Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

We retrospectively studied the evolution of histopathologic features in successive renal biopsies in patients with lupus nephritis, to evaluate the effects of various treatment regimens. Repeat renal biopsies had been performed in 62 patients after more than 18 months of observation (median interval, 44 months) in randomized therapeutic trials comparing prednisone with cytotoxic drugs. Renal histopathologic features were graded individually, and a composite score reflecting the number and severity of irreversible lesions was defined as a chronicity index. The chronicity index for patients treated with conventional high-dose prednisone increased linearly with the interval between biopsies, whereas the index in the group receiving cytotoxic-drug treatments did not increase over time. After statistical adjustment for important prognostic factors (age and initial chronicity index) identified by multiple linear regression, the difference in the slopes between the group receiving prednisone and the group receiving cytotoxic drugs was significant (P less than 0.0001). We conclude that cytotoxic-drug treatment reduces the likelihood of progressive renal scarring in lupus nephritis.

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Abstract. Between January 1976 and September 1987 renal medullary amyloidosis (RMA) was diagnosed in 17 Dorcas gazelles; the necropsy prevalence rate was 17/32 (53%). The most severe amyloid deposits were in the renal medulla; glomeruli were spared. Renal cortical lesions of interstitial fibrosis and tubular atrophy and dilatation significantly correlated with RMA (P < 0.01) and were considered to be secondary changes.There were varying degrees of lymphoplasmacytic inflammation and tubular cast formation which did not significantly correlate with RMA. Amyloid was confirmed histochemically and by electron microscopy and was identified as AA type by the permanganate method. Progressive renal failure was the cause of death or necessitated euthanasia in 7/17 (4 1 Yo) gazelles. RMA in Dorcas gazelles does not appear to be familial. A high prevalence of chronic or recurring Actinomyces (Corynebacterium) pyogenes infections may be an important factor.Currently, classification of the amyloidoses is based in part on the nature of the fibril p r~t e i n .~ Reactive systemic amyloidosis, in which the fibril protein (AA) is believed to be derived by proteolytic cleavage from an acute phase protein (SAA), is the most common form in manZZ and is the only form of systemic amyloid reported in nonhumans.' Any organ can be involved in reactive systemic amyloidosis, but renal involvement occurs with greatest f r e q u e n~y . '~.~~ Renal amyloid also has the most serious consequences, since deposition of amyloid in glomeruli causes disruption of the glomerular filtration bamer, with resultant proteinuria and associated sequelae. l 5 In addition, deposition of amyloid in the pentubular interstitium can lead to ischemia and pressure atrophy of nephrons with subsequent interstitial scarring and loss of renal function.I5Involvement of the renal medulla with amyloid is rare in man26 and most animals,I5 but may be the predominant form of renal amyloidosis in cats3J5J8 and ~a t t l e .~J~J~ In cattle, there is a spectrum from predominantly glomerular to predominantly medullary amy10idosis;~~l~ the glomerular form can lead to the nephrotic ~y n d r o m e~~J~J~ as in other species, but the medullary form is usually subclinical.I0We have identified a syndrome of renal medullary amyloidosis (RMA) in a herd of Dorcas gazelles at the National Zoological Park (NZP). In contrast to medullary amyloidosis in cattle, RMA in Dorcas gazelles frequently leads to renal failure and death. This paper reports the occurrence and describes the gross and light microscopic features of renal medullary amyloidosis in Dorcas gazelles. The clinical aspects of the disease will be published elsewhere. Materials and MethodsDorcas gazelles are small ruminants indigenous to desert regions of Northeast Africa. Body weights in adults range from 10 to 15 kg. The National Zoological Park (NZP) maintains a herd of Dorcas gazelles with an average year-end population of about 20 animals. Twice yearly each animal is treated prophylactically with anthelminthics, and a complete...