Analgesic nephropathy: A clinicopathologic study using electron microscopy

Abstract

A Clinicopathologic study was made in twenty-six patients who had consumed at least 2 kg of both acetylsalicylic acid and phenacetin. Renal function varied from normal to end-stage. Conventional histologic and electron microscopic studies confirmed a medullary site for the earliest lesion, which appeared to be an increase in interstitial collagen. Other early abnormalities included focal thickening of tubular basement membranes, degeneration, atrophy or loss of tubular epithelium, and casts. These abnormalities were apparent when renal function was not demonstrably reduced. They progressed to become a diffuse sclerosis or necrosis of the medulla, and only then were cortical histologic abnormalities present. These included peritubular, interstitial and periglomerular fibrosis; tubular atrophy, dilatation and basement membrane thickening; and in some focal round cell infiltration. Results of immunofluorescent microscopy were negative for immunoglobulin G (IgG) and beta 1-C globulin ( β 1 C) in kidney tissue from six patients. The earliest functional lesion was impaired ability to concentrate urine. When creatinine clearance was even slightly reduced, there was medullary sclerosis and in some patients pyelographic evidence of extensive papillary necrosis. Bacteriuria was found mainly in patients whose renal function was considerably reduced, and pyelonephritis, when present, appeared to be secondary. Renal function stabilized or improved in most patients who stopped taking mixed analgesics, but deteriorated further in those who did not.