Giovanni Maria Rossi, Chiara Pala, Francesco Fontana, Davide Gianfreda, Daniel Salvetti, Marco Delsante, Marco Allinovi, Domenico Giannese
The kidney biopsy is the cornerstone of prognostication in lupus nephritis, yet which features predict renal outcome-and which kind-remains incompletely defined. This narrative review relates eight histological axes to two families of renal outcome defined a priori: soft outcomes (renal flare/relapse and response/remission) and hard outcomes (doubling of serum creatinine, sustained decline in estimated glomerular filtration rate, and end-stage kidney disease; death is considered a competing, patient-level outcome). The axes span the ISN/RPS classification and its 2018 revision, individual glomerular and tubulointerstitial lesions, NIH activity and chronicity indices, lupus podocytopathy, lupus vasculopathy, antiphospholipid-antibody nephropathy, thrombotic microangiopathy and repeat biopsy. Across them, a consistent asymmetry emerges, although it is often not reproducible between studies. Chronicity-especially tubulointerstitial damage-predicts hard outcomes, whereas the activity index as a whole predicts response and flare. Cellular crescents and fibrinoid necrosis, active lesions that can signal hard outcomes, are the exceptions. Whether chronicity adds to baseline kidney function remains unsettled. Several prognostically important entities lie outside the proliferative classification; immune-deposit burden is largely diagnostic; and repeat histology adds information beyond the baseline biopsy. A recurring caveat is the therapeutic era, which modifies the very lesions scored.