Exostosin status predicts remission in patients with lupus membranous nephropathy (LMN), according to a new study.
Exostosins (EXO) are present in the podocyte Golgi apparatus, where they are responsible for the glycosylation of heparan sulfates that are eventually transported to the glomerular basement membrane, previous research suggests. Heparan sulfates may offer protection from leukocyte infiltration, complement activation, and cytokine production, researchers suggest. EXO and heparan sulfates may coat immune complexes and restrict immune deposits from generating an inflammatory response in LMN.
Of 86 patients with pure class 5 LMN, 33 were EXO-positive and 53 were EXO-negative upon immunohistochemistry with EXO anti-1 antibody. Although LMN stage did not differ between groups, EXO-positive cases displayed significantly fewer glomerular scars than EXO-negative cases at baseline: 9.1% vs 34.0% with 10% or more sclerosed glomeruli, according to investigators.
During follow-up, EXO-positive cases were less likely to require repeat kidney biopsy (26 vs 42 patients) and had significantly less proliferative lupus nephritis (7.7% vs 35.7%) than EXO-negative cases. Further, at 50 months, the EXO-positive group displayed better renal function, David Buob, MD, PhD, of Tenon Hospital in Paris, France, and colleagues reported in Kidney International Reports. Serum creatinine was significantly lower (0.60 vs 0.81 mg/dL, respectively) and estimated glomerular filtration rate (eGFR) significantly higher (114.6 vs 84.6 mL/min/1.73 m2, respectively) in the EXO-positive than EXO-negative group. Clinical remission, including both complete and partial remission, occurred in significantly more patients with EXO-positivity: 96.3% vs 68.4%, the investigators reported. Complete remission, defined as proteinuria of 0.5 g/d or less, serum albumin of more than 30 g/L, and normal serum creatinine, occurred in 70.4% vs 55.3%, respectively. Partial remission, defined as at least a 50% decrease in proteinuria to 0.5-3.5 g/d, an increase in serum albumin, and stable serum creatinine, occurred in 25.9% vs 13.2%, respectively. In an adjusted multivariate logistic regression model, EXO-positivity was associated with 17.7-fold increased odds of complete or partial remission, the investigators reported.
According to Dr Buob’s team, their study findings validate those of a Mayo Clinic study by Aishwarya Ravindran, MD, and colleagues in the Journal of the American Society of Nephrology, and suggest that EXO-positivity correlates with better renal outcomes, despite greater proteinuria at diagnosis.
“In light of these results, we recommend that immunohistochemical phenotyping of SLE-MN with anti-EXT antibody should be systematically performed by pathologists,” Dr Buob and colleagues wrote. Further studies are needed to determine whether therapeutic approach should be different according to the EXT status of SLE-MN patients.”
At diagnosis, patients who were EXO-positive were significantly younger (age 33.3 vs 39.9 years), with significantly higher eGFR (122.6 vs 95.5 mL/min/1.73 m2), and significantly higher urinary protein (3.0 vs 1.7 g/d), compared with patients who were EXO-negative. Treatment, however, did not differ between groups. Most patients received hydroxychloroquine (81.3% of EXO-positive and 82.0% of EXO-negative cases) and/or steroids (84.4% and 86.0%, respectively). The number of additional immunosuppressive drugs (eg, mycophenolate mofetil, rituximab, cyclophosphamide, and azathioprine) was comparable between groups.
Saïdi M, Brochériou I, Estève E, et al. The EXO immunohistochemical status differentiates lupus membranous nephropathy subsets with different outcomes. Kidney Int Rep. Published online May 4, 2021. doi:10.1016/j.ekir.2021.04.025