Filtration and reabsorption of endogenous low-molecular-weight protein in the rat kidney

The proteins of normal mammalian urine are thought to be mainly plasma proteins that have been filtered at the glomerulus and subsequently escaped tubular reabsorption. In human urine, over 20 individual plasma proteins have been identified [1–4]. Indeed, some proteins have first been identified in urine and then were proven to be of plasma origin [5]. Identification of these urinary proteins has been accomplished with increasing accuracy paralleling the refinement of analytic methods. In rats, there is evidence that some proteins are identical to plasma globulins and albumin and that others are derived from the genitourinary tract [6–8]. The magnitude of proteinuria is greater in the male than it is in the female rat [9, 10], and at least one specific sex-dependent protein is present in the male [11–15], Proteinuria in the male rat is also age dependent [16–18], one factor being the increased synthesis and excretion of a male sex-dependent protein at puberty [19].Urinary protein can be divided arbitrarily into two main groups according to size. One group contains albumin and high molecular weight plasma globulins. The other group consists of low-molecular-weight proteins (LMW) (mol wt < albumin, 69,000 daltons). This latter group constitutes the major fraction of urinary protein in the rat [11, 20, 21]. Their low concentrations in plasma and glomerular filtrate, however, has hindered an accurate description of the factors operating in their excretion. The kidney is thought to be a major site of ca-tabolism for these proteins [22–26], and hence tubular malfunction results in elevated excretion. A possible tubular secretory mechanism for some LMW proteins has also been suggested [27, 28].We have examined total urinary protein and the fractional contribution of LMW proteins in four strains of male rats common to our laboratory, Brown Norway, Wistar-Kyoto, Okamoto-Aoki Wistar, and Wistar-Rockland. In the latter strain, we have examined the rates of filtration and reabsorption of endogenous LMW proteins isolated from their urine. Isolated fractions were labeled and infused intravenously into rats prepared for micro-puncture of surface proximal tubules. Clearance ratios, sieving coefficients, and fractional excretion of the isolated protein fractions were measured and calculated. This permited an assessment of the relative contribution of filtration and reabsorption to the final excretion of these LMW protein fractions