Kidney international, Vol. 35 (1989), pp. 696—703

Frequency of development of early cortical scarring in acuteprimary pyelonephritis

ALAIN MEYRIER, MARIE-CLAUDE CONDAMIN, MARC FERNET, AGNES LABIGNE-ROUSSEL,PIERRE SIMON, PATRICE CALLARD, MURIEL RAINFRAY, MARC SOILLEUX, and ARLETTE GROC

Service de Néphrologie, Service de Radiologie, and Laboratoire de Bactériologie, Hôpita! Avicenne, Bobigny; Service des Entérobactéries &INSERM U199, Institut Pasteur, Paris; Service de Néphro!ogie, Hôpital La Bauchee, Saint-B rieuc; and Laboratoire d'Anatomo-patho!ogie,

ho pita! Jean-Verdier, Bondy, France

Frequency of development of early cortical scarring In acute primarypyelonephritis. Fifty-five cases of primary (that is, without urinary tractabnormalities), acute pyelonephritis (PN) were studied by computedtomodensitometry (CT). There were 48 women and 7 men. All werefebrile and 16 had positive blood cultures. In 7 cases, (4 diabetics and 3malnourished alcoholics) PN was painless, diagnosis was delayed andlesions were severe. Two diabetics underwent emergency nephrectomyfor sepsis. Conventional radiological techniques (IVP and ultrasonog-raphy) were poorly informative. In contrast, initial CT abnormalitieswere visible in 44 patients. They consisted of triangular or roundhypodense images, diffuse hypodensity in a grossly swollen kidney,and/or abscesses. Hypodense images were presumably due to acutefocal ischemia, Renal histology was available in five patients. It showedacute interstitial nephritis with leukocyte infiltrates, edema and hemor-rhagic streaks. Pyelonephntis was due to E. co/tin 48 cases (87.5%). In27 cases E. co/i isolates were studied by genotypic assays which detectthe three most frequent (pap, ala and sfa) of the four operons known toencode adhesin. In all cases, at least one of these genotypic markers ofuropathogenicity was found. In 27 cases, repeat CT was done shortlyafter treatment. It showed healing in only 12. Early cortical scarformation was visible in 2. Final evaluation in 27 cases with adequatefollow-up showed that (in addition to the 2 patients who had beennephrectomized), in only 17 of 27 (63%) had the kidneys recovered anormal appearance. In two cases one kidney had undergone atrophy;renal biopsy showed subacute-chronic interstitial nephritis. Corticalscars were visible in eight other cases. Our data do not substantiate thecommon opinion that, in the absence of urinary tract abnormalities,acute PN entails little risk of renal insult, On the contrary, we show thatsuch acute primary renal infection, due to uropathogenic E. co/i strainsencoding a pap or afa adhesin often leads to early cortical scarring andmay occasionally progress to unilateral renal atrophy.

Acute pyelonephritis (PN) may occur in the absence of renalstone, urinary tract obstruction or vesicoureteric reflux. It wasclaimed over the past 15 years that such "primary" acuteupper-tract infection was a benign condition, with no progres-sion to chronic pyelonephritis [1—4]. This opinion was based onintravenous pyelograms (IVP) performed months or years afterthe acute episode. Acute primary PN thus gained the reputationof being rapidly cured by antibiotics, and of bearing insignifi-cant risk of further renal insult. Hence, in contrast with ongoing

Received for publication May 17, 1988and in revised form September 23, 1988

© 1989 by the International Society of Nephrology

research on bacteriological and immunological aspects of uri-nary tract infection (UTI), the morphological study of acute PNwas relatively neglected.

In 1979 the first publication on acute PN studied by computedtomodensitometry (CT) rekindled interest, as it described im-pressive images within the pyelonephritic kidney [5]. Suchlesions had been overlooked by standard radiological tech-niques. Nonetheless, CT was only done at the acute phase ofinfection, and few studies addressed such points as the patho-logical counterpart of CT images, the uropathogenicity ofurinary organisms, the evolution of acute lesions or the bearingof these issues on treatment mode.

We therefore envisaged a prospective study of acute PN withthe following goals: 1) to analyze the CT images of acute PNand, when possible to correlate them with renal histology; 2) tostudy the uropathogenicity of bacteria in such patients withprimary PN; and 3) to assess the risk of renal scarring inpatients who seemed to fare clinically well after the acuteepisode.

Methods

PatientsFrom October 1983 to February 1987, 55 patients were

referred to us for acute upper urinary tract infection withoutevidence of urological abnormalities, and were considered tosuffer from primary pyelonephritis. The diagnosis was based onthe association of fever (>38.5°C) and pyuria (that is, >lOleukocytes and >10 organisms/mi of midstream, freshly voidedurine). Any case with renal stone(s) or with a history thereof,vesicoureteric reflux, medullary sponge kidney, urinary tractobstruction or clinical or ultrasonographic evidence of prosta-this was excluded, being considered "secondary" as opposedto "primary" PN. Acute PN in pregnant women were alsoexcluded.

All patients underwent IVP, retrograde cystography, renalultrasonography and CT. In some instances IVP was replacedby films taken just after CT, when the urinary tract was stillopacified by the contrast medium.

Computed tomodensitometry was done with a "C.E.10,000," Compagnie G6nérale de Radiologie" body scannerwith a 6.8 second exposure time and a 256 X 256 reconstructionmatrix. Some section slices were reconstructed with a 512 x

696

Meyrier et a!: Early cortical scarring in pyelonephritis 697

512 matrix. Sections were centrimetric and contiguous. Filmswere taken before and after i.v. bolus injection of iodinatedcontrast medium. The radiographs were submitted to doubleinterpretation. One was by the radiologists on duty when thepatient was admitted to the emergency department (theseradiologists were aware of the clinical status). The secondinterpretation was made independently by one of us (M.F.)without knowledge of the clinical background, at the time whenthe patients' files were reviewed for this publication.

In 27 cases repeat CT was done after one to three months oftreatment, and in eight a third CT was done 6 to 24 months afterthe second.

Renal histology was available in five cases. In two diabeticsemergency nephrectomy was deemed necessary by the surgicalteam on duty as a salvage procedure, a decision made on thebasis of the severe clinical picture, the diabetic background andthe extent of CT scan lesions. Percutaneous renal biopsy wasdone in three other patients after informed consent was ob-tained. Decision for performing renal histology was based onthe following grounds. In one case with severe sepsis andbilateral CT scan lesions, pyelonephritis was painless and renalbiopsy was deemed necessary for making a firm diagnosis ofacute bacterial interstitial nephritis before embarking on antibi-otic treatment, including an aminoside. In a second case, adiabetic patient, acute pyelonephritis was accompanied bytransitory low grade proteinuria and renal biopsy was done toverify the absence of concomitant glomerulopathy. The thirdcase was a patient with delayed diagnosis and in whom wewanted to determine the amount of interstitial fibrosis afterseveral weeks of untreated infection. In two of these patients,repeat biopsy was done after treatment. This treatment seemedto be satisfactory according to conventional bacteriologicalcriteria. In the other cases, we did not consider renal biopsy,which would have been ethically unjustified.

Urinary pathogens were identified after growth on API 20enterobacteriacae well galleries. Biotyping of E. co/i was donewith screening for 15 phenotypic factors.

Adhesins encoded by E. co/i were sought by a genotypicassay as follows: bacteria grown for three hours on nitrocellu-lose filters were used for colony hybridization [6]. Probes whichwere representative of pap, afa and sfa operons were extractedfrom hybrid plasmids pSN100 [7], pILL14 [8] and pANN8OI-13[91, respectively, as previously described [10]. Restriction en-donuclease fragments were separated by electrophoresis onagarose gels, purified by electroelution and labeled with 32P bynick-translation. They were used as DNA hybridization probes.

Results

Clinical

Table 1 shows the main features of the 55 patients. Therewere 48 females and 7 males. Nine patients were diabetics andfour others were either malnourished and/or alcoholics.

All patients had spiking fever and chills. Bladder symptomswere present in only 26. Loin pain was unilateral in 31, bilateralin 2, undetermined in 2 patients who were comatose or inshock, not specified in 13, and absent in 7. Pain did not correlatewith the severity of CT findings. Interestingly, the cases ofpainless PN were observed in patients with diabetes or malnu-trition. It is thus probable that autonomic neuropathy was

Table 1. Main characteristics of 55 patients with acute primarypyelonephritis

Sex ratio male/femaleAge range, in yearsPast history of UTI

Upper:Lower:

CT scan lesionsBilateralRightLeftNone

Positive blood culturesUrine cultures

E. coliKiebsiellaStaph. saprophyticusStrep.D + CitrobacterUnknown

Genotypic markers for adhesinexpression

present. In six patients diagnosis was delayed, and their renallesions were among the most severe in this series.

Reliable data on past histories were available in 42 patients.Twenty-three (54.8%) had had previous episodes of UTI (of thelower tract in 12, that is, signs and symptoms of afebrilecystitis, and with evidence of upper urinary tract involvementin 11, that is, bacteriuria accompanied by loin pain and fever).

Severe sepsis was rare (3 cases, all diabetics). Two had apicture of gram negative endotoxinemia. One of them wascomatose. In two emergency nephrectomy was done for thereasons specified above. None of the patients had acute renalfailure at the time of or following PN. Renal function, as judgedby serum creatinine levels, was normal or only marginallyimpaired (mean SD 88.7 21.3 moLfliter, range 55 to 138).

BacteriologyMost cases (48 of 55, 87.3%) were due to E. co/i. In 16 out of

36 (44.5%) blood cultures were positive and 14 of 16 cases werepositive for E. co/i. In 11 of these biotyping was done andshowed the identity of E. co/i recovered in the blood and in theurine. Cases with bacteremia were not always those with themost severe CT lesions. In two patients blind treatment hadbeen initiated before admission; urinalysis disclosed sterilepyuria but blood cultures were positive and allowed identifica-tion of E. co/i.

Genotypic assays of E. co/i were available in 27 cases. In all,at least one genotypic marker of adhesins was found. The mostfrequent operons were the pap (24 of 27, 89%) and the afa (8 of27, 29.6%). Nineteen isolates were pap+ afa—, five were pap+afa+ and only three were pap— afa+.

Conventional radiologyIVP was poorly informative as to degree of renal tissue

involvement, except in two cases with large abscesses in whicha mass effect was found. IVP was normal or little modified in 40.In 15, it showed a swollen kidney with compression of thepyelocalyceal system with edema, and in some cases a delay indye excretion. Likewise, ultrasonography detected only ab-scesses. In cases with renal edema, ultrasonography indicatedloss of corticomedullary differentiation but did not permit

48 Ff7 M19—76

23/42 (55%)11/2312/23

1022121116/36 (All E. coil)

48

+3

27/27 (pap: 24/27ala: 8/27)

further specification of lesions. Both methods had the maininterest of ruling out urinary tract obstruction.

Retrograde (or micturition) cystograms were normal, exceptin one case where it showed grade I unilateral vesicouretericreflux and thin ureters at the time of acute PN. A secondcystogram was normal after one month of treatment.

Computed tomodensitometryPlain films disclosed only increased kidney size and abscess

cavities and/or perirenal inflammation when present (Table 2).CT taken shortly after iodine injection were abnormal in 44 of

55 cases (79.6%). Triangular, wedge-shaped areas consisted ofimages of lobar topography, with a hilar summit and a corticalbase. Their low density, (30 to 80 Hounsfield units [HU]),contrasted with that of normal renal tissue (120 to 130 HU).Nodular images had the same density as the latter but not as lowas pus. Density of abscesses was lower than that of renal tissue.They were frequently accompanied by perirenal inflammation.In 23 cases the kidney was grossly swollen and the renal tissuewas diffusely mottled with ill-defined hypodense areas.

The bacteria responsible for these lesions were E. coli in 41cases, Klebsiella in one and not determined in two. In the 11remaining cases CT was normal. Urine cultures yielded E. coliin six, Staph. saprophyticus in two, and Strep. D + Citrobacterin 1.

Renal pathology

In two cases examination of kidneys removed surgicallyallowed correlations between lesions and CT images. Themacroscopic counterpart of hypodense images was whitishareas extending to the cortex. Histologically, the appearancewas that of severe interstitial nephritis, with interstitial edemaand massive infiltration with polymorphonuclear leukocytes,marked tubular atrophy and leukocyte casts. Several abscesseswere noted, one of which extended into the perirenal fat. In onecase, necrosis of a papilla was found.

In three cases renal biopsy was done at the lower pole of theleft kidney. It was not oriented by simultaneous CT, and it is

3rd CTand/orFinal

evaluation

not certain that the lesions were representative of hypodenseareas. Nonetheless, the biopsy sample comprised both cortexand medulla. The interstitium was invaded by inflammatorycells, with numerous polymorphs. Inflammation was accompa-nied by severe edema, and in one case hemorrhagic streakswere visible. There were numerous inspissated leukocyte castsin tubular lumens. Vessels were not markedly abnormal.

Evolution

Clinical. All patients were initially treated with two antibiot-ics. The majority received for one week a combination ofparenteral aminoglycoside and (depending on antibiograms)either oral ampicillin or a quinolone (pipemidic acid or norflox-acm), followed by oral treatment with ampicillin or quinolonefor three to six weeks.

The interval between diagnosis of acute PN and initiation oftreatment ranged from one day to six weeks, the longest delaysin diagnosis corresponding to cases with painless infection.Fever and pain subsided within one to six days, and urinecultures became negative in less than three days. High urinaryleukocyte counts and elevated sedimentation rates were theonly abnormalities persisting during the first month. Despitethis reassuring clinical impression, repeat CT was abnormal in15 of 27 cases (55.6%).

Of two patients who were nephrectomized, one was lost tofollow-up and the other was re-examined after 10 months. Shehad continued to suffer from recurrent episodes of urinary tractinfection. CT showed that the remaining kidney, which wasradiologically normal during the initial episode, remained nor-mal. Her serum creatinine level was the highest in the series(193 jsmollliter).

Radiological. Of44 patients with an abnormal initial CT scan,27 underwent a second examination (Table 2). In 12, the lesionshad subsided and PN was considered to be healed. In 15, thekidney(s) had not recovered a normal appearance. The imageswere of two types.

1) Persistent images. In eight cases abnormalities had notsubsided, although their severity was distinctly less than on

698 Meyrier et a!: Early cortical scarring in pyelonephritis

Table 2. Computed tomodensitometry in primary PN, N 55

2 Patients

nephrectomized

1st CT

2nd CT

Merrier ci a!: Ear/v cortical scarring in pyelonephritis 699

initial CT. They consisted of abscesses in two cases and ofhypodense lesions in six. The bacteria responsible were E. co/iin six, Klebsiella in one, and not determined in one. In five ofthese patients a third CT was done 6 to 12 months after thesecond. In one case with persistent hypodensity and in one withabscess, a cortical scar was now visible.

2) Fixed lesions. In seven patients, repeat CT one month totwo years after the first disclosed renal scarring or atrophy. Intwo cases a cortical scar was documented one month after theinitial CT. In one of them the scar developed on a zone adjacentto ajuxtacortical abscess. In the other it corresponded to a sitewhere hypodensity had been associated with marked perirenalinflammation. This patient underwent a third CT examinationafter a 12 month follow-up during which repeated urinalysesdisclosed normal urinary sediment and absence of bacteriuria.Two new scars were now visible close to the first (Fig. 1). Inthese seven cases the urinary pathogens were E. co/i.

Pathological. Two patients in whom renal biopsy had beenperformed at presentation underwent a second biopsy. In one,repeat biopsy was done after one month of treatment, at a timewhen CT showed persistence of some areas of hypodensity.Most of the interstitial inflammation, edema and hemorrhagicstreaks had subsided, but some foci of interstitial inflammationwere still visible, and there was a stripe of fibrosis across thebiopsy sample. In the second patient, in whom CT showedrelentless renal atrophy, surgical biopsy was performed threemonths after the first. The patient had received continuousantibiotic treatment over these three months. Biopsy showedsevere, widespread interstitial inflammation, with a mixedcellular population consisting of polymorphs, lymphocytes,plasma cells and fibroblasts. Half of the glomeruli were fibroticand several of the extant glomeruli were surrounded by layersof fibrosis. Several tubular lumens were plugged with leukocytecasts. The overall appearance was that of subacute chronicpyelonephritis (Fig. 2).

Final evaluation. Of 27 patients with abnormal images oninitial CT in whom follow-up was adequate and who underwentat least one control CT, only 17 (63%) were finally evaluated ashealed. Of the 10 others, eight had cortical scars with normalrenal function, and two had unilateral renal atrophy (Fig. 3) dueto chronic pyelonephritis with subnormal renal function. Inaddition, two patients had undergone emergency nephrectomy.One of them was lost to follow-up and the other had moderatechronic renal failure (creatinine clearance 43 mI/mn/I .73 m2).Overall, even in patients with cortical scars, blood pressureremained comparable to baseline values and renal function asjudged by serum creatinine level, which was generally un-changed except in the aforementioned nephrectomized patient(serum creatinine levels were 86 39 mol/liter; range 55 to193). Nonetheless, it must be stressed that the longest follow-upwas three years, and we have no relevant data regarding thelong-term evolution of renal function and/or of blood pressure,especially in case of pregnancy.

Discussion

This study shows that, in the absence of underlying urinarytract abnormalities, acute PN entails a frequent risk of earlyprogression to cortical scars, and in some cases of renalatrophy, a risk which seems to have been underestimated overthe last decade. This study also shows that computed tomoden-

Fig. 1. Computed iomodensitometrv in a 33-year-old patient with atypical picture of acute primary pyelonephritis. A. CT scan performedwithin 3 days after the clinical onset. A large hypodense lesion is visiblewithin the lower pole of the right kidney close to the renal cortex. Thislesion is accompanied by an inflammatory reaction within the perirenalfat. B. Repeat CT scan performed after a month of antibiotic treatmentwhich had sterilized the urine within 2 days. Hypodensity has disap-peared but a cortical scar is now visible in this area, indicated by +. C.A third CT scan examination performed after one year during which thepatient was regularly followed up clinically and bacteriologically. Noevidence of urinary infection was found during this surveillance.Nonetheless, CT showed that 3 cortical scars were now visible withinthe lower pole of the right kidney.

700 Meyrier et a!: Early cortical scarring in pyelonephritis

FIg. 2. A 52.year-old woman had afebrile illness of 6 weeks' duration. She never complained of renal pain or bladder discomfort. Bacteriuria andpyuriaeventually led to considering diagnosis of pyelonephritis. First CT scan examination showed a swollen left kidney with triangular hypodenseimages. Continuous antibiotic treatment was undertaken. Repeat CT scan (shown on this figure) performed 3 months later showed marked renalatrophy.

sitometry on the one hand, and a genotypic assay for detectinguropathogenicity on the other, compose a promising associationof diagnostic procedures in acute pyelonephritis.

The diagnosis of acute pyelonephritis cannot be reliably madeon IVP [Ii]. In 1979, Rosenfield et al [5]described "acute lobarnephronia" (ALN) studied by CT. They indicated that suchlesions could lead to cortical scars and concluded that "furtherstudy is required to determine whether all lesions of ALN resultin focal scars."

Since then, the images of acute PN have been analyzed inmore than 200 cases in the literature [12—14], but their subse-quent evolution has received little attention. It is not our goal todiscuss the literature on these images; even though our casesrepresent one of the largest single series, they do not bring newinformation on CT diagnosis of acute PN. Of greater interest isthe pathophysiology of hypodense images, and its relevance tocortical scar formation.

Hypodensity after injection of contrast medium is suggestiveof ischemia. Ischemia could be due to edema andlor lesions ofthe blood vessels. In cases where we could study the kidney byhistology, we found severe edema, polymorphonuclear infiltra-tion, abscesses and, in one case, hemorrhagic suffusions. Thesefeatures were strikingly similar to lesions of acute pyelonephri-tis induced in the primate by Roberts [15—171, lesions whichwere indeed accompanied by ischemia. In this model, withinminutes following intrarenal reflux of uropathogenic strains ofE. coli, complement was activated and chemotaxis of infiam-

matory cells began. The phagocytic respiratory burst causeddeath of renal tubular cells and a loss of up to 30% of renalfunction within 48 hours. This was followed by scar formation.Roberts commonly found hemorrhage, and interpreted thisfinding as a consequence of ischemia. He observed aggregatesof leukocytes which were formed in renal capillaries within 60minutes following inoculation, leading to ischemia with signifi-cant rise in plasma renin activity in the ipsilateral renal vein.

Interestingly, vascular involvement in acute renal infection isan old notion, and in our bibliographic screening we werepleased to find that as early as 1940, after creation of acutepyelonephritis in the rabbit, Mallory, Crane and Edwards [18]had observed the development of bacterial thromboses aroundand within infected areas. More recently, Hill and Clark con-ducted a series of elegant experiments [19, 20] in the rat and inthe rabbit. Neoprene vascular casting as well as microangiogra-phy clearly showed the importance of early vasoconstrictionafter renal tissue invasion by E. coli, followed by kinking andspiraling of vessels at a time when scar tissue appeared in thepreviously infected areas.

Thus, the weight of the evidence is in favor of early andprofound renal ischemia following infection by E. coli. Thisnotion has bearing on the understanding of scar formation aftera single acute episode of pyelonephritis in man.

Several of our cases evolved to early cortical scarring or renalatrophy despite the absence of urological abnormalities. Suchunfavorable evolution challenges the prevalent opinion that

Meyrier et a!: Early cortical scarring in pye!onephritis 701

Hg. 3. Samepatient as Figure 2. Renal biopsy was performed at the time of follow-up radiological investigations. It showed a typical image ofsubacute-chronic pyelonephritis. A heavy inflammatory infiltrate is visible in the interstitium. It is accompanied by tubular atrophy anddegeneration. Numerous leukocyte casts are present within the tubular lumens. Some glomeruli are undergoing fibrous degeneration.

acute PN isa benign condition. After the advent of antibiotics,thinking on the long-term hazards of acute PN followed adistinct trend from a notion of severity to the widely held beliefthat, in the absence of underlying urological lesion, acute PNseldom leads to cortical scars and very rarely to chronicpyelonephritis.

In 1960, when Kleeman, Hewitt and Guze [21] published anow classical review, "Pyelonephritis," the prevailing impres-sion was that upper UT!, even without any underlying urolog-ical lesion, represented a risk of progression to chronic pyelo-nephritis and to end-stage renal failure. Over the ensuing ISyears, several works rebutted the potential role of acute PN inthe genesis of chronic pyelonephritis [2—4]. Their conclusionswere reviewed by Freedman in this journal [1]. Huland, Buschand Riebel [31, in a prospective study based on IVP, concludedthat acute "primary" pyelonephritis entailed no risk of devel-opment to cortical scars, an opinion supported by Hodson inthe discussion following. Such optimism was only recentlyruffled by the Cardiff group [22], which showed that bacteriuriacan indeed lead to long term scarring, even in the absence ofvesicoureteral reflux, with significant further risk of toxemia ofpregnancy.

In fact, we show that the incidence of renal scarring or evenrenal atrophy following a single acute pyelonephritic episodehas been greatly underestimated by conventional radiologictechniques. This is easy to understand, as IVP shows theoutline of the kidney but affords no information on its surfaces.

What is the role of E. coli pathogenicity in scar formation?Except in patients with impaired immunity, such as diabeticsand perhaps some alcoholics, the absence of underlying urinarytract lesions leaves little place to factors pertaining to the host.This rather points to E. co/i uropathogenicity, which is essen-tially due to the presence of adhesins interacting specificallywith uroepithelial cells [15, 16, 23—29]. Scarring occurred rap-idly after the acute episode: in at least two patients corticalnotching was visible within a month. These patients had beenadequately treated within 48 hours of the onset of acuteinfection. More generally, the precocity of treatment did notappear to be a decisive factor in preventing cortical scars. Inonly one patient, with the longest interval between onset ofinfection and beginning of treatment, was this delay clearlyresponsible for progression to unilateral renal atrophy. Such ashort interval between the first signs and symptoms of acutepyelonephritis and the development of cortical scars is in

I, 'I

702 Mevrier et al: Ear/v cortical scarring in pvelonephritis

keeping with animal experiments performed by Mackenzie andAsscher [30], who showed how early (6 weeks) severe scarringdevelops in the rat after creation of pyelonephritis with auropathogenic strain of E. coil. In all our cases where uropath-ogenicity was sought, the E. co/i harbored in the urine carried atleast one genotypic marker for adhesin expression. This ex-plains why organisms gained access to the renal tissue, but doesnot necessarily mean that these adhesin-positive strains weremore liable to create scars than adhesin-negative E. co/i.

The notion that the presence of adhesin is a decisive factor inuropathogenicity is now well established, both in man [23—29]and in the experimental animal [15—17]. The snag is thatmethods for detecting uroepithelial cell adhesion of E. co/i arenot entirely reliable. Phenotypic assays include agglutinationtests of latex beads coated with alpha-D-galactosyl(l-4)beta-D-galactose, hemagglutination of human erythrocytes in presenceof alpha-methyl-mannoside, hemagglutination of bovine eryth-rocytes, adhesion tests on uroepithelial cells or to Hep2 cells,etc. [8—10, 27]. In our hands, such phenotypic assays werepositive in only 68.6% of 102 E. coil isolates from patients withpyelonephritis (primary or secondary), whereas genotypic as-says revealed that 87.2% of those germs contained DNAsequences related to at least one of the pap, sfa, or afa operons.False negative results may be due to the disappearance ofbacterial pill and/or adhe sin after growth in vitro. The genotypicassay we utilized escapes this pitfall. The constancy of positivetests in our cases of primary acute PN confirms the essentialrole of adhesin in promoting renal invasion within a normalurinary tract. A negative uropathogenicity genotypic assayshould therefbre be an incentive to seek an overlooked cause ofacute PN, such as vesicoureteric reflux. Nonetheless, as dis-cussed above, since 63% of our patients with adequate CT scanfollow-up recovered normal kidney appearance, one cannotinfer from a positive test that such "uropathogenic" organismsare more able to create renal scars than other strains when theyhave gained access to the renal interstitium.

The treatment of acute PN is not codified. The prevailingstrategy consists of a three-week course of antibiotics [31], butsome consider that shorter treatment is sufficient [32, 33]. Thereare few data to substantiate one or the other of these policies.This is understandable as urinary pathogens usually disappearfrom the urine a few hours after beginning treatment, andthereafter signs of renal inflammation subside within a fewdays. Despite this reassuring impression, we found that in 30%of cases repeat CT showed the persistence of initial images afterthree to four weeks of treatment.

These findings raise the question of persisting bacteria withinremnant hypodense areas. If such images correspond to smol-dering infection, treatment should presumably be continueduntil they have disappeared. If, on the contrary, such imagesand scar formation are the consequence of early ischemia,protracted treatment would be, at the least, useless.

This issue calls for a randomized, controlled study of twoseries of patients with acute PN, documented both with CTscanning and with reliable tests of uropathogenicity, one groupbeing treated with a short and the other with a long course ofantibiotics. Such a project is presently underway in our unit.

In summary, we observed that acute PN occurring in theabsence of underlying urinary tract lesion was due to uropatho-genic strains of E. co/i, and that uropathogenicity was best

identified by a genotypic assay of bacterial adhesin. Initialcomputed tomodensitometry suggested early renal ischemiawithin infected areas. This entailed a risk of rapid developmentto cortical scars and even to unilateral renal atrophy, and theincidence of such complications would have been greatly un-derestimated had the follow-up been based only upon conven-tional radiological techniques. The long-term implications ofsuch morphological lesions on the renal function and/or bloodpressure levels of a given patient remain entirely speculative.Nonetheless, our observations raise the issue of reconsideringthe possible role of past, overlooked infection in patientssuffering from idiopathic chronic pyelonephritis, in women withtoxemia of pregnancy, and perhaps even in some patients withhypertension.

Acknowledgments

Parts of this work were presented at the IVth International Sympo-sium on Pyelonephritis, Gotherburg, Sweden, June 23-25, 1986, and atthe 19 Annual Meeting of the American Society of Nephrology,Washington, D.C., December 10—13, 1986, abstract 53A. We aregrateful to Dr. Gary S. Hill for helpful suggestions and discussionduring the preparation of this paper. We are greatly indebted to DoreenBroneer for efficient assistance in preparing and typing this manuscript.

Reprint requests to A lain Meyrier, M.D., Department of Nephrology,Hôpitai Avicenne, /25, route de Stalingrad, F-93009 Bobigny, France.

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