Contributed by James T. Edinger, M.D., Ibrahim Batal, M.D. and Lawrence Kiss, M.D.
The patient is a 62 year-old male with no significant past medical history who presented with flank pain, chills, and hematuria. He was found to be in acute renal failure with a creatinine of 7.6 mg/dl. The patient's baseline creatinine level was 0.9 mg/dl five months earlier. He has no history of hypertension, diabetes mellitus, polyuria, or renal masses. There was no clinical evidence of nephrotic syndrome. His creatinine continued to rise to a level of 12.2 mg/dl. Urine dipstick showed 3+ protein. Urinalysis revealed many crenated red blood cell casts, many white blood cells, and few granular casts. Renal biopsy was performed.
Light microscopic examination revealed sixteen glomeruli, all of which showed evidence of a cellular crescent ranging from partial to circumferential. The crescents showed associated fibrin and inflammatory cells and were also associated with frequent basement membrane breaks (Figure 1 - H&E, Figure 2 - PAS, Figure 3 - Silver). Some crescents appeared to penetrate the basement membrane of Bowman's capsule with spilling of inflammatory cells into the surrounding interstitial space (Figure 4 - Silver). The remaining glomerular tufts were compressed with no significant mesangial proliferation. None of the glomeruli were globally or segmentally sclerotic.
There was mild tubular atrophy and interstitial fibrosis affecting less than 20% of the cortical area (Figure 5 - Trichrome). Severe mixed acute and chronic interstitial inflammation was present composed primarily of mature and activated lymphocytes with abundant admixed plasma cells and macrophages. Interstitial eosinophils were focally increased (Figure 6 - H&E). Many tubules contained red blood cell casts (Figure 7 - H&E). The tubules showed mild to moderate epithelial injury with flattening of some tubular epithelial cells and areas of sloughing of epithelial cells into luminal spaces. Mild to moderate intimal sclerosis of small arteries was noted.
Immunofluorescence studies revealed diffuse, strong (4+) linear glomerular basement staining with IgG (Figures 8 and 9) as well as kappa (Figure 10) and lambda (Figure 11). There was non-specific glomerular reactivity for C3 (Figure 12). Fibrin positive crescents were identified in all six examined glomeruli (Figure 13).
Electron microscopic studies showed segmental to cellular crescents in all glomeruli examined. Ultrastructurally, the glomeruli showed mildly thickened basement membranes (300-500 nm) with a well-preserved outer contour. No subepithelial, intramembranous, or subendothelial immune complexes were identified. There was fairly diffuse foot process effacement affecting greater than 75% of the capillary surfaces. There were multifocal areas of fibrin deposits associated with focal basement membrane breaks (Figure 14).