Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Hydronephrosis and Hydroureter Workup

  • Author: Dennis G Lusaya, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
 
Updated: Jul 18, 2016
 

Laboratory Studies

Urinalysis is used to assess for signs of infection. Pyuria suggests the presence of infection. Microscopic hematuria may indicate the presence of a stone or tumor.

Complete blood cell count may reveal leukocytosis, which may indicate acute infection.

Serum chemistry studies can reveal an elevation of BUN and creatinine levels, which may be the result of bilateral hydronephrosis and hydroureter. In addition, hyperkalemia can be a life-threatening condition.

Next

Imaging Studies

Imaging in adults

Early diagnosis of urinary tract obstruction is important because most cases can be corrected and a delay in therapy can lead to irreversible renal injury.

Bladder catheterization should be performed initially if there is reason to suspect that bladder neck obstruction leading to acute or chronic urinary retention may be present. Possible clues to this diagnosis include suprapubic pain, a palpable bladder, or unexplained renal failure in an older man.

Radiologic tests are generally used to exclude obstruction at the level of the ureters or above by detecting dilatation of the collecting system. It is important to remember, therefore, that obstruction can occur without dilatation in the following three settings:

  • Within the first 1-3 days, when the collecting system is relatively noncompliant and less likely to dilate: In this setting, unilateral obstruction can usually be diagnosed by duplex Doppler ultrasonography, which detects an increased resistive index (a reflection of increased renal vascular resistance) in the affected compared with the contralateral kidney. [8] This test is of no value with bilateral involvement because it cannot distinguish obstruction from intrinsic renal disease.
  • When the collecting systems are encased by retroperitoneal tumor or fibrosis: In this setting, hydronephrosis may be present in the absence of ureteral dilatation. Retroperitoneal fibrosis can occur in a number of settings, including retroperitoneal fibrosis (most commonly idiopathic or associated with beta-blocker or methysergide use, malignancy, or a connective-tissue disorder) and with the fibrotic reaction that surrounds a renal transplant. [9] Thus, the diagnosis of renal insufficiency due to asymptomatic obstruction in a transplanted kidney may be made based on renal biopsy findings, which show diffuse tubular dilatation, rather than the signs of rejection or cyclosporine nephrotoxicity.
  • When the obstruction is mild, a setting in which renal function is not usually impaired

Renal ultrasonography is the test of choice to exclude urinary tract obstruction, avoiding the potential allergic and toxic complications of radiocontrast media.[10] It can, in the majority of affected patients, help diagnose hydronephrosis and establish its cause; it can also detect other causes of renal disease such as polycystic kidney disease.

Although ultrasound can accurately identify hydronephrosis, it is less sensitive than computed tomography (CT) for detecting stones in the ureters. In one study, hydronephrosis on ultrasound had a positive predictive value of 0.77 for the presence of a ureteral stone and a negative predictive value of 0.71 for the absence of a ureteral stone.[11]

Indications for CT scanning include the following:

  • Ultrasonography results are equivocal
  • The kidneys cannot be well visualized
  • The cause of the obstruction cannot be identified

The combination of a plain film of the abdomen (including tomographic cuts to detect radiopaque calculi), ultrasonography, and, if necessary, CT scanning is adequate for diagnostic purposes in over 90% of cases.[12] It should be noted, however, that the false-positive rate for ultrasonography may be as high as 25% if only minimal criteria (any visualization of the collecting systems) are used to diagnose obstruction.

advantages in relation to ultrasonography. The false-positive rate is very low, it can identify the site of obstruction, and it can help detect associated conditions such as papillary necrosis or calyceal blunting from previous infection.[12] Disadvantages are that IVP is more cumbersome to perform and requires the administration of a radiocontrast agent. On balance, IVP can be used to screen for urinary tract obstruction in the following settings:

  • In patients with staghorn calculi or multiple renal or parapelvic cysts, since hydronephrosis is usually not distinguishable from cysts or stones by ultrasonography or CT
  • When CT scanning cannot identify the level of obstruction
  • With suspected acute obstruction due to kidney stones (or less frequently, to other problems, such as a sloughed papilla or blood clot): Dilatation of the collecting system may not be seen at this time, but the presence and location of the obstructing stone can be identified

Diffusion-weighted magnetic resonance imaging (MRI) may allow noninvasive detection of changes in renal perfusion and diffusion that occur during acute ureteral obstruction.[13] The advantage of this technique is that it does not require the use of contrast agents. However, the clinical utility of diffusion-weighted MRI has not been adequately tested.

Hydronephrosis without apparent obstruction or with asymptomatic obstruction

In some cases, one of the above radiologic tests demonstrates hydronephrosis without evidence of obstruction. This is a normal finding in pregnant women. Megaureter due to previous marked vesicoureteral reflux or a dilated but nonobstructed extrarenal pelvis is the most common example of this problem. These patients are often being evaluated for back or flank pain, and the following two questions need to be answered:

  • Is obstruction present?
  • Is the obstruction responsible for the pain?

In this setting, 3 different tests have been used, and these are diuretic renography, IVP (less often), and perfusion pressure flow studies.[1]

Diuretic renography involves the administration of a loop diuretic (eg, 0.5 mg/kg of furosemide) prior to radionuclide renal scanning or during IVP, while the latter involves percutaneous insertion of a catheter into the dilated renal pelvis, followed by fluid perfusion into the pelvis at a rate of 10 mL/min. The marked increase in urine flow should, if obstruction is present, slow the rate of washout of the radioisotope during renal scanning, further increase the size of the collecting system on IVP, or elevate the renal pelvic pressure to above 22 mm Hg during a perfusion study. Furthermore, any of these procedures may precipitate pain similar to the patient's initial complaint.

Noninvasive diuretic renography is generally preferred. However, optimal interpretation of any of these test results is uncertain, because both false-positive and false-negative results may be seen. Nevertheless, the following general recommendations have been made:

  • Surgical correction should be considered in a patient with pain and positive diuretic renography findings.
  • No therapy is necessary in an asymptomatic patient with positive diuretic renography findings but normal renal function. These patients often are adults and have therefore had the partial obstruction for many years without apparent damage to the kidney. Hydronephrosis may first be noted after a radiologic study is performed for some other reason, or, as noted above, obstruction may be suspected when pain is induced after a period of high fluid intake leads to a diuresis that exceeds the rate at which urine can flow through the obstructed area. Similarly, the decreased washout observed on renography occurs only at a urine flow rate much higher than the patient is likely to achieve on his or her own. Periodic monitoring of renal function and renal parenchymal size (by ultrasonography) is indicated in these patients to exclude progressive renal injury.
  • No therapy is indicated in an asymptomatic patient with negative renography findings. Long-term follow-up has demonstrated stable renal function in most of these patients.
  • A perfusion pressure flow study should be performed in a symptomatic patient with negative or equivocal diuretic renography findings. Some nonrenal cause for the pain is probably present if the perfusion study is negative. On the other hand, a positive study is suggestive of obstruction and the need for surgical correction.
  • A perfusion pressure flow study may also be performed in patients with hydronephrosis and poor renal function. The diuretic renogram may be falsely negative in this setting, because the diuretic may not sufficiently raise the urine flow.

In general, approximately 50% of patients with positive diuretic renography findings eventually require surgery, either for pain or progressive parenchymal loss.[14]

Imaging in children

Detection of antenatal hydronephrosis by ultrasound usually occurs in the second trimester with a renal pelvic dilation (RPD) cutoff of greater than or equal to 4 mm. Mild hydronephrosis (RPD of 4-10 mm or Society for Fetal Urology [SFU] grade 1 or 2) can be associated with Down syndrome or other chromosome anomalies. More severe dilatation increases the risk of renal and/or urinary tract disorders.

During the ultrasonography, the appearance of the fetal renal system can vary in both healthy fetuses without hydronephrosis and those with hydronephrosis. Therefore, this diagnosis should not be based on a single measurement.[15] An increase of maternal hydration can also increase the RPD in both healthy fetuses and those with hydronephrosis.[16]

If fetal hydronephrosis is detected, the following parameters need to be evaluated using ultrasonography, as they guide further need for evaluation and are helpful in determining the cause of hydronephrosis:

  • Severity of hydronephrosis: The likelihood of a congenital kidney or urinary tract anomaly increases with the severity of RPD.
  • Unilateral versus bilateral involvement: Bilateral involvement increases the risk of a significant renal abnormality and the risk of impaired postnatal renal function.
  • Ureter: Dilatation of the ureter can be consistent with vesicoureteral reflux (VUR) or obstructive uropathy distal to the ureteropelvic junction.

Postnatal radiologic studies

Postnatal radiologic evaluation of a newborn with antenatal hydronephrosis begins with an ultrasonography examination. The timing of ultrasonography and the need for other studies depend on the severity of postnatal hydronephrosis and whether there is bilateral involvement or an affected solitary kidney.

Ultrasonography of kidneys and bladder should be performed in the postnatal period on affected infants. The timing of the study depends on the severity of the antenatal hydronephrosis. In general, examination should be avoided in the first 2 days after birth because hydronephrosis may not be detected because of extracellular fluid shifts that underestimate the degree of hydronephrosis. However, infants with bilateral hydronephrosis and those with a severe hydronephrotic solitary kidney require urgent evaluation on the first postnatal day because of the increased likelihood of significant disease and a possible need for early intervention. For unilateral hydronephrosis without antenatal bladder pathology, performing postnatal sonography 1-4 weeks after birth is recommended.

A voiding cystourethrography (VCUG) is performed to detect VUR and, in boys, to evaluate the posterior urethra. For this procedure, a urinary catheter is inserted into the bladder and contrast material is instilled. Fluoroscopic monitoring is performed while the bladder is filling and during voiding. Infants usually tolerate this procedure well. Although the duration of fluoroscopy is minimized, the gonads, especially the ovaries, are exposed to radiation.[17]

Diuretic renography is used to diagnose urinary tract obstruction in infants with persistent hydronephrosis and is usually ordered after a VCUG has demonstrated no vesicoureteral reflux.[18] It measures the drainage time from the renal pelvis and assesses total and individual kidney renal function. The test requires insertion of a bladder catheter to relieve any pressure that can be transmitted to the ureters and kidneys. Intravenous access is needed for hydration and the administration of the radioisotope and diuretic. The preferred radioisotope is technetium Tc 99m-mercaptoacetyltriglycine (Tc99mMAG3), which is taken up by the renal cortex, filtered across the glomerular basement membrane to the renal tubules, and excreted into the renal pelvis and urinary tract.[19]

Diuretic renography includes two phases. First, radioisotope is injected intravenously and renal parenchymal (cortical) uptake is measured during the first 2-3 minutes. The relative contribution of each kidney to overall renal function (called the split renal function) is assessed quantitatively and is useful as a baseline study. Subsequent studies can be compared to assess whether kidney function remains stable or has deteriorated, suggesting true obstruction.[20]

Second, at peak renal uptake, intravenous furosemide is administered and the excretion of isotope from the kidney is measured, referred to as the washout curve. This phase indicates the extent of obstruction, if present. In a healthy kidney, furosemide administration results in a prompt washout. In a dilated system, if washout occurs rapidly after diuretic administration (<15 min), the system is not obstructed. If washout is delayed beyond 20 minutes, the pattern is consistent with obstructive uropathy. However, a delayed washout must be interpreted with caution.[21, 22]

In a series of 39 infants with antenatal unilateral hydronephrosis followed without surgery, diuretic renography indicated obstruction in 24 patients whose renal function never decreased and who thus did not have obstruction.[22] These results may be due, in part, to the normally low neonatal GFR that can be refractory to diuretic therapy. If washout is from 15-20 minutes, the study is indeterminate.

Gravity-assisted drainage imaging may assist in the assessment of pediatric hydronephrosis. Unlike customary diuretic renography, in which the patient remains supine, with gravity-assisted renography a single, static image is obtained after positioning the child in the upright position for 5 minutes to promote additional drainage of tracer from the collecting system. Notable improvement in drainage with this maneuver suggests that slowness in drainage is not due to urinary tract obstruction.[23]

Split renal function results are the most useful criteria to evaluate a decrease in renal function. In patients with unilateral hydronephrosis (which is the most common clinical scenario), if the normal nonhydronephrotic kidney and hydronephrotic kidney both have equal function, conservative management without surgery is a safe option. In a cohort of 831 cases of antenatal hydronephrosis, renal scanning performed in 229 newborns demonstrated that 16% of patients had a significant decrease in renal function of one kidney, defined as 35% or less differential renal function.[24] A decrease in differential renal function was associated with severe antenatal hydronephrosis (ie, renal pelvic diameter >10 mm at 20-24 wk gestation and >16 mm at 33 wk gestation).

Magnetic resonance urography (MRU) in children is becoming more commonly used in the diagnosis and management of congenital uropathies such as UPJ obstruction.[25, 26] MRU is especially useful in the management of obstructed kidneys that have rotation or ascent anomalies, or are solitary. MRU can more clearly define the anatomy and delineate the proper surgical approach (ie, retroperitoneal vs transperitoneal). Newer MRU technology may even define obstruction, eliminating the need for diuretic renal scanning.

The disadvantage of MRU is that the study often requires general anesthesia or heavy conscious sedation in children. Furthermore, the contrast agent gadolinium can only be used if renal function is normal (requiring a preprocedure serum creatinine test) because of reports of irreversible renal fibrosis in patients with renal insufficiency.

Previous
Next

Procedures

Antegrade or retrograde pyelography is usually used to relieve, rather than diagnose, urinary tract obstruction. These tests, however, can also be performed for diagnosis when the history is highly suggestive (unexplained acute renal failure in a patient with known pelvic malignancy), even though hydronephrosis may be absent (due to possible ureteral encasement) on ultrasonography and CT scanning.[12]

Previous
 
 
Contributor Information and Disclosures
Author

Dennis G Lusaya, MD Associate Professor II, Department of Surgery (Urology), University of Santo Tomas; Head of Urology Unit, Benavides Cancer Institute, University of Santo Tomas Hospital; Chief of Urologic Oncology, St Luke’s Medical Center Global City, Philippines

Dennis G Lusaya, MD is a member of the following medical societies: American Urological Association, Philippine Medical Association, Philippine College of Surgeons, Philippine Urological Association, Philippine Society of Urological Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF Clinical Professor of Medicine, Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine; Research Director, Internal Medicine Training Program, Advocate Christ Medical Center; Consulting Staff, Associates in Nephrology, SC

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF is a member of the following medical societies: American Heart Association, American Medical Association, American Society of Hypertension, American Society of Nephrology, Chicago Medical Society, Illinois State Medical Society, National Kidney Foundation, Society of General Internal Medicine

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Otsuka, Mallinckrodt, ZS Pharma<br/>Author for: UpToDate, ACP Smart Medicine.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, Society of Laparoendoscopic Surgeons, Society of University Urologists, Association of Military Osteopathic Physicians and Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

Additional Contributors

Richard A Santucci, MD, FACS Specialist-in-Chief, Department of Urology, Detroit Medical Center; Chief of Urology, Detroit Receiving Hospital; Director, The Center for Urologic Reconstruction; Clinical Professor of Urology, Michigan State University College of Medicine

Richard A Santucci, MD, FACS is a member of the following medical societies: American College of Surgeons, Societe Internationale d'Urologie (International Society of Urology), American Urological Association

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Srinivas Vourganti, MD, Prakash Maniam, MD, and martin I Resnick, MD, to the development and writing of this article.

References
  1. Rose BD, Black RM. Manual of Clinical Problems in Nephrology. Boston, Mass: Little, Brown & Co; 1988. 337-343.

  2. Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet. 2005 Jan 29-Feb 4. 365(9457):417-30. [Medline].

  3. Rasmussen PE, Nielsen FR. Hydronephrosis during pregnancy: a literature survey. Eur J Obstet Gynecol Reprod Biol. 1988 Mar. 27(3):249-59. [Medline].

  4. Pain VM, Strandhoy JW, Assimis, DG. Pathophysiology of urinary tract obstruction. Kavoussi LR, Novick AC, Partin AW, Peters CA, Wein AJ, eds. Campbell-Walsh Urology. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2007. Vol 2: 1227-73.

  5. Weidmann P, Beretta-Piccoli C, Hirsch D, Reubi FC, Massry SG. Curable hypertension with unilateral hydronephrosis. Studies on the role of circulating renin. Ann Intern Med. 1977 Oct. 87(4):437-40. [Medline].

  6. Vaughan ED Jr, Bühler FR, Laragh JH. Normal renin secretion in hypertensive patients with primarily unilateral chronic hydronephrosis. J Urol. 1974 Aug. 112(2):153-6. [Medline].

  7. Josephson S. Antenatally detected pelvi-ureteric junction obstruction: concerns about conservative management. BJU Int. 2000 May. 85(7):973. [Medline].

  8. Platt JF, Rubin JM, Ellis JH. Acute renal obstruction: evaluation with intrarenal duplex Doppler and conventional US. Radiology. 1993 Mar. 186(3):685-8. [Medline].

  9. Demko TM, Diamond JR, Groff J. Obstructive nephropathy as a result of retroperitoneal fibrosis: a review of its pathogenesis and associations. J Am Soc Nephrol. 1997 Apr. 8(4):684-8. [Medline].

  10. Klahr S. Pathophysiology of obstructive nephropathy. Kidney Int. 1983 Feb. 23(2):414-26. [Medline].

  11. Sternberg KM, Pais VM Jr, Larson T, Han J, Hernandez N, Eisner B. Is hydronephrosis on ultrasound predictive of ureterolithiasis in patients with renal colic?. J Urol. 2016 May 3. [Medline].

  12. Webb JA. Ultrasonography in the diagnosis of renal obstruction. BMJ. 1990 Oct 27. 301(6758):944-6. [Medline]. [Full Text].

  13. Thoeny HC, Binser T, Roth B, Kessler TM, Vermathen P. Noninvasive assessment of acute ureteral obstruction with diffusion-weighted MR imaging: a prospective study. Radiology. 2009 Sep. 252(3):721-8. [Medline].

  14. Lupton EW, Testa HJ. The obstructive diuresis renogram: an appraisal of the significance. J Urol. 1992 Apr. 147(4):981-3. [Medline].

  15. Persutte WH, Hussey M, Chyu J, Hobbins JC. Striking findings concerning the variability in the measurement of the fetal renal collecting system. Ultrasound Obstet Gynecol. 2000 Mar. 15(3):186-90. [Medline].

  16. Robinson JN, Tice K, Kolm P, Abuhamad AZ. Effect of maternal hydration on fetal renal pyelectasis. Obstet Gynecol. 1998 Jul. 92(1):137-41. [Medline].

  17. Woodward M, Frank D. Postnatal management of antenatal hydronephrosis. BJU Int. 2002 Jan. 89(2):149-56. [Medline].

  18. Chung S, Majd M, Rushton HG, Belman AB. Diuretic renography in the evaluation of neonatal hydronephrosis: is it reliable?. J Urol. 1993 Aug. 150(2 Pt 2):765-8. [Medline].

  19. Taylor A Jr, Clark S, Ball T. Comparison of Tc-99m MAG3 and Tc-99m DTPA scintigraphy in neonates. Clin Nucl Med. 1994 Jul. 19(7):575-80. [Medline].

  20. Gordon I. Diuretic renography in infants with prenatal unilateral hydronephrosis: an explanation for the controversy about poor drainage. BJU Int. 2001 Apr. 87(6):551-5. [Medline].

  21. Koff SA. Postnatal management of antenatal hydronephrosis using an observational approach. Urology. 2000 May. 55(5):609-11. [Medline].

  22. Gordon I, Dhillon HK, Gatanash H, Peters AM. Antenatal diagnosis of pelvic hydronephrosis: assessment of renal function and drainage as a guide to management. J Nucl Med. 1991 Sep. 32(9):1649-54. [Medline].

  23. Acker MR, Clark R, Anderson P. Gravity-assisted drainage imaging in the assessment of pediatric hydronephrosis. Can Urol Assoc J. 2016 Mar-Apr. 10 (3-4):96-100. [Medline]. [Full Text].

  24. Kim DY, Mickelson JJ, Helfand BT, Maizels M, Kaplan WE, Yerkes EB. Fetal pyelectasis as predictor of decreased differential renal function. J Urol. 2009 Oct. 182(4 Suppl):1849-53. [Medline].

  25. de Bruyn R, Marks SD. Postnatal investigation of fetal renal disease. Semin Fetal Neonatal Med. 2008 Jun. 13(3):133-41. [Medline].

  26. Grattan-Smith JD, Little SB, Jones RA. MR urography evaluation of obstructive uropathy. Pediatr Radiol. 2008 Jan. 38 Suppl 1:S49-69. [Medline].

  27. Mamì C, Paolata A, Palmara A, et al. Outcome and management of isolated moderate renal pelvis dilatation detected at postnatal screening. Pediatr Nephrol. 2009 Oct. 24(10):2005-8. [Medline].

  28. Dacher JN, Mandell J, Lebowitz RL. Urinary tract infection in infants in spite of prenatal diagnosis of hydronephrosis. Pediatr Radiol. 1992. 22(6):401-4; discussion 404-5. [Medline].

  29. Walsh TJ, Hsieh S, Grady R, Mueller BA. Antenatal hydronephrosis and the risk of pyelonephritis hospitalization during the first year of life. Urology. 2007 May. 69(5):970-4. [Medline].

  30. Coelho GM, Bouzada MC, Lemos GS, Pereira AK, Lima BP, Oliveira EA. Risk factors for urinary tract infection in children with prenatal renal pelvic dilatation. J Urol. 2008 Jan. 179(1):284-9. [Medline].

  31. Estrada CR, Peters CA, Retik AB, Nguyen HT. Vesicoureteral reflux and urinary tract infection in children with a history of prenatal hydronephrosis--should voiding cystourethrography be performed in cases of postnatally persistent grade II hydronephrosis?. J Urol. 2009 Feb. 181(2):801-6; discussion 806-7. [Medline].

  32. Lidefelt KJ, Herthelius M. Antenatal hydronephrosis: infants with minor postnatal dilatation do not need prophylaxis. Pediatr Nephrol. 2008 Nov. 23(11):2021-4. [Medline].

  33. Zareba P, Lorenzo AJ, Braga LH. Risk factors for febrile urinary tract infection in infants with prenatal hydronephrosis: comprehensive single center analysis. J Urol. 2014 May. 191(5 Suppl):1614-8. [Medline].

  34. Braga LH, Mijovic H, Farrokhyar F, Pemberton J, DeMaria J, Lorenzo AJ. Antibiotic prophylaxis for urinary tract infections in antenatal hydronephrosis. Pediatrics. 2013 Jan. 131(1):e251-61. [Medline].

  35. Herz D, Merguerian P, McQuiston L. Continuous antibiotic prophylaxis reduces the risk of febrile UTI in children with asymptomatic antenatal hydronephrosis with either ureteral dilation, high-grade vesicoureteral reflux, or ureterovesical junction obstruction. J Pediatr Urol. 2014 Jul 22. [Medline].

  36. Coplen DE. Prenatal intervention for hydronephrosis. J Urol. 1997 Jun. 157(6):2270-7. [Medline].

  37. Morris RK, Malin GL, Quinlan-Jones E, Middleton LJ, Hemming K, Burke D, et al. Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial. Lancet. 2013 Nov 2. 382(9903):1496-506. [Medline]. [Full Text].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.