Renal Elimination of Beta-2-Microglobulin and Myoglobin in Patients with Normal and Impaired Renal Function

Abstract

Since the demonstration that β₂-microglobulin (β₂M) is an amyloidogenic protein in man, the excretion of this low-molecular-weight protein under conditions with normal and reduced renal function has received increased interest. The renal arteriovenous extraction of β₂M, polyfructosan (an inulin analogue), and a second low-molecular-weight protein, myoglobin, was measured in vivo in 16 human kidneys with normal renal function/gross morphology and in 22 kidneys with reduced function. In kidneys with normal function, the extraction of β₂M significantly exceeded that of polyfructosan (0.198 ± 0.037 vs. 0.182 ± 0.05; p = 0.04), while that of myoglobin (0.177 ± 0.068) was not different from that of polyfructosan. In kidneys with reduced function, the extraction of polyfructosan or myoglobin was not significantly altered. In contrast, the β₂M extraction decreased to 0.110 ± 0.060 (p < 0.01 vs. extraction of polyfructosan or myoglobin). This decrease was significantly correlated with the decrease of the endogenous creatinine clearance or the total or unilateral ¹³¹I-hippuran clearance. These results indicate that in normal renal function the glomerular filtration of β₂M may be supplemented by a peritubular mode of removal. The mechanism(s) underlying the selective decrease of β₂M extraction in kidneys with reduced function remain speculative. However, this decrease will lead to a further augmentation of the retention of β₂M in renal failure.

Beta-2-Microglobulin-Associated Amyloidosis

“…It is the nonvariable light chain of the HLA class I complex [100,101] and as such is necessary for the expression of HLA class I on the surface of nearly all nucleated cells [102,103]. The p2-microglobulin synthesis rate in healthy individuals ranges from 2.4 to 3.7 mg/kg/day with a halflife of 2.5 h and plasma concentrations vary between 1 and 3 mg/ml [104][105][106][107], Most of the circulating p2-microglobulin is unbound to other molecules [108] and distributes throughout the extracellular space [105][106][107], 95% of the P2-microglobulin elimination is achieved via glomerular filtration, tubular reabsorption and subsequent intracellu lar proteolysis [105,106,109,110]. The remaining 5% of the protein is eliminated through yet unknown pathways [105,106], possibly the gastrointestinal tract [81].…”

Derangements of Protein Metabolism in Chronic Renal Failure

“…Several of these proteins accumulate in plas ma when the glomerular filtration rate fails and can have important clinical conse quences. Proteins of less than 50 kD in mass increase in the plasma of patients with CRF [57,58]. The most significant of these is (Tmicroglobulin.…”