I N A previous paper3 extensive forms of renal papillary necrosis from analgesic

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MIAMI, I N A previous paper3 extensive forms of renal papillary necrosis from analgesic abuse and from diabetes were described and illustrations of the medullary and the papillary types were

1 VoL. No. 2 EARLY FORMS OF RENAL PAPILLARY NECROSIS* By BENEDICT R. HARROW, M.D. MIAMI, I N A previous paper3 extensive forms of renal papillary necrosis from analgesic abuse and from diabetes were described and illustrations of the medullary and the papillary types were presented. However, an earlier form of renal papillary necrosis can also be identified with considerable confidence in a great number of patients, especially those with diabetes mellitus. We have found an incidence of i8 per cent ( out of o) in patients with long standing diabetes.4 The increased incidence over that reported in the past literature is due to an awareness of the pathology and to the use of double doses of contrast agent with marked abdominal compression duri ng intravenous u rography.5 ILLUSTRATIVE CASES CASE I. An elderly diabetic woman developed heft flank pain and pyuria with bacteriuria. Roentgenograms showed a ring-shaped calculus with a nonopaque center which proved to be a stone in the pelvis of the left kidney. A retrograde pyelogram revealed the pelvic stone and, in addition, small cavities typical of the medullary form of renal papillary necrosis. A left pyelohithotomy was done with an uneventful postoperative course. Sections of the stone disclosed the nonopaque center to be a sloughed papihla which undoubtedly arose from the elongated cavity extending from the upper calyx. Despite the large size of the sloughed papihla, the roentgenographic findings in regard to the calyces were not extensive. FLORIDA * From the Section of Urology, University of Miami School of Medicine, Miami, Florida. CASE II. An elderly diabetic woman developed bilateral flank pain, pyuria and early azotemia. On a roentgenogram of the kidney, ureter and bladder, 4 small ring-shaped calcifications were identified (Fig. ia). An intravenous urogram without compression demonstrated the calcifications to be at the apices of the pyramids (Fig. ib). Moreover, the calyceal fornices were intact, but contrast agent surrounded each calcification. The findings represented a medullary form of renal papillary necrosis with sloughed portions of necrotic papillae which remained in place and upon which calcium salts had been deposited. CASES III and Iv. Both patients were middle aged women with mild diabetes of about 8 years duration. The only symptoms were occasional frequency and dysuria due to a cystitis which was readily cured on antimicrobial therapy. Case iii (Fig. ) demonstrated cavities in the right kidney in the pyramids at the tip of every calyx. Case iv showed 3 similar medullary cavities. Both cases are considered a medullary form of renal papillary necrosis since the calyceal fornices were intact. CASE V. A 23 year old woman with juvenile diabetes of i years duration developed upper urinary tract infection which was controlled with difficulty by using large doses of antibiotics. Intravenous urograms demonstrated minute cavities of meduhiary renal papillary necrosis, representing about the earliest form of renal papillary necrosis that can be diagnosed roentgenographicahly. CASE VI. A 23 year old woman had mild diabetes for several years. Because of one episode of pyuria, which was easily controlled on therapy, intravenous urography was performed (Fig. 3A). A papillary form of renal necrosis was seen in the upper calyx. The cavity was larger than expected in the oblique view (Fig. 3B). CASE VII. A middle aged woman with mild diabetes and mild recurrent cystitis developed destruction of all the fornices, representing an early form of renal papillary necrosis (Fig. 4). CASE VIII. A middle aged diabetic man experienced sudden severe left renal colic. At cystoscopy a piece of tissue was recovered from the opening of the left ureter which showed a necrotic papilla on histologic sections. A retrograde pyelogram demonstrated a more advanced papillary necrosis with destruction of the fornices of all calyces and also several ring forms. 335

336 Benedict R. Harrow OCTOBER, 1965 0 0 FIG. i. Case ii. (A) Arrows point to 4 small ring-shaped calcifications in the left kidney of a diabetic patient.

2 336 Benedict R. Harrow OCTOBER, FIG. i. Case ii. (A) Arrows point to 4 small ring-shaped calcifications in the left kidney of a diabetic patient. (B) An excretory urogram shows contrast agent surrounding each calcification, proving that the nonopaque centers are sloughed medullary tissue which have become calcified. An arrow points to one calcification which illustrates best the relationship to the calyx. DISCUSSION Only Case i and Case VIII were proven histologically, but the clinical and roentgellographic findings in the other cases also strongk suggest the diagnosis of renal papillar\ necrosis. In the past, papillary necrosis was considered a rapidly fatal disease ill most instances; yet, in our experience as well as in that recently reported by others,7 nlost cases progress slowly or not at all. It is probable thlat man of these relativel\ early cases were not diagnosed properly and it should be noted that all except i of our patients were thought to have pvelonephri tis by the initial examiner. Diagnosis has become of more than academic interest for several reasons. In diabetes, the physician is alerted to the fact that more prolonged antimicrobial therapy and more careful evaluation of bacteriuria will be required. By good care, nlan\ useful lives can be considerably prolonged. Most evidence indicates that the infection is superimposed 011 the papillary Ilecrosis rather than vice versa, but control of infection prevents rapid deterioration of renal function. In tile abusers of analgesics, the withdrawal of the phenacetin-containing cornpounds ma\ arrest further renal damage. The evidence, ilowever, is not conclusive that phenacetin alone causes the danlage.6 Some authorities have suggested that salicvlates or other anti-inflammatory compounds ma also be incriminated,2 and

$\oi.. j, No. 2 Renal Papillary Necrosis 337 man cases of renal papillary necrosis occur in patients without diabetes or even excess phenacetin intake.$ In observations that are to be published, I have been unable to) validate ureteral obstruction as a sole factor in papillary Ilecrosis ill htllllalls.

In observations that are to be published, I have been unable to) validate ureteral obstruction as a sole factor in papillary Ilecrosis ill htllllalls.

3 \oi.. j, No. 2 Renal Papillary Necrosis 337 man cases of renal papillary necrosis occur in patients without diabetes or even excess phenacetin intake. Recognition of these cases from roentgenographic studies may lead to discovery of other lesions or other drugs as causes of the necrosis. In observations that are to be published, I have been unable to) validate ureteral obstruction as a sole factor in papillary Ilecrosis ill htllllalls. PROGRESSION OF LESIONS Some cases have been encountered where rapid changes led to a conclusive diagnosis o)f rellal papillary necrosis. Figure 3d shows a ring shadow in the upper calvx of a patient who overused phenacetin compounds. One and one-half years later an excretory urogram showed that the pvramid had sloughed away (Fig. 5B). In another abuser of allalgesics, an early urogram revealed normal cal ces (Fig. 61), but 2 years later extensive papillary necrosis was evident on a retrograde pyelogram (Fig. 6R). In a 48 year old diabetic worn- FIG. 2. Case 111. Every pyramid has a cavity separated by I or 2 mm. from the calyx. Medullary form of renal papillary necrosis. I (.... (#{149}J #{149} / ( Ct #{149} I j H I tic H 1 i:ll,l.!1tm ii rh iltl\ f tit1 l;\ltt.y 1.tlHIC #{149}trrH / \n Iltjll \tc\\ tc\ thu rim (Hi\ t\

338 Benedict R. Harrow OCTOBER, 19b5 V 0 FIG. 4. Case VII.

an, an intravenous pvehogram revealed no unusual findings (Fig. 7d).

7B). Several weeks later the papillae had sloughed and passed spontaneously leaving 3 cavities (Fig. 7C).

4 338 Benedict R. Harrow OCTOBER, 19b5 V 0 FIG. 4. Case VII. Papillary form of renal necrosis is seen with destroyed fornices of the calyces. an, an intravenous pvehogram revealed no unusual findings (Fig. 7d). One year later a left retrograde pvehogram revealed renal papillary necrosis with 3 large filling defects in tile upper pyramids (Fig. 7B). Several weeks later the papillae had sloughed and passed spontaneously leaving 3 cavities (Fig. 7C). The clinical history of these 3 patients has been reported previotlslv,1 without showing tile roentgellographicallv demonstrable progression o)f the lesions. In a different situation, 2 Ilondiabetic middle aged women who denied overuse of any drugs passed fragnlents of tissue spontaneously which histologically proved to be necrotic papillae. Yet, at tile time of pas-

5 OL. 5, No. 2 Renal Papillary Necrosis 339 s A B. Ii. 6. (A) An intravenous pyelogram without compression faintly demonstrates normal calyces. (B) Two years later this patient who overindulged in analgesics demonstrates typical renal papillary necrosis in every calyx. sage of rather large chunks of tissue, excretorv urograms and retrograde p\e1ograms were normal (Fig. 8d). In i of these patients, a repeat right retrograde study months later showed renal papillar\ necrosis for tile first time (Fig. 8B). On a repeat left retrograde study, tile secoild patient also denlonstrated severe papillary necrosis (Fig. 8C). DIFFERENILAL DIAGNOSIS Pelorenal backflow, calvceal diverticu- Ia, pvelogenic cysts, neoplasnls, blood clots and ordinary stones can alnlost always be differentiated froni renal papihlar\ necrosis b careful examinations. Renal dysplasia #{149}..4 superficially resembles renal papillary necrosis, but the calyces usually project much further into the cortex. Figure, A and B shows a right-sided renal dysplasia in a 24 year old woman without previous urinary tract infections or ureteral reflux; this is probabl a congenital form of d\splasia. In Figure 10, zi and B, 2 different types of true sponge kidneys are demonstrated which can hardly be confused with renal papillary necrosis. \Ve have encountered 12 patients with considerable dilatation of the ducts of Bellini diagnosed b\ others as sponge kidne\s but probabk representing congenitally dilated ducts witilout actual cyst formation. Moreover, abili tv to concentrate FIG. #{231}. (A) Large semicircular tracts in the upper calyx represent papillary renal necrosis involving the entire pyramid. Medullary forms can be identified in the other calyces. (B) Eighteen months later an excretory urogram shows that the upper pyramid has sloughed leaving a large cavity (arrows). A double (lose of contrast agent and abdominal compression were used because of hyposthenuria. The patient was an abuser of phenacetin. (A is reproduced with permission from 7.A.M.A., 1963, 184, )

340 Benedict R. Harrow OCTOBER, 1965 the urine was not impaired in these instances. Tuberculosis can mini i c renal papillary necrosis almost exactly.

6 340 Benedict R. Harrow OCTOBER, 1965 the urine was not impaired in these instances. Tuberculosis can mini i c renal papillary necrosis almost exactly. Figure ii A shows a forni which appears identical to renal papillary necrosis but cultures revealed tuberculosis. Figure ii B shows a more mottied and irregular appearance than that in renal papillar necrosis and again cultures revealed tuberculosis. In general, the marked irregularities, the infundibular and it... #{149} / \ it lit Vt HIM 11 \ HCr,t III 1 H uut CttutJVCi fl,ntk IM.1 CtJ\Cu 11 l it.tl)ctc (tic thur.ivcv t\tr li\ t.i,v\ it 1.1, MCI H HI Cttb\CC. HI H)ttCIu(J \ r.[i1mf IC 11th 1l C. ici CII. Ill H CI #{149}i \ Mt. #{149} li HI tl r.iuiitk huh hibltitcf.ti H.ini I ti ic H Vt I V Cl \ 11 C Ch Ii Cit C it 1 / VCVfluCCI it thu CV1ll II ii Iii //, 11/., 1H1 I / ureteral strictures, and the bacteriologic identification will eiiable a diagnosis to be made. Chronic pvelonepilritis, especially in the later stages, is most apt to be confused with renal papillary necrosis. Only if serial pvelograms are obtained or sloughed papillae are recovered by straining the urine or by cystoscopic removal can a definite diagnosis be made. I

7 \OI.. 5, No. 2 Renal Papillary Necrosis 341

a woman without pyelonephritis or ureteral reflux. (B) An oblique view of the same dysplastic kidney. FIG. 10.

8 342 Benedict R. Harrow OCTOBER, 1965 FIG.. (A) An anteroposterior view shows a congenital dysplastic kidney with calyces projecting deep into the cortex in a woman without pyelonephritis or ureteral reflux. (B) An oblique view of the same dysplastic kidney. FIG. 10. (A) A type of sponge kidney which should not be confused with renal papillary necrosis. (B) A sponge kidney with large communicating cysts without any resemblance to renal papillary necrosis.

9 VoL. 95, No. 2 Renal Papillary Necrosis 343 JIG. II. (J A case of proven tuberculosis of the kidney which mimics renal papillary necrosis exactly in regard to the roentgenographic pattern. (B) Another example of tuberculosis that resembles renal papillary necrosis but the pattern is too irregular. SUMMARY Cases are presented to show that early forms of renal papillary necrosis can be confidently recognized. In patients having long-standing diabetes, the incidence of renal papillary necrosis was 1 8 per cent. Identi fica tion is i mporta lit for directing proper treatmellt and for the search of unknown etiologies o)f renal papillar\ necrosis in patients without diabetes, analgesic abuse or urinary tract obstruction. Late stages of renal papillary necrosis na not be distinguished ill many instances from chronic pvelonephritis unless fragments of necrotic tissue have been recovered. In 2 patients who passed necrotic papillae, initial retrograde pvelogranls were nornlal S. \V. rd Avenue Miami 36, Florida REFERENCES I. EKSTROM, T. Renal hypoplasia: clinical study of 179 cases. Ada c/zir. scandinav., 1955, Suppl GILMAX, A. Analgesic nephrotoxicity: pharmacological analysis. Am. 7. Med., 1964,36, HARROW, 13. R., SLOANE, J. A., and LIEIIMAN, N. C. Renal papillary necrosis and analgesics: roentgen differentiation from sponge kidney and other diseases. 7.A.M.A., 1963, 184, HARROW, B. R. Nephropathy of diabetes with emphasis on papillary necrosis. Po.cigrad. Med., 1965, 37, A63-A HRROW, B. R., and SLOANE, J. A. Compression and nephrographic effects during intravenous urography. M. Times, 1963,9!, HARROW, B. R., and SLOANE, J. A. Analgesic nephritis. Correspondence. 7.A.M.A., 1963, z86, 6io. 7. RONY, H. R. Renal papillary necrosis in diabetes: report of case under good control. 7.A.M.A., 1961, 177,

10 This article has been cited by: 1. John C. Holder, Nabil K. Bissada Curvilinear calcification in renal cancers: Two etiologies. Urology 9:6, [Crossref] 2. Alex E. Finkbeiner, Robert Moyad, Phillip Hoskins Ring-shaped calcification of renal mass. Urology 8:3, [Crossref] 3. Peter H. Arger, Edward I. Bluth, Thomas Murray, Martin Goldberg Analgesic abuse nephropathy. Urology 7:2, [Crossref] 4. Harry Z. Mellins Chronic pyelonephritis and renal medullary necrosis. Seminars in Roentgenology 6:3, [Crossref] 5. Arlyne T. Shockman The Significance of Ring-Shaped Renal Calcification. The Journal of Urology 101:4, [Crossref] 6. Aaron M. Longacre, George L. Popky Papillary Necrosis in Patients With Cirrhosis: A Study of 102 Patients. The Journal of Urology 99:4, [Crossref] 7. Benedict R. Harrow Renal Papillary Necrosis: a Critique of Pathogenesis. The Journal of Urology 97:2, [Crossref]

Radiological changes of renal papillary necrosis

Kidney International, Vol. 13 (1978), pp. 93-1 06 Radiological changes of renal papillary necrosis NILs LINDVALL Department of Diagnostic Radiology, Karolinska Sjukhuset, Stockholm, Sweden Necrosis of