Renal lesions in multiple myeloma: their relationship to associated protein abnormalities

Renal biopsy and autopsy specimens were studied in 43 patients with renal complications of multiple myeloma and correlated with immunoelectrophoresis (IEP) and other clinical data at the time of biopsy. Lesions specifically related to multiple myeloma fell into two categories, with different patterns of protein excretion. (1) Myeloma Cast Formation: When other lesions which might contribute to renal insufficiency (RI) were excluded, there was a good correlation between the extent of myeloma cast formation and severity of RI. Sixteen of 19 patients excreted free light chains (LCs) in the urine, in seven as the predominant or sole urinary protein. (2) Tissue Deposition of Paraproteins: Nine cases had generalized glomerular, tubular basement membrane and vascular deposits of presumed κ-chains (one with associated alpha-heavy chains). Four patients, all with myelomas secreting lambda LCs, had diffuse amyloid deposits in similar distribution. All patients (save two who were anuric) had diffuse, nonselective proteinuria by IEP, most within the nephrotic range. Four patients had free LCs in the urine, but in none was this the predominant component. Cast nephropathy and LC tissue deposition tended to occur in mutually exclusive fashion. Cases with diffuse tissue deposits of LCs showed few or no myeloma casts. Cases with cast nephropathy had only occasional mild mesangial lesions and focal interstitial and vascular deposits of amyloid. Evidence indicates that these lesions represent incidental LC deposition in cases whose basic lesion is longstanding and/or severe cast nephropathy, and that their contribution to RI is minor in comparison to that of the myeloma casts. However, repeat specimens in six patients reveal that the basic pattern of lesions may change under therapy. All six had typical myeloma cast nephropathy on initial biopsy. Myeloma casts were markedly diminished or absent on repeat examination in all six, but in three cases they were replaced by massive tissue deposits of LCs (κ-chains in two, amyloid in one). The LC electrophoretic mobility (LCEM) was examined in 17 patients with arcs representing free LCs identifiable on serum or urine IEP The LCEM parallels the relative anionic charge/unit mass of the LCs. Cases with high LCEMs, and hence highly anionically charged, usually did not show typical myeloma casts, but might have extensive renal deposits of LCs. Cases with lower LCEMs had typical dense myeloma casts, progressively more prominent as the LCEM decreased. There was an excellent correlation between decreasing LCEM and increasing severity of RI. The explanation for these observations may be related to the charge of the LC at physiologic pH. Those with high LCEMs would be strongly negatively charged and, particularly if polymerized, pass the glomerular filtration barrier less easily than those with lower LCEMs, which would be neutral or even positively charged. This suggestion accords well with the above data indicating that free urinary LCs are an infrequent and minor component of the urinary protein in patients with tissue paraprotein deposits, but are found in the great majority of patients with cast nephropathy, often as the only urinary protein.