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The subdivisions of class IV-S and class IV-G were included in the ISN/RPS classification because of a long-term lupus nephritis outcome study (>10 years) that demonstrated a poor prognosis for diffuse segmental (class IV-S) LGN compared with diffuse global (class IV-G) LGN or combined membranous and diffuse global LGN (class V + class IV-G).
In class IV as well as in other classes of LGN, a variety of ultrastructural features may be observed, including focal or diffuse organized deposits (admixed with granular type), such as (1) crystalline/fingerprint-like structures in 5% to 10% of cases, usually with a thickness of 10 to 15 nm of the thin curvilinear bands and having cross-striations with a periodicity (Figure 7, A)37; and (2) cryoglobulins composed of larger hollow tubular-type deposits measuring 50 to 100 nm in thickness and occasional Congo red-negative fibrillary deposits, occurring at random or in parallel bundles, composed of polyclonal immunoglobulins (Figure 7, B).
Several clinical and pathologic parameters can be used to distinguish a non-lupus membranous GN from membranous LGN when overt SLE manifestations are not readily expressed, including hypocomplementemia, a full house fluorescence pattern, the presence of mesangial hypercellularity/ deposits, and the finding of occasional subendothelial deposits and tubuloreticular inclusions in endothelial cells by EM.
This represents a late stage of LGN and a culmination of multiple relapses of lupus nephritis, leading to progressive chronic tubulointerstitial scarring, global glomerular sclerosis, and vascular sclerosis.
Active/proliferative LGN is often accompanied by varying degrees of tubulointerstitial inflammation with or without tubular basement membrane and vascular immune complex deposits demonstrable by IF and EM.
(56,57) These bore no relationship to specific classes of LGN, titers of anti-phospholipid antibodies, or other lupus serologies.
When a retrospective biopsy study of 60 Japanese patients diagnosed with LGN was analyzed and compared with the World Health Organization 1995 schema, a higher histologic consensus was obtained using the ISN/RPS 2004 classification (98% vs 83%; P = .008), and it provided beneficial prognostic information to predict long-term outcome as well as to devise optimal therapy to delay end-stage renal failure.
The results revealed that 85% are using this classification of LGN in their nephropathology practice.