eMedicine Specialties > Radiology > Genitourinary

Papillary Necrosis

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Muthusamy Chandramohan, MBBS, DMRD, FRCR, Consultant Radiologist, Bradford Teaching Hospitals, UK; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute

Updated: Dec 5, 2008

Introduction

Excretory urography in a 53-year-old man with analgesic-induced nephropathy. A film obtained at 15 minutes after administration of contrast shows a wavy renal outline with tracks of contrast extending from fornix, ring shadows caused by the sloughing of papillae, and an egg-in-a-cup appearance characteristic of renal papillary necrosis. Note the bamboo spine, characteristic of ankylosing spondylitis.

Excretory urography in a patient with renal papillary necrosis and pyeloureteritis cystica. Note the bilateral loss of the renal mantle with contrast tracking from the renal fornix in the lower pole of the right kidney. Note also the multiple smooth filling defects in the ureter, caused by ureteritis cystica.

Background

Renal papillary necrosis refers to ischemic necrobiosis of the papilla in the medulla of the kidneys. A number of conditions may cause renal papillary necrosis; it may be associated with the use of analgesic agents. Renal papillary necrosis may be localized or diffuse and unilateral or bilateral. Earlier in the disease, renal size and function are preserved. Function may deteriorate; in the later stages of the disease, renal failure may occur.

Related eMedicine topics:

Papillary Necrosis (Urology)

Renal Failure, Acute

Anemia, Acute

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Presentation

Demographics

• In the United States, the overall incidence of papillary necrosis appears to be the same as is found internationally.
• Most cases of renal papillary necrosis are not reported; therefore, the incidence is not known with certainty.
• Prevalence of analgesic-induced renal papillary necrosis appears to be higher in North America, Europe, and Australia. The association of renal papillary necrosis with dehydration suggests that it may be more common and severe in hot and humid conditions.
• Renal papillary necrosis resulting from analgesic use is observed more often in middle-aged and elderly women. Gastroenteritis and dehydration associated with papillary necrosis are observed in infants and children.
• Progression of renal papillary necrosis may result in eventual renal failure, anemia, and uremia. Transitional cell carcinoma appears to be more common in patients with analgesic nephropathy.

The minor calices unite with their neighbors to form larger, major calices, which in turn fuse with each other to form the renal pelvis. The papilla is the site of drainage of the papillary ducts, which are a continuation of the terminal uriniferous ducts. The numerous openings of the papillary ducts at the papillary summit give rise to area cribrosa. Beside the papillary ducts, the renal papilla has a rich blood supply comprising the vasa recta, part of the loop of Henle, and meshes of capillary network. Medullary ischemia is the central finding in experimental analgesic nephropathy. Necrobiosis of the loops of Henle and the vasa recta is found as an early abnormality.

• Use of analgesics
• Diabetes mellitus (DM) with infection (no increase in incidence occurs in patients with uncomplicated DM)
• Urinary tract infection
• Urinary tract obstruction
• Hemoglobinopathies, such as sickle cell disease
• Prolonged hypotension
• Renal vein thrombosis
• Congestive heart failure
• Cirrhosis
• Hemophilia
• Christmas disease
• Pediatric gastroenteritis (infants)
• Severe neonatal jaundice
• Severe dehydration
• Acidosis and respiratory distress

In the early stage, medullary ischemia results in necrobiosis of the Henle loop and the vasa recta in the papillary tip. In the intermediate stage, patchy necrosis occurs in the papillae. In the advanced stage, necrosis occurs in all elements of the papillae, with clear demarcation between necrotic and viable papillary tissue. In the most advanced stage, diffuse fibrosis and chronic inflammatory cell infiltration into the interstitium occur; these developments account for the deterioration in renal function.

Analgesic nephritis (analgesic abuse nephropathy) is associated with renal papillary necrosis; it is a common cause of chronic renal insufficiency in certain parts of the world. In parts of Australia and Western Europe, analgesic nephritis ranks as one of the most common causes of chronic renal insufficiency. In the United States, the incidence of analgesic nephritis is low; however, analgesic nephritis may account for as much as 13% of cases of end-stage renal disease in the southeastern United States.^{[1 ]}

Renal damage was reported to occur with phenacetin use; phenacetin has largely been withdrawn. Renal damage was reported to occur after a minimum of 2-3 kg of phenacetin was taken over a period of 3 years. The diagnosis of analgesic nephropathy is often made in middle-aged and elderly women who describe a history of ingestion of large amounts of analgesics over long periods. This disorder is particularly severe in hot and dry climates, suggesting that dehydration may enhance the toxic effects of analgesics.

Although analgesic nephropathy was initially described with phenacetin use, the analgesic mixtures consumed by persons who later develop analgesic nephropathy often contain, in addition, aspirin, caffeine, acetaminophen (a metabolite of phenacetin), and codeine. Nonsteroidal anti-inflammatory agents that, in common with aspirin, inhibit prostaglandin synthetase activity may also cause papillary necrosis. At times, a history of excessive analgesic use in women who often take analgesics for migraine or menorrhagia may be difficult to elicit.^{[2,3,4 ]}

Preferred Examination

• Plain radiographs demonstrate calcification in a sloughed papilla, which is characteristically ring shaped; such calcification may be the only abnormal radiologic finding in necrosis in situ. Calcification is common in patients with analgesic-induced papillary necrosis, but it has not been reported in cases of renal papillary necrosis associated with hemoglobinopathy.^{[5,6,7,8 ]}
• On excretory urography, persistent streaking of contrast from the fornix at the upper and lower poles is almost diagnostic of renal papillary necrosis. Necrosis in situ is difficult to diagnose because the necrotic tissue does not slough.
• Retrograde pyeloureterograph images are sensitive, especially in the presence of renal impairment or when urographic findings are inconclusive.
• Ultrasound is a noninvasive technique that is frequently used to assess the urinary tract. Findings are nonspecific for papillary necrosis.^{[9 ]}
• CT findings are not diagnostic but may be useful in assessing urinary tract obstruction, hemoglobinopathies, and cirrhosis; these conditions are recognized causes of papillary necrosis.
• MRI findings are nonspecific in cases of papillary necrosis, although MRI may be useful for patients who are allergic to iodinated contrast medium because gadolinium may provide a useful alternative. Gadolinium-enhanced MRI is a useful alternative for patients with renal failure.

• Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.
• Radioisotope scanning provides a sensitive index of renal function.

Limitations of Techniques

• On plain radiographs, necrotic papillae may occasionally demonstrate a ring of calcification.
• On excretory urography, the ulcerated papillae may be observed. Sloughed papillae may cause filling defects within the calyx, pelvocalyceal system, or ureter.
• Retrograde pyelography may be helpful when the renal collecting system opacifies poorly or when renal insufficiency is present.
• On ultrasound, sloughed papillae may appear as echogenic material within the collecting system; this is a nonspecific finding. Correlation with clinical and laboratory findings help distinguish renal papillary necrosis from other renal abnormalities that have similar features on ultrasound and that are associated with areas of increased echogenicity (eg, nephrocalcinosis).
• No major role exists for CT and MRI in the evaluation of renal papillary necrosis. The usefulness of reformatted multislice spiral CT has yet to be determined. CT findings are not diagnostic but may be useful for patients with poor renal function in whom intravenous urogram radiographs are of poor resolution. Findings of a medullary cavity and calcification are nonspecific. MRI is an expensive tool, but it may be useful for patients with poor renal function and for those who experience hypersensitivity to iodinated contrast media.
• Radioisotope studies play a significant role in evaluating renal function, but they provide little anatomic information on the location of lesions.

Differential Diagnoses

Medullary Sponge Kidney
Tuberculosis, Genitourinary Tract

Other Problems to Be Considered

Calyceal diverticulum
Congenital megacalyx
Renal tuberculosis
Postobstructive atrophy
Postinflammatory atrophy
Reflux atrophy

Radiography

Excretory urography in a patient with diabetes. A film obtained at 5 minutes shows horns from the calices, ring shadows, and an egg-in-a-cup appearance (ring sign) characteristic of renal papillary necrosis.

Excretory urography in a 53-year-old man with analgesic-induced nephropathy. A film obtained at 15 minutes after administration of contrast shows a wavy renal outline with tracks of contrast extending from fornix, ring shadows caused by the sloughing of papillae, and an egg-in-a-cup appearance characteristic of renal papillary necrosis. Note the bamboo spine, characteristic of ankylosing spondylitis.

Nephrotomogram in a 53-year-old man with analgesic-induced nephropathy (same patient as above) clearly demonstrates a wavy contour of the renal outline (ie, renal scars with focal atrophy).

Excretory urography in a patient with renal papillary necrosis and pyeloureteritis cystica. Note the bilateral loss of the renal mantle with contrast tracking from the renal fornix in the lower pole of the right kidney. Note also the multiple smooth filling defects in the ureter, caused by ureteritis cystica.

Findings

Techniques and findings

• Plain radiograph findings
  • The kidneys are normal in size and contour except in the late stage of disease, during which they shrink and demonstrate a wavy contour as a result of the prominence of the septal cortex around the atrophied centrilobular cortex.
  • Sloughed papillae may calcify; they may be observed as curvilinear or ringlike calcification measuring up to 5-6 mm in diameter. The appearance of calcification implies that a change in urine bacteriology has occurred such that Proteus organisms predominate.
  • Tiny calcifications may be observed in the region of the liver, spleen, adrenal glands, and lymph nodes in patients with abdominal tuberculosis.
• Excretory urography findings (see Images above)
  • Urographic findings depend on the stage of the disease.
  • The kidneys are of normal size, and the contour is smooth until the late stage, in which the kidneys shrink and demonstrate a wavy contour.
  • In the early stage, papillary swelling may be the only abnormal finding; papillary necrosis may be difficult to diagnose.
  • Later, necrosis of the papillae, in association with disruption of the urothelial lining, causes tracking of contrast from the fornix parallel to the long axis of the papillae. These developments may produce the lobster claw sign. Cavitation of renal papillae then occurs; such cavitation may be incomplete (medullary) or complete (papillary) and may be either central or eccentric.
  • Shrinkage and sloughing of the necrotic papillae cause forniceal widening and calyceal clubbing.
  • Sloughed papillae cause a filling defect in the pelvocalyceal system and in the ureter.
  • Retrograde pyeloureterography findings
    • Findings are similar to those of excretory urography.
    • Minor abnormal papillary findings may be demonstrated readily when urographic findings are indeterminate.

Calcification in a sloughed papilla is characteristically ring shaped and may be the only abnormal radiologic finding in cases of necrosis in situ. Calcification is common in patients with analgesic-induced papillary necrosis; it has not been reported in patients who have papillary necrosis associated with hemoglobinopathy.

Persistent streaking of contrast from the polar fornix is almost diagnostic of renal papillary necrosis. Necrosis in situ is difficult to diagnose because necrotic tissue does not slough. Filling defects within the pelvocalyceal system and the ureter are nonspecific findings. Opacification of the collecting system is poor when renal function is impaired.

Medullary calcification may occur in patients with hyperparathyroidism, renal tubular acidosis, and medullary sponge kidney, as well as patients with hypercalcemia. The presence of ringlike calcifications of up to 5-6 mm in diameter is characteristic of sloughed papillae.

Findings of medullary calcification (nephrocalcinosis) are nonspecific.  Calcification may be the only abnormal radiologic finding in papillary necrosis in situ.

Imaging pearls

• Retrograde pyelography is sensitive, especially in the presence of renal impairment or for patients in whom urographic findings are inconclusive. The procedure cannot help in the assessment of renal function or the renal parenchyma.
• In the early stage, when papillary swelling may be the only abnormal radiologic finding, swelling is difficult to recognize. Necrosis in situ cannot be diagnosed unless calcification has occurred.
• Pyelosinus extravasation, which may occur with forceful injection of a large volume of contrast, may mimic the tracking of contrast from the fornix in papillary necrosis.
• Inadvertent injection of air bubbles may produce filling defects, but the defects appear smooth and rounded and therefore may be differentiated from the irregular filling defects found in sloughed papillae.

Computed Tomography

Findings

Techniques and findings

CT does not offer much help in the diagnosis of renal papillary necrosis, but reformatted multidetector images may change the role of CT.^{[7,10,11,12,13 ]}

• CT is sensitive in detecting calcifications.
• CT may demonstrate multiple bilateral ring shadows in the medulla, some of which are triangular.
• Contrast may fill the clefts in the renal parenchyma.
• CT may be helpful in evaluating the nature of the material (sloughed papillae)^{[14 ]}that causes the filling defect within the collecting system.
• Findings of a medullary cavity and calcification are nonspecific.

Imaging pearls

• CT findings are not diagnostic, but the scans may be useful for patients with poor renal function in whom intravenous pyelogram findings are not helpful.
• Iodinated contrast agents should be used cautiously in patients with compromised renal function.

Magnetic Resonance Imaging

Findings

Techniques and findings

MRI has no specific role in the management of papillary necrosis; however, it may provide a useful alternative to iodinated contrast for patients with depressed renal function and for those who are allergic to iodinated contrast medium.^{[5,6 ]}

Accuracy

There is insufficient experience with MRI in the diagnosis of papillary necrosis to draw conclusions about its reliability.

The rates of false-positive and false-negative diagnoses of renal papillary necrosis with the use of MRI have not yet been determined.

Ultrasonography

Findings

Techniques and findings

• Sonographically, areas of cavitation in the papillae may appear as multiple rounded or triangular cystic spaces in the medulla arranged around a renal sinus echo, demonstrating a garland pattern.
• Occasionally, bright echoes produced by arcuate arteries may be visualized at the periphery of the cystic space.
• Sloughed papillae may appear echogenic and cast shadows when calcified.
• The collecting system may be dilated when obstructed by sloughed papillae.
• A hyperechoic medulla may be observed in patients with hyperparathyroidism and medullary sponge kidney and in patients with conditions that cause hypokalemia or hypercalcemia.

Accuracy

• Sonographic findings are nonspecific for patients with renal papillary necrosis.

Nuclear Imaging

Findings

No role exists for isotope studies in the diagnosis of renal papillary necrosis; however, such studies are useful in evaluating renal function.

Intervention

Special Concerns

• Transitional cell carcinoma is more common in patients with analgesia-induced papillary necrosis.

Multimedia

Media file 1: Excretory urography in a patient with diabetes. A film obtained at 5 minutes shows horns from the calices, ring shadows, and an egg-in-a-cup appearance (ring sign) characteristic of renal papillary necrosis.

Media file 2: Excretory urography in a 53-year-old man with analgesic-induced nephropathy. A film obtained at 15 minutes after administration of contrast shows a wavy renal outline with tracks of contrast extending from fornix, ring shadows caused by the sloughing of papillae, and an egg-in-a-cup appearance characteristic of renal papillary necrosis. Note the bamboo spine, characteristic of ankylosing spondylitis.

Media file 3: Nephrotomogram in a 53-year-old man with analgesic-induced nephropathy (same patient as above) clearly demonstrates a wavy contour of the renal outline (ie, renal scars with focal atrophy).

Media file 4: Excretory urography in a patient with renal papillary necrosis and pyeloureteritis cystica. Note the bilateral loss of the renal mantle with contrast tracking from the renal fornix in the lower pole of the right kidney. Note also the multiple smooth filling defects in the ureter, caused by ureteritis cystica.

References

1. Gonwa TA, Hamilton RW, Buckalew VM Jr. Chronic renal failure and end-stage renal disease in northwest North Carolina. Importance of analgesic-associated nephropathy. Arch Intern Med. Mar 1981;141(4):462-5. [Medline].

2. De Broe ME, Elseviers MM. Analgesic nephropathy. N Engl J Med. Feb 12 1998;338(7):446-52. [Medline].

3. Henrich WL. Analgesic nephropathy. Trans Am Clin Climatol Assoc. 1998;109:147-58; discussion 158-9. [Medline].

4. Kovacevic L, Bernstein J, Valentini RP, et al. Renal papillary necrosis induced by naproxen. Pediatr Nephrol. Aug 2003;18(8):826-9. [Medline].

5. Pedrosa I, Chou MT, Ngo L, H Baroni R, Genega EM, Galaburda L, et al. MR classification of renal masses with pathologic correlation. Eur Radiol. Feb 2008;18(2):365-75. [Medline].

6. Pedrosa I, Sun MR, Spencer M, Genega EM, Olumi AF, Dewolf WC, et al. MR imaging of renal masses: correlation with findings at surgery and pathologic analysis. Radiographics. Jul-Aug 2008;28(4):985-1003. [Medline].

7. Craig WD, Wagner BJ, Travis MD. Pyelonephritis: radiologic-pathologic review. Radiographics. Jan-Feb 2008;28(1):255-77; quiz 327-8. [Medline].

8. Prasad SR, Narra VR, Shah R, Humphrey PA, Jagirdar J, Catena JR, et al. Segmental disorders of the nephron: histopathological and imaging perspective. Br J Radiol. Aug 2007;80(956):593-602. [Medline].

9. Vijayaraghavan SB, Kandasamy SV, Mylsamy A, Prabhakar M. Sonographic features of necrosed renal papillae causing hydronephrosis. J Ultrasound Med. Sep 2003;22(9):951-6; quiz 957-8. [Medline].

10. Hill SC, Hoeg JM, Avila NA. Nephrocalcinosis in homozygous familial hypercholesterolemia: ultrasound and CT findings. J Comput Assist Tomogr. Jan-Feb 1991;15(1):101-3. [Medline].

11. Saifuddin A, Bark M. Case report: computed tomography demonstration of renal papillary necrosis. Clin Radiol. Oct 1991;44(4):275-6. [Medline].

12. Jung DC, Kim SH, Jung SI, Hwang SI, Kim SH. Renal papillary necrosis: review and comparison of findings at multi-detector row CT and intravenous urography. Radiographics. Nov-Dec 2006;26(6):1827-36. [Medline].

13. Henrich WL, Clark RL, Kelly JP, Buckalew VM, Fenves A, Finn WF, et al. Non-contrast-enhanced computerized tomography and analgesic-related kidney disease: report of the national analgesic nephropathy study. J Am Soc Nephrol. May 2006;17(5):1472-80. [Medline].

14. Gordon M, Cervellione RM, Postlethwaite R, Shabani A, Hennayake S. Acute renal papillary necrosis with complete bilateral ureteral obstruction in a child. Urology. Mar 2007;69(3):575.e11-2. [Medline].

15. Chitale SV, Sams VR, Burgess NA. Pericalyceal haemangioma and papillary necrosis. J R Soc Med. Sep 2000;93(9):482-3. [Medline].

16. Laissy JP, Abecidan E, Karila-Cohen P, et al. [IVU: a test of the past without future?]. Prog Urol. Jun 2001;11(3):552-61. [Medline].

Keywords

papillary necrosis, renal medullary necrosis, necrotizing papillitis, renal papillary necrosis, localized papillary necrosis, diffuse papillary necrosis, unilateral papillary necrosis, bilateral papillary necrosis, renal dysfunction, renal failure, anemia, uremia

Contributor Information and Disclosures

Author

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England
Disclosure: Nothing to disclose.

Coauthor(s)

Muthusamy Chandramohan, MBBS, DMRD, FRCR, Consultant Radiologist, Bradford Teaching Hospitals, UK
Disclosure: Nothing to disclose.

Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute
Sumaira MacDonald, MBChB, PhD, MRCP, FRCR is a member of the following medical societies: British Medical Association, Royal College of Physicians, and Royal College of Radiologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Joshua A Becker, MD, Professor, Department of Radiology, New York University School of Medicine
Joshua A Becker, MD is a member of the following medical societies: Society of Uroradiology
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Clinical Assistant Professor of Radiology, University of Washington School of Medicine; Consulting Radiologist, Virginia Mason Medical Center
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

Related eMedicine topics:

Papillary Necrosis (Urology)

Renal Failure, Acute

Anemia, Acute

Related Medscape topics:

Radiology CME and News

Specialty Site Radiology

Specialty Site Urology

Resource Center Dialysis 

Resource Center Kidney & Pancreas Transplant

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