Renal tubular interactions of proteins

Abstract

One of the functions of the kidney is to reclaim amino acids from filtered proteins, but under certain pathologic conditions the kidney can be affected by these filtered proteins. Low molecular weight proteins and larger polypeptides are filtered into Bowman's space and reabsorbed by the tubules, hydrolyzed by the lysosomes to amino acids, and these amino acids are reused in other proteins. This reclamation process is accelerated when the tubules are presented with large amounts of protein, such as in the nephrotic syndrome, and the kidney takes up a lesser percentage of the protein as the filtered load increases. The fraction escaping reabsorption appears in final urine, and observations of increased protein excretion are termed “proteinuria”. Recently, it has become clear that the filtration of proteins such as Bence-Jones or myoglobin, which occurs in pathologic conditions such as myeloma or crush injury, can result in the interaction of these molecules with tubular structures. This interaction can drastically alter the normal physiology of tubular cells and possibly cause acute renal failure. Our current explanation for the nephrotoxic effect of these proteins involves a change in the ionic form of proteins with isoelectric points (near pH 7) as they pass along the nephron. This change in form is related to the pH gradient along the tubule. The more acidic the tubular fluid, the more cationic the filtered protein. Proof of this hypothesis has been partially derived from experiments in which human Bence-Jones proteins were infused into rats. Those proteins with a lower isoelectric point (more polyanionic) caused less change in renal function than did those with higher isoelectric points (more polycationic). These last observations can be translated into patient prognosis. Those patients producing Bence-Jones of higher isoelectric point probably have a greater risk of renal failure than those who produce one of a more polyanionic nature. In addition, it can be speculated that treatment of a hemolytic transfusion reaction with mannitol and alkalinization of the patient prevents renal failure by dilution of the pathologic protein and also by changing its polyionic character.