Renal system primary functions

The primary function of the renal system is the elimination of waste products, derived either from endogenous metabolism or from the metabolism of xenobiotics. The latter function is discussed in detail in Chapter 10. The kidney also plays an important role in regulation of body homeostasis, regulating extracellular fluid volume, and electrolyte balance. 

The renal system plays an important role in the regulation of fluids and electrolytes and is one of the two major systems involved in restoration of acid-base balance. In addition, the renal system has other vital roles, such as production of erythropoetin needed for red blood cells health, essential for oxygenation of tissues. The primary functions of the renal system are... 

The renal system is composed of functional units called nephrons. Nephrons have two portions, the cortex (i.e., glomerulus. Bowman capsule, and proximal and distal tubules) and the medulla (i.e., the loop of Henle and the collecting tubules). The nephron also contains two primary sections ... 

The primary goals of treatment are correction of the intraabdominal disease processes or injuries that have caused infection and drainage of collections of purulent material (abscess). A secondary objective is to resolve the infection without major organ system complications (e.g., pulmonary, hepatic, cardiovascular, or renal failure) or adverse drug effects. Ideally, the patient should be discharged from the hospital with full function for self-care and routine daily activities. 

Adverse Effects. The primary adverse effect of systemic pentamidine administration is renal toxicity. Renal function may be markedly impaired in some patients, but kidney function usually returns to normal when the drug is withdrawn. Other adverse effects include hypotension, hypoglycemia, gastrointestinal distress, blood dyscrasias (leukopenia, thrombocytopenia), and local pain and tenderness at the site of injection. Adverse effects are reduced substantially when the drug is given by inhalation, and this method of administration is desirable when pentamidine is used to prevent pneumocystis pneumonia in patients with human immunodeficiency virus (HIV) disease. 

Many primary and secondary glomerular diseases, such as those associated with diabetes mellitus or systemic lupus erythematosus, exhibit renal retention of salt and water. The cause of this sodium retention is not precisely known, but it probably involves disordered regulation of the renal microcirculation and tubular function through release of vasoconstrictors, prostaglandins, cytokines, and other mediators. When edema or hypertension develops in these patients, diuretic therapy can be very effective. If heart failure is also present, see the warnings mentioned above. 

Excretion The primary route of excretion is through the organic acid (tubular) secretory system of the kidney (see p. 224), as well as by glomerular filtration. Patients with impaired renal function must have dosage regimens adjusted. Thus the Xyz of penicillin G can increase from a normal of 1/2 -1 hour to 10 hours in individuals with renal failure. Probenecid inhibits the secretion of penicillins. Nafcillin is primarily eliminated through the biliary route. [Note This is also the preferential route for the acylureido penicillins in cases of renal failure.]... 

Carnitine is present in biological systems as both carnitine and acylcarnitines generated in tissues (see next section). Carnitine deficiency may be a primary defect due to a genetic defect in carnitine transport systems or may be secondary to other metabolic derangements. Normal carnitine homeostasis requires reabsorption of carnitine in the renal tubule via a specific transport protein. This same transport protein is responsible for the accumulation of carnitine in heart and skeletal muscle. If this transport system is not functional, then carnitine cannot reach tissues, and primary carnitine... 

New cell culture techniques, which may improve the applicability of renal epithelial cultures, are also required. Currenfly there exist two commercially available cell culture perfusion systems, which allow the continuous perfusion of culture media and optimized oxygenation [243]. These systems allow stable longterm culture of quiescent adherent cells [244]. Continuous medium perfusion furthermore may lead to the re-expression of lost functions in continuous cell hues and the maintenance of differentiated properties in primary cells. Recently our laboratory has demonstrated that LLC-PKj cells maintained in a newly developed perfusion system (EpiFlow ) changed from a glycolytic to a more oxidative phenotype [72]. Evidence is also available from experiments in our laboratory that this mode of cultivation helps to prolong the lifetime of primary cultures of proximal tubular cells. Combining perfusion culture with co-culture of a cell type that is an anatomical neighbour in vivo (e.g. epithelial with endothelial, interstitial or immune cells) may improve the state of differentiation of both partner cells and increase the complexity of autocrine and paracrine interaction [73]. 

Isolated renal cortical epithelial cells and cultured cell lines have become standard in vitro model systems for examining the nephrotoxic potential of toxicants, toxicant bioactivation and direct mechanisms of toxicity. Enriched populations of freshly isolated proximal and distal tubular cells can be obtained to examine the effects of toxicants on these distinct cell populations. Growing freshly isolated cells for several days can provide primary cultures of renal cells that can be used to study transport and toxicity of compounds. Such primary cultured cells can be obtained from proximal tubule or distal tubule/col-lecting duct cells. There are also several cell lines (e.g., LLC-PKi, MDKC, HK-2) to study the effects of chemicals on renal tissue. In addition, cell lines have been developed from specific segments of the proximal tubule. Overall, these cell systems allow for the rapid screening of chemicals, exposure to apical and/ or basolateral surfaces, and more detailed studies of specific cell populations. However, cells in culture can exhibit reduced functional and metabolic characteristics with time. These changes might impact on the potential effects of some chemicals in cell culture systems. Therefore, toxicity in the specific cell line to be used should be validated prior to mechanistic studies. 

Corticosteroids, CSA, TAC, and impaired kidney graft function may cause post-transplant hypertension. The primary mechanism of CI-associated hypertension in heart transplant recipients may be related to the Cl-induced stimulation of intact renal sympathetic nerves and the absence of reflex cardiac inhibition of the sympathetic nervous system, but a number of other mechanisms, including decreased prostacyclin and nitric oxide production, also have been proposed. " In addition to the propensity to cause peripheral vasoconstriction, CIs promote sodium retention, resulting in extracellular fluid volume expansion. TAC appears to have less potential to induce hypertension following transplantation than CSA. Most classes of antihypertensive medications effectively reduce blood pressure in transplant patients (see Chap. 13). ... 

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