1 Describe the anatomy of the kidney

The kidneys are paired organs lying retroperitoneally against the posterior abdominal wall. Although their combined weight is only 300 g (about 0.5% of total body weight), they receive 20% to 25% of the total cardiac output. The renal arteries are branches of the aorta, originating below the superior mesenteric artery. The renal veins drain into the inferior vena cava. Nerve supply is abundant; sympathetic constrictor fibers are distributed via celiac and renal plexuses. There is no sympathetic dilator or parasympathetic innervation. Pain fibers, mainly from the renal pelvis and upper ureter, enter the spinal cord via splanchnic nerves.

On cross section of the kidney, three zones are apparent: cortex, outer medulla, and inner medulla (Figure 44-1). Eighty percent of renal blood flow is distributed to cortical structures. Each kidney contains about 1 million nephrons. Nephrons are classified as superficial (about 85%) or juxtamedullary, depending on location and length of the tubules. The origin of all nephrons is within the cortex.

Figure 44-1 This scheme depicts a short-looped and a long-looped nephron together with the collecting system (not drawn to scale). Within the cortex a medullary ray is delineated by a dashed line. 1, Renal corpuscle, including Bowman’s capsule and the glomerulus (glomerular tuft). 2, Proximal convoluted tube. 3, Proximal straight tubule. 4, Descending thin limb. 5, Ascending thin limb. 6, Distal straight tubule (thick ascending limb). 7, Macula densa located within the final portion of the neck of the thick ascending limb. 8, Distal convoluted tube. 9, Connecting tubule of the juxtamedullary nephron that forms an arcade. 10, Cortical collecting tubule. 11, Outer medullary collecting duct. 12, Inner medullary collecting duct.

(From Kriz W, Bankir I: A standard nomenclature for structures of the kidney, Am J Physiol 254:F1, 1988, with permission.)

The glomerulus and capsule are known collectively as the renal corpuscle. Each Bowman’s capsule is connected to a proximal tubule that is convoluted within its cortical extent but becomes straight limbed within the outer cortex; at this point the tubule is known as the loop of Henle. The loop of Henle of superficial nephrons descends only to the intermedullary junction, where it makes a hairpin turn, becomes thick limbed, and ascends back into the cortex, where it approaches and touches the glomerulus with a group of cells known as the juxtaglomerular apparatus. The superficial nephrons form distal convoluted tubules that merge to form collecting tubules within the cortex. The renal corpuscles of juxtamedullary nephrons are located at juxtamedullary cortical tissue. They have long loops of Henle that descend deep into the medullary tissue; the loops also reascend into cortical tissue, where they form distal convoluted tubules and collecting tubules. These nephrons (15% of the total) are responsible for conservation of water.

About 5000 tubules join to form collecting ducts. Ducts merge at minor calyces, which in turn merge to form major calyces. The major calyces join and form the renal pelvis, the most cephalic aspect of the ureter.

2 List the major functions of the kidney

Regulation of body fluid volume and composition

Acid-base balance

Detoxification and excretion of nonessential materials, including drugs

Elaboration of renin, which is involved in extrarenal regulatory mechanisms

Endocrine and metabolic functions such as erythropoietin secretion, vitamin D conversion, and calcium and phosphate homeostasis

3 Discuss glomerular and tubular function

Glomerular filtration results in production of about 180 L of glomerular fluid each day. Filtration does not require the expenditure of metabolic energy; rather it is caused by a balance of hydrostatic and oncotic forces. Glomerular filtration rate (GFR) is the most important index of intrinsic renal function. Normal GFR is 125 ml/min in males, slightly less in females.

Tubular function reduces the 180 L/day of filtered fluid to about 1 L/day of excreted fluid, altering its composition through active and passive transport. Transport is passive when it is the result of physical forces such as electrical or concentration gradients. When transport is undertaken against electrochemical or concentration gradients, metabolic energy is required, and the process is termed active.

Substances may be either resorbed or secreted from tubules and may move bidirectionally, taking advantage of both active and passive transport. The direction of transit for resorbed substances is from tubule to interstitium to blood, whereas the direction for secreted substances is from blood to interstitium to tubule. Secretion is the major route of elimination for drugs and toxins, especially when they are plasma protein bound.

4 Review the site of action and significant effects of commonly used diuretics

See Table 44-1.

TABLE 44-1 Diuretics*

DCT, Distal convoluted tubule; GFR, glomerular filtration rate.

* With the exception of osmotic diuretics, all diuretics interfere with sodium conservation.

5 Describe the unique aspects of renal blood flow and control

Renal blood flow (RBF) of about 1200 ml/min is well maintained (autoregulated) at blood pressures of 80 to 180 mm Hg. The cortex requires about 80% of blood flow to achieve its excretory and regulatory functions, and the outer medulla receives 15%. The inner medulla receives a small percent of blood flow; a higher flow would wash out solutes responsible for the high tonicity (1200 mOsm/kg) of the inner medulla. Without this hypertonicity, urinary concentration would not be possible.

Control of RBF is through extrinsic and intrinsic neural and hormonal influences; a principal goal of blood flow regulation is to maintain GFR. The euvolemic, nonstressed state has little baseline sympathetic tone. Under mild-to-moderate stress RBF decreases slightly; but efferent arterioles constrict, maintaining GFR. During periods of severe stress (e.g., hemorrhage, hypoxia, major surgical procedures) both RBF and GFR decrease secondary to sympathetic stimulation.

The renin-angiotensin-aldosterone axis also has an effect on RBF. A proteolytic enzyme formed at the macula densa of the juxtaglomerular apparatus, renin acts on angiotensinogen within the circulation to produce angiotensin I. Enzymes within lung and plasma convert angiotensin I to angiotensin II, which is a potent renal vasoconstricting agent (especially of the efferent arteriole) and a factor in the release of aldosterone. During periods of stress levels of angiotensin are elevated and contribute (along with sympathetic stimulation and catecholamines) to decreased RBF.

Prostaglandins (PGs) are also found within the kidney. PGE2 and PGE3 are intrinsic mediators of blood flow, producing vasodilation.

6 Describe the sequence of events associated with decreased renal blood flow

The initial response to decreased RBF is to preserve ultrafiltration through redistribution of blood flow to the kidneys, selective afferent arteriolar vasodilation, and efferent arteriolar vasoconstriction. Renal hypoperfusion results in active absorption of sodium and passive absorption of water in the ascending loop of Henle. Oxygen demand is increased in an area particularly vulnerable to decreased oxygen delivery. Compensatory sympathoadrenal mechanisms redistribute blood flow from the outer cortex to the inner cortex and medulla. If renal hypoperfusion persists or worsens despite early compensatory mechanisms and as sodium is resorbed in the ascending loop, increased sodium is delivered to the macula densa, producing afferent arteriolar vasoconstriction and decreasing glomerular filtration. Because GFR is decreased, less solute is delivered to the ascending loop. Because less solute is delivered, less is resorbed (an energy requiring process); thus less oxygen is needed, and the net effect is that afferent arteriolar vasoconstriction decreases oxygen-consuming processes. The result is oliguria. However, the kidney is attempting to maintain intravascular volume and, to that end, the process described has been denoted renal success. In reality oliguria is a poor measure of renal function since more often than not acute renal failure (ARF) is nonoliguric.

7 What preoperative risk factors are associated with postoperative renal failure?

Preoperative renal risk factors (increased blood urea nitrogen [BUN] and creatinine and a history of renal dysfunction), left ventricular dysfunction, advanced age, jaundice, and diabetes mellitus are predictive of postoperative renal dysfunction. Patients undergoing cardiac or aortic surgery are particularly at risk for developing postoperative renal insufficiency.

8 Discuss the major causes of perioperative acute renal failure

ARF is defined as a significant decrease in GFR over a period of 2 weeks or less. Renal failure, or azotemia, can be categorized into prerenal, renal, and postrenal etiologies. Prerenal azotemia is caused by decreased blood flow to the kidney and accounts for about 60% of all cases of ARF. In the perioperative setting ischemia may be caused by inadequate perfusion from blood and volume losses. Other mechanisms include hypoperfusion secondary to myocardial dysfunction or shunting of blood away from the kidneys, as in sepsis.

Renal causes account for 30% of all cases of ARF. Acute tubular necrosis is the leading cause and may be to the result of either ischemia or toxins. In the setting of preexisting renal disease nephrotoxins include radiocontrast media, aminoglycosides, ACE inhibitors and fluoride associated with volatile anesthetic metabolism. Hemolysis and muscular injury (producing hemoglobinuria and myoglobinuria) are also causes of intrinsic ARF.

Postrenal causes (10% of cases) are caused by obstructive nephropathy and may be observed in men with conditions such as prostatism and ureteral obstruction from pelvic malignancies.

“Acute Kidney Injury” is now increasingly replacing the term “Acute Renal Failure.”

9 What laboratory abnormalities are observed in renal failure?

Patients have uremia (elevation of BUN and creatinine), hyperkalemia, hyperphosphatemia, hypocalcemia, hypoalbuminemia and metabolic acidosis. They are also anemic and have platelet and leukocyte dysfunction, rendering them prone to bleeding and infection.

10 Comment on various laboratory tests and their use in detecting acute renal dysfunction

Indices of renal function can be roughly divided into measures of glomerular or tubular function. Measures of clearance assess glomerular function, whereas the ability to concentrate urine and retain sodium are indices of tubular function. The majority of renal function tests are neither sensitive nor specific in predicting perioperative renal dysfunction and are affected by many variables common to the perioperative environment.

The ammonia generated from amino acid metabolism in the liver is converted to BUN. Urea is cleared rapidly by glomerular filtration but also resorbed in the tubules. Thus BUN cannot be used as a marker of glomerular filtration, only azotemia. Creatinine is the end product of creatinine phosphate metabolism and is generated from muscle and handled by the kidney in a relatively uniform fashion. Dietary meat is also a source of creatinine. Serum creatinine (Scr) is a function of muscle mass and such factors of activity, diet, and hemodilution alter its serum concentration. Scr can be artifactually increased by barbiturates or cephalosporins. Additional nonrenal variables may also be responsible for elevation of BUN and creatinine, including increased nitrogen absorption, muscle trauma from burns or injury, hypercatabolism, hepatic disease, diabetic ketoacidosis, hematoma resorption, gastrointestinal bleeding, hyperalimentation, and many drugs (e.g., steroids). The usual ration of BUN to creatinine is 10:1, and a ratio greater than 20:1 implies a prerenal syndrome.

Elevation of Scr is a late sign of renal dysfunction. The relationship between Scr and GFR is inverse and exponential. That is to say, a doubling of Scr reflects halving the GRF. This is of greater clinical significance at lower levels of creatinine; an increase of creatinine from 4 to 8 mg/dl does not represent a large absolute decrease in GFR because GFR is already remarkably diminished at 4 mg/dl.

When renal function is stable, using nomograms, creatinine is a reasonable measure of GFR. However, Scr measurements are inaccurate when GFR is rapidly changing. GFR may be reduced by 50% or more before abnormal elevation is observed. Because creatinine production is proportionate to muscle mass, in situations in which substantial wasting has already occurred (e.g., chronic illness, advanced age) creatinine levels may be normal despite markedly reduced GFR.

GFR declines with age. A healthy individual of age 20 has a GFR of about 125 ml/min; an otherwise healthy patient at age 60 has a GFR about 60 ml/min. Scr does not begin to increase until GFR falls to about 50 ml/min. GFR can be estimated using population studies based on the patient’s age, Scr, sex, and weight. The method of Cockroft and Gault uses the following formula for estimating GFR: GFR = (140 – age) × weight (kg)/(Scr × 72). This is the formula for male, and the result is multiplied by 0.85 to determine the GFR for females. It is obvious that this overestimates GFR in obese patients when total body weight, not ideal body weight, is used. This formula may also overestimate GFR in cachectic patients in whom creatinine production is low.

Creatinine clearance (Ccr) is a sensitive test of renal function. Creatinine is filtered at the glomerulus and not resorbed. There is also some secretion of creatinine with the tubules, and this results in about a 15% overestimation of Ccr. (In actuality, clearance of inulin, a polyfructose sugar, is the gold standard for measurement of GFR because it is filtered at the glomerulus and neither resorbed nor secreted at the tubules.) It has been a long held belief that measurement of Ccr required 12- to 24-hour urine collections. In fact, if Scr is rapidly changing, calculations of Ccr based on 24 hours of urine collection and a single creatinine measurement may be inaccurate. In addition, this method requires meticulous urine collection, and failure to accomplish this is a common source of laboratory error. Two-hour spot tests are thought to be reasonably accurate, and serial 2-hour spot tests may be particularly valuable when renal function is acutely deteriorating. Table 44-2 describes various tests of renal function.

11 What are measures of tubular function?

As opposed to the measures of glomerular function previously discussed (creatinine, GFR, Ccr), tests of tubular function describe the ability of the kidney to concentrate urine and handle sodium. Tests of concentrating ability differentiate between prerenal azotemia (dehydration, decreased renal perfusion) and acute tubular necrosis (ATN) and demonstrate abnormalities 24 to 48 hours before increases in BUN and creatinine. Measures of tubular function give no estimate of renal reserve.

With hypovolemia, renal tubules retain salt and water and result in a relatively hyponatremic, concentrated urine. Concentrating ability is lost during ATN and results in increased volumes of dilute urine high in sodium. As mentioned, in ATN loss of concentrating ability may be detected 24 to 48 hours before BUN or creatine begins to rise. Other tests of tubular function include urine-to-plasma osmolar ratio, free water clearance, urine-to-plasma creatinine ratio, urine sodium (U_Na), and fractional excretion of sodium (FENa). With hypovolemia or dehydration U_Na is less than 20 mEq/L. In ATN U_Na exceeds 60 mEq/L. However, diuretics may increase U_Na to this level despite hypovolemia.

12 At what point is renal reserve lost and do patients develop laboratory evidence of renal insufficiency?

Patients will remain asymptomatic with only 40% of nephrons functioning. Renal insufficiency describes the state in which between 10% and 40% of nephrons remain; and, because there is no renal reserve, these patients are at risk for ARF with any renal insult such as hypovolemia are administration of nephrotoxins. Patients require dialysis when fewer than 10% of nephrons remain. In terms of Ccr, patients with renal insufficiency have Ccr of less than 40 ml/min, with renal failure they have CCr less than 25 ml/min, and they require dialysis when Ccr is less than 10 ml/min.

13 Discuss the usefulness of urine output in assessing renal function

Urine output is easily measured through insertion of an indwelling Foley catheter and connection to a urometer. A daily output of 400 to 500 ml of urine is required to excrete obligatory nitrogenous wastes. In adults an inadequate urine output (oliguria) is often defined as <0.5 ml/kg/hr. GFR is decreased by the effects of anesthesia, sympathetic activity, hormonal influences, and redistribution of blood away from outer cortical nephrons. Invariably urine output decreases as blood pressure falls; thus perioperative oliguria is not uncommon, is usually prerenal in origin, and is not a reflection of ARF. A normal urine output does not rule out renal failure.

14 What is the best way to protect the kidneys during surgery?

There are no magic bullets to prevent perioperative ARF. The best way to maintain renal function during surgery is to ensure an adequate intravascular volume, maintain cardiac output, and avoid drugs known to decrease renal perfusion.

15 Does dopamine have a role in renal preservation?

There is now considerable evidence that dopamine is not renoprotective (i.e., improves renal perfusion) nor does it improve splanchnic perfusion (see Chapter 15).

16 Describe the effects of volatile anesthetics on renal function

General anesthesia temporarily depresses renal function as measured by urine output, GFR, RBF, and electrolyte excretion. Renal impairment is usually short lived and completely reversible. Maintenance of systemic blood pressure and preoperative hydration decrease the effect on renal function. Spinal and epidural anesthesia also appear to depress renal function but not to the same extent as general anesthesia.

Fluoride-induced nephrotoxicity has been noted with volatile anesthetics used in the past (e.g., methoxyflurane). Sevoflurane, a volatile anesthetic in current use, has fluoride as a metabolic product (about 3.5% of the total fluoride burden appears in the urine as inorganic fluoride; peak concentrations of about 25 μmol appear within 2 hours of discontinuing the agent). Extensive experience with sevoflurane confirms its safety. Its remarkable insolubility when compared to methoxyflurane may be explanatory; there is simply less sevoflurane deposited in lipid stores to be later metabolized to fluoride, and the overall fluoride burden is less.

An additional breakdown product of sevoflurane is known as Compound A and is noted mostly during low-flow anesthetic techniques. Although renal failure has been noted in animal models, no such problems have been observed in humans.

17 What is the best relaxant for patients with renal insufficiency?

Atracurium undergoes spontaneous degradation under physiologic conditions (Hofmann degradation and ester hydrolysis) and is preferred. Because atracurium is water soluble, patients with altered body water composition may require larger initial doses to produce rapid paralysis but smaller and less frequent doses to maintain paralysis. Succinylcholine may be used in patients with renal insufficiency if the serum potassium concentration is <5 mEq/L (Table 44-3).

18 How are patients with renal insufficiency managed perioperatively?

Preoperative preparation is of benefit for patients with end-stage renal disease (ESRD), who have up to a 20% mortality for emergent surgical procedures. Primary causes of death include sepsis, dysrhythmias, and cardiac dysfunction. Hemodynamic instability is common. From the standpoint of renal dysfunction, there may be a decreased ability to concentrate urine, decreased ability to regulate extracellular fluid and sodium, impaired handling of acid loads, hyperkalemia, and impaired excretion of medications. Renal impairment is confounded by anemia, uremic platelet dysfunction, arrhythmias, pericardial effusions, myocardial dysfunction, chronic hypertension, neuropathies, malnutrition, and susceptibility to infection. Nephrotoxic agents (e.g., amphotericin, nonsteroidal antiinflammatory drugs, aminoglycosides) should be avoided. If a radiocontrast is contemplated, the real value of the test should be considered. If the contrast study is definitely indicated, the patient should be well hydrated, and the contrast dose limited to the minimum needed.

Medications commonly used perioperatively may have increased effects in patients with chronic renal insufficiency. Because these patients are hypoalbuminemic, medications that are usually protein bound such as barbiturates and benzodiazepines may have increased serum levels. Both morphine and meperidine have metabolites that are excreted by the kidney. Succinylcholine increases extracellular potassium but can be used if serum potassium is normal. Hyperkalemia should be considered in patients with ESRD who develop ventricular arrhythmias or cardiac arrest. Rapid administration of calcium chloride temporizes the cardiac effects of hyperkalemia until further measures (administration of insulin and glucose, hyperventilation, administration of sodium bicarbonate and potassium-binding resins, and dialysis) can be taken to shift potassium intracellularly and decrease total body potassium.

Before surgery patients must be euvolemic, normotensive, normonatremic, normokalemic, not acidotic or severely anemic, and without significant platelet dysfunction. Ideally they should have had dialysis the day of or day before surgery. Dialysis usually corrects uremic platelet dysfunction and is best performed within the 24 hours before surgery, although 1-deamino-8-d-arginine vasopressin (DDAVP) may also be administered if bleeding is persistent. Other indications for acute dialysis include uremic symptoms, pericardial tamponade, bleeding, hypervolemia, congestive heart failure, hyperkalemia, and severe acidosis.

Patients with ESRD who have left ventricular dysfunction or undergo major procedures with significant fluid shifts require invasive monitoring to guide fluid therapy. A sterile technique should be strictly followed when inserting any catheters. In minor procedures fluids should be limited to replacement of urine and insensible losses. Normal saline is the fluid of choice as it is free of potassium. However, if large fluid requirements are necessary, normal saline administration may result in hyperchloremic metabolic acidosis. Clearly cases of this magnitude require invasive monitoring and repeated laboratory analysis.

19 What is accomplished during hemodialysis?

Blood is drawn from the patient and flows toward a semipermeable membrane, the area of which is about 1 to 1.8 m². Across the membrane is a dialysate with normal electrolyte concentrations. Electrolytes and waste products move down their concentration gradients. In addition, alkali within the dialysate moves into the patient. Negative pressure within the dialysate results in excess fluid removal. The duration of hemodialysis (HD) depends on flow rates and usually lasts from 4 to 6 hours. High flow rates are associated with rapid changes in electrolytes and volume status that are poorly tolerated by the patient. Usually these patients have dialysis three times weekly. The mortality associated with intermittent dialysis is 5% annually.

Critically ill patients in ARF with hypotension and sepsis frequently tolerate HD poorly. In this case, continuous veno-venous HD (CVVHD) or filtration (CVVHF) is used. Only fluid is drawn off during CVVHF, whereas CVVHD also removes waste products, acid metabolites, and potassium.