The pathogenesis of cast nephropathy

Abstract

The initial description of the disease we now know as multiple myeloma occurred in 1848 when Bence Jones [1] described a novel protein in the urine of MacIntyre’s patient with bone pain, edema, and constitutional symptoms. However, it was not until 1920 that Thannhauser and Krauss [2] reported unusual renal tubular structural abnormalities in a myeloma patient with proteinuria who succumbed from the illness. They described and illustrated a peculiar type of tubular cast; following contributions by other investigators, this renal lesion eventually became known as myeloma kidney, or more recently since the elucidation of the composition of the cast [3], Bence Jones cast nephropathy [4]. It is somewhat surprising that almost 75 years elapsed before the recognition of the distinctive pathological change in the kidneys, for it is well known that in excess of 50% of patients with multiple myeloma develop renal failure [5–11] and that the cast lesion is the most common structural feature [10, 12]. It is also surprising that virtually all patients with multiple myeloma do not develop renal impairment and cast formation, for it has been shown that abnormal free light chains are directly responsible for renal damage [7, 8, 13]. Finally, although the morphological features of the casts are well characterized [11], the events leading to their formation and the tissue reaction to their presence are controversial [6,10,15–21].