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Papillary Necrosis Treatment & Management

  • Author: Christopher Powell, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
 
Updated: Mar 14, 2014
 

Medical Therapy

Because ischemia is such a prominent underlying factor in the development of renal papillary necrosis, promptly resuscitate patients and treat their hypoxia, if present. In addition, patients with acute disease may require broad-spectrum intravenous antibiotics, hydration, glycemic control, and urinary alkalinization. Cessation of analgesic abuse stabilizes and may improve renal function.

In patients without acute ureteral obstruction, treat the infectious and metabolic complications of renal papillary necrosis by replacing insensible losses, maintaining hydration, alkalinizing the urine, and administering antibiotics directed toward the pathogen (as revealed by culture or Gram stain and by observing for the development of obstruction or sepsis). Patients with hematuria significant enough to cause an acute drop in their hematocrit level may require blood transfusions. Patients with sickle cell disease may require exchange transfusions, and patients with diabetes who have acute infectious complications and refractory hyperglycemia may require insulin therapy. Basically, ameliorate the ischemia with hydration and alkalinization, treat the underlying cause of the renal papillary necrosis (eg, maintain normal glycemic state), and institute targeted antibiotic therapy.

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Surgical Therapy

Patients with renal papillary necrosis may require diagnostic and therapeutic urologic intervention. The urologist is responsible for evaluating any obstruction, hematuria, overwhelming infection, and associated malignancies and for preventing recurrences of these sequelae.

Acute obstruction with concomitant urinary tract infection is a urologic emergency that requires immediate percutaneous nephrostomy to relieve the obstruction, ureteral stent placement, or endoscopic retrieval of the obstructing sloughed papillae. Endoscopic retrieval is not recommended unless the offending papillae are crowning or extruding from the ureteral orifice; even then, the procedure is challenging. Retrograde pyelography and ureteroscopy are useful diagnostic tools, but consider these only when the patient is afebrile and after intravenous administration of antibiotics. Otherwise, a ureteral stent would suffice, delaying retrograde instrumentation until the patient is afebrile.

The recommended treatment is to drain the dilated collecting system either endoscopically or percutaneously. In patients with severe disease who are febrile and have smoldering sepsis, percutaneous nephrostomy is preferred because it does not require general anesthesia and carries a smaller risk of pyelovenous reflux and worsening sepsis. Cystoscopy and ureteral stent placement allow cystoscopic surveillance of the bladder, which is necessary if hematuria is the presenting symptom. However, in a patient with hydronephrosis, high fever, leukocytosis, and overt sepsis, the preferred treatment is to percutaneously drain the kidney. Perform diagnostic cystoscopy and RPGs (if necessary) later, when the patient's situation is not so dire.

Nephrectomy may be life-saving in patients with overwhelming infection (ie, emphysematous pyelonephritis). Consider that papillary necrosis is primarily a bilateral disease, and these patients must be informed that this may result in progressive renal failure and possible dialysis dependency in the future.

In selected patients, ureteroscopic investigation of a ureteral filling defect may be warranted. A basket catheter can be introduced through the ureteroscope to extract the offending sloughed papilla. This is performed only in afebrile patients, after broad-spectrum intravenous antibiotics have been administered.

Patients who present with hematuria, even if all the diagnostic interventions indicate papillary necrosis, require a full urologic workup for their hematuria. A thorough evaluation of the urinary tract, as outlined in Lab Studies, limits the differential diagnoses of hematuria, excluding other possible causes. Attribute the hematuria to papillary necrosis only after performing the studies listed in Lab Studies and deeming the results negative.

Keep in mind that, if the patient's system is acutely obstructed with possible pyonephrosis, retrograde studies such as RPG and ureteroscopy are contraindicated because they are likely to cause or exacerbate sepsis from pyelovenous reflux of purulent material from the lower urinary tract. If this clinical scenario occurs, decompress the system with either a double-J ureteral stent or, preferably, a nephrostomy tube. Send any urine or pus obtained from these procedures for microscopic analysis, Gram stain, and culture. After proper decompression, administer systemic antibiotics with empiric coverage until the Gram stain and culture results are received. Once the patient responds systemically, with stable hemodynamics, no fever, no acidosis, and no leukocytosis, the urologist can proceed with the diagnostic workup.

If the infection rages and the patient does not improve despite supportive measures and proper antibiotic coverage, a nephrectomy may be life-saving. However, remember that the disease is usually bilateral.

Surgery may be indicated for associated anatomic anomalies that predispose patients to urinary stasis and recurrent urinary tract infections. Treatable conditions include calculi, ureteropelvic junction obstruction, vesicoureteral reflux, ureteral strictures, and ureteroceles.

If transitional cell carcinoma of the collecting system is identified, thoroughly evaluate the patient for metastatic disease. If metastases are not found, the proper treatment for presumed invasive transitional cell carcinoma of the upper urinary tract is radical nephroureterectomy, removing the entire transmural ureter and a cuff of bladder mucosa. Recently, some physicians are resecting and staging tumors endoscopically and are treating selected patients more conservatively (ie, surveillance, if the tumor does not invade the muscle layer). Nevertheless, nephroureterectomy remains the criterion standard.

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Preoperative Details

Give the patient intravenous hydration and withhold food for 8 hours. Obtain informed consent; the patient must be aware that ureteroscopy and ureteral stent placement are possibilities.

Ensure that the patient has medical clearance to undergo a procedure that requires general anesthesia.

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Postoperative Details

Common complications after any instrumentation of the ureter include infection, extravasation and urinoma formation, bleeding, ureteral stricture, and urosepsis due to pyelovenous backflow. Persistent postoperative fever or failure to thrive may be harbingers of the complications listed above.

Ensure that patients clearly understand that, if they require an indwelling ureteral stent, these devices are associated with a host of unique complications.

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Follow-up

Proper follow-up includes a visit with a general practitioner to prevent further exacerbations and to manage any associated conditions. Follow-up may include a referral to specialists, as deemed necessary by the primary care doctor.

Stopping analgesic intake and controlling blood pressure help to preserve renal function, and preventing symptomatic urinary infections with long-term, low-dose medical therapy reduces the morbidity associated with renal papillary necrosis. If analgesic use is indispensable to certain patients, instruct them to hydrate accordingly. Reports indicate that adequate hydration may help prevent lesions in persons who must take analgesics long-term.

Physicians may find prophylactic antibiotics useful for treating patients with obstructed urinary tracts who are not surgical candidates. Patients who receive urinary tract intervention require follow-up evaluations with a urologist, particularly if they require further treatment. In any case, hematuria in these patients requires a complete evaluation by the urologist.

For patient education resources, see the Kidneys and Urinary System Center, as well as Blood in the Urine.

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Complications

Necrotic papillae represent a fertile environment for the deposition of both infectious organisms and lithogenic sediment. This necrotic deposition can lead to the development of florid pyelonephritis, perirenal abscesses, and sepsis. Calculous formation compounds the necrosis because certain bacteria thrive within the calculi. Calculi can also propagate, which may lead to further obstruction, increased pyelovenous pressure, and worsened ischemia.

Always consider sloughed papillae as a cause of ureteral obstruction in the differential diagnoses of flank pain, colic, and hematuria, especially when no calculi are visible and particularly in patients with diabetes.

The development of transitional cell carcinoma of the renal pelvis or calyces is a serious complication, particularly in patients with papillary necrosis associated with analgesic abuse.

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Outcome and Prognosis

The prognosis of renal papillary necrosis depends on the etiology of the ischemic insult, the number of associated pathologic factors, the dispersal of the necrosis, the involvement of one or both kidneys, and the overall health of the patient. Elderly debilitated patients with multiple medical problems have a poor prognosis, as do patients with overwhelming sepsis and multiple comorbidities. The prognosis is generally worse in patients with diabetes, specifically those who are not compliant and who are prone to severe episodes of hyperglycemia because of the systemic nature of their disease.

Considering the synergistic nature of its predisposing factors, papillary necrosis may be avoided by controlling chronic diseases such as sickle cell disease, diabetes, and cirrhosis. Patients with such conditions should be careful to avoid excessive use of analgesics that are known to be associated with papillary necrosis. Patients who use such analgesics should be screened for signs and symptoms of urinary tract infections and/or urinary obstruction and treated accordingly. When papillary necrosis arises unexpectedly (ie, in a patient with sepsis), the treatment focus should be to prevent urinary tract infections (eg, by avoiding unnecessary use of indwelling catheters), to maintain adequate hydration and homeostasis, to avoid analgesics and other nephrotoxic medications, and to maintain tight glycemic control in patients with diabetes.

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Future and Controversies

Significant contributions aimed at improving the prevention, diagnosis, and treatment of renal papillary necrosis include preliminary studies by Falkenberg et al, who are investigating monoclonal antibodies that may provide direct diagnostic access to the renal papilla and may allow for early detection of papillary damage.[13] Monoclonal antibodies specific for papillary antigens have been used to detect these antigens in urine following toxic insults to the kidney. Further work has been performed by Price et al in which renal papillary antigen 1 (RPA-1) has been demonstrated to be an excellent marker of renal papillary necrosis that can be used to detect this toxicity in preclinical safety testing.[14]

Studies by Garber et al have revealed that the angiotensin-converting enzyme (ACE) inhibitor enalapril has a protective and therapeutic effect in rats with bromoethylamine-induced renal papillary necrosis, which is characterized by marked interstitial fibrosis, impressive decreases in the glomerular filtration rate, and albuminuria.[15] Histologic examination of rats treated with enalapril reveals a 67-88% decrease in renal papillary necrosis. These studies also demonstrate renoprotective effects of enalapril, including a significant improvement in the glomerular filtration rate and elimination of albuminuria.

A report from Abe et al described the treatment of renal papillary necrosis in a patient with diabetes.[16] Prostaglandin E1 was infused intravenously at a dose of 40 mg/d for 14 days. This attempt at improving renal circulation increased both creatinine clearance and renal plasma flow, with a concomitant decrease in proteinuria. Vasodilatory agents such as prostaglandin E1 may improve renal circulation and hemodynamics and should be considered as possible therapy for renal papillary necrosis, particularly in patients with diabetes.

Finally, although they are a reasonable course of preventive treatment, prophylactic antibiotics are by no means standard treatment in patients with renal papillary necrosis. The utility of antibiotics requires further study. More importantly, prevention of nosocomial urinary tract infection should take precedence. If indwelling catheters are necessary or if the patient has risk factors for urinary stasis or frank obstruction, prophylactic antibiotics may prove useful.

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Contributor Information and Disclosures
Author

Christopher Powell, MD Resident Physician, Department of Urology, University of Kansas Medical Center

Christopher Powell, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Jack H Mydlo, MD Chief, Department of Urology, Woodhull Hospital; Chair and Professor, Department of Urology, Temple University School of Medicine

Jack H Mydlo, MD is a member of the following medical societies: American College of Surgeons, American Urological Association, International College of Surgeons US Section, Society of University Urologists

Disclosure: Nothing to disclose.

Jeffrey M Donohoe, MD, FAAP Assistant Professor of Pediatric Urology, Department of Surgery, Division of Urology, Children’s Medical Center, Medical College of Georgia

Jeffrey M Donohoe, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Urological Association

Disclosure: Nothing to disclose.

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

Gamal Mostafa Ghoniem, MD, FACS Professor and Vice Chair of Urology, Chief, Division of Female Urology, Pelvic Reconstructive Surgery, and Voiding Dysfunction, Department of Urology, University of California, Irvine, School of Medicine

Gamal Mostafa Ghoniem, MD, FACS is a member of the following medical societies: American Urogynecologic Society, International Continence Society, International Urogynaecology Association, Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, American College of Surgeons, American Urological Association

Disclosure: Received honoraria from Astellas for speaking and teaching; Received grant/research funds from Uroplasty for none; Partner received honoraria from Allergan for speaking and teaching.

References
  1. Friedrich N. Ueber necrose der nierenpapillen bei hydronephrose. Virchows Arch A Path Anat. 1877. 69:308-12.

  2. Gunther GW. Die papillennekrosen der niere bei diabetes. Munchen Med Wochenschr. 1937. 84:1695-9.

  3. Edmondson HA, Martin HE, Evans N. Necrosis of renal papillae and acute pyelonephritis in diabetes mellitus. Arch Intern Med. 1947. 79:148.

  4. Spuhler O, Zollinger HU. [Chronic interstitial nephritis.]. Z Klin Med. 1953. 151(1):1-50. [Medline].

  5. Mandel EE. Renal medullary necrosis. Am J Med. 1952 Sep. 13(3):322-7. [Medline].

  6. Simon HB, Bennett WA, Emmett JL. Renal papillary necrosis: a clinicopathologic study of 42 cases. J Urol. 1957 Apr. 77(4):557-67. [Medline].

  7. Delfino VD, Santiago NM, Mocelin AJ, Kunii LF, Bortoliero AL. Indinavir-associated toxicity mimicking urinary tuberculosis in a patient with AIDS. Braz J Infect Dis. 2008 Feb. 12(1):99-100. [Medline].

  8. Iba-Ba J, Yombi JC, Danse E, Van Beers B, Vandercam B. [Bilateral papillary necrosis during indinavir treatment]. Presse Med. 2008 Jun. 37(6 Pt 1):967-9. [Medline].

  9. Lang EK, Macchia RJ, Thomas R, Davis R, Ruiz-Deya G, Watson RA. Detection of medullary and papillary necrosis at an early stage by multiphasic helical computerized tomography. J Urol. 2003 Jul. 170(1):94-8. [Medline].

  10. Lang EK, Macchia RJ, Thomas R, Davis R, Ruiz-Deya G, Watson RA, et al. Multiphasic helical CT diagnosis of early medullary and papillary necrosis. J Endourol. 2004 Feb. 18(1):49-56. [Medline].

  11. Ulreich S. Ultrasound in the evaluation of renal papillary necrosis [letter]. Radiology. 1983 Sep. 148(3):864. [Medline].

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

  13. Falkenberg FW, Hildebrand H, Lutte L, Schwengberg S, Henke B, Greshake D, et al. Urinary antigens as markers of papillary toxicity. I. Identification and characterization of rat kidney papillary antigens with monoclonal antibodies. Arch Toxicol. 1996. 71(1-2):80-92. [Medline].

  14. Price SA, Davies D, Rowlinson R, Copley CG, Roche A, Falkenberg FW, et al. Characterization of renal papillary antigen 1 (RPA-1), a biomarker of renal papillary necrosis. Toxicol Pathol. 2010. 38(3):346-58. [Medline].

  15. Garber SL, Mirochnik Y, Desai SS, Arruda JA, Dunea G. Angiotensin-converting enzyme inhibition reduces the effect of bromoethylamine-induced papillary necrosis and renal fibrosis. J Am Soc Nephrol. 1998 Jun. 9(6):1052-9. [Medline].

  16. Abe K, Ozono Y, Miyazaki M, Furusu A, Shioshita K, Sasaki O, et al. Prostaglandin E1 for renal papillary necrosis in a patient with diabetes mellitus. J Int Med Res. 1999 Mar-Apr. 27(2):90-5. [Medline].

  17. Akhund L, Quinet RJ, Ishaq S. Celecoxib-related renal papillary necrosis. Arch Intern Med. 2003 Jan 13. 163(1):114-5. [Medline].

  18. Barnes DJ. Beethoven's final illness. Lancet. 1996 Mar 16. 347(9003):766. [Medline].

  19. Bing RJ. Cyclooxygenase-2 inhibitors: is there an association with coronary or renal events?. Curr Atheroscler Rep. 2003 Mar. 5(2):114-7. [Medline].

  20. Breyer MD, Hao C, Qi Z. Cyclooxygenase-2 selective inhibitors and the kidney. Curr Opin Crit Care. 2001 Dec. 7(6):393-400. [Medline].

  21. Campbell MF, Walsh PC. Campbell's Urology. 7th ed. Philadelphia: W.B. Saunders Co; 1998. 3 v. (xli, 3432, lxxxix p.

  22. Cotran RS, et al. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia: Saunders; 1999. xv, 1424 p.

  23. Davies PJ. Beethoven's nephropathy and death: discussion paper. J R Soc Med. 1993 Mar. 86(3):159-61. [Medline].

  24. Eknoyan G, Qunibi WY, Grissom RT, Tuma SN, Ayus JC. Renal papillary necrosis: an update. Medicine (Baltimore). 1982 Mar. 61(2):55-73. [Medline].

  25. Gower PE. A prospective study of patients with radiological pyelonephritis, papillary necrosis and obstructive atrophy. Q J Med. 1976 Apr. 45(178):315-49. [Medline].

  26. Hagiwara N, Fujihiro S, Deguchi T. [Renal papillary necrosis managed by transurethral procedures: a case report]. Hinyokika Kiyo. 2003 Jun. 49(6):329-31. [Medline].

  27. Harrison TR, Wilson JD. Harrison's Principles of Internal Medicine. 12th ed. New York: McGraw-Hill, Health Profession Division; 1991.

  28. Kamath S, Moody MP, Hammonds JC, Wells IP. Papillary necrosis causing hydronephrosis in renal allograft treated by percutaneous retrieval of sloughed papilla. Br J Radiol. 2005 Apr. 78(928):346-8. [Medline].

  29. Kankuri E, Solatunturi E, Vapaatalo H. Effects of phenacetin and its metabolite p-phenetidine on COX-1 and COX-2 activities and expression in vitro. Thromb Res. 2003 Jun 15. 110(5-6):299-303. [Medline].

  30. Kovacevic L, Bernstein J, Valentini RP, Imam A, Gupta N, Mattoo TK. Renal papillary necrosis induced by naproxen. Pediatr Nephrol. 2003 Aug. 18(8):826-9. [Medline].

  31. Lange S. Diseases. Lange S, ed. Teaching Atlas of Urologic Radiology. First ed. New York, NY: Thieme Medical; 1995. 88-9.

  32. Lange S. Differential Diagnosis: Urographic findings. Lange S, ed. Teaching Atlas of Urologic Radiology. First ed. New York, NY: Thieme Medical; 1995. 198-203.

  33. Lauler DP, Schreiner GE, David A. Renal medullary necrosis. Am J Med. 1960 Jul. 29:132-56. [Medline].

  34. Lindvall N. Radiological changes of renal papillary necrosis. Kidney Int. 1978 Jan. 13(1):93-106. [Medline].

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

  36. Salo JO, Talja M, Lehtonen T. Ureteroscopy in the treatment of ureteral obstruction caused by papillary necrosis. Eur Urol. 1987. 13(1-2):140-1. [Medline].

  37. Sargent JC, Sargent JW. Unilateral renal papillary necrosis. J Urol. 1955 May. 73(5):757-64. [Medline].

  38. Schrier RW, Gottschalk. Diseases of the Kidney. 4th ed. Boston: Little, Brown; 1988. 3 v. (xxviii, 3506, 74).

  39. Schwarz A. Beethoven's renal disease based on his autopsy: a case of papillary necrosis. Am J Kidney Dis. 1993 Jun. 21(6):643-52. [Medline].

  40. von Seyfried I. Autopsy protocol of Ludwig van Beethoven, translated from Latin. Ludwig van Beethovens Studien im Generalba. 2nd ed. Contrapunkt und in der Compositions: 1852-1853.

  41. Voulgarelis M, Ziakas PD. Images in clinical medicine. Renal papillary necrosis unmasking sickle cell disease. N Engl J Med. 2005 Mar 24. 352(12):1237. [Medline].

  42. Wen SF. Nephrotoxicities of nonsteroidal anti-inflammatory drugs. J Formos Med Assoc. 1997 Mar. 96(3):157-71. [Medline].

  43. Zadeii G, Lohr JW. Renal papillary necrosis in a patient with sickle cell trait. J Am Soc Nephrol. 1997 Jun. 8(6):1034-9. [Medline].

 
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In this figure, the multifactorial nature of renal papillary necrosis is represented by 5 of the disease's most frequently associated conditions: infection, obstruction, diabetes mellitus, analgesic abuse, and sickle cell disease. Each circle represents a condition. Note how the conditions overlap; the red areas show the coexistence of 2 conditions, and the black areas represent 3 coexistent conditions. Multiple conditions exhibit synergism and, therefore, worsen both the severity of the disease and the prognosis.
Cystoscopic photograph of sloughed papilla extruding from the ureteral orifice. The patient was a 51-year-old man with poorly controlled diabetes and a history of microhematuria and an acute onset of severe left flank pain. Findings of upper tract imaging with a renal ultrasonography and intravenous pyelography were remarkable only for mixed heterogeneity consistent with medical renal disease. Urine cytology results were negative, and culture showed no growth. In-office flexible cystoscopy revealed the mass extruding from the left ureteral orifice, which required sedation and rigid cystoscopy to extract. Gross examination yielded a tan, friable, irregular, wedge-shaped soft tissue mass 1.7 cm X 1.6 cm X 1.5 cm. Bilateral retrograde pyelography revealed a clubbed left upper pole calyx and no other filling defects. The pathology was necrotic epithelial tissue.
 
 
 
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