Two Biomarkers Predictive of ESRD in Patients With Lupus Nephritis

A new retrospective analysis proposes cutoff values that could help physicians identify patients at highest risk of severe kidney complications.

A new report suggests 2 biomarkers—proteinuria and serum creatinine (sCr)—can help predict which patients with lupus nephritis (LN) are at highest risk of long-term adverse renal outcomes such as chronic kidney disease (CKD) and end-stage renal disease (ESRD).

In findings published in the journal Advances in Rheumatology, corresponding author Fernanda Nogueira Holanda Ferreira Braga, PhD, of Brazil’s State University of Ceará, and colleagues noted that more than half of patients with systemic lupus erythematosus (SLE) will develop LN, and 10-25% of those patients will eventually be diagnosed with ESRD.

“The identification of short-term prognostic factors predictive of poor long-term outcomes in LN would be helpful in clinical practice and in treat-to-target strategies in clinical trials,” the investigators said.

Among potential biomarkers that have already been investigated, the authors said 24-hour proteinuria (24PTU) appears to be the best-known predictor of poor long-term outcomes in LN. Other studies have looked at sCr in combination with 24PTU and/or other biomarkers, although the potential benefits of sCr have been unclear.

The investigators conducted a retrospective analysis of 214 patients with LN who sought care at their single center. As with the SLE population in general, most of the patients (90.6%) were female. About three-quarters were non-White, and their mean (SD) age at LN diagnosis was 27.3 years (9.2).

“Clinical manifestations were mostly musculoskeletal (82.2%), mucocutaneous (73.8%), serositis (46.7%) and leukopenia/lymphopenia (41.5%),” they wrote.

Patients were assessed for 24PTU and sCr at baseline, at 3, 6, and 12 months, and at 5 years and/or their final evaluation. The average follow-up time was 11.2 years (7.2).

After comparing outcomes of 24PTU and sCr assessments, the authors used receiver operating characteristics (ROC) curves to determine cut-off values for each marker.

In the case of CKD, the authors said 0.9 g/24 h and 0.9 mg/dL were the best cutoffs for 24PTU and sCR, respectively. Patients with higher levels at 12 months tended to have a higher risk of CKD.

In terms of ESRD, the authors calculated cut-offs of 0.9 g/24h and 1.3 mg/dL for 24PTU and sCr, respectively.

Conversely, the authors said patients with readings below the cutoff levels were unlikely to progress to more serious kidney disease.

“Patients with 24PTU < 0.9 g/day and sCr < 1.3 mg/dL at 12 months are not likely to develop ESRD because of the high negative predictive values (NPV) (93.2% and 82%),” they wrote.

Although 24PTU was already viewed as a meaningful predictor of renal outcomes, the investigators said the addition of other factors, such as sCr, should help physicians make more accurate assessments. They said the 2 markers appear to be relevant data points for a treat-to-target approach to LN care.

“The high NPV values for both variables emphasize the need for a 1-year PTU- and sCr-based LN treat-to-target treatment as predictors of long-term renal outcomes,” the investigators wrote. “Further studies are crucial to define the therapeutic and follow-up approach in this high risk of developing ESRD population.”


Braga FNHF, das Chagas Medeiros MM, Junior ABV, et al. Proteinuria and serum creatinine after 12 months of treatment for lupus nephritis as predictors of long-term renal outcome: a case-control study. Adv Rheumatol. Published online January 4, 2022. doi:10.1186/s42358-021-00232-1