Tubulointerstitial nephritis in systemic lupus erythematosus: innocent bystander or ominous presage.

SLE-associated tubulointerstitial injury (SLETIN) is increasingly recognized in two forms, i. e., secondary and primary. The secondary form coexists with lupus glomerulonephritis, whereas the primary form develops against the background of no or mild glomerular or vascular involvement. Secondary SLETIN is frequent, but its frequency and severity correlate with the class of the associated lupus glomerulonephritis (GN), being almost universal in Class IV lupus GN and less frequent in GN of other classes. Although the presence of underlying GN may mask its clinical manifestation, secondary SLETIN has a major prognostic implication for the renal outcome. Yet, SLETIN is not factored in the current therapyfocused International Society of Nephrology/Renal Pathology Society schema of renal lupus classification, and its management remains to be elucidated. The pathogenesis of secondary SLETIN is either immunologic, i.e., the tubulointerstitial injury being mediated by SLE-related immunologic mechanisms akin to those responsible for lupus GN; or non-immunologic, i.e., a nonspecific tubulointerstitial injury secondary to any type of advanced glomerular lesion, regardless of etiology. Primary SLETIN is rare with about 15 reported cases. It has a rather uniform and distinctive clinical manifestation including acute kidney injury with no or mild proteinuria. It responds well to steroid and usually carries a good prognosis. Its pathogenesis is almost certain immunologic, with immunoglobulin/complement deposits along the tubular basement membrane in each reported case. In spite of these profound clinical implications, the current review underlies a limited knowledge on the pathobiology of SLETIN.