Serology ‘significantly different’ between membranous vs. proliferative lupus nephritis
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Key takeaways:
- Proteinuria levels don’t predict lupus nephritis type, suggesting separate study approaches are needed.
- Distinct serological profiles between MLN and PLN indicate differing pathogenesis.
Proteinuria levels are not predictive of membranous lupus nephritis vs. proliferative lupus nephritis, according to data published in Rheumatology.
The two forms of lupus nephritis additionally displayed distinct serological profiles, suggesting that future studies of their pathogenesis “should probably look at these two groups separately,” Filipa Farinha, MD, a PhD student at University College London, and colleagues wrote. They had previously reported on long-term outcomes and differences between proliferative lupus nephritis (PLN) and membranous lupus nephritis (MLN) in a single-center study.
“However, to our knowledge, there are no other studies directly comparing PLN vs MLN,” Farinha and colleagues wrote. “A multicenter study, with a different population, would be important to confirm and validate our previous findings.”
To compare the laboratory presentation and long-term outcomes of patients with PLN and MLN, and to examine predictors of chronic kidney (CKD) in each — the researchers conducted a retrospective analysis of multicenter, prospective cohort data from the Rheumatic Diseases Portuguese Registry. The team’s analysis included 260 patients with biopsy-proven PLN (n = 203), MLN (n = 47) or mixed lupus nephritis (n = 10) followed for a median period of 8 years.
Clinical data, laboratory results and long-term outcomes between MLN and PLN groups were compared using statistical tests, while factors predicting CKD were assessed using Cox regression analysis.
According to the researchers, the analysis showed no difference in proteinuria levels between the two groups (P = .641). However, patients with MLN showed significantly lower serum creatinine, at 0.7 mg/dL (IQR = 0.2; 95% CI, 0.5-1.3), vs. 0.8 mg/dL (IQR = 0.31; 95% CI, 0.26-2.6) for those with PLN. There was also a “highly significant difference” in anti-dsDNA positivity at time of diagnosis — 48% in MLN and 92% in PLN (P < .001).
The strongest predictor of progression to CKD was an estimated glomerular filtration rate of 75 mL/minute/1.73 m2 or less at 1 year (HR = 22.86; 95% CI, 8.38-62.36). Patients meeting this threshold “should receive special attention,” the researchers wrote.
They added that their work represented “the first multicenter study directly comparing patients with PLN vs. MLN.” The researchers concluded the two conditions’ “serological profiles are significantly different ... which might suggest a different pathophysiology.”
“A repeated renal biopsy may be useful to help distinguish between ongoing active disease (needing more aggressive immunosuppression) from irreversible damage,” Farinha and colleagues wrote. “All patients should be closely monitored to ensure that any flares are rapidly detected and treated in order to avoid further loss of [glomerular filtration rate]. Furthermore, tight blood pressure control, treatment with [angiotensin-converting enzyme inhibitors] and, in those with CKD and mild proteinuria, the use of sodium-glucose cotransporter-2 inhibitors may be extremely important to improve outcomes.”
Perspective
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Systemic lupus erythematosus is a complex multisystem disease that can be challenging for even the most seasoned rheumatologist. One of the most serious complications, lupus nephritis, affects up to 50% of all lupus patients and is associated with end-stage renal disease and death.
This unique multicenter, observational study identified differences in clinical and laboratory presentations of proliferative lupus nephritis and membranous lupus nephritis. These findings may allow earlier identification of a patient population for which more aggressive monitoring and therapy may be necessary.
Results also suggest these differences may represent a unique pathogenesis that could lead to more precise therapy in the future. However, additional research is required. Differences in serological profiles were consistent with previous research, while predictors of progression to chronic kidney disease were not.
As with all diseases, earlier lupus nephritis diagnosis and treatment improve patient outcomes, and this study offers information that may make that possible.
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