Pathology of lupus nephritis

The glomerular pathology of lupus nephritis is the result of diverse immune insults which are probably of independent pathogenetic origins. Although lupus nephritis is looked upon as a classic example of immune complex-induced microvascular injury resulting from circulating DNA double stranded polynucleotide antigens/anti-DNA antibody complexes, other mechanisms, including in situ reactivity of free antibody with fixed antigens and the role of sensitized T-cells, are probably an important part of the picture. This complexity makes categorization of glomerular pathology into a clinically relevant classification an important goal so that our experiences can be reliably compared. This review describes the various glomerular lesions commonly encountered in lupus nephritis and, based upon data derived from experimental models, emphasizes the importance of understanding the clinical relevance of the reported morphology. We point out that the severity of glomerular damage is not merely the accrued result of immune complex induced injury to individual capillaries, but involves capillary necrosis and thrombosis, neither of which may have anything to do with immune complexes or immune aggregates. In fact, the segmental lesions of glomerular capillary necrosis and thrombosis may have a great deal to do with the response to therapy and the ultimate outcome of the patient. While discrete morphologic lesions such as mesangiopathy, acute inflammation, necrosis, thrombosis, epimembranous lesions and podocytopathy are readily described, it is important to note that any given case can represent any combination of these insults. In this context, the new proposed International Society of Nephrology Classification is presented and its strengths and weaknesses discussed.