Phenotypic shift from active class IV lupus nephritis to lupus podocytopathy: a case report highlighting the treatment-altering role of repeat kidney biopsy

Background The underlying pathophysiological mechanisms of proteinuria relapse in lupus nephritis (LN) patients during immunological remission are complex, often involving non-immune complex-mediated podocyte injury. Case presentation We report a 21-year-old male with class IV LN and thrombotic microangiopathy (TMA). After multi-target induction and maintenance therapy, the patient achieved complete clinical remission. During subsequent follow-up, he developed progressive nephrotic-range proteinuria while maintaining serological remission (persistently negative autoantibodies and normal complement levels). Intensification of conventional immunosuppressants was ineffective. A repeat kidney biopsy revealed significant resolution of immune complex deposits but prominent focal segmental glomerulosclerosis (FSGS)-like changes with extensive podocyte foot process effacement. The regimen was adjusted to a podocyte-targeted therapy centered on tacrolimus, resulting in a rapid and sustained reduction in proteinuria. Conclusion This case suggests that in the clinico-serological dissociation phase of LN, repeat kidney biopsy is of significant clinical value for identifying pathological phenotypic shifts, avoiding excessive immunosuppression, and guiding precision medicine.