Renal handling of low molecular weight proteins. I. L-chain metabolism in experimental renal disease

determining the role of the kidney in the metabolism of various classes of serum proteins and to define the uri-nary protein excretion patterns and the pathogenesis of disorders of protein metabolism in patients with pro-teinuria. To this end, the metabolic fates of a small pro-tein, 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), re-spectively. 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 metab-olism accounted for by proteinuria was increased 40-fold whereas endogenous catabolism was correspondingly de-creased. Thus, tubular proteinuria results from a failure of proximal tubular uptake and catabolism of small pro-teins that are normally filtered through the glomerulus. Patients with the nephrotic syndrome had a slight in-crease in X-L chain survival whereas IgG survival was decreased and the fraction of IgG lost in the urine wa