Renal Complications
Kenneth S. Kleinman
Dennis A. Casciato
I. OVERVIEW.
Acute renal failure (ARF) syndrome is a constellation of worsening renal function, electrolyte, acid base changes, and changes in fluid and volume status. The three categories of ARF syndrome are prerenal failure, direct renal tubular damage (acute tubular necrosis [ATN], tubulointerstitial nephritis, acute glomerulonephritis), and postrenal failure (obstruction of the renal and urinary collecting system). These syndromes often overlap but are helpful to define diagnostic and therapeutic approaches.
The renal failure may be due to direct or indirect consequences of the tumor, anticancer therapy, immunosuppression, infectious complications, postoperative ARF, or treatments for complications (antibiotics, diagnostic tests, etc.). Furthermore, with improved response and cure rates for cancer patients, residual chronic kidney disease (CKD) is becoming an increasingly common complication of successful cancer treatments.
ARF, especially in the hospitalized patient, is often “multifactorial” and often includes diagnostic tests (contrast agents for CT scans), changing volume status, and nephrotoxic agents. A careful and thorough history, physical examination, and appropriate diagnostic tests including a urinalysis are most helpful for diagnosis, since urine output may decrease and not be available at future times. When ARF occurs in hospitalized patients, review of all physician orders, medication lists, nursing records, vital signs, and surgical records may yield valuable information.
II. PRERENAL FAILURE
A. Pathogenesis. Decreased effective circulating volume (ECV, i.e., from vomiting, diarrhea, blood loss) provides a physiologic stimulus for metabolic and biochemical changes, which lead to reduced renal blood flow and glomerular filtration rate (GFR). The patient with decreased ECV has a baroreceptor-mediated stimulus for increased secretion of antidiuretic hormone (ADH), diminished renal blood flow, and physiologically increased circulating levels of renin, angiotensin II, and aldosterone.
The combined effects of decreased renal blood flow and increased levels of ADH, angiotensin II, and aldosterone result in excretion of a low urine volume that is highly concentrated (elevated urine specific gravity and osmolality), contains little sodium, and often contains large amounts of potassium (the potassium can be variable and is typically not used as a diagnostic test). The body is trying to maintain blood pressure and hemodynamic stability at the expense of renal function. Table 31.1 shows laboratory values that distinguish prerenal failure from renal failure in oliguric patients.
1. Decreased GFR leads to retention of urea (along with sodium) and creatinine. Reabsorption of filtered urea is increased in the proximal nephron as well as in the distal nephron due to slow tubular flow, a high concentration of urea in tubular fluid, and elevated ADH. Thus, more urea than creatinine is retained, leading to a characteristic elevated blood urea nitrogen (BUN) to serum creatinine ratio.
Table 31.1 Distinguishing Prerenal from Renal Causes of Azotemia | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||
2. The serum creatinine level is primarily reflective of muscle mass and GFR, when in a “stable state.” Elderly patients and poorly nourished patients with less muscle mass have a relatively low serum creatinine. Because of this, an important clinical pearl/caveat is that serum creatinine levels may still be in the “normal lab range” yet GFR may have dropped significantly.
3. BUN is a metabolic waste product of protein intake, produced within the liver and excreted by the kidney. Although ARF will lead to increases in creatinine and BUN, a lower protein intake and/or diminished liver function, and cachexia with muscle wasting may result in BUN levels that may not be as elevated. Conversely, high protein intake, significant catabolic states, blood in the gastrointestinal tract, and severe prerenal states may result in BUN levels that are dramatically elevated in relation to the serum creatinine.
B. Causes of prerenal failure. Table 31.2 shows general causes of prerenal failure with specific factors that may predispose patients with malignancies to prerenal failure.
C. Diagnosis. The history often reveals likely causes of increased fluid loss (e.g., diarrhea, vomiting, bleeding) or of sequestration (e.g., pleural effusions, ascites, edema, “third spacing,” retroperitoneal hemorrhage, congestive heart failure). Decreased intake of sodium, protein, and fluids may be more difficult to elicit. The physical examination is of paramount importance in assessing volume status and finding clues to the pathogenesis of aberrations, as follows:
1. Hypotension is recognized with a supine systolic blood pressure (BP) of <90 mm Hg. Changes in hemodynamic parameters (orthostatic changes) are recognized by a drop in systolic BP of 20 mm Hg or in diastolic BP of 10 mm Hg and increased heart rate (10 to 20 beats/min) when moving the patient from the supine to sitting or standing positions. These findings are suggestive of intravascular volume depletion and thus low ECV. Medications that affect blood pressure (antihypertensives) and heart rate (beta-blockers and calcium channel blockers) should be taken into account and be associated with more modest changes in these hemodynamic parameters. Early recognition of intravascular volume depletion by careful measurement can prevent later complications.
2. Flat neck veins in the supine position (in patients whose neck veins can be demonstrated by gentle occlusion) suggest volume depletion.
3. In patients without the finding of volume depletion, careful palpation and percussion of the bladder, rectal examination of the prostate of male patients, and pelvic examination in female patients may divert attention to an obstructive cause.
Table 31.2 Cause of Decreased Effective Circulating Volume and Prerenal Failure in Patients with Malignancies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
4. Occult prerenal failure may be present that escapes detection by any of the above measures. In such patients, there should always be a high clinical suspicion and consideration of an occult change in cardiac function, which is often from subclinical myocardial infarction, transient or persistent arrhythmias, valvular dysfunction, or myocardial dysfunction related to medications, aortic dissection, or other causes. Acute adrenal insufficiency may develop as a consequence of metastasis to the adrenal or pituitary glands, discontinuance of chronic corticosteroid therapy in the acutely hospitalized patient (for whatever reason), or the requirement for “stress doses” with associated emergency surgery, sepsis, or other reasons. Thus, many clinical scenarios require the careful administration of a fluid challenge and review of the changing clinical status.
5. Loop diuretics given as an intravenous challenge are often used in acutely oliguric patients. An increased urinary output suggests that obstruction is not present and that the renal tubules are functioning. Such response, however, does not clarify or correct the underlying abnormality causing the initial decrease in urine production, and except for overload states such as congestive heart failure. The diuretic may make the prerenal failure worse.
D. Management of prerenal failure is to correct the underlying cause and, when possible, to restore ECV to normal.
1. Hypovolemic patients usually require large volumes of crystalloids (i.e., 0.9% sodium chloride with or without glucose) or colloidal solutions, (i.e., albumin). Plasmanate contains 5% albumin and often requires a larger infused volume, whereas 25% albumin contains 12.5 g of albumin per 25 mL, which is a lesser volume and is preferred in the patient who may have occult volume overload. These solutions also contain significant amounts of sodium. Although albumin solutions specifically increase intravascular volume, they are expensive, and the effect is often transient. Some nephrologists will give an additional trial of an osmotic diuretic such as mannitol, 12.5 to 25 g, either once or twice, to improve the ECV.
2. Obstruction to urinary outflow should be considered in all patients who do not respond to a fluid challenge. In such patients (especially men), insertion of a Foley catheter should be performed. If the problem is still not corrected, all such patients should undergo an imaging procedure to visualize the kidneys and collecting system. Ultrasonography is the safest, most convenient, and available, noninvasive choice and does not require the use of intravenous contrast agents. Computed tomography (CT) scan of the pelvis may also be useful, although intravenous dye may be required; the dye itself can be nephrotoxic, especially in the patient with a low ECV.
3. Reversible renal failure is diagnostic of prerenal failure and often not known until some time after a therapeutic trial and repeat blood and urine testing. If not treated effectively or completely, prerenal failure can lead to more significant kidney damage and ATN. Once established, ATN may be prolonged, more difficult to manage, associated with prolonged hospital stays, and associated with significant morbidity and dramatically increased mortality.
III. POSTRENAL FAILURE: OBSTRUCTIVE UROPATHY
A. Pathogenesis
1. Ureteral obstruction. Uremia may be caused by bilateral obstruction (or unilateral obstruction in the case of a single functioning kidney) as a result of the following:
a. Bladder tumors and tumors of the collecting systems
b. Uterine tumors, especially carcinoma of the cervix
c. Retroperitoneal tumors (rare), including lymphoma, sarcomas, and metastatic tumors
d. Intrinsic renal tumors (rare)
e. Retroperitoneal fibrosis, including that induced by irradiation, drugs (busulfan), carcinoid tumors (especially rectal), Gardner syndrome (intestinal polyposis), or desmoplastic reactions to metastases
f. Blood clots within the collecting system or bladder from bleeding
g. Renal papillary necrosis
h. Nephrolithiasis
i. Stone and/or crystal accumulations from high production or excretion of uric acid
j. Some medications in rare cases may crystallize from supersaturation of the agent and become the primary component of stones. Drugs that induce calculi include magnesium trisilicate, ciprofloxacin, sulfa medications, triamterene, indinavir, and ephedrine (alone or in combination with guaifenesin).
2. Outlet obstruction of the urethra. Causes include primary cancer of the prostate, urethra, cervix, ovary, bladder, or endometrium. Metastases from the lung, gastrointestinal tract, breast, and melanoma to the pelvic organs, prostate, or urethra are rare causes of this complication.
B. Diagnosis
1. Symptoms are often absent or insidious in onset. Anuria is highly suggestive, but partial high-grade obstruction of ureters can occasionally cause renal failure with a normal urine volume. A variable urine output or overflow incontinence causing dribbling (and the strong smell of urine during physical examination) suggests bladder outlet obstruction.
2. Physical findings are those of the underlying disease. Dullness to percussion in the suprapubic region suggests a mass or distended bladder.
3. Ultrasonography may show hydronephrosis. However, acute obstruction or chronic obstruction wherein the collecting system is encased in tumor may show minimal abnormalities. A normal-appearing but full collecting system in an oliguric patient suggests obstruction. Blockage of only one kidney may be less severe. In some cases, ultrasound may miss obstruction, especially when ECV and urine volume are low.
4. Postvoid residual urine determination is often useful in evaluating for outlet obstruction from urethral swelling, stenosis, or scarring; benign prostatic hypertrophy in the male or an ovarian mass in the female patient; or other urologic disease that may be precipitated by medications or not be apparent. A high clinical index of suspicion and brief trial of urethral catheterization (Foley or red Robinson catheter) with significant urine volume and improvement in renal function are gratifying to the patient and clinician alike.
5. Cystoscopy demonstrates bladder outlet obstruction, shows the extent of bladder tumors, and permits retrograde ureterography, which may demonstrate ureteral stenosis or blockage of the ureterovesicular junction. Once again, this procedure can be not only diagnostic but also therapeutic for the cancer patient with renal failure.
C. Management
1. Obstruction of the urinary tract is accompanied by infection and in some cases renal calculi (i.e., struvite/magnesium ammonium phosphate, uric acid stones). Obstruction is a medical emergency requiring immediate diagnosis, treatment, and management. As in prerenal failure, postrenal obstruction, if not corrected, can lead to ARF syndrome and is also a cause of CKD.
2. Stones may pass spontaneously or can be removed by shock lithotripsy or by one of several available urologic procedures.
3. Blood clots in the collecting system will lyse spontaneously; larger clots in the bladder should be removed by continuous bladder irrigation and/or cystoscopy.
4. Retroperitoneal fibrosis may be treated by percutaneous nephrostomies or by surgical release of the involved ureters.
5. Obstructing lymphomas are usually successfully managed with chemotherapy, with or without focal radiation therapy.
6. Solid tumors usually require percutaneous catheter placement under combined ultrasound and fluoroscopic guidance. Stents placed from below are less commonly used. Systemic chemotherapy may be considered for responsive tumors. High-dose pelvic irradiation may be considered as an alternative, as may diverting ureteral surgery. Most patients with pelvic tumors causing obstruction, however, are at an advanced stage of disease; therapy, including percutaneous drainage of the renal pelvis, must be carefully considered in light of the potential for palliation, the extent of disease, and the overall prognosis.
IV. DIRECT RENAL TUBULAR DAMAGE CAUSING RENAL FAILURE
A. Acute renal failure may have an abrupt onset immediately after renal insult (e.g., radiocontrast administration, hyperuricemia after tumor lysis, cholesterol embolization after intravascular procedures). ARF may also arise more insidiously over days to weeks as an indirect consequence of malignancy (e.g., hypercalcemia, myeloma kidney resulting from deposits of Bence-Jones proteins) or therapy (e.g., interstitial nephritis after administration of certain therapeutic agents).
1. Oliguria is often present in more severe and dramatic episodes of ARF; in this case, laboratory parameters in Table 31.1 may be useful in distinguishing it from prerenal failure. Most causes of ARF and many patients with ARF, however, present with normal or nearly normal urine volumes.
2. Oliguria is defined as >400 to 500 mL/24 hours. These “magical numbers” are not arbitrary but rather based upon renal physiology. Since 600 mOsm of solute need to be excreted each day, and the maximal concentrating ability of the kidney is 1,200 mOsm, a minimum of 400 to 500 mL of urine needs to be excreted each day to excrete these solutes. Also called “nonoliguric” renal failure, a normal or higher urinary output in ARF is typically related to less severe renal failure. Despite the reduction in GFR and inability to remove adequate metabolic waste products, kidney tubular cells increase fractional excretion of water and maintain what appears to be a normal urine volume, often fooling the patient and clinical staff into complacency despite a marked reduction in GFR and highly abnormal laboratory markers of renal function.
