconcelos, C., Petrović, R., Fiehn, C., Garrido, E. D. R., Gilboe, I., Tektonidou, M. G., et al. (2010) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2010.131995 · Cited by 499 · see citing works
Self-citationHoussiau, F., Vasconcelos, C., D’Cruz, D. P., Sebastiani, G. D., Garrido, E. D. R., Danieli, M. G., Abramowicz, D., Blockmans, D., Mathieu, A., Di̇reskeneli̇, H., et al. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20666 · Cited by 391 · see citing works
Self-citationThe interpretation of diagnostic tests
Shapiro, D. E. (1999) · Statistical Methods in Medical Research · doi:10.1177/096228029900800203 · Cited by 375 · see citing works
Factors predictive of outcome in severe lupus nephritis
Korbet, S. M., Lewis, E. J., Schwartz, M. M., Reichlin, M., Evans, J., & Rohde, R. D. (2000) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(00)70262-9 · Cited by 372 · see citing works
Efficacy and Safety of Abatacept in Lupus Nephritis: A Twelve‐Month, Randomized, Double‐Blind Study
Furie, R. A., Nicholls, K., Cheng, T., Houssiau, F., Burgos‐Vargas, R., Chen, S., Hillson, J., Meadows-Shropshire, S., Kinaszczuk, M., & Merrill, J. T. (2013) · Arthritis & Rheumatology · doi:10.1002/art.38260 · Cited by 343 · see citing works
Self-citationThe ACCESS Trial Group (2014) · Arthritis & Rheumatology · doi:10.1002/art.38790 · Cited by 287 · see citing works
Liang, M. H., Schur, P. H., Fortin, P. R., Clair, E. W. S., Balow, J. E., Costenbader, K. H., Crofford, L. J., de Pablo, P., Dooley, M. A., Finckh, A., et al. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21625 · Cited by 263 · see citing works
Prognostic determinants in lupus nephritis: a long-term clinicopathologic study
Donadio, J., Hart, G. W., Bergstralh, E., et al. (1995) · Lupus · doi:10.1177/096120339500400206 · Cited by 197 · see citing works
Wofsy, D., Hillson, J., & Diamond, B. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34624 · Cited by 156 · see citing works
Dall’Era, M., Stone, D., Levesque, V., et al. (2010) · Arthritis Care & Research · doi:10.1002/acr.20397 · Cited by 92 · see citing works
Self-citationComparison of Alternative Primary Outcome Measures for Use in Lupus Nephritis Clinical Trials
Wofsy, D., Hillson, J., & Diamond, B. (2013) · Arthritis & Rheumatism · doi:10.1002/art.37940 · Cited by 91 · see citing works
Urine protein-to-creatinine ratio is a reliable measure of proteinuria in lupus nephritis.
Christopher‐Stine, L., Petri, M., Astor, B. C., & Fine, D. M. (2004) · PubMed · Cited by 87 · see citing works
Cortés-Hernández, J., Torres-Salido, M. T., Medrano, A. S., et al. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq322 · Cited by 87 · see citing works
Response to treatment as a predictor of longterm outcome in patients with lupus nephritis.
Fraenkel, L., MacKenzie, T. A., Joseph, L., et al. (1994) · PubMed · Cited by 53 · see citing works
Ten Common Mistakes in the Management of Lupus Nephritis
Bose, B., Silverman, E. D., & Bargman, J. M. (2013) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2013.10.056 · Cited by 40 · see citing works
Inability of Community-Based Laboratories to Identify Pathological Casts in Urine Samples
Rasoulpour, M. (1996) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1996.02170360091015 · Cited by 30 · see citing works
Quantitative analysis of urine sediment using newly designed centrifuge tubes.
Kim, Y., Jin, D. C., Lee, E. J., et al. (2002) · PubMed · Cited by 14 · see citing works
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2019 update of the EULAR recommendations for the management of systemic lupus erythematosus
Fanouriakis, A., Kostopoulou, M., Alunno, A., Aringer, M., Bajema, I., Boletis, J. N., Cervera, R., Doria, A., Gordon, C., Govoni, M., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-215089 · Cited by 2,011 · see citing works
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Gomez Mendez, L. M., Cascino, M. D., Garg, J., Katsumoto, T. R., Brakeman, P., Dall’Era, M., Looney, R. J., Rovin, B., Dragone, L., & Brunetta, P. (2018) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.01070118 · Cited by 188 · see citing works
Self-citationTedeschi, S. K., Johnson, S. R., Boumpas, D., Daikh, D., Dörner, T., Jayne, D., Kamen, D., Lerstrøm, K., Mosca, M., Ramsey‐Goldman, R., et al. (2018) · Arthritis Care & Research · doi:10.1002/acr.23317 · Cited by 112 · see citing works
- Authors
- Dall'Era, M., Cisternas, M. G., Smilek, D. E., Straub, L., Houssiau, F. A., Cervera, R., Rovin, B. H., & Mackay, M.
- Affiliations
- University of California San Francisco
- MGC Data Services Carlsbad California
- Immune Tolerance Network (US)
- Cliniques Universitaires Saint-Luc (BE)
- Hospital Clínic de Barcelona (ES)
- The Ohio State University Wexner Medical Center (US)
- Feinstein Institute for Medical Research (US)
- Venue
- Arthritis & Rheumatology
- Publisher
- Wiley
- Published
- 2015-04-27
- Volume
- 67
- Issue
- 5
- Pages
- 1305-1313
- ISSN
- 2326-5191 (ISSN-L)
- 2326-5205
- OpenAlex
- W2104259706
- Cited by
- 329
- References
- 24
- Citations by year
- 2026: 29 · 2025: 39 · 2024: 26 · 2023: 31 · 2022: 42 · 2021: 41 · 2020: 24 · 2019: 19 · 2018: 26 · 2017: 18 · 2016: 21 · 2015: 12 · 2014: 1
- FWCI
- 21.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Keywords
- lupus nephritis, long-term renal outcomes, proteinuria, serum creatinine, urinary red blood cells, prognostic factors, renal function estimation
- MeSH terms
- Creatinine, Glucocorticoids, Hematuria, Humans, Longitudinal Studies, Lupus Nephritis, Proteinuria, ROC Curve, Cohort Studies, Biomarkers, Disease Progression, Renal Insufficiency, Chronic
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