The role of Bence Jones proteins (BJPs) in the genesis of the renal dysfunction that develops in patients with multiple myeloma is not clearly defined. We previously evaluated renal function and morphology in a unique strain of rats (LOU/m) bearing tumors which synthesized BJPs with isoelectric points of 5.2, 4.3 and 6.7. Myeloma cast nephropathy developed in one tumor bearing group (pI 5.2), tubular necrosis was observed in another (pI 4.3), and renal function and histology remained normal in a third group (pI 6.7). To seen if these renal outcomes were a function of the BJP being excreted or other factors which could be present in the tumor bearing animals, we have examined the effect of chronic intravenous administration of these three BJPs on renal function and histology in non-tumor-bearing LOU/m rats. Urine containing the BJP was collected from tumor bearing rats, sterilized by passage through a 0.2 μ millipore filter, concentrated to 50 mg/ml, and dialyzed extensively so as to remove material with a molecular weight < 3500. Chronic indwelling-venous catheters were placed in nontumor-bearing LOU/m rats and these rats were given 100 mg/day for five days of one of the three BJPs. Polyfructosan clearance (C(in)) was measured prior to and following the five days of BJP administration. Renal histology was examined at the completion of the second C(in). In the pI 5.2 group (N = 6), a severe distal nephron cast nephropathy occurred and C(in) fell from 2.88 ± 0.24 to 0.90 ± 0.17 ml/min (P < 0.002). In the pI 4.3 group, a less-severe cast nephropathy was observed and C(in) fell from 2.71 ± 0.15 to 1.80 ± 0.20 ml/min (P < 0.05). In the pI 6.7 group (N = 8), renal histology remained largely unaltered and there was no significant change in C(in). These observations provide further and more direct evidence that the renal response to exposure to different BJPs is not uniform and that the diversity in renal functional and pathologic alterations observed in patients with myeloma and Bence Jones proteinura may be due to differences in the physicochemical nature of the individual BJP being excreted.
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