Lack of EULAR/ERA-EDTA lupus response at 1 year predicts chronic kidney disease
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A lack of EULAR/European Renal Association-European Dialysis and Transplant Association response at 1 year among patients with lupus nephritis predicted chronic kidney disease, researchers reported.
“There is a general agreement that response to therapy can be one potentially predictive endpoint for renal survival,” Gabriella Moroni, MD, of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, in Milan, Italy, and colleagues wrote. “However, no definition of renal response has unanimously been agreed and no time interval for assessment of renal response has clearly been established.”
They added: “The EULAR/ERA-EDTA (European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association) recommendations, developed by the review of available literature and expert opinion, have coined a shared definition of renal response to therapy (as categorized in the section Definition of renal variables).”
To test the EULAR/ERA-EDTA definition of response with the aim of analyzing the rate or renal response at 1 year following the start of therapy, as well as its ability to predict chronic kidney disease, Moroni and colleagues followed 381 patients with lupus nephritis from January 1970 to December 2016. All included participants had undergone renal biopsy followed by induction therapy at one of three referral centers in Italy. Inclusion criteria included follow-up longer than 1 year from the start of induction treatment, and at least three clinical and laboratory assessments during that time.
Response was defined according to EULAR/ERA-EDTA recommendations. As such, complete response required a proteinuria of less than 0.5 g per 24 hours and normal, or near normal, estimated glomerular filtration rate (eGFR). Partial response was defined as 50% or more proteinuria reduction to sub-nephrotic levels, as well as normal or near normal eGFR. All other cases were classified as “no response.” The researchers used logistic regression analysis for 12-month response, as well as Cox regression for predicting chronic kidney disease. The renal outcome was chronic kidney disease.
According to the researchers, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, based on EULAR/ERA-EDTA definitions, after 1 year of therapy. During a median follow-up of 10.7 years, 53 patients developed chronic kidney disease. At 15 years, the rate of survival without chronic kidney disease was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 1 year, respectively (P < .0001). Chronic-kidney-disease-free survival rates did not differ between those with complete and partial responses (P = .067).
Serum creatinine (HR = 1.485; 95% CI, 1.276-1.625), eGFR (HR = 0.967; 95% CI, 0.957-0.977) and proteinuria at 1 year (HR = 1.234; 95% CI, 1.111-1.379) were associated with chronic kidney disease. However, the researchers were unable to identify any reliable cut-offs on the receiver operating characteristic curve. In their multivariable analysis, Moroni and colleagues determined that no response at 1 year (HR = 5.165; 95% CI, 2.77-7.628), low C4 (HR = 1.053; 95% CI, 1.019-1.089) and persistent arterial hypertension (HR = 3.154; 95% CI, 1.5-4.547) independently predicted chronic kidney disease.
“According to our data, EULAR/ERA-EDTA response can be considered a good straightforward short-term endpoint for CKD prediction and a promising target to treat patients with LN,” Moroni and colleagues wrote. “During treatment to achieve renal remission, careful attention should be paid to uncontrolled arterial hypertension.”
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