Authors: Macfarlane, Michael T.
Title: Urology, 4th Edition
Copyright 2006 Lippincott Williams & Wilkins
> Table of Contents > Part Two - Selected Topics > Chapter 30 - Renal Failure
Acute Renal Failure
Acute renal failure (ARF) is a condition of abrupt deterioration in renal function as evidenced by increasing blood urea nitrogen (BUN) and creatinine and usually decreased urine output. Approximately half of all cases occur in the surgical setting, and early recognition can minimize the extent of renal injury. The following is a brief review of the three major classifications of acute renal failure.
Prerenal azotemia is the direct result of inadequate renal perfusion. If the reason for poor perfusion can be rapidly reversed, resolution of the problem can usually be expected. However, prolonged low-flow states can produce an intrinsic ischemic injury to the kidney [i.e., acute tubular necrosis (ATN)].
Causes of Prerenal Azotemia
Volume depletion (hemorrhage, dehydration)
Low cardiac output (congestive heart failure, cardiogenic shock, tamponade)
Renal artery (stenosis, occlusion, vasoconstriction)
Systemic vasodilatation (sepsis, anaphylaxis, overdose)
Obstruction to urine flow can occur anywhere in the urinary tract. Proximal to the obstruction, pressures within the collecting system and renal tubules will increase. Ultimately renal injury will result because of cellular atrophy and necrosis if the obstruction to urine flow is not relieved. Recovery of some renal function can generally be expected in cases of complete unilateral ureteral obstruction if flow is restored within 6 weeks.
Causes of Urinary Obstruction
Bladder outlet (benign prostatic hyperplasia, strictures, bladder-neck contracture, stones, foreign body, tumor, blood clots, etc.)
Ureters (stones, intrinsic and extrinsic tumors, retroperitoneal fibrosis, papillary necrosis, ureteropelvic junction obstruction)
Acute parenchymal renal failure is the result of tubular cell damage from hypoperfusion, nephrotoxic injury, or an inflammatory process.
Causes of Intrinsic Parenchymal Renal Disease
ATN can be conveniently divided into three phases: (a) onset, (b) oliguric, and (c) postoliguric. The oliguric period (urine output <500 mL/24 hours) typically lasts 10 to 14 days; however, it may be as brief as 2 days or as long as 6 to 8 weeks. A nonoliguric ATN can occur particularly when secondary to nephrotoxic injury such as aminoglycosides or radiographic contrast agents. Causes of ATN include the following:
Ischemic injury from renal hypoperfusion (hypotensive episodes, cardiogenic or septic shock, etc.) is the most common cause of ATN in hospitalized patients.
Nephrotoxins [aminoglycosides, anesthetics, iodinated contrast media, nonsteroidal antiinflammatory drugs (NSAIDs)].
Hemoglobinuria or myoglobinuria (intravascular hemolysis or rhabdomyolysis).
Acute glomerular nephritis urinalysis is important [proteinuria, hematuria, and red blood cell (RBC) casts].
Acute interstitial nephritis sterile pyuria, white blood cell (WBC) casts, and eosinophiluria, most often caused by drugs [NSAIDs, percutaneous nephrostolithotomy (PCN), sulfonamides, cimetidine, allopurinol, ciprofloxacin].
Evaluation of Acute Renal Failure
The workup of a patient with sudden elevation of BUN and creatinine with or without decreased urine output requires a prompt, systematic approach to exclude any reversible pathophysiologic states and to remove any potentially nephrotoxic agents. Prerenal and postrenal causes must be excluded before diagnosing intrinsic renal disease.
Evaluate Circulatory System
Measure heart rate, blood pressure, postural hypotension, jugular venous distention, central venous pressures, and cardiac output (Swan-Ganz catheter if necessary), and listen to the chest for evidence of heart failure.
Check Volume Status
Assess weights, input/output records, skin turgor, mucous membranes, recent surgery, gastrointestinal bleeding, urine specific gravity (usually >1.015 1.020) and/or osmolality, BUN/creatinine ratio (>20:1), spot urine sodium (<5 mEq/L), and fractional excretion of sodium.
Urinalysis is typically unremarkable.
Evaluate Renal Vasculature
Obtain diethylene triamine pentaacetate (DTPA) renal scan, arteriography, or venography.
Place a Foley catheter or irrigate existing catheter.
Perform renal ultrasound or stone protocol computed tomography (CT) and retrograde urograms.
Intrinsic Renal Injury
The urinary sediment will typically show renal tubular cell casts during the early stages of ATN. Urine specific gravity is usually fixed at 1.010 to 1.012, and the urinary sodium concentration is greater than 30 to 40 mEq/L. Proteinuria is observed with glomerular disease and to a lesser extent with interstitial disease.
Look for periods of hypotension (e.g., recent surgery or septic or cardiogenic shock).
Carefully check for medications that can cause ATN (e.g., aminoglycoside, antibiotics, recent radiographic contrast studies) or interstitial nephritis [e.g., sulfa drugs, penicillin, furosemide, hydrochlorothiazide (HCTZ), dilantin] or medications that exacerbate prerenal azotemia (e.g., prostaglandin inhibitors, NSAIDs).
Hemoglobinuria or Myoglobinuria
Look for recent trauma, burns, or surgery.
Management of Acute Renal Failure
Reverse any pathophysiologic states restore volume, support blood pressure, and treat sepsis or cardiac failure.
Relieve any urinary obstruction ensure adequate drainage of urinary tract as needed (e.g., Foley catheter, suprapubic tube, ureteral stents, or nephrostomy tubes). Monitor and treat postobstructive diuresis.
Remove any nephrotoxic agents; stop any nephrotoxic drugs (i.e., change antibiotics as needed, discontinue NSAIDs).
Restrict sodium, potassium, and fluid intake.
Minimize risk of infectious complications avoid use of Foley catheters or central venous lines if possible.
Convert to nonoliguria if possible persistent oliguria after correction of pre- and postrenal causes is strong evidence of intrinsic renal failure. A trial of furosemide or an osmotic diuretic may convert the patient from oliguric to nonoliguric renal failure. This will make patient management easier and decrease the frequency and duration of dialysis during the recovery phase.
Support with dialysis as needed.
Indications for Dialysis in Acute Renal Failure
Volume overload manifested by pulmonary edema and decreased po2 unresponsive to diuretics
Hyperkalemia or marked acidosis or both in the setting of volume overload
Uremic manifestations (e.g., change in mental status, seizures, cardiac complications, gastrointestinal bleeding)
BUN greater than 100 or creatinine greater than 10 without clear prospects for early recovery
Chronic Renal Failure
Chronic renal failure (CRF) is caused by a spectrum of diseases resulting in progressive irreversible loss of functioning nephrons, ultimately leading to end-stage renal disease (ESRD) requiring
Uremic symptoms of CRF rarely occur until the glomerular filtration rate (GFR) is less than 25 mL/minute (25% of normal) or the serum creatinine is more than 3 to 4 mg/dL. A wide variety of systemic symptoms involving all organ systems can be seen. This multisystem involvement can make management of these patients quite difficult.
Hyperphosphatemia is an early and cardinal manifestation of ESRD and is in itself responsible for many secondary stigmata of the disease. Some evidence suggests that reducing dietary phosphate intake can slow progression of CRF.
Hyperkalemia is generally not a problem in CRF until the GFR decreases to less than 5 mL/minute.
A positive anion-gap metabolic acidosis occurs because of the impaired ability of the kidneys to produce ammonia (if GFR is <25 mL/minute).
Gastrointestinal involvement includes nausea, vomiting, anorexia, a metallic taste, uremic stomatitis, glossitis, esophagitis, gastritis, peptic ulcer disease from gastric hypersecretion, colitis, diverticulosis, constipation, and fecal impaction. Upper and lower gastrointestinal bleeding is a not uncommon complication.
A normochromic normocytic anemia secondary to marrow suppression and decreased renal erythropoietin occurs when the BUN exceeds 60 to 80 mg/dL or the creatinine increases to greater than 2 to 3 mg/dL. Thrombocytopenia and platelet dysfunction also occur. Patients undergoing surgery (especially transurethral resection of the prostate) are at increased risk for bleeding complications. Dialysis helps to reverse these problems partially.
Uremic peripheral neuropathy and encephalopathy can be controlled with adequate dialysis or transplantation.
CRF is associated with an increased incidence and severity of atherosclerosis. Derangements in protein and lipid metabolism with hypertriglyceridemia and prolonged hypertension are considered to be major factors involved.
The abnormal bone metabolism found in CRF has a multifactorial origin. First, hyperphosphatemia, due to reduced GFR, directly reduces serum ionized calcium. This reduction stimulates parathyroid hormone (PTH) secretion (secondary hyperparathyroidism) and consequent bone resorption. Second, loss of renal parenchyma results in decreased renal conversion of 25-hydroxy-D3 to the active 1,25-dihydroxy-D3. Additionally, hyperphosphatemia inhibits this synthesis. Third, chronic metabolic acidosis is buffered by bone with consequent demineralization. Patients will have bone pain, particularly arthralgias, and pleuritic chest-wall pain. Management is directed toward control of hyperphosphatemia by limiting dietary intake of phosphorus to less than 1 g/day. Only after serum phosphorus levels have been reduced can supplemental calcium and the active metabolite of vitamin D [1,25-dihydroxycholecalciferol (Rocaltrol)] be given. Parathyroidectomy is rarely necessary.
Glucose intolerance secondary to peripheral insulin resistance is common in CRF and generally does not require treatment.
Sexual dysfunction is a prominent component of renal failure. Loss of libido and development of impotence occurs in more than 50% of patients. Serum testosterone levels are usually low. Women commonly have loss of libido with dysmenorrhea and amenorrhea.
The general management of patients with CRF centers on slowing the progression of functional renal deterioration. No
Fortunately most symptomatic manifestations of CRF and ESRD are greatly improved by dialysis.
Principles of Hemodialysis
The basic elements of hemodialysis involve blood flow on one side of a semipermeable membrane and the dialysate, an osmotically balanced solution of electrolytes and glucose in water, on the other side of the membrane. Primarily small-molecular-weight molecules passively diffuse down concentration gradients across the membrane, which accounts for the clearance effect. Additionally, a positive blood pressure on one side of the membrane allows mass fluid transfer known as ultrafiltration. By these two mechanisms of clearance and ultrafiltration, the dialyzer can remove toxic waste products from the blood and maintain fluid homeostasis. Serum electrolytes can be kept within limits by carefully adjusting their concentration in the dialysate. The patient's fluid status can be controlled by manipulating the positive and negative transmembrane pressures to remove just as much volume as needed.
Maintenance of proper access for hemodialysis can be a major challenge for both the surgeon and the patient. The various options available must be understood.
Temporary access is often necessary for immediate urgent dialysis of patients with life-threatening situations.
Percutaneous transvenous catheters using the Seldinger technique and an internal jugular or femoral approach is generally the preferred method. A dual-lumen coaxial catheter with separate inflow and outflow works well. Patency is maintained by continuous or intermittent flushing with heparinized saline. These catheters can be maintained for 2 to 3 weeks in the internal jugular vein.
External Scribner shunt this is still occasionally used when efficient high-flow dialysis is needed or when the percutaneous transvenous approach is contraindicated.
Maintenance access is provided by a subcutaneous arteriovenous (AV) fistula (Cimino) with endogenous vein or prosthetic graft material. External shunts (Scribner) have been generally abandoned for long-term access.
Endogenous AV fistula the classic choice is the endogenous radial-cephalic side-to-side AV fistula, described by Cimino in 1966, in the nondominant arm. Three-year patency rates of almost 80% have been reported. Failure is usually from thrombosis or aneurysms.
Prosthetic AV fistula use of a vascular prosthesis [6-mm polytetrafluoroethylene (PTFE)] is necessary in patients without suitable endogenous veins available. Infection is the most common cause of failure.
In general, the predialysis BUN ranges between 50 and 200 mg/dL, and the creatinine, from 5 to 25 mg/dL, and both can be expected to be reduced by about 50% during dialysis. A typical stable patient will require dialysis 3 times per week for a total of 12 to 18 hours.
Complications of Hemodialysis
Patients are generally kept as close to dry weight as possible. The potential for major fluid shifts must be strictly controlled.
Systemic heparinization can result in major bleeding complications, particularly gastrointestinal. Do not perform diagnostic or therapeutic procedures on recently dialyzed patients (e.g., lumbar puncture).
Rapid Osmotic Changes
Rapid osmotic changes can produce significant central nervous system dysfunction from cerebral edema (referred to as the dialysis disequilibrium syndrome).
Hemolysis can result from a failure to maintain proper dialysate osmolarity.
Membrane rupture within the dialyzer can result in significant blood loss if not recognized promptly.
Air embolus can occur when administering medications or solutions into the arterial line.
The principles of peritoneal dialysis are similar to those of hemodialysis. Dialysate is placed within the peritoneal cavity for specific lengths of time (dwell time), and the peritoneum acts as the semipermeable membrane separating the dialysate and blood. It can be performed in the short term by using a simple straight peritoneal catheter or on a long-term basis, which requires placement of a Tenckhoff catheter. An advantage of peritoneal dialysis is that it can provide more even control of hyperkalemia without the hyperdynamic effects of hemodialysis. Peritonitis is the most common complication of peritoneal dialysis.
Indications for Peritoneal Dialysis
Patients without vascular access
Patients with contraindications for heparinization (e.g., bleeding diathesis)
Patients with unstable coronary artery disease or low ejection fractions who may not tolerate hypotensive episodes
Contraindications for Peritoneal Dialysis
Recent abdominal surgery
Compromised respiratory function
Long-term Peritoneal Dialysis
Prolonged peritoneal dialysis is performed either intermittently with 10- to 14-hour dwell times, three times per week, or almost continuously by the patient changing the dialysate four or five
Renal transplantation is clearly the preferred treatment for patients with permanent renal failure (GFR, <10 mL/minute, or serum creatinine, >8 mg/dL). It provides significantly longer survival over dialysis and a better quality of life. Because of the increasing numbers of patients requiring transplantation and the long waits for cadaveric kidneys, living related-donor renal transplantation is increasing. Living related donors have a better probability of graft survival and can allow patients to have preemptive renal transplantation before ever needing to go on dialysis.
Contraindications to Transplantation
Recent malignant disease
Presensitization to donor class I human leukocyte antigen (HLA) antigens
Pretransplant Blood Transfusions
Data have paradoxically shown that nontransfused patients have the highest risk of graft failure and that performing up to 14 transfusions before transplantation appears to impart a dose-related increase in cadaveric graft survival.
Living Related Donors
Living related and unrelated donors are an increasing source of kidney transplants in the United States because of superior graft survival and a shortage of cadaveric kidneys. Donors are expected to be in perfect physical and mental health with negative blood and tissue cross-matches. Compatibility by mixed lymphocyte culture is demonstrated by negative HLA antigenic stimulation. Graft success can be improved between responders by using donor-specific transfusions.
Cadaver donors are generally persons between ages 2 and 60 years without evidence of significant hypertension, atherosclerosis, renal disease, malignancy, or infection. Blood and urine cultures should be negative, with creatinine less than 2 mg/dL, and hepatitis B antigen (HBsAg) negative. The heart must be pumping, and no longer than 10 minutes of warm ischemia should exist. Blood pressure (systolic blood pressure >100 mm Hg) and urine output (>100 mL/hour) should be maintained by volume expansion, diuretics, and, if necessary, vasopressors as needed (dopamine preferred). After removal, kidneys are flushed with ice-cold Collins' solution and stored in ice slush (for 24 48 hours) or preserved by pulsatile perfusion (for 48 72 hours).
A single chromosomal complex of closely linked genes codes for a group of antigens that have been shown to represent the strongest immunologic barrier to transplantation. These major histocompatibility antigens are the product of two sets of HLA genes on homologous paired chromosomes, one set or haplotype from each parent. The HLA gene products (cell-surface antigens) from each haplotype are classified as class I serologically defined HLA-A, -B, and -C and the class II HLA-DR (D-related) antigens, the major initiator of the mixed lymphocyte reaction (MLR). The paternal and maternal alleles from each of the four HLA loci are expressed in a codominant fashion. Matching for major HLA antigens among closely related living donors has been shown to predict results superior to those with cadaveric donors because of compatibility among other less important gene products of the major histocompatibility complex (MHC) region. HLA type matching for cadaveric transplants is less successful because of the greater variation among the minor transplantation antigens, and its usefulness has been questioned. However, many centers still attempt to use a four-antigen match, referring to two A and two B locus antigen matching, in addition to testing for preexisting anti-HLA antibodies by the lymphocytotoxic cross-match. This improves the statistical probability of identical HLA-C and -D locus antigens, but it is not a certainty. The MLR test for HLA-DR antigens takes 6 to 8 days and is therefore not clinically useful for cadaveric transplants. Serologic typing for class II antigens can provide an approximation of mixed lymphocyte culture reactivity.
Living related transplants between HLA identical siblings (two-haplotype match) yield the highest 1-year graft survival
The ABO (H) blood group antigens are expressed on vascular endothelium and therefore must be matched for renal transplantation. However, Rh antigens are not expressed on nucleated cells and need not be of concern.
The allograft response is directed primarily against mismatched HI.A antigens and is T cell dependent. Class II HLA alloantigens activate helper T lymphocytes, resulting in release of macrophage-stimulating lymphokine (MSL) and expression of interleukin-1 (IL-1) and -2 (IL-2) receptors on helper T cells. Class I HLA alloantigens activate cytotoxic T lymphocytes to form IL-2 receptors. Stimulated macrophages release IL-1, which in turn causes the release of IL-2 from helper T cells. It is the IL-2 that then causes the specific clonal proliferation of activated helper and cytotoxic T cells. Immunosuppressive therapies are directed toward interfering with one or more of these steps in the allograft response.
Corticosteroids inhibit IL-2 dependent T-cell proliferation by preventing monocytes from releasing IL-1 that is necessary for release of IL-2. They also have an inhibitory effect on neutrophilic inflammatory response.
Azathioprine is a mainstay of therapy for acute rejection and functions by inhibiting the multiplication of rapidly dividing immunologically competent lymphoid cells. Its major toxic side effect, myelosuppression, is best guarded against by monitoring the peripheral leukocyte count.
Mycophenolate Mofetil (CellCept)
Mycophenolate is a product of Penicillium species, and its mode of action is similar to that of azathioprine. Its main advantage over azathioprine is less bone marrow suppression.
Cyclosporine (Sandimmune or Neoral)
Cyclosporine (CsA) acts primarily by the specific and reversible inhibition of activated T-cell proliferation and by blocking the
Tacrolimus is a macrolide antibiotic similar to CsA in its activity. It can cause nephrotoxicity, neurotoxicity, and a drug-induced diabetes mellitus. It is used primarily in women because of the lack of associated hirsutism.
Antithymocyte -globulin (ATG) is the pooled polyclonal globulin fraction of sera from horses immunized to human thymocytes (nonspecific antibodies are absorbed out). ATG has shown itself to be a potent suppressor of cell-mediated immunity and allograft response. It is used either for early immunosuppression or to treat acute rejection. Anaphylactoid responses occur, and it is given preferentially via a central line or AV fistula.
Monoclonal Antibodies (OKT3)
Monoclonal anti T-cell antibodies produced from murine hybridomas to the T3 antigen of T lymphocytes have been successfully used for the treatment of acute rejection episodes. Again, anaphylactoid reactions can occur, and most patients will develop antimouse antibodies, making it useful for only one course of treatment.
The usual preoperative laboratory tests, including a urine culture, chest radiograph, and electrocardiogram (ECG), should be obtained. Most patients will require preoperative dialysis. Immunosuppressive medications should be started preoperatively as dictated by the prescribed protocol. Prophylactic antibiotics should be given on call to the operating room. A living related donor should be kept well hydrated with optimal urine output. An 18 F Foley catheter is placed in the recipient after induction of anesthesia. Crystalloids without potassium should be given to the
Early oligoanuria after renal transplantation requires immediate evaluation.
Check Foley catheter for obstruction hand irrigate.
Check for signs of dehydration and central venous pressure. Give fluid challenge if suggestive (500 mL normal saline over a 1-hour period).
Check output of surgical drains for possible urine leak.
Perform MAG3 or DTPA renal scan to evaluate renal perfusion.
Perform Doppler ultrasound of graft to rule out obstructive uropathy, to assess blood flow to the graft, and to evaluate for signs of rejection (e.g., enlargement from edema, indistinct corticomedullary junction, and loss of central renal-sinus fat echo).
Perform renal biopsy when poor function persists or diagnosis remains in doubt.
Acute Tubular Necrosis
ATN is the most common cause of early oliguria or anuria after transplantation and is the result of ischemic insult to the kidney. Recovery will generally occur within 3 to 6 weeks; however, a renal biopsy may be helpful to rule out rejection. The diagnosis is made primarily by exclusion.
Cyclosporine or Tacrolimus Nephrotoxicity
Cyclosporine or tacrolimus nephrotoxicity produces a difficult diagnostic dilemma in evaluating poor function in the postoperative period. Differentiating among ATN, acute rejection, and drug-induced nephrotoxicity is not easy. It has no pathognomonic features and does not correlate with drug blood levels. Diagnosis is usually made by a process of exclusion, often necessitating renal biopsy. Patients are managed by switching to azathioprine.
Hyperacute or Accelerated Rejection.
Hyperacute rejection is generally an irreversible process that begins within minutes to hours after transplantation and is the result of presensitization of the recipient with cytotoxic antibodies to donor ABO or HLA antigens.
Acute rejection occurs within 3 months after transplantation and is clinically characterized by fever, swelling, and tenderness over the graft, with decreased function and urine output. Hypertension also may be present.
Management of Acute Rejection
Steroid pulses methylprednisolone (Solu-Medrol) 1 g IV qd 3 days
ATG antithymocyte globulin (Thymoglobulin)
OKT3 monoclonal anti T-cell antibodies
Chronic rejection results in a gradual deterioration of function, months to years after transplantation, without clear evidence of a rejection episode.
Vascular complications occur infrequently after transplantation; however, when they occur, they can be disastrous and must be recognized immediately.
Arterial occlusion can occur within the first few postoperative days. A DTPA renal scan can help make the diagnosis. Nephrectomy is usually necessary; salvage is rare.
Acute hemorrhage occurring within the first few hours after transplantation can be from dehiscence of a vascular suture line or from undetected or poorly ligated vessels. Late hemorrhage is most often from a pseudoaneurysm or a mycotic aneurysm. Transplant nephrectomy is usually necessary.
Transplant artery stenosis may produce uncontrollable hypertension months to years after transplantation. Surgical correction is often possible.
Thrombophlebitis is a relatively uncommon occurrence; however, if it is suspected, ultrasound or phlebography should be performed.
Graft rupture usually occurs as spontaneous severe pain and shock from massive life-threatening hemorrhage. It is believed to be caused by acute rejection and ischemia. Immediate nephrectomy is indicated.
Lymphatic drainage from the area of dissection may occasionally be excessive, resulting in leakage from the incision or surgical
Decreased urine output in the immediate postoperative period may be due to a blood clot in the ureter or bladder. Irrigation of the bladder should be attempted. Mechanical obstruction at the ureterovesical anastomosis is common and can be caused by edema at the anastomosis or infarction of the distal ureter. Ureteral ischemia also can result in urinary extravasation with fever and graft tenderness. Ultrasound will usually make the diagnosis. Prompt and aggressive open surgical intervention is indicated.
Infections are the most common and life-threatening complications for the transplant recipient. Immunosuppressive therapy coupled with leukopenia, hyperglycemia, and azotemia markedly increases the risk of serious complicated infections. Bacterial sepsis is most common; however, opportunistic infections such as those with cytomegalovirus (CMV), Pneumocystis carinii, or Candida albicans are major problems. Opportunistic infections are rare in the first posttransplant month. Treatment of infections should be aggressive with intravenous antibiotics. Cyclosporine, tacrolimus, or azathioprine should be discontinued during life-threatening infections, and corticosteroids should be given at physiologic doses.
Urinary Tract Infections
Urinary tract infections are a common source of bacterial sepsis in the posttransplant patient. Use of prophylactic antibiotics and early removal of the Foley catheter can help lessen their incidence.
Wound infection must always be suspected in the posttransplant patient with high fever. The incision will often look benign, even in the face of a grossly purulent abscess. Do not underestimate the masking effect of immunosuppressive agents.
Pulmonary infection with gram-negative bacteria, fungi, P. carinii, and CMV usually appears with fever and pulmonary infiltrates.
Meningitis will often be masked by immunosuppressive therapy. Patients with unexplained fever, dull headache, photophobia, or mental-status changes should undergo lumbar puncture. Look for Listeria, Candida, Cryptococcus, and Aspergillus.