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Systemic Complications: Renal
Acknowledgment
This text is supported by a Veterans Affairs Merit Grant.
Comprehension of renal anatomy and physiology is necessary to understand the complex changes in renal function that can occur during treatment of vascular disorders. This chapter provides a brief summary of renal function and physiology underlying renal complications in the vascular surgical patient population.
Renal Anatomy
Renal components include nephrons, collecting ducts, and the microvasculature. The human kidney contains approximately 1 million nephrons, which consist of short or long loops of Henle. The long loops extend to the inner medulla and the short loops to either the outer medulla or the cortex. The collecting ducts descend within the medullary rays of the cortex and fuse to form papillary ducts ( Fig. 46.1A ).
The renal artery divides into the cortical interlobar arteries, which divide into the arcuate arteries at the junction of the cortex and the medulla. These vessels then divide into the cortical radial arteries (none penetrate the medulla) that give rise to the afferent arterioles, which supply the glomeruli. The glomeruli are drained by efferent arterioles that can be cortical or juxtamedullary. The cortical efferent arterioles are derived from the superficial and midcortical glomeruli and supply the capillary plexus of the cortex. The juxtamedullary efferent arterioles supply the renal medulla. At the level of the outer stripe of the medulla, the juxtamedullary efferent arterioles divide into the descending vasa recta to supply the adjacent medullary plexus. Ascending vasa recta drain the renal medulla. They traverse the outer medulla and form the capillary plexus of the outer stripe and then empty into the arcuate veins.
The microvasculature provides a unique countercurrent exchange between the blood entering and leaving the medulla. The unique vascular anatomy also separates blood flow in the inner stripe from in the inner medulla. The descending vasa recta supplying the inner medulla are not exposed to the tubules of the inner or outer stripe (outer medulla). Blood flow in the ascending vasa recta from the inner medulla and inner stripe perfuses the outer stripe. Venous drainage accompanies the arteries. The arcuate veins drain the cortex and medulla. The arcuate veins join to form the interlobar veins, parallel to the interlobar arteries (see Fig. 46.1A ).
Renal Function
The kidney is the major site responsible for maintenance of intravascular volume and composition. The kidney provides three basic physiologic processes: glomerular filtration, selective tubular secretion, and selective tubular reabsorption. , The kidney receives a fourth of the cardiac output, approximately 900 L/day of plasma flow. The glomeruli filter 20% of renal plasma flow and must reabsorb 99% of the 180 L of plasma filtered per day to provide a urine output of 1.8 L/day (for a 70-kg man). This ultrafiltrate has the same electrolyte and solute concentration as plasma, and is almost totally reabsorbed. The solute content and volume of urine that enters the renal pelvis are very different compared to the glomerular filtrate. The filtrate flows through the different portions of the tubule, where the solute content and volume are altered by tubular reabsorption and tubular secretion. Solute movement from the tubular lumen to the peritubular capillary plasma is termed tubular reabsorption (tubular secretion is the opposite).
The descending loop of Henle is permeable to water but only minimally permeable to sodium and chloride, whereas the ascending loop is not permeable to water but has active transport mechanisms that readily transport the chloride ion with concomitant passive transport of sodium. This is the underlying basis for the countercurrent mechanisms that produce the medullary osmotic gradient that is important in the regulation of urine osmolarity. Reabsorption of sodium from the distal tubule and from the proximal collecting ducts is controlled by aldosterone secretion. Only 0.2% to 0.8% of sodium is excreted per day of the total sodium filtered ( Fig. 46.1B ). Potassium is reabsorbed in the proximal convoluted tubule and the thick ascending limb of Henle. Ten percent of the filtered load reaches the early distal tubule. Potassium secretion by connecting cells in the late distal tubule and/or cortical collecting system is variable.
Neuroendocrine Modulators of Renal Function
Intravascular volume is regulated primarily by a series of baroreceptors located in the arterial tree and the atria. These receptors not only sense changes in pressure or volume (atrial receptors) but also monitor the rates of change during the cardiac cycle. Factors that decrease cardiac performance alter intravascular volume and are perceived by these receptors, which then alter renal function to retain salt and water. Similarly, when the concentration of circulating plasma proteins is reduced, there is a net diffusion of intravascular water into the extravascular space secondary to the decreased intravascular oncotic pressure. This net decrease in circulating volume is sensed by these same receptors, and neuroendocrine regulators of urinary output inhibit excretion of water in response. When the baroreceptors perceive a reduction in circulating volume, their afferent signals are reduced, which decreases their tonic inhibition over the neuroendocrine system leading to increased secretion of vasopressin, 13-endorphins growth hormone, adrenocorticotropic hormone through the central nervous system, and an increased release of adrenal medullary epinephrine. A reduction in arterial pressure or central venous pressure (or both) results in an increase in renal sympathetic nerve stimulation that reduces urinary sodium excretion via three mechanisms: (1) constriction of afferent and efferent arterioles, which reduces renal blood flow and GFR; (2) reabsorption of sodium in the proximal tubule and the thick ascending loop of Henle; and (3) stimulation of renin secretion. Baroreceptors within the macula densa cells of the juxtaglomerular apparatus perceive a decrease in intravascular pressure or plasma ion concentration and stimulate juxtaglomerular cells to release renin. Renin is released in response to increased sympathetic nerve activity, reduced stretch of the afferent arteriole, and decreased transport of NaCl to the macula densa. Renin catalyzes angiotensinogen to form angiotensin I which is then converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II induces arteriolar constriction of the afferent and efferent arterioles and thereby causes an increase in blood pressure while decreasing renal blood flow; second, it stimulates renal sodium reabsorption in the proximal tubule; and third, it induces secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Aldosterone secretion results in sodium reabsorption in the distal tubule and collecting duct.
Paracrine and Endocrine Modulators of Renal Function
A number of paracrine and endocrine substances influence renal function. Eicosanoids are a class of vasoactive metabolites of three different enzymes: cyclooxygenase (COX), lipoxygenase, and cytochrome P-450. COX is present as both constitutive (COX-1) and inducible forms (COX-2). Conversion of arachidonic acid to prostaglandins and thromboxane occurs via both enzymes. The major renal eicosanoids are prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2). These potent vasodilators buffer renal vasoconstrictors such as thromboxane A2, angiotensin II, and norepinephrine. Decreased synthesis of the renal vasodilators PGE2 and PGI2 has been associated with renal vasoconstriction in several injuries. PGE2 has been shown to inhibit sodium reabsorption from the thick ascending limb of Henle, and thus contributes to protecting the renal medulla during hypoxia. COX-2 expression has been found in the macula densa and is thought to contribute to release of renin via PGE2. This could be one of the mechanisms responsible for the low renin levels found in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). The loss of COX-2 expression can also reduce medullary blood flow.
Nitric oxide (NO) is another endogenous renal vasodilator that contributes to the maintenance of normal renal blood flow and function. Zou and Cowley demonstrated NO synthesis in the medulla and the cortex and concluded that NO might play a role in the control of vascular tone and tubular function in the kidney. Loss of endogenous NO synthesis has been suggested to contribute to renal vasoconstriction after renal ischemia-reperfusion injury from either local or systemic causes. , , NO is present in the macula densa as the neuronal synthase form (nNOS). Downregulation of nNOS may contribute to arteriolar vasoconstriction by down-regulating COX-2 and subsequent PGE2 synthesis. NO has also been shown to help mediate the increased natriuresis following an increase in renal interstitial hydrostatic pressure. Atrial natriuretic peptide (ANP) is released from atrial myocytes after atrial stretch secondary to increased blood volume. ANP increases sodium excretion directly and by down-regulating renin and aldosterone secretion and increases GFR by afferent arteriolar vasodilation.
The kidney is a rich source of endothelins, vasoconstrictor peptides, which function as autocrine and paracrine substances. Endothelin-1 (ET-1) is synthesized in the afferent and efferent arterioles, where it induces vasoconstriction, and in mesangial cells, where it induces contraction. Upregulation of ET-1 synthesis induces a marked reduction in renal blood flow and GFR. ET-1 can inhibit sodium reabsorption in the medullary thick ascending limb, and this may, in part, be mediated by NO. There is recent evidence that ET-1/NO interactions are important in sodium and water excretion.
Purines are another complex class of autocrine substances that may be involved in renal physiology. Purinoreceptors are divided into P1 and P2 purinergic receptors (P1R, P2R). P1R are upregulated in response to adenosine. P2R are stimulated by nucleotides such as ATP and adenosine diphosphate (ADP). P2 receptors are subdivided into P2XR (there are 7) and P2YR (there are 8) receptors. P1R and P2XR are located in the afferent arteriole and contribute to vasoconstriction. P1R, P2XR, and P2YR are located along the nephron. Endogenous adenosine enhances proximal tubular reabsorption, whereas luminal ADP inhibits it. In the collecting duct, basolateral ATP inhibits vasopressin-sensitive water reabsorption, and basolateral and luminal ATP inhibits sodium reabsorption. There is evidence that uric acid may cause renal vasoconstriction, possibly by inhibiting release of NO and stimulation of renin. ,
Renal Dysfunction After Vascular and Endovascular Procedures
Renal dysfunction after vascular and endovascular procedures can vary from mild natriuresis to fulminant acute tubular necrosis (ATN) and acute renal failure (ARF). Postoperative renal dysfunction can be classified as prerenal, renal, or postrenal ( Fig. 46.2 ). The incidence of renal dysfunction complicating vascular and endovascular procedures has decreased with the development of appropriate fluid resuscitation, better surgical and endovascular techniques, and less nephrotoxic radiocontrast agents, although the mortality remains high (10% to 80%). ,
General Approach to Patients with Renal Dysfunction
Postoperative renal dysfunction is usually identified by oliguria or increases in serum creatinine.
Prerenal causes of renal dysfunction occur most frequently in the early postoperative period. A patient with signs of volume depletion requires replenishment of intravascular volume with physiologic saline (without potassium supplement until renal failure is ruled out). If diminished cardiac performance is responsible for the oliguria, judicious inotropic support is provided while indices of cardiac performance are measured. , If correction of filling pressures or myocardial performance fails to improve urinary output, samples of urine and blood are obtained, and diuretic therapy is considered. Serum electrolytes, blood counts, and urine studies allow evaluation of other possible sources of oliguria such as ATN or myoglobinuria ( Table 46.1 ).
TABLE 46.1
Urinary and Blood Parameters in Renal Dysfunction
From Muther RS. Acute renal failure: acute azotemia in the critically ill. In: Civetta JM, Taylor RW, Kirby RR, editors. Critical Care , 2nd ed, Philadelphia, PA: JB Lippincott; 1992:1583–1598.
| Characteristic | Prerenal Dysfunction | Renal Parenchymal Dysfunction | Postrenal Dysfunction |
|---|---|---|---|
| Urine specific gravity | >1.020 | 1.010 | 1.012 |
| Urine osmolarity (mOsm/L and mmol/kg) | >400 | 300 ± 20 | 300 ± 40 |
| Urine/plasma osmolarity | >1.5 | 1 | 1 |
| Urinary sodium (mEq/L) | <20 | >30 | <30∗ |
| Fractional excretion of sodium | <1% | >1% | <1%∗ |
| Urinary sodium/[urine/plasma creatinine] | <1 | >1 | <1 |
| BUN/creatinine | 20 | 10 | 10–20∗ |
| Urine/plasma creatinine | >40 | <20 | <20 |
BUN, blood urea nitrogen.
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