Clinicopathological Features and Outcomes of PLA2R-Related Membranous Nephropathy with Renal Glycosuria

Background: Membranous nephropathy (MN) is an immune complex mediated disease. The loss of massive proteinuria can lead to Fanconi syndrome, clinically, manifesting as renal glycosuria. The prevalence and prognosis of M type phospholipase A2 receptor (PLA2R)-related MN with renal glycosuria remain unknown. Methods Patients diagnosed as PLA2R-related MN with renal glycosuria were reviewed, and the control group comprised of patients with MN without renal glycosuria who were randomly selected in a ratio of 1:3. Results From January 2015 to January 2020, a total of 50 patients identified as PLA2R-related MN with renal glycosuria were included, with a prevalence of 2.3%. Compared with patients without renal glycosuria, those with renal glycosuria exhibited greater proteinuria, lower estimated glomerular filtration rate (eGFR), as well as higher use of diuretics, anticoagulants, antibiotics, traditional Chinese medicine and tacrolimus within 3 months prior to renal biopsy (all p < 0.05). Histologically, patients with renal glycosuria exhibited more severe degrees in pathological stages, acute/chronic tubulointerstitial lesions and tubulointerstitial inflammation (all p < 0.05). Of the 10 cases treated with rituximab (RTX), 6 (60%) maintained proteinuria remission, and 5/6 (83.3%) achieved urine glucose remission. Multivariate Cox regression analysis showed that renal glycosuria and age > 50 years were independent risk factors for end-stage renal disease (ESRD) or 30% reduction of eGFR in patients with PLA2R-related MN. Conclusion PLA2R-related MN patients with renal glycosuria presented with more severe clinicopathological manifestations and worse prognosis. Suspected nephrotoxic drugs should be used rationally, and RTX could be used as a treatment option.