The renal handling of low molecular weight proteins

Abstract

A B S T R A C T The present study was directed toward determining the role of the kidney in the metabolism of various classes of serum proteins and to define the urinary protein excretion patterns and the pathogenesis of disorders of protein metabolism in patients with proteinuria. To this end, the metabolic fates of a small protein, X-L chain (mol wt 44,000), and a protein of intermediate size, IgG (mol wt 160,000), were studied in controls and patients with renal disease. Controls metabolized 0.28%/hr of circulating IgG and 22.3%/hr of circulating X-L chain. All the IgG and 99% of the X-L chain was catabolized with the remaining X-L chain lost intact into the urine. The kidney was shown to be the major site of catabolism for small serum proteins. Three distinct disorders of protein metabolism were noted in patients with renal tubular disease and tubular proteinuria, glomerular disease (the nephrotic syndrome), and disease involving the entire nephrons (uremia), respectively. Patients with renal tubular disease had a 50-fold increase in the daily urinary excretion of 1540,000 molecular weight proteins such as lysozyme and X-L chains. Serum IgG and X-L chain survivals were normal; however, the fraction of the over-all X-L chain metabolism accounted for by proteinuria was increased 40-fold whereas endogenous catabolism was correspondingly decreased. Thus, tubular proteinuria results from a failure of proximal tubular uptake and catabolism of small proteins that are normally filtered through the glomerulus. Patients with the nephrotic syndrome had a slight increase in X-L chain survival whereas IgG survival was decreased and the fraction of IgG lost in the urine was An abstract of this work appeared in J. Clin. Invest. 1970. 49: 99a. (Abstr.)

The Relationship Between L-Chain Synthesis and γ-Globulin Production

“…Ra.). Since one of our patients, J. Ga., was studied before and after bilateral nephrectomy and showed almost identical degradation rates under the two circumstances, we confirm the finding that catabolism may occur at sites other than the kidney when renal disease is advanced (32).…”

Comparison between On-Line High-Efficiency Hemodiafiltration and Conventional High-Flux Hemodialysis for Polyclonal Free Light Chain Removal

“…Cubilin, a glycoprotein receptor located in the apical membrane of apical tubular cells, is involved in the tubular trafficking of FLC [1,2]. Light chain serum half-lives are between 2 and 6 h in normal subjects [3]. …”

Protein Handling by the Renal Tubule

“…There is evidence that the renal tubules play a significant role in the metab olism of large [19] and small [35,47] serum proteins and polypeptide hormones such as insulin [17]. With tubular disease, failure of proximal absorption and catabolism of small serum proteins results in proteinuria of the tubular type [47].…”