Kidney Sodium reabsorption

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

The COX-2 enzyme is also produced normally in the kidney thus COX-2 inhibitors exert renal effects similar to those of conventional NSAIDs. Both drug classes may increase sodium reabsorption and fluid retention and can provoke renal insufficiency and hyperkalemia. COX-2 inhibitors should be used with caution in patients with heart failure or hypertension. 

Sodium reabsorption is also influenced by ANP. The original decrease in plasma volume leads to a decrease in atrial filling and a decrease in the release of ANP from the myocardium. Atrial natriuretic peptide, which acts on vascular smooth muscle, granular cells of the kidney, and the adrenal cortex, normally causes the following ... 

Spironolactone and eplerenone block the mineralocorticoid receptor, the target site for aldosterone. In the kidney, aldosterone antagonists inhibit sodium reabsorption and potassium excretion. However, diuretic effects are minimal, suggesting that their therapeutic benefits result from other... 

Other actions of kinins include activation of clotting factors simultaneously with the production of bradykinin. In the kidney, bradykinin production results in an increase in renal papillary blood flow, with a secondary inhibition of sodium reabsorption in the distal tubule. In the peripheral nervous system, bradykinin is important for the initiation of pain signals. It is also associated with the edema, erythema, and fever of inflammation. 

Aldosterone It is a mineralocorticoid. Its actions are retention of sodium and reduction of serum potassium. It acts on distal tubules of kidney to increase sodium reabsorption (details are discussed in chapter Diuretics ... 

Ang II acts on the kidney to cause renal vasoconstriction, increase proximal tubular sodium reabsorption, and inhibit the secretion of renin. 

Acute exposure to inorganic lead can cause reversible damage to the kidneys, manifested as tubular dysfunction. Chronic exposure to lead, however, causes permanent interstitial nephropathy, which involves tubular cell atrophy, pathological changes in the vasculature, and fibrosis. The most pronounced changes occur in the proximal tubules. Indeed, lead-protein complexes are seen as inclusion bodies in tubular cells, and the mitochondria in such cells have been shown to be altered with impaired oxidative phosphorylation. Clearly, this will influence the function of the proximal tubular cells in reabsorption and secretion of solutes and metabolites. Consequently, one indication of renal dysfunction is amino aciduria, glycosuria, and impairment of sodium reabsorption. 

Thiazide diuretics such as chlorothiazide (Diuril) and hydrochlorothiazide (HCTZ) work by blocking the action of aldosterone, a hormone that promotes sodium reabsorption by the kidneys. They are potassium-deplet-... 

G7. Grausz, H., Lieberman, R., and Earley, L. E., Effect of plasma albumin on sodium reabsorption in patients with nephrotic syndrome. Kidney Int. 1, 47-54 (1972). 

The adrenal glands are located anatomically above the kidneys. They comprise a three-layer cortex and a medulla. The medulla is the source of catecholamines such as epinephrine, the fight-or-flight hormone. The cortex is the source of aldosterone, the primary mineralocorticoid that is involved in the regulation of sodium reabsorption in the kidneys. In addition, the cortex is also the source of steroids known as glucocorticoids, of which cortisol is the principal endogenous representative. Synthesis and release of cortisol is under the control of adrenocorticotropic hormone (ACTH). 

Spironolactone competes for the mineralocorticoid receptor and thus inhibits sodium reabsorption in the kidney (see p. 232). It can also antagonize aldosterone and testosterone synthesis. It is effective against hyperaldosteronism. The drug is also useful in the treatment of hirsutism in women, probably due to interference at the androgen receptor of the hair follicle. 

All components of the RAS can be found in the brain, heart, vasculature, adipose tissue, gonads, pancreas, placenta, and kidney, among others. Biochemical measurements of ACE activity show that the enzyme is tissue-based. Indeed, <10% of ACE is found circulating in the plasma [4]. The potential importance of the tissue RAS is supported by observations that the beneficial effects of RAS blockers cannot reliably be predicted by measurements of the activity of the circulating RAS. The antihypertensive actions of ACE-inhibitors are better correlated with inhibition of tissue ACE rather than plasma ACE, and hypertensive patients with normal or even low levels of systemic RAS activity can be effectively treated with inhibitors of the RAS. The intrarenal RAS is hypothesized to regulate systemic blood pressure and aspects of renal function such as blood flow and sodium reabsorption. In the brain, the RAS may facilitate neurotransmission and stimu-... 

The renal toxicity of ciclosporin has been described as being an adverse effect of the drug on the compensatory mechanisms of the kidney, without effects on proximal tubular function (urea and sodium reabsorption) (91). A rise in serum creatinine concentration may be adequate to identify acute-onset ciclosporin nephrotoxicity, but it is not suitable for identification of chronic, late-onset ciclosporin nephrotoxicity (92). 

Insulin edema is a rare complication, more often seen in the earlier years of insulin therapy (SEDA-11, 364). It is mostly seen when dysregulated patients with progressive weight loss are treated with relatively high amounts of insulin. Reduced sodium excretion (88), sodium reabsorption, and water retention by a possible direct action of insulin on the kidney may be involved (89). The role of aldosterone or of inhibition of the renin-angiotensin-aldosterone system in insulin edema is unclear. Insulin edema is a specific adverse effect, but it can aggravate pulmonary edema, congestive heart failure, and hypertension. Treatment consists of reduction of the insulin dose, after which the edema resolves within 3 days. 

Nishiitsutsuji-Uwo JM, Ross BD, Krebs FIA Metabolic activities of the isolated perfused rat kidney. Biochem J 103 852-62,1967 Ross BD, Epstein FFI, Leaf A Sodium reabsorption in the perfused rat kidney. Am J Physiol 225 1165-1171,1973... 

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