Lack of EULAR/ERA-EDTA Response Predicts Chronic Kidney Disease in Patients With Lupus Nephritis

Lack of renal response to therapy at 12 months predicts chronic kidney disease (CKD) in patients with lupus nephritis, according to study results published in Annals of the Rheumatic Diseases.

Renal response was jointly determined by the European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) as a potential predictive end point of CKD. Investigators studied a large cohort of Italian patients to examine the rate of renal response at 12 months from therapy initiation, the ability of response to predict long-term CKD, and the predictors of no response to therapy at the time of diagnosis.

A total of 381 patients (90.5% Caucasian; 86% women, median age, 30.4 years) were included in the study. Baseline was considered to be initiation of therapy after lupus nephritis diagnosis. After renal biopsy, patients were evaluated at 1 month after diagnosis, then every 2 to 3 months, at 12 months, and every 3 to 6 months thereafter. Renal variables were recorded throughout the observation period, with parameters defined for complete (proteinuria, <0.5 g/24 h and near normal estimated glomerular filtration rate [eGFR]), partial (≥50% proteinuria reduction to subnephrotic levels and near normal eGFR), or no renal response (all other cases). Logistic and Cox regression models were used for analysis of 12-month response and CKD prediction, respectively.

At diagnosis, none of the patients had CKD or developed it during the first 12 months of observation. At 12 months, 16% of patients had no response, 26% had partial response, and 58% achieved complete renal response, according to the EULAR/ERA-EDTA criteria. After a median follow-up of 10.7 years, 13.9% (n=53) of patients had developed CKD. Compared with 7.9% of patients who had normal renal function at baseline, 33.3% had acute renal dysfunction. Among patients with no response at the time of last observation, 39.3% of patients developed CKD (P <.0001). At 15 years, CKD-free survival rate in patients with complete, partial, and no response at 12 months were 95.2%, 87.6%, and 55.4, respectively (P <.0001)

Investigators determined that complete or partial response at 12 months of therapy was associated with long-term renal survival; failure to achieve a response predicted a worse renal outcome. In a multivariable analysis of patients with no response, arterial hypertension (hazard ratio [HR], 3.154; 95% CI, 1.500-4.547; P =.013) and low C4 levels (HR, 1.053; 95% CI, 1.019-1.089; P =.0014) were independent predictors of CKD. In addition, the researchers observed that serum creatinine (HR, 1.485; 95% CI, 1.276-1.62), eGFR (HR, 0.967, 95% CI, 0.957-0.977) and proteinuria at 12 months (HR, 1.234; 95% CI, 1.111-1.369; all P <.0001) were associated with CKD; however, no reliable cutoffs were observed on the receiver operating characteristic curve.

Study limitations included the fact that some patients may have been excluded because of incomplete records at 12 months, and since a majority of the participants were Caucasian, the study could not be extended to include other ethnicities.

Researchers concluded, “… according to our data, EULAR/ERA-EDTA response can be considered a good straightforward short-term end point for CKD prediction and a promising target to treat patients with [lupus nephritis].”

Reference

Moroni G, Gatto M, Tamborini F, et al. Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis [published online June 5, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-216965