Renal handling of drugs and amino acids after impairment of kidney or liver function--influences of maturity and protective treatment.
Renal tubular cells are involved both in secretion and in reabsorption processes within the kidney. Normally, most xenobiotics are secreted into the urine at the basolateral membrane of the tubular cell, whereas amino acids are reabsorbed quantitatively at the luminal side. Under different pathological or experimental circumstances, these transport steps may be changed, e.g., they may be reduced by renal impairment (reduction of kidney mass, renal ischemia, administration of nephrotoxins) or they may be enhanced after stimulation of transport carriers. Furthermore, a distinct interrelationship exists between excretory functions of the kidney and the liver. That means liver injury can influence renal transport systems also (hepato-renal syndrome). In this review, the following aspects were included: based upon general information concerning different transport pathways for xenobiotics and amino acids within kidney cells and upon a brief characterization of methods for testing impairment of kidney function, the maturation of renal transport and its stimulation are described. Similarities and differences between the postnatal development of kidney function and the increase of renal transport capacity after suitable stimulatory treatment by, for example, various hormones or xenobiotics are reviewed. Especially, renal transport in acute renal failure is described for individuals of different ages. Depending upon the maturity of kidney function, age differences in susceptibility to kidney injury occur: if energy-requiring processes are involved in the transport of the respective substance, then adults, in general, are more susceptible to renal failure than young individuals, because in immature organisms, anaerobic energy production predominates within the kidney. On the other hand, adult animals can better compensate for the loss of renal tissue (partial nephrectomy). With respect to stimulation of renal transport capacity after repeated pretreatment with suitable substances, age differences also exist: most stimulatory schedules are more effective in young, developing individuals than in mature animals. Therefore, the consequences of the stimulation of renal transport can be different in animals of different ages and are discussed in detail. Furthermore, the extent of stimulation is different for the transporters located at the basolateral and at the luminal membranes: obviously the tubular secretion at the contraluminal membrane can be stimulated more effectively than reabsorption processes at the luminal side.
D000042:Absorption; D000375:Aging / Q000473:pathology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000628:therapy; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000628:therapy; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity*; D010130:p-Aminohippuric Acid / Q000378:metabolism
D000596:Amino Acids; D015262:Xenobiotics; D010130:p-Aminohippuric Acid