Anesthesia and the Renal and Genitourinary Systems

Key Points

▪
Innervation of the intraabdominal components of the genitourinary system—the kidney and the ureter—is primarily thoracolumbar (T8-L2). The nerve supply of the pelvic organs—the bladder, prostate, seminal vesicles, and urethra—is primarily lumbosacral with some lower thoracic input.
▪
The spinal level of pain conduction for the external genitourinary organs is S2-4, except for the testes (T10-L1).
▪
The kidneys receive 15% to 25% of the total cardiac output, with most of this blood directed to the renal cortex. Renal medullary papillae are more vulnerable to ischemic insults. Kidneys successfully autoregulate their blood flow between 60 and 160 mm Hg mean arterial pressures.
▪
The glomerular filtration rate (GFR) is the best measure of glomerular function. Creatinine clearance is a good measure of the GFR; urine output is not.
▪
Hypervolemia, acidemia, hyperkalemia, cardiorespiratory dysfunction, anemia, and bleeding disturbances are manifestations of chronic renal failure.
▪
Serum creatinine, most commonly used as a marker of renal function, has several limitations. Newer biomarkers, such as serum cystatin C, are better and earlier measures of acute kidney injury and the risk of end-stage renal disease, as well as related mortality.
▪
Although renal transplantation reverses most of the abnormalities in end-stage renal disease, dialysis improves only some and introduces additional complications of its own.
▪
Newer techniques, such as laser prostatectomy, are making transurethral resection of the prostate (TURP) syndrome a rare event. TURP syndrome is a constellation of symptoms caused by the absorption of hypotonic bladder irrigants. Cardiovascular and neurologic changes are due to hypoosmolality, hyponatremia, hyperglycinemia, hyperammonemia, and hypervolemia.
▪
Regional anesthesia offers several advantages over general anesthesia for standard, but not laser, TURP. Yet, 30-day mortality rates remain unchanged at 0.2% to 0.8%.
▪
Laparoscopic surgery in urology frequently requires insufflation of carbon dioxide into the retroperitoneal space. In lengthy procedures, pneumomediastinum and subcutaneous emphysema of the head and neck may occur.
▪
Extracorporeal shock wave lithotripsy (ESWL) historically caused significant physiologic changes related to immersion in a water bath, but newer generations have eliminated the water bath and hence those risks. Shock waves can cause clinically insignificant dysrhythmias. Pregnancy and untreated bleeding disorders are contraindications to ESWL.
▪
Regarding renal tumors, 5% to 10% extend into the renal vein, inferior vena cava, and right atrium. Complications ranging from circulatory failure to embolization of tumor during surgery may occur. Cardiopulmonary bypass may be necessary for surgery.
▪
Radical prostatectomy may cause significant blood loss, and intraoperative venous air emboli can occur. Regional anesthesia with spontaneous ventilation is associated with less blood loss than general anesthesia and intermittent positive pressure ventilation. Other advantages of epidural anesthesia include a decreased incidence of deep vein thrombosis and the initiation of preemptive analgesia. Whether outcomes are dependent on the choice of anesthesia is not clear.
▪
Robotic radical prostatectomy is associated with reduced blood loss and postoperative pain compared with open radical prostatectomy. Anesthetic concerns are related to steep head-down tilt and pneumoperitoneum and include hypercarbia, hypoxemia, increased intraocular and intracranial pressures, decreased perfusion pressure to lower extremities, and positional injuries.
▪
Anesthetic concerns of robotic-assisted surgery include the length of surgical time, intravenous fluid management, pneumoperitoneum, and positioning. The most frequent reported complications are peripheral neuropathies, corneal abrasions, vascular complications (including compartment syndrome, rhabdomyolysis, and thromboembolic disease), and the effects of edema.
▪
Postoperative urinary retention should be considered as a source of postoperative pain after urologic surgery. Prompt diagnosis, either clinically or with ultrasound, and bladder catheterization if indicated (postvoid residual >600 mL) is effective and can prevent sequelae.

Acknowledgment

The authors, editors, and publisher thank Drs. Vijeyandra Sudheendra and Jerome O’Hara for their contribution to the prior edition of this chapter. It has served as a foundation for the current chapter.

Patients requiring anesthesia for renal and genitourinary surgery are frequently at the extremes of age. In addition to the physiologic changes of aging in older patients, concomitant cardiovascular and respiratory comorbidity is common. A medical history, physical examination, and appropriate laboratory tests are necessary to evaluate concomitant disease. In pediatric urologic patients, a careful history should exclude other nonurologic congenital lesions.

Urologic procedures are performed mostly on the kidneys, adrenals, ureters, urinary bladder, prostate, urethra, penis, scrotum, testis, and spermatic cord. Because their sensory nerve supply is primarily thoracolumbar and sacral outflow ( Table 59.1 ), these structures are well adapted for regional anesthesia.

Table 59.1

Pain Conduction Pathways and Spinal Segment Projection of Pain of the Genitourinary System

Organ	Sympathetics, Spinal Segments	Parasympathetics	Spinal Levels of Pain Conduction
Kidney	T8-L1	CN X (vagus)	T10-L1
Ureter	T10-L2	S2-4	T10-L2
Bladder	T11-L2	S2-4	T11-L2 (dome), S2-4 (neck)
Prostate	T11-L2	S2-4	T11-L2, S2-4
Penis	L1 and L2	S2-4	S2-4
Scrotum	NS	NS	S2-4
Testes	T10-L2	NS	T10-L1

NS , Not significant for nociceptive function.

Innervation of the Genitourinary System

The parts of the genitourinary system that are in the abdomen receive their nerve supply from the autonomic nervous system by means of sympathetic and parasympathetic pathways. The pelvic urinary organs and genitalia are supplied by somatic and autonomic nerves. Table 59.1 summarizes the pain conduction pathways and spinal levels of the genitourinary system.

Kidney and Abdominal Ureter

Sympathetic nerves to the kidney originate as preganglionic fibers from the eighth thoracic through the first lumbar segments and converge at the celiac plexus and aorticorenal ganglia ( Fig. 59.1 ). Postganglionic fibers to the kidney arise mainly from the celiac and aorticorenal ganglia. Some sympathetic fibers may reach the kidney via the splanchnic nerves. Parasympathetic input is from the vagus nerve. Sympathetic fibers to the ureter originate from the tenth thoracic through the second lumbar segments and synapse with postganglionic fibers in the aorticorenal and superior and inferior hypogastric plexuses. Parasympathetic input is from the second through fourth sacral spinal segments. Nociceptive fibers travel along the sympathetics to the same spinal segments. Pain from the kidney and ureter is referred mainly to the somatic distribution of the tenth thoracic through the second lumbar segments—the lower part of the back, flank, ilioinguinal region, and scrotum or labia. Effective neural block of these segments is necessary to provide adequate analgesia or anesthesia.

Fig. 59.1, Autonomic and sensory innervation of the kidney and ureters.

Bladder and Urethra

Sympathetic nerves to the bladder and urethra originate from the eleventh thoracic to the second lumbar segments, travel through the superior hypogastric plexus, and supply the bladder through the right and the left hypogastric nerves. Parasympathetic nerves arise from the second through the fourth sacral segments and form the pelvic parasympathetic plexus, which is joined by the hypogastric plexus. Vesical branches proceed toward the bladder base, where they provide the nerve supply to the bladder and proximal part of the urethra ( Fig. 59.2 ). Parasympathetic fibers are the main motor supply to the bladder (with the exception of the trigone) and far outnumber sympathetic fibers in the bladder.

Fig. 59.2, (A) Nerve supply of the urinary bladder and prostate showing the relationship of the various nerve structures to the large intestine and their distribution in the bladder and prostate. (B) Schematic illustration showing the segmental nerve supply to the bladder, penis, and scrotum. Solid lines indicate preganglionic fibers; dashed lines indicate postganglionic fibers; and dotted lines indicate sensory fibers.

The afferents carrying sensations of stretch and fullness of the bladder are parasympathetic, whereas pain, touch, and temperature sensations are carried by sympathetic nerves. Sympathetic fibers are predominantly α-adrenergic in the bladder base and urethra, and β-adrenergic in the bladder dome and lateral wall. Knowledge of these aspects of neuroanatomy is important to appreciate the pharmacologic effects on the urologic system of neural ablation or regional block and drugs with adrenergic or cholinergic effects.

Prostate and Prostatic Urethra

The prostate and the prostatic urethra receive sympathetic and parasympathetic supply from the prostatic plexus arising from the pelvic parasympathetic plexus, which is joined by the hypogastric plexus. The spinal origin of the nerve supply is primarily lumbosacral (see Fig. 59.2 ).

Penis and Scrotum

The autonomic supply to the penile urethra and the cavernous tissue comes from the prostatic plexus. Somatic fibers from the pudendal nerve (S2-4) supply the external sphincter. The dorsal nerve of the penis, the first branch of the pudendal nerve, is its main sensory supply. The scrotum is innervated anteriorly by the ilioinguinal and genitofemoral nerves (L1 and L2) and posteriorly by perineal branches of the pudendal nerve (S2 and S4).

Testes

The testes descend from their intraabdominal location to the scrotum during fetal development. Because they share their embryologic origin with the kidney, their nerve supply is similar to that of the kidney and upper part of the ureter and extends up to the T10 spinal segment.

Renal Blood Flow

The kidneys receive approximately 15% to 25% of total cardiac output, or 1 to 1.25 L/min of blood, through the renal arteries, depending on the state of the body. Most of the blood is received by the renal cortex, with only 5% of cardiac output flowing through the renal medulla, which makes the renal papillae vulnerable to ischemic insults. Renal blood flow is regulated by various mechanisms that control the activity of vascular smooth muscle and alter vascular resistance. Sympathetic tone of renal vessels increases during exercise to shunt renal blood flow to exercising skeletal muscle; similarly, renal blood vessels relax during the resting condition of the body. Sympathetic stimulation resulting from surgery can increase vascular resistance and reduce renal blood flow, whereas anesthetics may reduce renal blood flow by decreasing cardiac output.

Glomerular capillaries separate afferent arterioles from efferent arterioles. Glomerular capillaries are high-pressure systems, whereas peritubular capillaries are low-pressure systems. Consequently, the glomerular capillaries are a fluid-filtering system, whereas the peritubular capillaries are a fluid-absorbing system. The vasa recta, a specialized portion of peritubular capillaries formed from efferent arterioles, are important in the formation of concentrated urine by a countercurrent mechanism. An intrinsic mechanism that causes vasodilation and vasoconstriction of renal afferent arterioles regulates the autoregulation of renal blood flow. A decrease in mean arterial pressure also decreases renal blood flow and eventually affects the glomerular filtration rate (GFR) when the pressure decreases to less than 60 mm Hg. A persistently low mean arterial pressure greater than 60 mm Hg affects renal blood flow but does not affect the GFR because of the intrinsic mechanism of autoregulation ( Fig. 59.3 ). Autoregulation maintains mean arterial pressure between 60 and 160 mm Hg in intact and denervated kidneys.

Fig. 59.3, Autoregulation of renal blood flow (RBF) and the glomerular filtration rate (GFR) .

Although knowledge of neuroanatomy and renal blood flow is essential to provide adequate anesthesia, a thorough understanding of renal physiology and pharmacology is equally important. Genitourinary surgical patients frequently have mechanical or functional renal disease. Anesthetics and surgery can significantly alter renal function. Conversely, renal dysfunction significantly affects the pharmacokinetics and pharmacodynamics of anesthetics and adjuvant drugs. Evaluation of a patient with renal disease is discussed later.

Anesthesia for Patients With Renal Disease

Evaluation of Renal Function

Renal disease can be discovered incidentally during a routine medical evaluation, or patients may exhibit evidence of renal dysfunction, such as hypertension, edema, nausea, and hematuria. The initial approach in both situations should be to assess the cause and severity of renal abnormalities. In all cases, this evaluation includes (1) an estimation of disease duration, (2) a careful urinalysis, and (3) an assessment of the GFR. The history and physical examination, although equally important, are variable among renal syndromes; specific symptoms and signs are discussed in sections on each disease entity. Further diagnostic categorization is based on anatomic distribution: prerenal disease, postrenal disease, and intrinsic renal disease. Intrinsic renal disease can be divided further into glomerular, tubular, interstitial, and vascular abnormalities. Laboratory tests useful in evaluating renal function are described next ( Table 59.2 ).

Table 59.2

Commonly Ordered Renal Function Tests

From Miller ED Jr. Understanding renal function and its preoperative evaluation. In: Malhotra V, ed. Anesthesia for Renal and Genitourinary Surgery . New York: McGraw-Hill; 1996:9.

Test Name	Reference Range	Units
Urea nitrogen	5-25	mg/dL
Creatinine	0.5-1.5	mg/dL
Sodium	133-147	mmol/L
Potassium	3.2-5.2	mmol/L
Chloride	94-110	mmol/L
CO ₂	22-32	mmol/L
Uric acid	2.5-7.5	mg/dL
Calcium	8.5-10.5	mg/dL
Phosphorus	2.2-4.2	mg/dL
Urinalysis, routine
Color	Straw-amber
Appearance	Clear-hazy
Protein	0	mg/dL
Blood	Negative
Glucose	0	mg/dL
Ketones	0	mg/dL
pH	4.5-8.0
Specific gravity	1.002-1.030
Bilirubin	Negative
Urinalysis, microscopic
Red blood cells	0-3	per high-power field
White blood cells	0-5	per high-power field
Casts	0-2	per low-power field

Glomerular Function

Glomerular Filtration Rate

The GFR is the best measure of glomerular function. Normal GFR is approximately 125 mL/min. However, manifestations of reduced GFR are not seen until the GFR has decreased to 50% of normal. When GFR decreases to 30% of normal, a stage of moderate renal insufficiency ensues. Patients remain asymptomatic with only biochemical evidence of a decline in GFR (i.e., an increase in serum concentrations of urea and creatinine). Further workup usually reveals other abnormalities, such as nocturia, anemia, loss of energy, decreasing appetite, and abnormalities in calcium and phosphorus metabolism.

As the GFR decreases further, a stage of severe renal insufficiency begins. This stage is characterized by profound clinical manifestations of uremia and biochemical abnormalities, such as acidemia; volume overload; and neurologic, cardiac, and respiratory manifestations. At the stages of mild and moderate renal insufficiency, intercurrent clinical stress may compromise renal function further and induce signs and symptoms of overt uremia. When the GFR is 5% to 10% of normal, it is called end-stage renal disease (ESRD), and continued survival without renal replacement therapy becomes impossible ( Table 59.3 ).

Table 59.3

Clinical Abnormalities in Chronic Renal Failure and Their Response to Dialysis and Erythropoietin Treatment

Improved by Dialysis	Improved by Adding Erythropoietin	Variable Response	Not Improved	Develop After Dialysis Therapy
Volume expansion and contraction Hypernatremia and hyponatremia Hyperkalemia and hypokalemia Metabolic acidosis Hyperphosphatemia Hypocalcemia Vitamin D–deficient osteomalacia Carbohydrate intolerance Hypothermia Asterixis Muscular irritability Myoclonus Coma Congestive heart failure or pulmonary edema Pericarditis Uremic lung Ecchymoses Uremic frost Anorexia Nausea and vomiting Uremic fetor Gastroenteritis	Fatigue Impaired mentation Lethargy Pallor Anemia Bleeding diathesis	Secondary hyperparathyroidism Hyperuricemia Hypertriglyceridemia Protein-calorie malnutrition Headache Peripheral neuropathy Restless legs syndrome Paralysis Seizures Myopathy Arterial hypertension Cardiomyopathy Accelerated atherosclerosis Vascular calcification Hyperpigmentation Peptic ulcer Gastrointestinal bleeding Increased susceptibility to infection	Increased lipoprotein level Decreased high-density lipoprotein level Impaired growth and development Infertility and sexual dysfunction Amenorrhea Sleep disorders Pruritus Lymphocytopenia Splenomegaly and hypersplenism	Adynamic osteomalacia β ₂ -Microglobulinemia Muscle cramps Dialysis dysequilibrium syndrome Hypotension and arrhythmias Hepatitis Idiopathic ascites Peritonitis Leukopenia Hypocomplementemia

Blood Urea Nitrogen

The blood urea nitrogen (BUN) concentration is not a direct correlate of reduced GFR. BUN is influenced by nonrenal variables, such as exercise, bleeding, steroids, and massive tissue breakdown. The more important factor is that BUN is not elevated in kidney disease until the GFR is reduced to almost 75% of normal.

Creatinine and Creatinine Clearance

Measurements of creatinine provide valuable information regarding general kidney function. Creatinine in serum results from turnover of muscle tissue and depends on daily dietary intake of protein. Normal values are 0.5 to 1.5 mg/100 mL; values of 0.5 to 1 mg/100 mL are present during pregnancy. Creatinine is freely filtered at the glomerulus, and apart from an almost negligible increase in content because of secretion in the distal nephron, it is neither reabsorbed nor secreted. Serum creatinine measurements reflect glomerular function ( Fig. 59.4 ), and creatinine clearance is a specific measure of GFR. Creatinine clearance can be calculated by the following formula derived by Cockcroft-Gault that accounts for age-related decreases in GFR, body weight, and sex:

\begin{matrix} \begin{matrix} Creatinine clearance (mL/min) = \\ [(140 - Age) \times Lean body weight (kg)] / \end{matrix} \\ \begin{matrix} [Plasma creatinine (mg/dL) \times 72] \end{matrix} \end{matrix}

$\begin{matrix} \begin{matrix} Creatinine clearance (mL/min) = \\ [(140 - Age) \times Lean body weight (kg)] / \end{matrix} \\ \begin{matrix} [Plasma creatinine (mg/dL) \times 72] \end{matrix} \end{matrix}$

Fig. 59.4, Theoretic relationship between blood urea nitrogen and creatinine versus glomerular filtration rate (GFR) .

This value should be multiplied by 0.85 for women because a lower fraction of body weight is composed of muscle.

Because there is such a wide range in normal values, a 50% increase in serum creatinine concentration, indicative of a 50% reduction in GFR, may go undetected unless baseline values are known. In addition, excretion of drugs dependent on glomerular filtration may be significantly decreased despite what might seem to be only slightly elevated serum creatinine values (1.5-2.5 mg/100 mL). The serum creatinine concentration and clearance are better indicators of general kidney function and GFR than are similar measurements of urea nitrogen ( Box 59.1 ). However, there are disease states in which even the serum creatinine can be affected independent of the GFR ( Table 59.4 ). The main limitation of current GFR estimates is the greater inaccuracy in populations without known chronic kidney disease than in those with the disease. Nonetheless, current GFR estimates facilitate detection, evaluation, and management of the disease, and they should result in improved patient care and better clinical outcomes.

Box 59.1

Conditions Affecting Blood Urea Nitrogen Independently of Glomerular Filtration Rate

Increased Blood Urea Nitrogen

▪
Reduced effective circulating blood volume (prerenal azotemia)
▪
Catabolic states (gastrointestinal bleeding, corticosteroid use)
▪
High-protein diets
▪
Tetracycline

Decreased Blood Urea Nitrogen

▪
Liver disease
▪
Malnutrition
▪
Sickle cell anemia
▪
Syndrome of inappropriate secretion of antidiuretic hormone

Table 59.4

Conditions Affecting Serum Creatinine Independently of Glomerular Filtration Rate

Condition	Mechanism
CONDITIONS CAUSING ELEVATION
Ketoacidosis	Noncreatinine chromogen
Cephalothin, cefoxitin	Noncreatinine chromogen
Flucytosine	Noncreatinine chromogen
Other drugs—aspirin, cimetidine, probenecid, trimethoprim	Inhibition of tubular creatinine secretion
CONDITIONS CAUSING DECREASE
Advanced age	Physiologic decrease in muscle mass
Cachexia	Pathologic decrease in muscle mass
Liver disease	Decreased hepatic creatine synthesis and cachexia

Tubular Function

Concentration

Urinary specific gravity is an index of the kidney’s concentrating ability, specifically renal tubular function. Determination of urinary osmolality (i.e., measurement of the number of moles of solute [osmoles] per kilogram of solvent) is a similar, more specific test. Excretion of concentrated urine (specific gravity, 1.030; 1050 mOsm/kg) is indicative of excellent tubular function, whereas a urinary osmolality fixed at that of plasma (specific gravity 1.010; 290 mOsm/kg) indicates renal disease. The urinary dilution mechanism persists after concentrating defects are present, so a urinary osmolality of 50 to 100 mOsm/kg still may be consistent with advanced renal disease.

Protein

Patients without renal disease can excrete 150 mg of protein per day; greater amounts may be present after strenuous exercise or after standing for several hours. Massive proteinuria (i.e., >750 mg/day) is always abnormal and usually indicates severe glomerular damage.

Glucose

Glucose is freely filtered at the glomerulus and is subsequently reabsorbed in the proximal tubule. Glycosuria signifies that the ability of the renal tubules to reabsorb glucose has been exceeded by an abnormally heavy glucose load and is usually indicative of diabetes mellitus. Glycosuria also may be present in hospitalized patients without diabetes who are receiving intravenous glucose infusions.

Additional Diagnostic Tests

Urinalysis and Appearance

Gross and microscopic observations of urine and its sediment, along with determination of urinary pH, specific gravity, protein content, and glucose content, are two of the most readily available, inexpensive, and informative laboratory tests. The gross appearance of urine may indicate the presence of bleeding or infection in the genitourinary tract. Microscopic examination of urinary sediment may reveal casts, bacteria, and various cell forms, supplying diagnostic information in patients with renal disease.

Urine and Serum Electrolytes With Blood Gases

Sodium, potassium, chloride, and bicarbonate concentrations should be determined if impairment in renal function is suspected. However, the results of these tests usually remain normal until frank renal failure is present and hyperkalemia does not occur until patients are uremic. Measuring urinary sodium or chloride excretion is especially useful when attempting to differentiate between causes of hyponatremia, as seen in volume contraction (whether a decrease in total circulatory volume or a decrease in effective arterial blood volume), versus conditions associated with increased salt loss, such as the syndrome of inappropriate secretion of antidiuretic hormone, salt-losing nephropathy, or adrenal insufficiency. If significant renal disease is present, patients consuming a diet high in animal protein may develop metabolic acidosis.

Novel Biomarkers of Renal Function

Although serum creatinine is most commonly used as a marker of GFR and hence renal function, it has some limitations in that it is influenced by nonrenal factors such as age, gender, muscle mass and metabolism, diet, and hydration. Furthermore, creatinine levels may take several hours or days to reach a steady state to accurately reflect the GFR as indicator of renal function in acute kidney injury (AKI). Several new markers of renal function have been identified. Serum cystatin C, a ubiquitous protein that is exclusively excreted by glomerular filtration, is less influenced by variations in muscle mass and nutrition than is creatinine. It may better predict risk of death and ESRD across diverse populations.

Other novel biomarkers such as N -acetyl-β- d -glucosaminidase, kidney injury molecule-1, interleukin-18, uromodulin, and microRNA are also showing promise at early detection of kidney injury. These biomarkers may have a future role in reducing morbidity and mortality associated with kidney injury in the perioperative setting.

Electrocardiogram

The electrocardiogram reflects the toxic effects of potassium excess more closely than determination of the serum potassium concentration.

Imaging Studies

Renal Ultrasound

Ultrasound is the most frequently used diagnostic examination for the evaluation of the kidneys and urinary tract. It is noninvasive, uses no ionizing radiation, and requires minimal patient preparation. It is the first-line examination in patients with renal dysfunction for assessing kidney size and the presence or absence of hydronephrosis and obstruction. It can be used to assess the vasculature of native and transplanted kidneys. Ultrasound is also used to evaluate renal structure and to characterize renal masses.

Computed Tomography Scan of Kidneys

A stone protocol computed tomography (CT) scan of the kidneys, ureter, and bladder has become the study of choice for the detection of kidney stones because of its ability to detect stones of all kinds, including uric acid stones and nonobstructing stones in the ureter. Even in areas in which ultrasound is the first-line imaging modality, CT offers a complementary and sometimes superior means of imaging. Masses in the kidney can be evaluated using either contrast-enhanced CT or renal ultrasound.

Computed Tomography Angiography

CT angiography is used for the evaluation of renal artery stenosis and is emerging rapidly as a useful diagnostic tool. Although it is comparable with magnetic resonance angiography (MRA) as a noninvasive study, it requires the use of iodinated contrast material, which may cause contrast media–induced nephropathy.

Magnetic Resonance Imaging With Magnetic Resonance Angiography

Magnetic resonance imaging allows for detailed tissue characterization of the kidney and surrounding structures. It is a good alternative to contrast-enhanced CT, especially in patients who cannot tolerate iodinated contrast material and in patients for whom reduction of radiation exposure is desired, such as pregnant women and children. Gadolinium, a paramagnetic intravenous contrast agent, is used routinely in MRA because it improves lesion detection and diagnostic accuracy. It is generally well tolerated with a good safety profile. However, nephrogenic systemic fibrosis, a rare, multiorgan, fibrosing condition for which there is no known effective treatment, has been recognized to occur in patients with moderate to severe renal disease.

Important Pathophysiologic Manifestations of Chronic Renal Failure

Hypervolemia

Total body contents of sodium and water are increased in chronic renal failure (CRF), although this increase might not be clinically apparent until the GFR is reduced to very low levels. Weight gain is usually associated with volume expansion and is offset by the concomitant loss of lean body mass. The combination of loop diuretics with metolazone, which acts by inhibiting the Na-Cl cotransporter of the distal convoluted tubule, can overcome diuretic resistance.

Acidemia

Although urine can be acidified normally in most patients with CRF, these patients have a reduced ability to produce ammonia. In the early stages, the accompanying organic anions are excreted in urine, and the metabolic acidosis is of the non–anion gap variety. With advanced renal failure, a fairly large “anion gap” can develop (to approximately 20 mmol/L), however, with a reciprocal decrease in plasma bicarbonate ion (HCO ₃ ) concentration. This acidemia is usually corrected by hemodialysis. Although acidemia is well compensated in moderate CRF, patients can become acidemic and hyperkalemic in the postoperative period ( Table 59.5 ).

Table 59.5

Metabolic Acidosis in Chronic Renal Failure

	Pa CO ₂ (mm Hg)	pH	HCO ₃ ⁻ (mEq/L)	K ⁺ (mEq/L)
Preoperative	32	7.32	17	5
Intraoperative	40	7.25	18	5.3
Postoperative	44	7.21	19	5.6
	48	7.18	19	5.9

The patient is a 36-year-old man with severe diabetic nephropathy and end-stage renal failure undergoing cadaver renal transplantation. Preoperatively, the patient has a chronic metabolic acidosis (HCO ³⁻ , 17 mEq/L) with partial respiratory compensation (Pa CO ₂ , 32 mm Hg; pH 7.32). Potassium is high normal at 5 mEq/L. Intraoperatively, he is given “standard” mechanical minute ventilation, and with “normal” Pa CO ₂ (40 mm Hg), the metabolic acidosis is unmasked (pH 7.25), and potassium increases to 5.3 mEq/L. His trachea is extubated at the end of the procedure, but graft function is sluggish, and the metabolic acidosis remains unchanged. With residual opioid-induced narcosis, moderate CO ₂ retention occurs (Pa CO ₂ , 44 mm Hg and 48 mm Hg), pH decreases further to 7.18, and a dangerous degree of hyperkalemia develops (K ⁺ , 5.9 mEq/L).

Hyperkalemia

The approximate daily filtered load of potassium (K ⁺ ) is 700 mmol. Most of this filtered load is reabsorbed in tubule segments, and most of the K ⁺ excreted in the final urine reflects events governing K ⁺ handling at the level of the cortical collecting tubule and beyond. K ⁺ excretion in the gastrointestinal tract is augmented in patients with CRF. However, hyperkalemia may be precipitated in numerous clinical situations, including protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, metabolic acidosis, and exposure to various medications that inhibit K ⁺ entry into cells or K ⁺ secretion in the distal nephron.

Cardiac and Pulmonary Manifestations

Hypertension is a common complication of CRF and ESRD. Because hypervolemia is the major cause of hypertension in uremia, normotension is usually restored by the use of diuretics in predialysis patients or by dialysis in ESRD patients. However, despite therapy, patients remain hypertensive due to activation of the renin-angiotensin system and autonomic factor. Patients generally have left ventricular hypertrophy and accelerated atherosclerosis (disordered glucose and fat metabolism). Pericarditis can be observed in patients with inadequate dialysis unlike patients with CRF who undergo regular dialysis.

Pulmonary edema and restrictive pulmonary dysfunction are a common feature of patients in renal failure. Hypervolemia, heart failure, decreased serum oncotic pressure, and increased pulmonary capillary permeability contribute to the development of pulmonary edema. Diuretic therapy or dialysis can be effectively used to treat pulmonary congestion and edema due to excess intravascular volume.

Hematologic Manifestations

CRF usually causes a normochromic, normocytic anemia. Anemia is generally observed when the GFR decreases to less than 30 mL/min and is due to insufficient production of erythropoietin by the diseased kidneys. Other factors are iron deficiency, either related to or independent of blood loss from repeated laboratory testing, blood retention in the dialyzer, or gastrointestinal bleeding. Treatment of anemia with iron, darbepoetin alfa, and human recombinant erythropoietin ( Table 59.6 ) restores a normal hematocrit and avoids repetitive red blood cell transfusions, reduces the requirement for hospitalization, and decreases cardiovascular mortality by approximately 30%.

Table 59.6

Management Guidelines for Correction of Anemia of Chronic Renal Disease

ERYTHROPOIETIN
Starting dosage	50-150 U/kg per week IV or SC (once, twice, or three times per week)
Target hemoglobin	11-12 g/dL
Optimal rate of correction	Increase hemoglobin by 1-2 g/dL over 4 wk
DARBEPOETIN ALFA
Starting dosage	0.45 mg/kg administered as single IV or SC injection once weekly
	0.75 mg/kg administered as a single IV or SC injection once every 2 wk
Target hemoglobin	12 g/dL
Optimal rate of correction	Increase hemoglobin by 1-2 g/dL over 4-wk period
Iron
Monitor iron stores by TSat and serum ferritin If patient is iron-deficient (TSat <20%; serum ferritin <100 g/L), administer iron, 50-100 mg IV twice per week for 5 wk; if iron indices are still low, repeat the same course If iron indices are normal but hemoglobin is still inadequate, administer IV iron as outlined above; monitor hemoglobin, TSat, and ferritin. Withhold iron therapy when TSat >50% or ferritin >800 ng/mL (>800 g/L)

IV , Intravenous; SC , subcutaneous; TSat , percent transferrin saturation.

Prolongation of the bleeding time because of decreased activity of platelet factor 3, abnormal platelet aggregation and adhesiveness, and impaired prothrombin consumption contributes to the clotting defects. The abnormality in platelet factor 3 correlates can be corrected with dialysis, although prolongation of the bleeding time can be observed in well-dialyzed patients. Abnormal bleeding times and coagulopathy in patients with renal failure may be managed with desmopressin, cryoprecipitate, conjugated estrogens, blood transfusions, and erythropoietin use.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here