Smith’s General Urology - part 8 pdf

528 / CHAPTER 32 The formation of cysts on the cortex of the kidney is thought to result from failure of union of the collecting tubules and convoluted tubules of some nephrons. Intrare- nal cysts may be of a proximal or a distal luminal type, dif- fering on analysis by their cyst electrolyte content. This is important if one or more of these cysts become infected, and an antibiotic (with varying cyst-type penetrance) is chosen. New cysts do not form, but those present enlarge and, by exerting pressure, cause destruction of adjacent renal tissue. The incidence of cerebral vessel aneurysms and cardiac valve prolapse is higher than normal. Cases of polycystic disease are discovered during the investigation of hypertension, by diagnostic study in patients presenting with pyelonephritis or hematuria, or by investigation of families of patients with known polycystic disease. At times, flank pain due to hemorrhage into a cyst occurs. Otherwise the symptoms and signs are those com- monly seen in hypertension or renal insufficiency. On physical examination, the enlarged, irregular kidneys are often easily palpable. The urine may contain leukocytes and erythrocytes. With bleeding into the cysts, there may also be bleeding into the urinary tract. The blood chemistry findings reflect the degree of renal insufficiency. Examination by sonogra- phy, CT scan, or x-ray shows the enlarged kidneys, and urography demonstrates the classic elongated calyces and renal pelves stretched over the surface of the cysts. No specific therapy is available, and surgical interfer- ence is only indicated to decompress very large cysts in patients with severe pain. Patients with polycystic kidney disease live in reason- able comfort with slowly advancing uremia. Both hemodi- alysis and renal transplantation extend the life of these patients. Nephrectomy is indicated only in patients with recurrent infections, severe recurrent bleeding, or markedly enlarged kidneys. B. CYSTIC DISEASE OF THE RENAL MEDULLA 1. Medullary cystic disease— Medullary cystic disease is a familial disease that may become symptomatic during adolescence. Anemia is usually the initial manifestation, but azotemia, acidosis, and hyperphosphatemia soon become evident. Urine findings are not remarkable, although there is often an inability to concentrate and renal salt wasting often occurs. Many small cysts are scat- tered through the renal medulla. Renal transplantation is indicated by the usual criteria. 2. Medullary sponge kidney— Medullary sponge kid- ney is asymptomatic and is discovered by the characteristic appearance of tubular ectasia in the urogram. Enlargement of the papillae and calyces and small cavities within the pyramids is demonstrated by the contrast media in the excretory urogram. Many small calculi often occupy the cysts, and infection may be troublesome. Life expectancy is not affected and only therapy for ureteral stone or for infection is required. ANOMALIES OF THE PROXIMAL TUBULE Defects of Amino Acid Reabsorption A. CONGENITAL CYSTINURIA Increased excretion of cystine results in the formation of cystine calculi in the urinary tract. Ornithine, arginine, and lysine are also excreted in abnormally large quantities. There is also a defect in absorption of these amino acids in the jejunum. Nonopaque stones should be examined chemically to provide a specific diagnosis. Treatment goals include a large fluid intake and keep- ing the urine pH above 7 by giving sodium bicarbonate and sodium citrate plus acetazolamide at bedtime to ensure an alkaline night urine. In refractory cases, a low- methionine (cystine precursor) diet may be necessary. Pen- icillamine has proved useful in some cases. B. AMINOACIDURIA Many amino acids may be poorly absorbed, resulting in unusual losses. Failure to thrive and the presence of other tubular deficits suggest the diagnosis. There is no treatment. C. HEPATOLENTICULAR DEGENERATION (WILSON’S DISEASE) In this congenital familial disease, aminoaciduria and renal tubular acidosis (RTA) are associated with cirrhosis of the liver and neurologic manifestations. Hepatomegaly, evi- dence of impaired liver function, spasticity, athetosis, emo- tional disturbances, and Kayser-Fleischer rings around the cornea constitute a unique syndrome. There is a decrease in synthesis of ceruloplasmin, with a deficit of plasma ceru- loplasmin and an increase in free copper that may be etio- logically specific. Penicillamine is given to chelate and remove excess copper. Edathamil (EDTA) may also be used to remove copper. D. MULTIPLE DEFECTS OF TUBULAR FUNCTION (DE TONI-FANCONI-DEBRÉ SYNDROME) Aminoaciduria, phosphaturia, glycosuria, and a variable degree of RTA characterize this syndrome. Osteomalacia is a prominent clinical feature; other clinical and laboratory manifestations are associated with specific tubular defects described previously. Treatment consists of replacing cation deficits (espe- cially potassium), correcting acidosis with bicarbonate or citrate, replacing phosphate loss with isoionic neutral phos- phate (mono- and disodium salts) solution, and ensuring a DIAGNOSIS OF MEDICAL RENAL DISEASES / 529 liberal calcium intake. Vitamin D is useful, but the dose must be controlled by monitoring levels of serum calcium and phosphate. E. DEFECTS OF PHOSPHORUS & CALCIUM REABSORPTION Several sporadic, genetically transmitted, and acquired dis- orders are grouped under this category and are character- ized by persisting hypophosphatemia because of excessive phosphaturia and an associated metabolic bone disorder, rickets in childhood, and osteomalacia in adulthood. Response to vitamin D therapy (1,25,-dihydroxycholecal- ciferol, the active analog of vitamin D) is variable. F. DEFECTS OF GLUCOSE ABSORPTION (RENAL GLYCOSURIA) Renal glycosuria results from an abnormally poor ability to reabsorb glucose and is present when blood glucose levels are normal. Ketosis is not present. The glucose tolerance response is normal. There is no treatment for renal glyco- suria, just reassurance. G. DEFECTS OF BICARBONATE REABSORPTION Proximal RTA, type II, is due to reduced bicarbonate reclamation in the proximal tubule, with resultant loss of bicarbonate in the urine and decreased bicarbonate con- centration in extracellular fluid. There are increased K + losses into the urine and retrieval of Cl - instead of HCO 3 . The acidosis is therefore associated with hypoka- lemia and hyperchloremia. Transport of glucose, amino acids, phosphate, and urate may be deficient as well (Fanconi syndrome). ANOMALIES OF THE DISTAL TUBULE Defects of Hydrogen Ion Secretion & Bicarbonate Reabsorption (Classic Renal Tubular Acidosis, Type I) Failure to secrete hydrogen ion and to form ammonium ion results in loss of “fixed base” sodium, potassium, and calcium. There is also a high rate of excretion of phos- phate. Vomiting, poor growth, and symptoms and signs of chronic metabolic acidosis are accompanied by weakness due to potassium deficit and bone discomfort due to osteomalacia. Nephrocalcinosis, with calcification in the medullary portions of the kidney, occurs in about one-half of cases. The urine is alkaline and contains larger than nor- mal quantities of sodium, potassium, calcium, and phos- phate. An abnormality in urinary anion gap (U.Na + + U.K + – U.Cl – ) is noted (low), which is associated with the reduced NH 4 + production. This abnormality differentiates this condition from type II RTA and from the metabolic acidosis seen with diarrhea. The blood chemistry findings are those of metabolic acidosis with low serum potassium. Treatment consists of replacing deficits and increasing the intake of sodium, potassium, calcium, and phospho- rus. Sodium and potassium should be given as bicarbonate or citrate. Additional vitamin D may be required. Excess Potassium Secretion (Potassium “Wastage” Syndrome) Excessive renal secretion or loss of potassium may occur in 4 situations: (1) moderate renal insufficiency with diminished H + secretion; (2) RTA (proximal and distal RTA); (3) hyperaldosteronism and hyperadrenocorti- cism; and (4) tubular secretion of potassium, the cause of which is unknown. Hypokalemia indicates that the defi- cit is severe. Muscle weakness and polyuria and dilute urine are signs attributable to hypokalemia. Treatment consists of correcting the primary disease and giving sup- plementary potassium. Reduced Potassium Secretion Reduced potassium secretion is noted in conditions in which extrarenal aldosterone is reduced or when intrare- nal production of renin (and secondary hypoaldoster- onism) occurs. The latter condition is termed RTA, type IV, and is associated with impaired H + and K + secretion in the distal tubule. Drug-induced interstitial nephritis, gout, and diabetes mellitus are clinical circumstances that may produce type IV RTA and resulting hyperkale- mia and mild metabolic acidosis. Treatment is to pro- mote kaliuresis (with loop diuretics) to prescribe potas- sium-binding gastrointestinal resins (Kayexalate), or to provide the patient with a mineralocorticoid, fludrocor- tisone acetate. Defects of Water Absorption (Renal Diabetes Insipidus) Nephrogenic diabetes insipidus occurs more frequently in males than females. Unresponsiveness to antidiuretic hor- mone is the key to differentiation from pituitary diabetes insipidus. In addition to congenital refractoriness to antidiuretic hormone, obstructive uropathy, lithium, methoxyflurane, and demeclocycline also may render the tubule refractory to vasopressin. Symptoms are related to an inability to reabsorb water, with resultant polyuria and polydipsia. The urine volume approaches 12 L/d, and osmolality and specific gravity are low. Treatment consists primarily of an adequate water intake. Chlorothiazide may ameliorate the polyuria; the mechanism of action is unknown, but the drug may act by increasing isosmotic reabsorption in the proximal segment of the tubule. 530 / CHAPTER 32 UNSPECIFIED RENAL TUBULAR ABNORMALITIES In idiopathic hypercalciuria, decreased reabsorption of cal- cium predisposes to the formation of renal calculi. Serum calcium and phosphorus are normal. Urine calcium excre- tion is high; urine phosphorus excretion is low. Micro- scopic hematuria may be present. See treatment of urinary stones containing calcium (Chapter 16). REFERENCES Adler S: Diabetic nephropathy: Linking histology, cell biology, and ge- netics. Kidney Int 2004;66:2095. Alric L et al: Influence of antiviral therapy in hepatitis C virus-associ- ated cryoglobulinemic MPGN. Am J Kidney Dis 2004;43:617. Appel GB et al: Membranoproliferative glomerulonephritis Type II (dense deposit disease): An update. J Amer Soc Neph 2005;16: 1392. Barratt J, Feehally J: IgA nephropathy. J Amer Soc Neph 2005;16: 2088. Braden GL et al: Tubulointerstitial diseases. Am J Kidney Dis 2005; 46:560. Buhaescu I et al: Systemic vasculitis: Still a challenging disease. Am J Kidney Dis 2005;46:173. Chesney R: The changing face of childhood nephrotic syndrome. Kid- ney Int 2004;66:1294. Flanc RS et al: Treatment of diffuse proliferative lupus nephritis: A meta-analysis of randomized controlled trials. Am J Kidney Dis 2004;43:197. Couser WG (guest editor): Frontiers in nephrology: Membranous nephropathy. J Amer Soc Neph 2005;16:1184. Ginzler EM et al: Mycophenolate mofetil or intravenous cyclophos- phamide for lupus nephritis. N Engl J Med 2005;353:2219. Grantham JJ: Advancement in the understanding of polycystic kidney disease: A system approach. Kidney Int 2003;64: 1154. Heering P et al: Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis. Am J Kidney Dis 2004;43:10. Hruska KA: Treatment of chronic tubulointerstitial disease: A new concept. Kidney Int 2002;61:1911. Imaging the Kidney-Radiologic Imaging 2006. (Excerpts) Nephron Clin Pract 2006;103:c19. Izzedine H et al: Oculorenal manifestations in systemic autoimmune diseases. Am J Kidney Dis 2004;43:209. Javaid B, Quigg RJ: Treatment of glomerulonephritis: Will we ever have options other than steroids and cytotoxics? Kidney Int 2005;67:1692. Nair R, Walker PD: Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA? Kidney Int 2006;69:1455. Noris M, Remuzzi G: Hemolytic uremic syndrome. J Amer Soc Neph 2005;16:1035. Perna A et al: Immunosuppressive treatment for idiopathic membra- nous nephropathy: A systematic review. Am J Kidney Disease 2004;44:385. Rosner MH, Bolton WK: Renal function testing. Am J Kidney Dis 2006;47:174. Rossert J: Drug-induced acute interstitial nephritis. Kidney Int 2001; 60:804. Tenenhouse HS, Murer H: Disorders of renal tubular phosphate trans- port. J Am Soc Neph 2003;14:240. Troyanov S et al: Renal pathology in idiopathic membranous nephrop- athy: A new perspective. Kidney Int 2006;69:1641. Wilmer WA et al: Management of glomerular proteinuria: A commen- tary. J Amer Soc Neph 2003;14:3217. 531 33 Oliguria; Acute Renal Failure William J.C. Amend, Jr., MD, & Flavio G. Vincenti, MD Oliguria literally means “reduced” urine volume—less than that necessary to remove endogenous solute loads that are the end products of metabolism. If the patient concentrates urine in a normal fashion, oliguria (for that person) is present at urine volumes under 400 mL/day, or approximately 6 mL/kg body weight. If the kidney con- centration is impaired and the patient can achieve a spe- cific gravity of only 1.010, oliguria is present at urine vol- umes under 1000–1500 mL/day. Acute renal failure is a condition in which the glomeru- lar filtration rate is abruptly reduced, causing a sudden retention of endogenous and exogenous metabolites (urea, potassium, phosphate, sulfate, creatinine, administered drugs) that are normally cleared by the kidneys. The urine volume is usually low (under 400 mL/day). If renal con- centrating mechanisms are impaired, the daily urine vol- ume may be normal or even high (high-output or nono- liguric renal failure). Rarely, there is no urine output at all (anuria) in acute renal failure. The causes of acute renal failure are listed in Table 33–1. Prerenal renal failure is reversible if treated promptly, but a delay in therapy may allow it to progress to a fixed intrinsic renal failure (eg, acute tubular necrosis). The other causes of acute renal failure are classified on the basis of their involve- ment with vascular lesions, intrarenal disorders, or postrenal disorders. PRERENAL RENAL FAILURE The term prerenal denotes inadequate renal perfusion or lowered effective arterial circulation. The most common cause of this form of acute renal failure is dehydration due to renal or extrarenal fluid losses from diarrhea, vomiting, excessive use of diuretics, and so on. Less common causes are septic shock, “third spacing” with extravascular fluid pooling (eg, pancreatitis), and excessive use of antihyper- tensive drugs. Heart failure with reduced cardiac output also can reduce effective renal blood flow. Careful clinical assessment may identify the primary condition responsible for prerenal renal failure, but many times several condi- tions can coexist. In the hospital setting, these circulatory abnormalities often lead to more fixed, acute renal failure (acute tubular necrosis). Acute reductions in glomerular filtration rate may also be noted in patients with cirrhosis (hepatorenal failure) or in patients taking cyclosporine, tacrolimus, nonsteroidal anti-inflammatory drugs, or angiotensin-converting enzyme inhibitors. It is felt that these conditions represent signifi- cant intrarenal hemodynamic functional derangements. In these clinical circumstances, the urinary findings may mimic prerenal renal failure, but the patient’s clinical assessment does not demonstrate the extrarenal findings seen in common prerenal conditions, as noted in the fol- lowing section. Improvements in glomerular filtration rate are usually noted after drug discontinuance or, in cases of hepatorenal renal failure, with management of the liver disease or liver transplantation. Clinical Findings A. SYMPTOMS AND SIGNS Except for rare cases with associated cardiac or “pump” failure, patients usually complain of thirst or of dizziness in the upright posture (orthostatic dizziness). There may be a history of overt fluid loss. Weight losses reflect the degree of dehydration. Physical examination frequently reveals decreased skin turgor, collapsed neck veins, dry mucous membranes, and, most important, orthostatic or postural changes in blood pressure and pulse. B. LABORATORY FINDINGS 1. Urine— The urine volume is usually low. Accurate assessment may require bladder catheterization followed by hourly output measurements (which will also rule out lower urinary tract obstruction; see discussion following). High urine specific gravity (>1.025) and urine osmolality >600 mOsm/kg) also are noted in this form of acute apparent renal failure. Routine urinalysis usually shows no abnormalities. 2. Urine and blood chemistries— The blood urea nitro- gen-creatinine ratio, normally 10:1, is usually increased with prerenal renal failure. Other findings are set forth in Table 33–2. Because mannitol, radiocontrast dyes, and diuretics affect the delivery and tubular handling of urea, sodium, and creatinine, urine and blood chemistry tests performed after these agents have been given to produce misleading results. 3. Central venous pressure— A low central venous pressure indicates hypovolemia. If severe cardiac failure is Copyright © 2008, 2004, 2001, 2000 by The McGraw-Hill Companies, Inc. Click here for terms of use. 532 / CHAPTER 33 the principal cause of prerenal renal failure (it is rarely the sole cause), reduced cardiac output and high central venous pressure are apparent. 4. Fluid challenge— An increase in urine output in response to a carefully administered fluid challenge is both diagnostic and therapeutic in cases of prerenal renal failure. Rapid intravenous administration of 300–500 mL of physiologic saline is the usual initial treatment. Urine out- put is measured over the subsequent 1–3 hours. A urine volume increase of more than 50 mL/h is considered a favorable response that warrants continued intravenous infusion. If the urine volume does not increase, the physi- cian should carefully review the results of blood and urine chemistry tests, reassess the patient’s fluid status, and repeat the physical examination to determine whether an additional fluid challenge (with or without furosemide) might be worthwhile. Treatment In states of dehydration, fluid losses must be rapidly cor- rected to treat oliguria. Inadequate fluid management may cause further renal hemodynamic deterioration and even- tual renal tubular ischemia (with fixed acute tubular necro- sis; see discussion following). If oliguria and hypotension persist in a well-hydrated patient, vasopressor drugs are indicated in an effort to correct the hypotension associated with sepsis or cardiogenic shock. Pressor agents that restore systemic blood pressure while maintaining renal blood flow and renal function are most useful. Dopamine, 1–5 µg/kg/min, may increase renal blood flow without sys- temic pressor responses. Higher doses of 5–20 µg/kg may be necessary if systemic hypotension persists after volume correction. Discontinuance of antihypertensive medica- tions or diuretics can, by itself, cure the apparent acute renal failure resulting from prerenal conditions. VASCULAR RENAL FAILURE Common causes of acute renal failure due to vascular dis- ease include atheroembolic disease, dissecting arterial aneu- rysms, and malignant hypertension. Atheroembolic disease is rare before age 60 and in patients who have not under- gone vascular procedures or angiographic studies. Dissect- ing arterial aneurysms and malignant hypertension are usually clinically evident. Rapid assessment of the arterial blood supply to the kidney requires arteriography or other noncontrast blood flow studies (eg, magnetic resonance imaging or Doppler ultrasound). The cause of malignant hypertension may be identified on physical examination (eg, scleroderma). Pri- mary management of the vascular process is necessary to affect the course of these forms of acute renal failure. INTRARENAL DISEASE STATES; INTRARENAL ACUTE RENAL FAILURE Diseases in this category can be divided into specific and nonspecific parenchymal processes. Table 33–1. Causes of Acute Renal Failure. I. Prerenal renal failure: 1. Dehydration 2. Vascular collapse due to sepsis, antihypertensive drug therapy, “third spacing” 3. Reduced cardiac output II. Functional–hemodynamic: 1. Angiotensin-converting enzyme inhibitor drugs 2. Nonsteroidal anti-inflammatory drugs 3. Cyclosporine; tacrolimus 4. Hepatorenal syndrome III. Vascular: 1. Atheroembolism 2. Dissecting arterial aneurysms 3. Malignant hypertension IV. Parenchymal (intrarenal): 1. Specific: a. Glomerulonephritis b. Interstitial nephritis c. Toxin, dye-induced d. Hemolytic uremic syndrome 2. Nonspecific: a. Acute tubular necrosis b. Acute cortical necrosis V. Postrenal: 1. Calculus in patients with solitary kidney 2. Bilateral ureteral obstruction 3. Outlet obstruction 4. Leak, posttraumatic Table 33–2. Acute Renal Failure versus Prerenal Azotemia. Acute Renal Failure Prerenal Azotemia Urine osmolarity (mOsm/L) < 350 > 500 Urine/plasma urea < 10 > 20 Urine/plasma creatinine < 20 > 40 Urine Na (mEq/L) > 40 < 20 Renal failure index* = > 1 < 1 > 1 < 1 *Excreted fraction of filtered sodium. See Espinel CH: JAMA 1976;236:579; and Miller TR et al: Ann Intern Med 1978; 89:47. U Na UP cr ⁄ FE Na UP Na ⁄ UP cr ⁄ 100×= OLIGURIA; ACUTE RENAL FAILURE / 533 1. Specific Intrarenal Disease States The most common causes of intrarenal acute renal failure are acute or rapidly progressive glomerulonephritis, acute interstitial nephritis, toxic nephropathies, and hemolytic uremic syndrome. Clinical Findings A. SYMPTOMS AND SIGNS Usually the history shows some salient data such as sore throat or upper respiratory infection, diarrheal illness, use of antibiotics, or intravenous use of drugs (often illicit types). Bilateral back pain, at times severe, is occasionally noted. Gross hematuria may be present. It is unusual for pyelonephritis to present as acute renal failure unless there is associated sepsis, obstruction, or involvement of a soli- tary kidney. Systemic diseases in which acute renal failure occurs include Henoch-Schönlein purpura, systemic lupus erythematosus, and scleroderma. Human immunodefi- ciency virus (HIV) infection may present with acute renal failure from HIV nephropathy. B. LABORATORY FINDINGS 1. Urine— Urinalysis discloses variably active sediments: many red or white cells and multiple types of cellular and granular casts. Phase contrast microscopy usually reveals dysmorphic red cells in the urine. In allergic interstitial nephritis, eosinophils may be noted. The urine sodium concentration may range from 10 to 40 mEq/L. 2. Blood test— Components of serum complement are often diminished. In a few conditions, circulating immune complexes can be identified. Other tests may disclose sys- temic diseases such as lupus erythematosus. Thrombocyto- penia and altered red cell morphologic structure are noted in peripheral blood smears in the hemolytic uremic syn- drome. Rapidly progressive glomerulonephritis can be evaluated with tests for ANCA (antineutrophil cytoplas- mic antibodies) and anti-GBM titers (anti-glomerular basement membrane antibodies). 3. Renal biopsy— Biopsy examination shows characteris- tic changes of glomerulonephritis, acute interstitial nephri- tis, or glomerular capillary thrombi (in hemolytic uremic syndrome). There may be extensive crescents involving Bowman’s space. C. X-RAY FINDINGS Dye studies should be avoided because of the risk of dye- induced renal injury. For this reason, sonography is prefer- able to rule out obstruction. Treatment Therapy is directed toward eradication of infection, removal of antigen, elimination of toxic materials and drugs, suppression of autoimmune mechanisms, removal of autoimmune antibodies, or a reduction in effector- inflammatory responses. Immunotherapy may involve drugs or the temporary use of plasmapheresis. Initiation of supportive dialysis may be required (see discussion below). 2. Nonspecific Intrarenal States Nonspecific intrarenal causes of acute renal failure include acute tubular necrosis and acute cortical necrosis. The lat- ter is associated with intrarenal intravascular coagulation and has a poorer prognosis than the former. These forms of acute renal failure usually occur in hospital settings. Var- ious morbid conditions leading to septic syndrome–like physiologic disturbances are often present. Degenerative changes of the distal tubules (lower neph- ron nephrosis) are believed to be due to ischemia. With dialysis, most of these patients recover—usually com- pletely—provided intrarenal intravascular coagulation and cortical necrosis does not occur. Elderly patients, who are more prone to have this form of oliguric acute renal failure, develop following hypoten- sive episodes. It appears that exposure to some drugs such as nonsteroidal anti-inflammatory agents may increase the risk of acute tubular necrosis. Although the classic picture of lower nephron nephrosis may not develop, a similar nonspecific acute renal failure is noted in some cases of mercury (especially mercuric chloride) poisoning and fol- lowing exposure to radiocontrast agents, especially in patients with diabetes mellitus or myeloma. Clinical Findings A. SYMPTOMS AND SIGNS Usually the clinical picture is that of the associated clinical state. Dehydration and shock may be present concur- rently, but the urine output and acute renal failure fail to improve following administration of intravenous fluids, in contrast to patients who have prerenal renal failure (see preceding discussion). On the other hand, there may be signs of excessive fluid retention in patients with acute renal failure following radiocontrast exposure. Symptoms of uremia per se (eg, altered mentation or gastrointestinal symptoms) are unusual in acute renal failure (in contrast to chronic renal failure). B. LABORATORY FINDINGS (See also Table 33–2.) 1. Urine— The specific gravity is usually low or fixed in the 1.005–1.015 range. Urine osmolality is also low (<450 mOsm/kg and U/P osmolal ratio <1.5:1). Urinalysis often discloses tubular cells and granular casts; the urine may be muddy brown. If the test for occult blood is positive, one must be concerned about the presence of myoglobin or 534 / CHAPTER 33 hemoglobin. Tests for differentiating myoglobin pigment are available. 2. Central venous pressure— This is usually normal to slightly elevated. 3. Fluid challenges— There is no increase in urine vol- ume following intravenous administration of mannitol or physiologic saline. Occasionally, following the use of furo- semide or “renal doses” of dopamine (1–5 µg/kg/min), a low urine output is converted to a high fixed urine output (low-output renal failure to high-output renal failure). Treatment If there is no response to the initial fluid or mannitol chal- lenge, the volume of administered fluid must be sharply curtailed to noted losses. An assessment of serum creati- nine and blood urea nitrogen and of the concentrations of electrolytes is necessary to predict the possible use of dialy- sis. With appropriate regulation of the volume of fluid administered, solutions of glucose and essential amino acids to provide 30–35 kcal/kg are used to correct or reduce the severity of the catabolic state accompanying acute tubular necrosis. Serum potassium must be closely monitored to ensure early recognition of hyperkalemia. This condition can be treated with (1) intravenous sodium bicarbonate adminis- tration, (2) Kayexalate, 25–50 g (with sorbitol) orally or by enema, (3) intravenous glucose and insulin, and (4) intra- venous calcium preparations to prevent cardiac irritability. Peritoneal dialysis or hemodialysis should be used as necessary to avoid or correct uremia, hypokalemia, or fluid overload. Hemodialysis in patients with acute renal failure can be either intermittent or continuous (with arteriove- nous or venovenous hemofiltration techniques). Vascular access is obtained with percutaneous catheters. The contin- uous dialysis techniques allow for easier management in many hemodynamically unstable patients in intensive care units. Prognosis Most cases are reversible within 7–14 days. Residual renal damage may be noted, particularly in elderly patients. POSTRENAL ACUTE RENAL FAILURE The conditions listed in Table 33–1 involve primarily the need for urologic diagnostic and therapeutic interven- tions. Following lower abdominal surgery, urethral or ure- teral obstruction should be considered as a cause of acute renal failure. The causes of bilateral ureteral obstruction are (1) peritoneal or retroperitoneal neoplastic involvement, with masses or nodes; (2) retroperitoneal fibrosis; (3) calcu- lous disease; and (4) postsurgical or traumatic interruption. With a solitary kidney, ureteral stones can produce total urinary tract obstruction and acute renal failure. Urethral or bladder neck obstruction is a frequent cause of renal failure, especially in elderly men. Posttraumatic urethral tears are discussed in Chapter 17. Clinical Findings A. SYMPTOMS AND SIGNS Renal pain and renal tenderness often are present. If there has been an operative ureteral injury with associated urine extravasation, urine may leak through a wound. Edema from overhydration may be noted. Ileus is often present along with associated abdominal distention and vomiting. B. LABORATORY FINDINGS Urinalysis is usually not helpful. A large volume of urine obtained by catheterization may be both diagnostic and therapeutic for lower tract obstruction. C. X-RAY FINDINGS Radionuclide renal scans may show a urine leak or, in cases of obstruction, retention of the isotope in the renal pelvis. Ultrasound examination often reveals a dilated upper col- lecting system with deformities characteristic of hydrone- phrosis. D. INSTRUMENTAL EXAMINATION Cystoscopy and retrograde ureteral catheterization demon- strate ureteral obstruction. Treatment For further discussion of ureteral injuries, see Chapter 17. REFERENCES Forni LG, Hilton PJ: Continuous hemofiltration in the treatment of acute renal failure. N Engl J Med 1997;336:1303. Gines P, Arroyo V: Hepatorenal syndrome. J Am Soc Nephrol 1999; 10:1833. Intensive care nephrology. J Am Soc Nephrol 2001;12(suppl 17):S1. Marik PE et al: Low-dose dopamine does not prevent acute renal fail- ure in patients with septic shock and oliguria. Am J Med 1999;107:387. Murphy SW et al: Contrast nephropathy. J Am Soc Nephrol 2000;11: 177. Nolan CR, Anderson RJ: Hospital-acquired acute renal failure. J Am Soc Nephrol 1998;9:710. Schiffl H et al: Daily hemodialysis and the outcome of acute renal fail- ure. N Engl J Med 2002;346:305. Schor N: Acute renal failure and the sepsis syndrome. Kidney Int 2002;61:764. Star RA: Treatment of acute renal failure. Kidney Int 1998;54:1817. Tepel M et al: Prevention of radiographic-contrast-agent-induced re- ductions in renal function by acetylcysteine. N Engl J Med 2000;343:180. 535 34 Chronic Renal Failure & Dialysis William J.C. Amend, Jr., MD, & Flavio G. Vincenti, MD Overview In chronic renal failure, reduced clearance of certain sol- utes principally excreted by the kidney results in their retention in the body fluids. The solutes are end products of endogenous metabolism as well as exogenous substances (eg, drugs). The most commonly used indicators of renal failure are blood urea nitrogen and serum creatinine. The clearance of creatinine can be used as a reasonable measure of glomerular filtration rate (GFR). Renal failure may be classified as acute or chronic depending on the rapidity of onset and the subsequent course of azotemia. An analysis of the acute or chronic development of renal failure is important in understanding physiologic adaptations, disease mechanisms, and ultimate therapy. In individual cases, it is often difficult to establish the duration of renal failure. Historical clues such as pre- ceding hypertension or radiologic findings such as small, shrunken kidneys tend to indicate a more chronic process. Acute renal failure may progress to irreversible chronic renal failure. For a discussion of acute renal failure, see Chapter 32. A new classification has been made to delineate chronic kidney disease (CKD) by varying degrees of reduced GFR (or creatinine clearance). This is presented in Table 34–1. This has been useful in studies of the progression of CKD, especially in varying drug regimens to reduce the rate of worsening of GFRs. The incidence of end-stage renal disease (ESRD) is 330 cases per million population. These patients with ESRD require chronic dialysis or renal transplantation for life support. All age groups are affected. The severity and the rapidity of development of uremia are hard to predict. The use of dialysis and transplantation is expanding rapidly worldwide. A large increase in CKD in the past 20 years has been due to type 2 diabetes. Over 330,000 ESRD patients in the United States are currently treated with dialysis. Besides diabetes, increasingly older patients are being treated for other renal diseases. At the present time, 128,000 patients have functioning kidney transplants. Historical Background There are various causes of progressive renal dysfunction leading to end-stage or terminal renal failure. In the 1800s, Bright described several dying patients who pre- sented with edema, hematuria, and proteinuria. Chemi- cal analyses of sera drew attention to retained nitroge- nous compounds and an association was made between this and the clinical findings of uremia. Although the pathologic state of uremia was well described, long-term survival was not achieved until chronic renal dialysis and renal transplantation became available after 1960–1970. Significant improvements in patient survival have been made in the past 50 years. Etiology A variety of disorders are associated with CKD. Either a primary renal process (eg, glomerulonephritis, pyelone- phritis, congenital hypoplasia) or a secondary one (owing to a systemic process such as diabetes mellitus or lupus erythematosus) may be responsible. Once there is kidney injury, it is now felt that hyperfiltration to undamaged nephron units produces further stress and injury to rem- nant kidney tissue. The patient will show progression from one stage of CKD severity to the next. Superimposed physiologic alterations secondary to dehydration, infec- tion, obstructive uropathy, or hypertension may put a bor- derline patient into uncompensated chronic uremia. Clinical Findings A. SYMPTOMS AND SIGNS With milder CKD, there may be no clinical symptoms. Symptoms such as pruritus, generalized malaise, lassitude, forgetfulness, loss of libido, nausea, and easy fatigability are frequent and nonfocal complaints in moderate to severe CKD. Growth failure is a primary complaint in preadoles- cent patients. Symptoms of a multisystem disorder (eg, systemic lupus erythematosus) may be present coinciden- tally. Most patients with CKD have elevated blood pres- sure secondary to volume overload or from hyperrenine- mia. However, the blood pressure may be normal or low if patients have marked renal salt-losing tendencies (eg, med- ullary cystic disease). The pulse and respiratory rates are rapid as manifestations of anemia and metabolic acidosis. Clinical findings of uremic fetor, pericarditis, neurologic findings of asterixis, altered mentation, and peripheral neu- ropathy are present only with severe, stage V CKD. Palpa- ble kidneys suggest polycystic disease. Ophthalmoscopic Copyright © 2008, 2004, 2001, 2000 by The McGraw-Hill Companies, Inc. Click here for terms of use. 536 / CHAPTER 34 examination may show hypertensive or diabetic retinop- athy. Alterations involving the cornea have been associated with metabolic disease (eg, Fabry disease, cystinosis, and Alport hereditary nephritis). B. HISTORY In 20% of cases, there is a family history of CKD. A report of antecedent nephritis episodes or a history of previous proteinuria may be elicited. It is important to review drug usage and possible toxic exposures (eg, lead). C. LABORATORY FINDINGS 1. Urine composition— The urine volume varies depend- ing on the type of renal disease. Quantitatively normal amounts of water and salt losses in urine can be associated with polycystic and interstitial forms of disease. Usually, however, urine volumes are quite low when the GFR falls below 5% of normal. The urinary concentrating and acidi- fication mechanisms are impaired. Daily salt losses become more fixed, and, if they are low, a state of positive sodium balance occurs with resulting edema. Proteinuria can be variable. Urinalysis examinations may reveal mononuclear white blood cells (leukocytes) and occasionally broad waxy casts, but usually the urinalysis is nonspecific and inactive. 2. Blood studies— Anemia is the rule with normal plate- let counts. Platelet dysfunction or thrombasthenia is char- acterized by abnormal bleeding times. Several abnormali- ties in serum electrolytes and mineral metabolism become manifest when the GFR drops below 30 mL/min. Progres- sive reduction of body buffer stores and an inability to excrete titrable acids result in progressive acidosis charac- terized by reduced serum bicarbonate and compensatory respiratory hyperventilation. The metabolic acidosis of uremia is associated with a normal anion gap, hyperchlore- mia, and normokalemia. Hyperkalemia is not usually seen unless the GFR is below 5 mL/min. In patients with inter- stitial renal diseases, gouty nephropathy, or diabetic neph- ropathy, hyperchloremic metabolic acidosis with hyper- kalemia (renal tubular acidosis, type IV) may develop. In these cases the acidosis and hyperkalemia are out of pro- portion to the degree of renal failure and are related to a decrease in renin and aldosterone secretion. In moderate to severe CKD, multiple factors lead to an increase in serum phosphate and a decrease in serum calcium. The hyper- phosphatemia develops as a consequence of reduced phos- phate clearance by the kidney. In addition, vitamin D activity is diminished because of reduced conversion of vitamin D 2 to the active form of vitamin D 3 in the kidney. These alterations lead to secondary hyperparathyroidism with skeletal changes of both osteomalacia and osteitis fib- rosa cystica. Uric acid levels are frequently elevated but rarely lead to calculi or gout during chronic uremia. D. X-RAY FINDINGS Patients with reduced renal function should not be rou- tinely subjected to contrast studies. Renal sonograms are helpful in determining renal size (usually small) and corti- cal thickness (usually thin) and in localizing tissue for per- cutaneous renal biopsy. Bone x-rays may show retarded growth, osteomalacia (renal rickets), or osteitis fibrosa. Soft-tissue or vascular calcification may be noted on plain films. Patients with polycystic kidney disease will have vari- ably large kidneys with evident cysts (on sonograms or plain abdominal CT scans). E. RENAL BIOPSY Renal biopsies may not reveal much except nonspecific interstitial fibrosis and glomerulosclerosis. There may be pronounced vascular changes consisting of thickening of the media, fragmentation of elastic fibers, and intimal pro- liferation, which may be secondary to uremic hypertension or due to primary arteriolar nephrosclerosis. Percutaneous or open biopsies of end-stage shrunken kidneys are associ- ated with a high morbidity rate, particularly bleeding. Treatment Recent studies indicate some benefit of drugs to reduce progression of CKD. These approaches include the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, lipid-lowering agents, and aldosterone antagonists. Patients need to be followed closely for poten- tial hyperkalemia. Overall, management should be conservative until it becomes impossible for patients to continue their custom- ary lifestyles. Restriction of dietary protein (0.5 g/kg/day), potassium, and phosphorus is recommended. As well, maintenance of close sodium balance in the diet is neces- sary so that patients become neither sodium-expanded nor -depleted. This is best done by the accurate and frequent monitoring of the patient’s weight. Use of oral bicarbonate can be helpful when moderate acidemia occurs. Anemia can be treated with recombinant erythropoietin given sub- cutaneously. Prevention of possible uremic osteodystrophy and secondary hyperparathyroidism requires close atten- Table 34–1. Chronic Kidney Disease (CKD) Stages. GFR (cc/min) Stage I >90 with microalbuminuria Stage II 60–89 with microalbuminuria Stage III 30–59 Stage IV 15–29 Stage V <15 or dialysis Ref. K/DOQI Guidelines for Chronic Liver Disease: Evaluation, classifi- cation, and stratification (excerpts). Am J Kidney Dis 2002;39(Suppl 1):1. [...]... exposed through a retroperitoneal approach, a selfretaining retractor is used The renal-to-iliac-vein anastomosis is usually performed first, in an end-to-side fashion with 5-0 nonabsorbable monofilament suture, using a running quadrant technique The renal artery can be anastomosed end-to-end to the internal iliac using 6-0 nonabsorbable monofilament suture However, in older recipients and diabetics this... Muromonab-CD3 binds to the T-cell-receptor-associated CD3 complex, which first triggers a massive cytokine-release syndrome before both depleting and functionally modulating T cells Humans can make neutralizing (human antimouse) antibodies against muromonab-CD3 that terminate its effect and limit its reuse Adverse effects from a typical 5-mg dose include a first-dose response that simulates a severe flu-like... urinary tract dysfunction J Urology 1 983 ; 130 :87 80 Flechner SM, Avery RK, Fisher R et al: A prospective randomized, controlled trial of oral acyclovir vs oral ganciclovir for CMV prophylaxis in high risk kidney transplant recipients Transplantation 19 98; 66:1 682 8 Flechner SM, Novick AC: Renal transplantation In: Gillenwater JY, Grayhack JT, Howards SS (eds.) Adult and Pediatric Urology 4th edition, 2002... Transplantation 2005;79:27 7 -8 6 Hobart MG, Modlin CS, Kapoor A, et al: Transplantation of pediatric en bloc cadaver kidneys into adult recipients Transplantation 19 98; 66:1 689 –94 Hourmant M, Cesbron-Gautier A, Terasaki PI, et al: Frequency and clinical implications of development of donor-specific and nondonor-specific HLA antibodies after kidney transplantation J Am Soc Nephrol 2005;16: 280 4–12 Humar A, Ramcharan... age (Flechner, 539 Copyright © 20 08, 2004, 2001, 2000 by The McGraw-Hill Companies, Inc Click here for terms of use 540 / CHAPTER 35 95.1% 100 80 .2% 89 % % Survival 80 55.4% 60 66.7% 40 20 0 40.5% Deceased 86 ,315 Live Donor 50,205 0 3 12 36 48 60 72 84 96 1 08 120 Months Post Transplant abscesses, filling defects, enhancing masses, complex or very large cysts, etc that may lead to persistent infections... suppression Because expression of CD25 (interleukin-2 receptor a chain) requires T-cell activation, anti-CD25 antibody causes little depletion of T cells Anti-CD25 antibodies are useful as safe induction agents in low- to moderate-risk recipients, but have little effect in treating an established rejection episode Their use appear to offer a favorable risk-benefit compared to depleting agents, providing... transplantation after localized prostate cancer treatment: Are they still appropriate? Transplantation 2004; 78: 710–2 Serrano D, Flechner SM, Modlin C et al: Transplantation into the long-term defunctionalized bladder J Urol 1996;156 :88 5 8 Shoskes DA, Cecka JM: Effect of delayed graft function on short- and long-term kidney graft survival Clin Transplant 1997;11:297– 303 Streeter E, Little DM, Cranston D, and... Zietse R et al: Long-term graft survival after urological complications of 695 kidney transplantations J Urol 2001;165: 188 4 87 Vincenti F, Larsen C, Durrbach A et al: Costimulation blockade with belatacept in renal transplantation N Engl J Med 2005;353: 770 81 Wilson CH, Bhatti A, and Manas DM: Routine intraoperative stenting for renal transplant recipients Transplantation 2005 ;80 : 87 7–2 Wolfe RA, Ashby... Exp Clin Transplant 2005;3: 283 8 Davis C: Evaluation of living kidney donor: Current perspectives Am J Kidney Disease 2004;53:5 08 30 Davis C, Delmonico F: Living-donor kidney transplantation: A review of the current practices for the live donor J Am Soc Nephrol 2005;16:20 98 2110 Delmonico FL: Exchanging kidneys—Advances in living donor transplantation N Engl J Med 2004;350: 181 2–4 Delmonico FL, Sheehy... (Narkun-Burgess et al, 1993), and after kidney donation (Najarian et al, 1992; Fehrman-Ekholm et al, 1997) The effect of reduced renal mass by uninephrectomy on 3124 patients was compared to 1703 matched controls in a meta-analysis (Kasiske et al 1995) The reason for nephrectomy included organ donation in 60.5%, cancer 10.1%, infection 8. 1%, stones/obstruction 6 .8% , agenesis 3.4%, trauma 2.5%, and other 8. 4% . trans- plant graft survival over 10 years. From the OPTN/UNOS annual report 2005. 0 0 3 12 36 48 Months Post Transplant % Survival 60 72 84 96 1 08 120 20 40 60 80 100 95.1% Deceased 86 ,315 Live. How- ever, over 65,000 patients were actively waiting for a kid- ney, and the gap between the number waiting and avail- able organs widens every year (Port et al, 2006). Currently, 1- and 5-year. 19 98; 54: 181 7. Tepel M et al: Prevention of radiographic-contrast-agent-induced re- ductions in renal function by acetylcysteine. N Engl J Med 2000;343: 180 . 535 34 Chronic Renal Failure & Dialysis William