Nephrolithiasis; Valvular Cardiac Disease

Transcription

1 INTERNAL MEDICINE BOARD REVIEW MANUAL PUBLISHING STAFF PRESIDENT, GROUP PUBLISHER Bruce M. White EDITORIAL DIRECTOR Debra Dreger SENIOR EDITOR Bobbie Lewis ASSISTANT EDITOR Rita E. Gould EXECUTIVE VICE PRESIDENT Barbara T. White EXECUTIVE DIRECTOR OF OPERATIONS Jean M. Gaul PRODUCTION DIRECTOR Suzanne S. Banish PRODUCTION ASSOCIATE Mary Beth Cunney ADVERTISING/PROJECT MANAGER Patricia Payne Castle SALES & MARKETING MANAGER Deborah D. Chavis NOTE FROM THE PUBLISHER: This publication has been developed without involvement of or review by the American Board of Internal Medicine. Endorsed by the Association for Hospital Medical Education The Association for Hospital Medical Education endorses HOSPITAL PHYSICIAN for the purpose of presenting the latest developments in medical education as they affect residency programs and clinical hospital practice. Nephrolithiasis; Valvular Cardiac Disease Series Editor and Contributor: Richard J. Simons, MD, FACP Professor of Medicine, Acting Vice Dean for Educational Affairs, Staff Physician, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA Contributors: Brian S. Rifkin, MD Chief Medical Resident and Instructor, Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA C. Randy Hubbard, MD Chief Resident, Department of Internal Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA Table of Contents Chapter 1 Nephrolithiasis Brian S. Rifkin, MD, and Richard J. Simons, MD, FACP Chapter 2 Valvular Cardiac Disease Richard J. Simons, MD, FACP, and C. Randy Hubbard, MD Cover Illustration by mb cunney Copyright 2003, Turner White Communications, Inc., 125 Strafford Avenue, Suite 220, Wayne, PA , All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of Turner White Communications, Inc. The editors are solely responsible for selecting content. Although the editors take great care to ensure accuracy, Turner White Communications, Inc., will not be liable for any errors of omission or inaccuracies in this publication. Opinions expressed are those of the authors and do not necessarily reflect those of Turner White Communications, Inc. Internal Medicine Volume 10, Part 4 1

2 INTERNAL MEDICINE BOARD REVIEW MANUAL Chapter 1 Nephrolithiasis Brian S. Rifkin, MD, and Richard J. Simons, MD, FACP I. INTRODUCTION The incidence of nephrolithiasis appears to be on the rise, and it has been increasing in developed countries throughout the 20th century. Diet, an aging population, and the use of certain medications are all likely contributing factors to the increasing incidence, although the exact cause is not known. Kidney stones now account for 5 to 10:1000 of all hospital admissions. The overall lifetime risk is 3% to 5% in the United States. By age 70 years, 12% of men and 5% of women will develop a symptomatic stone; children also can develop kidney stones. Several predisposing risk factors (Table 1) for stone development may increase stone prevalence to as high as 25% to 30% in some populations. 1 The natural history of kidney stone formation is marked by recurrence. Nearly 50% of patients will have a recurrence after 5 years, and 66% will have a recurrence after 9 years. 2 More than 15 different etiologic categories of nephrolithiasis exist, making a thorough workup seem daunting. Unfortunately, a single underlying etiology is found in only a few patients and more than 60% of patients have a multifactorial cause. 3 It is important to complete a focused and cost-effective evaluation of patients with kidney stones. Diagnostic evaluation and selective treatment of metabolic abnormalities clearly decrease the incidence of new stone formation. Two case patients are presented to highlight the management of patients with nephrolithiasis. II. CASE PATIENT 1 INITIAL PRESENTATION Patient 1 is a 35-year-old man who presents to the emergency department for sudden onset of nausea, vomiting, and gross hematuria. Physical examination reveals that patient 1 is obese (220 lb at 5 ft 8 in) and hypertensive, with blood pressure of 150/90 mm Hg. He has right flank tenderness without rebounding or guarding. On further questioning, he also admits to urinary frequency and dysuria. The patient notes no prodrome or precipitating event. He appears uncomfortable and is unable to sit in any one position for a prolonged period of time. He describes a sharp pain that comes in waves, is not changed with position, and extends from his right inguinal region to the tip of his penis. The patient reports that he does not have a personal or family history of kidney stones. He is given intravenous (IV) fluids and meperidine for pain. What would be the appropriate initial workup for this patient? A) Serum BUN and creatinine levels B) Serum calcium, phosphorus, and uric acid levels C) Complete blood count (CBC) with differential D) Urinalysis and culture E) All of the above The correct answer is E. This patient s history strongly suggests the presence of a kidney stone. The 1999 National Institutes of Health (NIH) consensus conference set guidelines for evaluation of a patient with a suspected first episode of nephrolithiasis (Table 2). 4,5 The evaluation should contain pertinent history (including family, occupational, and dietary history), a list of current medications, and any history of kidney stones or predisposing conditions (eg, Crohn s disease). Supporting laboratory tests also are recommended. Therefore, testing should include all the items previously listed. Other laboratory tests may be indicated depending on findings of the initial testing, the type and severity of the stone, and the presence of a systemic disorder that would predispose to recurrent stones. The differential diagnosis in a male patient may include common genitourinary infections, including epididymitis or prostatitis. In a female patient, ovarian torsion or an ovarian cyst may have a similar presentation of excruciating lower abdominal pain, nausea, and vomiting. Other emergent disorders, including testicular torsion in men and ectopic pregnancy in women, also should be considered in the initial workup depending on supporting information in the history and on physical examination. Infectious and catastrophic abdominal 2 Hospital Physician Board Review Manual

3 Chapter 1 Nephrolithiasis Table 1. Risk Factors for the Development of Nephrolithiasis Advanced age (older than 70 years) Male sex Caucasian race Higher socioeconomic status Living in warmer/dryer climate Medications Systemic medical disorders (eg, Crohn s disease, hyperparathyroidism, sarcoidosis, malignancies, tuberculous) processes also warrant consideration. Appendicitis, cholecystitis, diverticulitis, colitis, hernia incarceration, and arterial aneurysms should all be considered in the differential diagnosis pending laboratory and imaging confirmation. Adequate analgesia is a mainstay of therapy for patients in the emergency department. Opiates are useful for masking the pain but do not do anything to alter the underlying process. Nonsteroidal anti-inflammatory drugs (NSAIDs) including diclofenac, ibuprofen, aspirin, and ketorolac also have been used effectively to control renal colic. Some studies have even shown ketorolac to be superior to meperidine. 6 The newer cyclooxygenase-2 (COX-2) inhibitors have not been studied extensively, but they may provide adequate analgesia with the added benefit of decreased risk of bleeding; use of COX-2 for renal colic has not been approved by the Food and Drug Administration. DIAGNOSIS The patient has gross blood on the urinalysis without other significant findings. Laboratory tests (including electrolytes, calcium, phosphorus, magnesium, BUN, creatinine levels, and a CBC) are all within normal limits. The emergency department physician obtains a radiograph that confirms the diagnosis of a small (< 5 mm), calcified distal ureteral calculus. The patient has relief of his pain while in the emergency department. He is given a urine strainer in order to collect a passed stone and a prescription for propoxyphene with acetaminophen; he is discharged with an appointment for a follow-up visit with his primary care provider. What is the pathogenesis of nephrolithiasis? Renal calculus formation is a complex process that has still not been completely elucidated. The process Table 2. Summary of Recommendations from the National Institutes of Health Consensus Conference on the Evaluation of Stone Formers Evaluation of patients with a first stone episode History: medications, occupation, family history of stones or other kidney disease, inflammatory bowel disease (eg, Crohn s disease) Diet: intake of purines, protein, sodium, fluids, oxalate, and calcium Laboratory tests: electrolytes, blood urea nitrogen, creatinine, calcium, phosphorus, uric acid, urinalysis, urine culture, and stone analysis (if available) Radiology: plain radiographs, ultrasound, and/or intravenous pyelography (or helical computed tomography) to find more stones, radiolucent stones, or anatomic abnormalities Consider: renal tubular acidosis, hyperparathyroidism, and sarcoidosis Evaluation of patient with recurrent stone formation (and all children) 24-hr urine collection: volume, ph; levels of calcium, phosphorous, sodium, uric acid, oxalate, citrate, creatinine, calcium-oxalate (supersaturation), calcium-phosphate, and uric acid Repeat as necessary: 24-hr urine collection and analysis to monitor response to dietary changes and effectiveness of treatment Adapted with permission from Goldfarb DS, Coe FL. Prevention of recurrent nephrolithiasis. Am Fam Physician 1999;60:2270. Information from the Consensus Conference. Prevention and treatment of kidney stones. Available at odp.od.nih.gov/concensus/cons/067/067_ intro.htm. Accessed 12 Aug starts with precipitation of particles from a solution, termed nucleation. These urinary crystals proceed to aggregate into larger crystals, which are deemed a nidus. The nidus then attaches to the urothelial surface or aggregates too rapidly to be passed. Because urine contains other material besides dissolved elemental salts (eg, macromolecules and cellular debris), crystallization is often heterogeneous. Additionally, some substances inhibit and others promote stone formation, allowing crystals to form in undersaturated, saturated, or supersaturated solutions. These different processes make predicting nidus formation very difficult with in vitro testing. Computer models have been established that are helpful but not entirely accurate in predicting stone formation. Finally, urinary ph and urine volume appear to play very significant roles in nephrolithiasis. What is the evaluation of a patient with a kidney stone? Internal Medicine Volume 10, Part 4 3

4 Chapter 1 Nephrolithiasis Table 3. Classification and Characteristics of Renal Calculi Type Frequency, % Patient Sex Crystals Radiography Calcium-oxalate 75 M* Envelope Round, radiodense Uric acid M = F Diamond Round or staghorn; radiolucent Struvite F* Coffin lid Staghorn, radiodense Cystine 1 M = F Hexagon Staghorn, intermediate F = female; M = male. (Adapted from Greenberg A, Cheung AK, editors. Primer on kidney diseases. 3rd ed. San Diego: Academic Press; 2001:349. Copyright 2001, with permission from Elsevier.) *Gender plays a role in stone formation for calcium-oxalate and struvite stones. FIRST STONE EPISODE Kidney stones vary in their pathogenesis, prognosis, and composition and appropriate therapy will vary. Most stones contain some or all of the following components: calcium, oxalate, phosphorus, uric acid, and cystine. Nearly 80% of stones contain calcium; most of these are calcium-oxalate stones (Table 3). If the calculus is available, stone analysis should be performed. Stone analysis is a relatively inexpensive process that can be quite helpful in guiding therapy and educating the patient. Uric acid and cystine stones are readily recognized by the appearance of classic microscopic crystals. Hydroxyapatite stones suggest underlying medical conditions including renal tubular acidosis (RTA) and hyperparathyroidism. Identification of calcium-oxalate stones is not helpful in terms of pathogenesis because of the large number of predisposing conditions, but their detection can be helpful for guidance of medical and dietary therapy. Further evaluation for any predisposing risks factors should be sought and modified when possible. Certain demographic information may predispose patients to nephrolithiasis. For instance, men are 3 to 4 times as likely to be affected as women. As previously mentioned, other factors that increase the incidence of stone formation are Caucasian race, advanced age, higher socioeconomic status, and living in a warmer and dryer climate. The southern United States is often referred to as the stone belt because of the convergence of these risk factors in the population there. Several medications also have been implicated in the development of nephrolithiasis. Triamterene and the sulfonamides have been shown to decrease the solubility of urinary components. Carbonic anhydrase inhibitors alter urine ph and can cause calcium-phosphorus stones to precipitate. Certain medications, like indinavir, have been shown to crystallize and form a nidus for stone formation. Calcium and vitamin D, which are mainstays of osteoporosis prevention, have been shown in certain instances to contribute to hypercalciuria. Recent evidence, however, suggests that calcium supplementation may decrease the incidence of nephrolithiasis. 7 A patient s occupation may contribute to calculus formation. Low urine volume has been incriminated as a major factor in stone formation. Heat, prolonged sun exposure, or decreased access to a bathroom or drinking water can add to the risk. In occupations where a person is prone towards dehydration (eg, outdoor laborer, working in a hot kitchen, athletes, marathon runners, delivery person), proper hydration should be emphasized. Finally, several systemic medical disorders are associated with a substantial risk of nephrolithiasis. Any one of the conditions that cause hypercalcemia ultimately cause hypercalciuria and supersaturation of calcium in the urine. Diagnostic testing for hyperparathyroidism, sarcoidosis, malignancies, or tuberculosis may be necessary in patients with hypercalcemia. Other conditions that affect the bowel have been shown to increase risk. Patients with bowel disorders (such as Crohn s disease, short bowel syndrome) have been shown to have hyperoxalemia, which may contribute to stone formation. These conditions also cause a metabolic acidosis because of the wasting of bicarbonate in the stool, which can lead to acidification of the urine and precipitation of cystine and uric acid stones. Type 1 (distal) RTA similarly causes a metabolic acidosis that ultimately contributes to stone formation by increasing the release of calcium and phosphorus during bone buffering of retained acid and by decreasing tubular reabsorption of these ions. 8 Type 1 RTA patients typically have a urine ph greater than 6.5, which favors calcium-phosphate stone formation. Sometimes it is not a metabolic but an anatomic abnormality that creates an environment for calculus precipitation. Patients with medullary sponge kidneys, polycystic kidney disease, or horseshoe kidneys all have an associated increased relative risk. Further imaging beyond a radiograph may be needed to evaluate for these conditions. 4 Hospital Physician Board Review Manual

5 Chapter 1 Nephrolithiasis PATIENT FOLLOW-UP Patient 1 returns to his primary care physician in 1 week. The patient has had some mild recurrent pain that has responded to medication. He still notes some blood in his urine. What is the most appropriate imaging study to follow the progression of this patient s stone? A) Magnetic resonance imaging (MRI) B) Radiographs of the kidneys, ureter, and bladder (KUB) C) Computed tomography (CT) scan D) Intravenous pyelogram (IVP) E) Ultrasound IMAGING The correct answer is B. Simple radiograph images of the abdomen can be quite useful in diagnosis and subsequent follow-up of nephrolithiasis. Calcium-containing stones are readily visualized on abdominal radiographs; 90% of stones are considered radiopaque. Less radiopaque stones, including pure uric acid and cystine stones, may not be readily apparent on plain radiographs. Even pure calcium stones may be obscured by stool, bowel gas, or the bony structures of the pelvis. Calcified structures (including lymph nodes, gallstones, and phleboliths) may be mistaken for renal calculi on plain radiographs. However, the overall sensitivity and specificity of plain radiographs remain poor for identification of nephrolithiasis (45% 55% and 70% 75%, respectively). 9 Radiographs are most useful in patients with a known history of radiopaque stones (Figure 1). They are also the most cost-effective method for following the progression of previously noted radiopaque stones. MRI has no role in following kidney stones. A non-contrast helical CT scan of the abdomen is the most sensitive and specific (95% 100%) radiologic test for nephrolithiasis. 10 In patients with abdominal pain, a CT scan can definitively rule out a kidney stone as a potential cause. CT is fast, accurate, and identifies all types of stones at all locations in the collecting system. In addition, the chemical composition of a calculus can be identified based on the Hounsfield density of the stone. 11 CT can accurately differentiate cystine and uric acid stones from calcium stones. Calcium stones can be accurately further subtyped into calcium phosphorus or calcium oxalate, which can direct therapy. CT scans have the additional advantage of providing information about other intra-abdominal processes if a kidney stone is not identified. It would be useful to obtain a CT scan on patient 1 in order to potentially gain more information about the composition of the stone and to evaluate for anatomic abnormalities. When being done for other reasons, CT may identify stones that are asymptomatic. Treatment of these incidental stones would depend on their size, location, and the patient s ability to receive emergent treatment if necessary. Another imaging technique that has been used to identify renal calculi is an IVP. In this procedure, the patient has a radiopaque dye (which is subsequently excreted by the kidney) injected into the blood steam, allowing for visualization of the renal collecting system by radiograph. An IVP can often provide information on the size, location, and radiodensity of the kidney stone. Unfortunately, this imaging modality has 2 major drawbacks. First, an IVP cannot be done acutely in the emergency department because patients need to undergo a bowel preparation to improve the accuracy of the test. Second, the dye load associated with an IVP is significant and can lead to adverse events including renal failure. Patients with multiple myeloma, diabetes, cardiovascular disease, or a creatinine level greater than 1.5 mg/dl have a relative contraindication to the test because of this potential renal toxicity. IVP is most useful in those situations where CT is unavailable (Figure 1). The sensitivity and specificity of IVP (64% 87% and 92% 94%, respectively) are greater than that of a KUB (45% 59% and 71% 77%, respectively) or ultrasound (19% and 97%, respectively). 5 Ultrasound may be used under certain circumstances to identify renal stones. Ultrasound would be the imaging study of choice if the patient is pregnant or if the initial presentation leads to a high suspicion of cholecystitis (Figure 1). 9 Ultrasound, like plain radiographs, is readily available in most medical centers. Although ultrasound is very sensitive to renal calculi, it typically cannot detect any stone that has progressed to the ureters. Ureteral stones, however, may be implied by the presence of unilateral hydronephrosis. Ultrasound is most helpful in evaluating for a gynecologic process that may mimic a stone, which is much more common than nephrolithiasis in women of childbearing age. IMAGING RESULTS Patient 1 undergoes a CT scan as an outpatient procedure. The CT scan identifies a 3-mm calcium-oxalate stone at the ureterovesicular junction. Calcium-oxalate crystals also are confirmed by microscopy. What is the significance of hypercalciuria in stone formers? As mentioned earlier, calcium stones, in their various forms, account for most nephrolithiasis. Patients often Internal Medicine Volume 10, Part 4 5

6 Chapter 1 Nephrolithiasis Renal colic suspected Diagnostic imaging Patient is pregnant, or cholecystitis or gynecologic process is suspected Patient has history of radiopaque calculi All other patients Ultrasound examination Plain-film radiography Intravenous pyelography if CT is not available Non-contrast helical CT Stone detected Stone not detected Stone detected Stone not detected Clinical suspicion of urolithiasis Figure 1. Approach to diagnostic imaging in suspected renal colic. CT = computed tomography. (Adapted with permission from Portis AJ, Sundaram CP. Diagnosis and initial management of kidney stones. Am Fam Physician 2001;63:1331. Copyright American Academy of Family Physicians. All rights reserved.) have a normal serum calcium but demonstrate increased concentration of calcium in the urine. The average daily excretion of calcium is 4 mg/kg or about 300 mg in adult men and 250 mg in adult women receiving 1000 mg or greater of dietary calcium each day. Approximately 10% of non-stone formers have calcium excretion rates in excess of these values. Patients with a urinary calcium of less than 200 mg/day probably have a negligible risk for stone formation. 12 Hypercalciuria is seen in 40% to 50% of stone formers and is most often idiopathic. Certain common characteristics are found among those with idiopathic hypercalciuria. Obese men with hypertension and a familial history of hypercalciuria most often manifest with increased urinary calcium excretion. These patients often demonstrate increased absorption of calcium in the gastrointestinal tract, with a normal parathyroid hormone level and increased urinary calcium excretion with fasting. Medical treatment of hypercalciuria may be beneficial to certain patients. Hydrochlorothiazide has been shown to be useful in decreasing urinary calcium concentrations through passive and active transport in the renal tubules. Hydrochlorothiazides may decrease calcium excretion by as much as 50 to 150 mg/day. Patients initially receive a hydrochlorothiazide dose of 25 to 50 mg per day. This therapy has some drawbacks including the risk of dehydration, tachyphylaxis, and electrolyte imbalances. Rarely, hypercalciuria can be attributed to a systemic condition like hyperparathyroidism, sarcoid, RTA, or familial hypercalciuria (< 5% of cases). It is important to increase calcium supplementation in patients with hypercalciuria to prevent the negative balance of total body calcium from leading to osteopenia and ultimately osteoporosis. The patient inquires about the possible need for surgery. What advice should be given about the likelihood of spontaneous passage versus the need for surgery? A) Given the size of the stone, the patient should proceed directly to surgery. B) Given the location of the stone, the patient should proceed directly to surgery. C) Because his stone is small and already at the ureterovesicular junction, surgery is not indicated; spontaneous passage is approximately 90% likely. D) Because the stone has been present for 1 week, the patient should be referred for surgery. 6 Hospital Physician Board Review Manual

7 Chapter 1 Nephrolithiasis SPONTANEOUS STONE PASSAGE The correct answer is C. Advising patients about the possibility of spontaneous passage of kidney stones can save them from undergoing unnecessary procedures. In 1999, Miller and colleagues followed 75 patients prospectively in an attempt to analyze the natural history of nephrolithiasis and to define factors predictive of spontaneous passage. 13 Overall, 83% of patients experienced spontaneous resolution of the stone. As might be expected, smaller stones (< 2 mm) had a 95% rate of passage with an average duration of 8.2 days. Nearly 50% of stones greater than 4 mm required surgical intervention, although the other half required 22.1 days on average for spontaneous passage. 13 Perhaps surprisingly, they also demonstrated that right-sided calculi on average passed 1 week earlier than left-sided stones. Stones typically are retained and obstruct urine flow at 3 locations: the ureteropelvic junction, the mid-ureter as it crosses the iliac artery, and the ureterovesicular junction. As would be expected, stones that migrate to a more distal point before becoming symptomatic are more likely to pass. Up to 90% of stones will pass spontaneously depending on size and location. In addition, up to 98% of stones less than 0.5 cm in diameter, especially those in the distal ureter, will pass spontaneously. 14 Emergent evaluation and intervention by a urologist is required in a few patients with stones smaller than 5 mm. If the patient is experiencing urosepsis resulting from urinary calculus, a percutaneous nephrostomy tube or ureteral stent may need to be placed immediately. Additionally, a patient with anuria or renal failure secondary to bilateral stones (or unilateral in a patient with a single kidney) should have an emergent evaluation. Patients with refractory severe pain, those at the extremes of age, and those with other comorbid conditions may require hospital admission and more urgent evaluation by a specialist. Patients with adequate analgesia who have access to emergent treatment should a stone cause a problem may be followed as outpatients for a short period of time. Early intervention of distal stones may be required in certain circumstances where stones would not be expected to spontaneously pass. In patients who demonstrate complete obstruction, surgery should be performed within 2 weeks to prevent permanent damage to the kidney. Similarly, definitive treatment should take place in 4 to 6 weeks in patients with a partial obstruction. In general, a painful stone is at least partially obstructing the renal collecting system; however, the opposite is not true and completely obstructing stones may be asymptomatic. 1 Therefore, asymptomatic stones may destroy renal function in as short as 6 to 8 weeks, although the risk is small. Physicians should be diligent about following up radiopaque stones with radiographs at 1- to 2-week intervals until passage is noted or the patient retrieves the stone from straining urine. If the stone has failed to spontaneously pass after 4 weeks, a urology consultation should be obtained because the complication rate triples to nearly 20% if a stone has failed to pass. 15 Potential complications include renal failure, ureteral stricture, infection, perinephritic abscess, and urine extravasation. ADDITIONAL FOLLOW-UP The patient returns to the office in 1 week having spontaneously passed the stone, which he has brought with him. He had been reading on the internet that he should alter his diet to decrease his risk of recurrent stones. What dietary intervention would be the most beneficial for this patient? A) Tell him to avoid all calcium and vitamin D supplementation. B) Advise him to avoid foods that are high in oxalate. C) Encourage him to increase his fluid intake to get his urine output to more than 2 L per day. D) Inform him to increase his protein intake to 250 g/day (3 g/kg per day). DIETARY INTERVENTIONS The correct answer is C. Some dietary elements have been shown to be preventive. First and foremost is the intake of adequate amounts of fluid. The fluid most recommended is plain water. Enough fluid should be ingested to increase the urine output from 1.5 to 2 L/day, which is generally an adequate volume to decrease the concentration of calculi-forming substances (ie, uric acid). Drinking large amount of soft drinks acidified with phosphoric or carbonic acid may modestly increase the risk of stone disease. Fruit juice often contains an oxalate load, which again has not been linked to stones in controlled trials, but oxalate is still recommended to be limited. Fiber is another dietary component that has been shown to be beneficial. Controlled studies of hypercalciuric patients treated with rice, soy, and wheat bran showed decreased calciuria. 16 No studies, however, have shown that fiber is prophylactic in healthy non-stone forming patients. Some elemental supplements also may be beneficial. Magnesium has been shown in vitro to decrease nucleation and growth of calcium-oxalate crystals. Several dietary components may increase or decrease the risk of recurrent nephrolithiasis. Specific Internal Medicine Volume 10, Part 4 7

8 Chapter 1 Nephrolithiasis Table 4. Summary of Strategies for Preventing Calcium and Urate Nephrolithiasis Calcium stones All patients Increase fluid intake to yield an output of at least 2 L of urine per day Patients with hypercalciuria Dietary restriction of protein, oxalate, and sodium; no restriction of dietary calcium Medications: thiazides, usually given with potassium citrate; amiloride (Midamor) Patients with hypocitraturia Dietary restriction of protein and sodium Potassium citrate supplementation (sodium citrate if potassium citrate is not tolerated) Patients with hyperoxaluria Dietary restriction of oxalate Patients with hyperuricosuria Dietary restriction of purine (ie, protein) Allopurinol (Zyloprim) Uric acid stones Increasing fluid intake is less important for the prevention of uric acid stones than calcium stones. Patients with a low urinary ph level Dietary restriction of protein and sodium. Avoid kidney, liver, sweetbreads, hering, salmon, sardines, mussels, scallops. Limit meat, poultry, seafood, beans, spinach. Alkalinization of the urine with potassium citrate (sodium citrate if potassium citrate is not tolerated) Patients with hyperuricosuria Dietary restriction of protein and sodium Alkalinization of the urine with potassium citrate if urinary ph level is low Allopurinol in selected situations Adapted with permission from Goldfarb DS, Coe FL. Prevention of recurrent nephrolithiasis. Am Fam Physician 1999;60:2273. Copyright American Academy of Physicians. All rights reserved. dietary recommendations also may vary depending on the composition of the renal calculus (Table 4). Many different dietary components have been examined as potential aggravating agents. Sodium has been implicated in stone genesis because the kidney handles calcium and sodium similarly. Many agents that cause a natriuresis also stimulate calcium excretion. It is generally recommended to limit sodium intake to 100 to 125 meq/day. Protein also has been positively correlated with nephrolithiasis. A high protein diet creates an optimal urinary environment for stone formation with increased uric acid as well as decreased citrate and urinary ph. It is currently recommended that patients with kidney stones particularly uric acid based and calcium-based stones should limit protein intake to 1 g/kg per day or about 70 to 80 g, which includes protein from all meat sources (beef, pork, fowl, and fish). 16 Dietary oxalate, which contributes to hyperoxaluria, has a more questionable role in stone formation. Foods high in oxalate include the following: nuts, chocolate, green leafy vegetables, tomatoes, jams, rhubarb, beets, chard, kale, sweet potatoes, endive, okra, tea, and beer. In general, population studies have failed to show an increase in oxalate in the diet of stone formers versus non-stone formers. Although low-oxalate diets have been shown to decrease oxalate in the urine, no one has shown a corresponding decrease in stone formation in these patients. In fact, people on a strict vegetarian diet, which is often high in oxalate, have had a decrease in stone formation believed to be secondary to increased citrate ingestion. 16 Most serum oxalate may actually be derived from endogenous synthesis. Cases of nephrolithiasis secondary to enzymatic defects leading to increased oxalate synthesis have been described. Studies have additionally looked at pyridoxine (vitamin B 6 ) which is a co-factor in oxalate metabolism. A deficiency in pyridoxine has not been associated with an increased incidence of stones. Carbohydrates, vitamin C (except in megadoses), and vitamin D also have shown no direct correlation to nephrolithiasis. No studies have been done on the incidence of nephrolithiasis in alcoholics, but moderate alcohol intake has not been associated with increased kidney stones. An inverse relationship has been noted between calcium intake and stone formation. For a long time, calcium restriction was a hallmark of calcium stone prevention. However, no studies had been done to prove the harmful relationship of dietary calcium to stone formation. Now, more evidence to the contrary is available, and ongoing long-term studies are underway. Initial results reveal that nephrolithiasis may be decreased as much as 50% in some patients by increasing calcium intake. 7 Current recommendations advocate age and sex appropriate intake of daily calcium ( mg). It has been hypothesized that increased oral intake of calcium leads to intestinal complexing with oxalate and phosphorous, leading to the decreased absorption of all 3. Calcium citrate is the preferred form of supplementation in those patients with a history of calcium stones. Citrate is a naturally occurring urinary stone inhibitor found in fruits and vegetables; citrate binds to calcium and inhibits nucleation. 8 Hospital Physician Board Review Manual

9 Chapter 1 Nephrolithiasis Unfortunately, the quantity of fruits and vegetables required to achieve a therapeutic dose of citrate also would be accompanied by a large oxalate load, which is still recommended to be limited in the diet of stone formers. Therefore, citrate supplements are preferred over naturally occurring citrate. Citrate is converted to bicarbonate, creating a metabolic alkalosis, which is required for optimum excretion of citrate in the urine. All causes of metabolic acidosis, but particularly distal RTA, are associated with decreased citrate excretion. Nearly half of stone formers have some degree of hypocitraturia. RECURRENCE IN CASE PATIENT 1 Patient 1 returns with recurrent symptoms 2 years later. What additional workup might be indicated? A) Perform a 24-hour urine collection B) Measure serum angiotensin-converting enzyme level to evaluate for sarcoidosis C) Measure an intact parathyroid hormone level to evaluate for primary hyperparathyroidism disease D) Perform a colonoscopy to evaluate for Crohn s disease The correct answer is A. Approximately 50% of patients have a second stone episode 10 years after the initial episode. More than 80% of patients with nephrolithiasis will have more than 2 stone episodes in a 20- to 30-year period. Patients with recurrent stones require further work-up for a potential etiology. It is generally recommended that any person with recurrent stone formation, or a child with a first stone episode, undergo a 24-hour urine collection. Evaluation of a 24-hour urine sample should include measurement of specific electrolytes and metabolites, including calcium, phosphorus, sodium, uric acid, oxalate, citrate, and creatinine. In addition, urinary volume and urinary ph should be quantified. Computer models are now available that can calculate the likelihood of crystallization based on the (super)saturation of urinary constituents. A single 24-hour urine may be inadequate secondary to variation in daily dietary habits. Repeat 24-hour urine collections should be performed after a prescribed change in diet. A repeat history and basic laboratory values should be performed in patients with findings that suggest systemic disorders, and further work-up should be completed if indicated. Imaging of patient 1, on this occasion with a CT scan, shows the stone to be 8 mm and located at the renal pelvis. The patient does not wish to wait and see if the stone passes spontaneously because of the severe pain he experienced with his first episode. What therapeutic option would be best for patient 1 now? A) Tell the patient that surgery would not be beneficial and that he should just wait. B) Tell the patient surgery is not possible because the stone is still located in the renal pelvis. C) Noninvasive extracorporeal shock wave lithotripsy (ESWL) would be a therapeutic option for this patient. D) Explain that an open procedure would be the best choice for stone retrieval. SURGICAL INTERVENTION The correct answer is C. Surgical intervention differs depending on the location of the stone. ESWL is a minimally invasive, outpatient procedure that can be used to break up stones and allow for spontaneous passage. 14 Generally for ESWL, renal stones must be smaller than 2 cm and ureteral stones must be smaller than 1 cm. It is considered less effective for obese patients or very hard stones. ESWL also is relatively contraindicated in women of childbearing age because the effects on the ovaries are unknown. Complications from obstruction by calculi fragments or the possibility of formation of a perinephric hematoma are possible. NSAIDs, which may be used for analgesia, should be stopped 3 days before ESWL to decrease the risk of bleeding. ESWL is the treatment of choice for small (< 1 cm) proximal ureteral calculi. 14 The success rate of ESWL with distal ureteral stones is much poorer (70% 80%). Patient 1 undergoes ESWL with successful fragmentation of the stone and no complications. Another, more invasive option for intervention is ureteroscopy. This technique is useful for stones located in the middle or lower ureters. In this procedure, the ureteroscope is placed up through the urethra and bladder to the ureters. A holmium laser can be used to break up stones, and a basket can be used to capture fragments. Additionally, stents can be placed if there is a concern for strictures after the procedure. Finally, percutaneous nephrolithotomy is an invasive surgical option for large renal stones (> 2 cm) and proximal ureteral stones. Telescoping instruments are placed through the skin to retrieve large complex stones. This procedure is preferred in patients with anatomically abnormal kidneys. Because the procedure is invasive, there is an increased risk of bleeding and injury to the collecting system and surrounding structures. Open surgery is usually successful but is often unnecessary Internal Medicine Volume 10, Part 4 9

10 Chapter 1 Nephrolithiasis and leads to prolonged recovery as well as postoperative morbidity. Even with successful surgical treatment, only about 75% of patients are stone free at 18 months. Unfortunately, stone fragments left behind by any of these procedures may serve at a focal point for recurrent calculus formation. VII. CASE PATIENT 2 Patient 2 is a 32-year-old woman with a C7 spinal cord injury, secondary to a motor vehicle accident 8 years ago. She presents to the emergency department with 3 days of fever, nausea, and vomiting. Because of a history of urinary retention, the patient straight catheters herself 3 times a day. She has a medical history of multiple urinary infections. The patient also has a history of kidney stones, for which she required percutaneous nephrolithotomy. What type of stone would be the most likely in this patient? A) Calcium oxalate C) Struvite B) Uric acid D) Cystine The correct answer is C. Struvite stones account for approximately 10% of calculi. Struvite is composed primarily of magnesium ammonium phosphate, and the crystals have a coffin-lid shape when viewed under the microscope (Table 3). Patients often have an underlying structural abnormality to the kidney and collecting system that predisposes them to calculi formation. Those with spinal cord injuries and indwelling catheters are also at greatest risk. Struvite often can lead to the formation of staghorn calculi that are the result of and also the source of persistent infections. Urease splitting organisms have been implicated primarily in this process. These include Proteus, Providencia, Klebsiella, Serratia, and Pseudomonas species. Escherichia coli is almost never involved with struvite formation. Staghorn calculi can lead to progressive renal failure, urosepsis, perinephric abscesses, and intractable urinary tract infections, pain, and bleeding. Systemic antibiotics, with favorable antimicrobial sensitivities, often are inadequate at sterilizing the urine (< 20%). The stones create immunologically privileged sites similar to an abscess. Acetohydroxamic acid, an inhibitor of the urease enzyme, has been used to prevent further stone growth. It unfortunately has an unfavorable side effect profile and has been associated with anemia, thrombocytopenia, and headache. Surgical removal is the treatment of choice, particularly for complex stones. As mentioned previously, calcium is the predominant constituent of most renal stones. Other components may predominate based on certain systemic or hereditary processes. Additional history may be helpful in assessing for stone risk. Uric acid stones comprise about 10% of stones diagnosed in the United States; generally, these patients have no demonstrable abnormality in uric acid metabolism. Uric acid may be the solitary component in the stone or it may combine with calcium. Patients with uric acid stones can have isolated hyperuricosuria or systemic gout. Patients with gout may present with uric acid stones before development of joint involvement. Approximately 20% of patients with gout have stones and, 80% of these stones are pure uric acid. 17 Patients with gout also are 10 to 30 times more likely to form calcium-oxalate stones than those without gout. Other disease states may predispose to uric acid stone formation. Those with chronic diarrhea, which leads to decreased serum bicarbonate and dehydration, are at increased risk. Similarly, patients with myeloproliferative disease (ie, polycythemia vera) have an increased total body uric acid content and are thus at greater risk. A history of the use of uricosuric agents, including aspirin or probenecid, also should be sought. Uric acid solubility is dependent on urinary ph, and any process that decreases urinary ph increases the risk of precipitation. Uric acid stones are radiolucent on plain radiographs. Under microscopy, the crystals are often described as amorphous or diamond shaped (Table 3). Patients often complain of passing gravel in their urine. Treatment for uric acid stones involves increasing urine output to decrease uric acid concentration in the urine. Alkalinization of the urine with potassium citrate also has been shown to be beneficial. Finally, allopurinol is indicated in selected patients with uricosuria. Cystine stones result from an inherited disorder of amino acid resorption in the kidney. These stones also have a unique pattern and are readily identified by their hexagonal shape under the microscope (Table 3). Cystine may form staghorn calculi similar to struvite. Cystine stones are often visible on plain radiographs because of the density of sulfa. The natural history of cystine stones is that of frequent recurrence. Treatment consists of increasing fluid intake, especially at night when the excretion of cystine by the kidney is disproportionate. Dietary restriction of methionine, a precursor of cystine, is often difficult because it is an essential amino acid. Foods containing methionine include kidney, liver, sweetbreads, herring, salmon, sardines, mussels, and scallops. Cystine stones are often refractory to lithotripsy; thus, percutaneous or open nephrolithotomy is needed if surgical intervention is necessary. 10 Hospital Physician Board Review Manual

11 Chapter 1 Nephrolithiasis FOLLOW-UP Patient 2 s urine is positive for Proteus infection. A radiograph reveals that she has recurrent nephrolithiasis. She is admitted to the hospital for treatment with IV antibiotics and is scheduled for repeat nephtolithotomy. IV. SUMMARY POINTS Nephrolithiasis prevalence is increasing and accounts for 5 to 10:1000 hospitalizations. The natural history of stone formation is marked by recurrence. Calcium is present in approximately 80% of all stones. Male sex; occupation; a hot, arid environment; and limited water access are risk factors for stone formation. Evaluation for underlying systemic disorders or medication side effects should be undertaken in appropriate patients. Plain radiographs are useful for following stones in patients with a history of calcium stones; nearly 90% of stones are radiopaque. Computed tomography scans can pinpoint the location of stone and possibly identify its composition. Spontaneous passage of small (< 4 mm) distally located stones takes from 1 to 3 weeks on average. Physicians should diligently follow up radiopaque stones with radiographs at 1- to 2-week intervals until passage is noted. If the stone has not spontaneously passed after 4 weeks, a urology consultation should be obtained. Adequate fluid intake (preferably plain water) is recommended for stone prevention. Dietary restriction of protein, oxalate, and sodium may be indicated in calcium stone formers. Magnesium, fiber, calcium, and citrate supplements may prevent recurrent stone formation. For recurrent stones, a 24-hour urine collection should be performed. A repeat collection should be done with any recommended changes in diet to evaluate for a therapeutic change. Medical therapy with hydrochlorothiazide can prevent recurrence in patients with hypercalciuria. Surgical procedures for nephrolithiasis include ESWL, uteroscopic laser techniques, and percutaneous nephrolithotomy. Uric acid stones should be considered in patients with gout, chronic diarrhea, myeloproliferative diseases, or patients on uricosuric agents. Struvite stones are associated with infection and often require surgery as a definitive procedure. Cystine stones are a rare hereditary form of nephrolithiasis. Dietary restriction of methionine is often recommended but is difficult because it is an essential amino acid. REFERENCES 1. Wasserstein AG. Nephrolithiasis. In: Greenberg A, Cheung AK, editors. Primer on kidney diseases. 3rd ed. San Diego: Academic Press; 2001: Uribarri J, Oh MS, Carroll HJ. The first kidney stone. Ann Intern Med 1989;111: Hruska KA. Nephrolithiasis. In: Schrier RW, editor. Diseases of the kidney and urinary tract. Philadelphia: Lippincott, Williams & Wilkins; 2001: Baum N. Cost effective workup for kidney stones. Postgrad Med 1999;106: Goldfarb DS, Coe FL. Prevention of recurrent nephrolithiasis. Am Fam Physician 1999;60: Larkin GL, Peacock WF 4th, Pearl SM, et al. Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. Am J Emerg Med 1999;17: Borghi L, Schianchi T, Meschi T, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 2002;10:346: Buckalew VM Jr. Nephrolithiasis in renal tubular acidosis. J Urol 1989;141: Portis AJ, Sundaram CP. Diagnosis and initial management of kidney stones. Am Fam Physician 2001;63: Begun FP, Foley WD, Peterson A, White B. Patient evaluation. Laboratory and imaging studies. Urol Clin North Am 1997;24(1): Mostafavi MR, Ernst RD, Saltzman B. Accurate determination of chemical composition of urinary calculi by spiral computerized tomography. J Urol 1998;159: Coe FL, Parks JH, Asplin JR. The pathogenesis and treatment of kidney stones. N Engl J Med 1992;327: Miller OF, Kane CJ. Time to stone passage for observed ureteral calculi: a guide for patient education. J Urol 1999;162: Segura JW, Preminger GM, Assimos DG, et al. Ureteral Stones Clinical Guidelines Panel summary report on the management of ureteral calculi. The American Urological Association. J Urol 1997;158: Glowacki LS, Beecroft ML, Cook RJ, et al. The natural history of asymptomatic urolithiasis. J Urol 1992;147: Parivar F, Low RK, Stoller ML. The influence of diet on urinary stone disease. J Urol 1996;155: Asplin JR. Uric acid stones. Semin Nephrol 1996;16: Copyright 2003 by Turner White Communications Inc., Wayne, PA. All rights reserved. Internal Medicine Volume 10, Part 4 11

12 Chapter 2 Chapter 2 Valvular Cardiac Disease Richard J. Simons, MD, FACP, and C. Randy Hubbard, MD I. INTRODUCTION Valvular heart disease is an important topic in cardiology and internal medicine, especially with the increasing age of the population. The field has made major advances in the past 15 to 20 years, largely due to improved methods of noninvasive assessment of valvular as well as ventricular function. There also have been advances in treatments, both surgical and medical, leading to less morbidity and mortality than in the past. In this article, common presentations, physical examination findings, and diagnostic and therapeutic strategies will be highlighted. II. AORTIC STENOSIS CASE 3 INITIAL PRESENTATION A 64-year-old man presents for his annual physical examination. He is in good health and is very active, running his own company and travelling extensively. He recently returned from a 2-week hiking and camping trip. He denies any complaints on review of systems. On physical examination, a grade 3/6 systolic ejection murmur is noted at the right upper sternal border. There is a soft S 2. An echocardiogram is obtained, which shows aortic stenosis with a valve area of 0.8 cm 2 and a transvalvular gradient of 40 mm Hg. Which of the following is appropriate for managing this patient? A) Schedule cardiac catheterization to assess for coronary disease prior to valve replacement B) Refer to cardiothoracic surgeon for valve replacement C) Watchful waiting D) 24-hour Holter monitoring to evaluate for arrhythmia The best answer is C. Aortic stenosis is one of the most common valvular lesions in the United States. Between 1% and 2% of the population are born with a bicuspid aortic valve, which is more prone to stenosis than are tricuspid valves. There is evidence that some of the same risk factors that predispose to coronary arteriosclerosis (ie, hypertension, hyperlipidemia, and inflammation) (Table 5) may play a role in aortic stenosis as well. A characteristic murmur and a diminished or absent S 2, even in the absence of symptoms, should prompt an echocardiographic evaluation. 1 3 In patients with symptomatic aortic stenosis, there is strong evidence that valve replacement surgery prolongs survival. 4 6 However, the course is less clear in asymptomatic patients with severe stenosis. It is estimated that 1% to 2% of patients with severe asymptomatic aortic stenosis will have sudden death or rapid progression to severe symptomatic disease. 4,5,7 The perioperative mortality rate is about 1% for aortic valve surgery. 8,9 Several studies have compared early surgical intervention with watchful waiting. These studies show that it is generally safe to delay surgery until symptoms develop. 4,7,10,11 Some suggest that serial echocardiography may be helpful to assist in earlier identification of patients who may require surgery for worsening stenosis and increasing left ventricular hypertrophy. Concentric hypertrophy is the normal adaptive response to stenosis. The hypertrophied myocardium has higher oxygen demands and aortic stenosis can diminish coronary blood flow, which can in turn lead to both systolic and diastolic dysfunction. 4 Stress testing is contraindicated in patients with symptomatic disease. In asymptomatic patients, stress testing under close physician supervision may be done. Testing may demonstrate symptoms that had not been previously noted by the patient. In one study, 21 of 58 patients developed symptoms for the first time during stress testing. 12 This test may help to identify patients earlier who may benefit from surgical intervention. 2,4,13 CASE 3 FOLLOW-UP The patient returns 8 months later. He has had progressive shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, and lower extremity edema. He reports chest pain with exertion. What is the next most appropriate step in this patient s management? 12 Hospital Physician Board Review Manual