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Radiology > GENITOURINARY
Papillary Necrosis
Article Last Updated: Feb 21, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
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 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
Coauthor(s):
Muthusamy Chandramohan, MBBS, DMRD, FRCR, Special Registrar, Department of Radiology, Manchester Radiology;
Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute
Editors: Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Joshua A Becker, MD, Professor, Department of Radiology, New York University School of Medicine; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
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
Background
Renal papillary necrosis refers to ischemic necrobiosis of the papilla in the medulla of the kidneys. A number of conditions can cause renal papillary necrosis but it may be associated with the use of analgesic agents. Renal papillary necrosis can be localized or diffuse and unilateral or bilateral. Earlier in the disease, renal size and function are preserved. Function may deteriorate with eventual renal failure in the later stages of the disease.
Pathophysiology
Renal papillary necrosis occurs in association with the following conditions:
- Use of analgesics
- Diabetes mellitus (DM) with infection (no increase occurs 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 and, 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, which account for the deterioration in renal function.
Analgesic nephritis (analgesic abuse nephropathy) is associated with renal papillary necrosis and 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. Incidence in the United States is low but may account for as much as 13% of endstage renal disease in the southeastern United States (Gonwa, 1981).
Renal damage was first described to occur with phenacetin use but the drug has largely been withdrawn. The minimum requirement for developing renal damage has been calculated at 2-3 kg of phenacetin 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 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 can 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.
Frequency
United States
Overall incidence in the United States appears to be the same as is found internationally.
International
Most cases of renal papillary necrosis are not reported; therefore, quoting the exact incidence is difficult.
Mortality/Morbidity
Progression of renal papillary necrosis can result in eventual renal failure, anemia, and uremia. Transitional cell carcinoma appears to be more common in patients with analgesic nephropathy.
Race
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.
Sex
Analgesic-induced renal papillary necrosis is often observed in middle-aged and elderly women.
Age
Renal papillary necrosis resulting from analgesic use is observed more often in middle-aged and elderly women. Gastroenteritis and dehydration that are associated with papillary necrosis are observed in infants and children.
Anatomy
The renal cortex is subcapsular and arches around the renal medulla. The renal medulla comprises triangular-shaped, pale, striated, conical renal pyramids; their apices converge to the renal sinus. The base of the renal pyramid is capped by renal cortical tissue to form a renal lobe. The conical renal pyramids project into calices as papillae. Each minor calyx receives 1-3 of these papillae.
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.
Clinical Details
Clinical presentation may be related to symptoms of urinary tract infection, such as recurrent fever, malaise, dysuria, flank pain, proteinuria, hematuria, and leukocytosis. Passage of sloughed papillae can cause renal colic, ureteric obstruction and, rarely, urinoma. Rarely, renal papillary necrosis can present as acute oliguric renal failure. In the advanced stage, renal function may be impaired and anemia and uremia may be noted.
Preferred Examination
- Plain radiographs demonstrate calcification in a sloughed papilla, which is characteristically ring shaped and may be the only abnormal radiologic finding in necrosis in situ. Calcification is common in patients with analgesic-induced papillary necrosis but has not been reported in renal papillary necrosis associated with hemoglobinopathy.
- 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.
- CT findings are not diagnostic but may be useful in assessing urinary tract obstruction, hemoglobinopathies, and cirrhosis, which are recognized causes of papillary necrosis.
- MRI findings are nonspecific in papillary necrosis, although MRI may be useful in patients who are allergic to iodinated contrast medium because gadolinium may provide a useful alternative. Gadolinium-enhanced MRI is a useful alternative in patients with renal failure.
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently 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. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. 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 withtroublemovingorstraightening 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 scan findings provide a sensitive index of renal function.
Limitations of Techniques
- On plain radiographs, necrotic papillae can occasionally demonstrate a ring of calcification.
- On excretory urography, the ulcerated papillae can be observed. Sloughed papillae can cause filling defects within the calyx, pelvocalyceal system, or ureter.
- Retrograde pyelography can be helpful when the renal collecting system opacifies poorly or when renal insufficiency is present.
- On ultrasound, sloughed papillae can be revealed as echogenic material within the collecting system, which is a nonspecific finding. Correlation with clinical and laboratory findings help distinguish renal papillary necrosis from other renal abnormalities with similar ultrasound features such as other causes 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 can be useful in patients with poor renal function in whom intravenous urogram radiographs provide poor resolution. Medullary cavity and calcification are nonspecific findings. MRI is an expensive tool but may be useful in patients with poor renal function and in those with hypersensitivity to iodinated contrast media.
- Radioisotope studies play a significant role in evaluating renal function but provide little anatomic information on the location of lesions.
Medullary Sponge Kidney
Tuberculosis, Genitourinary Tract
Other Problems to be Considered
Calyceal diverticulum
Congenital megacalyx
Renal tuberculosis
Postobstructive atrophy
Postinflammatory atrophy
Reflux atrophy
Findings
- Plain radiograph findings
- Kidneys are normal in size and contour except in the late stage in which they shrink and demonstrate a wavy contour due to the prominence of the septal cortex around the atrophied centrilobular cortex.
- Sloughed papillae may calcify and can be observed as curvilinear or ringlike calcification up to 5-6 mm in diameter. The appearance of calcification infers a change in urine bacteriology to proteus organisms.
- 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
- Urographic findings depend on the stage of the disease.
- Kidneys are normal in 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 and papillary necrosis may be difficult to diagnose.
- Later, necrosis of the papillae with disruption of the urothelial lining causes tracking of contrast from the fornix parallel to the long axis of the papillae. This can produce the lobster claw sign. Then cavitation of renal papillae occurs, which can be incomplete (medullary) or complete (papillary) and can 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 can be demonstrated readily when urographic findings are indeterminate.
Degree of Confidence
Calcification in a sloughed papilla is characteristically ring shaped and may be the only abnormal radiologic finding in necrosis in situ. Calcification is common in patients with analgesic-induced papillary necrosis and 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 and opacification of the collecting system is poor when renal function is impaired.
Retrograde pyelography is sensitive, especially in the presence of renal impairment or in patients in whom urographic findings are inconclusive. The procedure cannot help assess renal function or the renal parenchyma.
False Positives/Negatives
Findings of medullary calcification (nephrocalcinosis) are nonspecific and can occur in patients with hyperparathyroidism, renal tubular acidosis, and medullary sponge kidney and in conditions associated with hypercalcemia. The presence of ringlike calcifications of up to 5-6 mm in diameter is characteristic of sloughed papillae and calcification may be the only abnormal radiologic finding in papillary necrosis in situ.
In the early stage when papillary swelling may be the only abnormal radiologic finding, swelling is difficult to differentiate from normal findings. Necrosis in situ cannot be diagnosed unless calcification has occurred.
Pyelosinus extravasation, which can occur with forceful injection of a large volume of contrast, can mimic contrast tracking from the fornix in papillary necrosis. Inadvertent injection of air bubbles can produce filling defects but the defects are seen as smooth and rounded and can be differentiated from the irregular filling defects found in sloughed papillae.
Findings
CT does not offer much help in the diagnosis of renal papillary necrosis. Reformatted multidetector images may change the role of CT.
- CT is sensitive in detecting calcifications.
- CT can demonstrate multiple bilateral ring shadows in the medulla, some of which are triangular.
- Contrast can be detected filling the clefts in the renal parenchyma.
- CT can be helpful in evaluating the nature of the material (sloughed papillae) that causes the filling defect within the collecting system.
Degree of Confidence
CT findings are not diagnostic but the scans can be useful in patients with poor renal function in whom intravenous pyelogram findings are not helpful. However, use iodinated contrast agents cautiously in patients with compromised renal function.
False Positives/Negatives
Medullary cavity and calcification are nonspecific findings.
Findings
MRI has no specific role in the management of papillary necrosis; however, it may provide a useful alternative to iodinated contrast in patients with depressed renal function and in those who are allergic to iodinated contrast medium.
Degree of Confidence
Sufficient experience is not available with the use of MRI in the diagnosis of papillary necrosis.
False Positives/Negatives
False-positive and false-negative diagnoses have not yet been established with MRI.
Findings
- Sonographically, areas of cavitation in the papillae can be observed 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 can be visualized at the periphery of the cystic space.
- Sloughed papillae can appear echogenic and cast shadows when calcified.
- The collecting system may be dilated when obstructed by sloughed papillae.
Degree of Confidence
Sonographic findings are nonspecific.
False Positives/Negatives
A hyperechoic medulla can be observed in patients with hyperparathyroidism and medullary sponge kidney and in patients with conditions that cause hypokalemia or hypercalcemia.
Findings
No role exists for isotope studies in the diagnosis of renal papillary necrosis; however, they are useful in evaluating renal function.
Special Concerns
- Transitional cell carcinoma is more common in patients with analgesia-induced papillary necrosis.
| 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. |
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Media type: X-RAY
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| Media file 2:
Excretory urography in a 53-year-old man with analgesic-induced nephropathy. A film obtained at 15 minutes following contrast administration shows a wavy renal outline with tracks of contrast extending from fornix, ring shadows due to sloughing of papillae, and an egg-in-a-cup appearance characteristic of renal papillary necrosis. Note the bamboo spine due to ankylosing spondylitis. |
 | View Full Size Image | |
Media type: X-RAY
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| Media file 3:
Papillary necrosis. Nephrotomogram in a 53-year-old man with analgesic-induced nephropathy (same patient as Image 2) clearly demonstrates a wavy contour of the renal outline, ie, renal scars with focal atrophy. |
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Media type: X-RAY
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| 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 the multiple smooth filling defects in the ureter due to ureteritis cystica. |
 | View Full Size Image | |
Media type: X-RAY
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Papillary Necrosis excerpt Article Last Updated: Feb 21, 2007
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