Journal of Pediatric Urology (2010) 6, 355e358

REVIEW ARTICLE

Xanthogranulomatous pyelonephritis in pediatricpatients: Case report and review of literature

Sushil Gupta, Carlos E. Araya, Vikas R. Dharnidharka*

Division of Pediatric Nephrology, University of Florida College of Medicine, 1600 SW Archer Road, P.O. Box 100296/HD 214,Gainesville, FL 32610-0296, USA

Received 28 July 2009; accepted 23 September 2009Available online 27 October 2009

KEYWORDSXanthogranulomatouspyelonephritis;Staghorn;Chronic pyelonephritis;Pediatric

* Corresponding author. Tel.: þ1 357107.

E-mail address: vikasmd@peds.ufl.

1477-5131/$36 ª 2009 Journal of Peddoi:10.1016/j.jpurol.2009.09.014

Abstract Xanthogranulomatous pyelonephritis (XPN) is an unusual and rare form of chronicrenal suppuration. XPN is often mistaken for renal malignancy; hence nephrectomy is commonlyperformed and the diagnosis confirmed by histopathology. Recent advances in imaging have al-lowed the radiological features to be characterized, such that routine nephrectomy is avoided.

Approximately 240 cases of XPN have been reported in children. We report a 17-year-oldfemale who presented with a 2-month history of increasing abdominal pain and intermittentepisodes of increased frequency and dysuria. Plain antero-posterior radiograph of the abdomenrevealed a left staghorn calculus. Computed tomography scan with intravenous contrastrevealed a low-density inflammatory area and reduced cortical dye uptake on the left renalparenchyma as compared to the opposite side. A dimercapto-succinic acid renal scan revealedthat the affected kidney contributed 18% of differential function. A diagnosis of XPN was made.The patient underwent percutaneous nephrostomy tube placement in an attempt to salvage thekidney.

The patient eventually failed conservative management. Our review of the literature suggeststhat medical management has worked in some focal XPN cases, but has not been sufficientlytested in diffuse XPN.ª 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Introduction

Xanthogranulomatous pyelonephritis (XPN) is a severe,chronic variant of pyelonephritis [1], characterized by

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iatric Urology Company. Publishe

destruction of the renal parenchyma and replacement with achronic inflammatory infiltrate and lipid-laden macrophages[2e4], resulting in a poorly functional or non-functionalenlarged kidney. Synchronous obstruction of the affectedrenal unit with concomitant UTI is the most common associ-ated pathology. This obstruction is usually secondary to anunderlying calculus of the renal pelvis or ureter. XPN appearsto have a multi-factorial pathogenesis, predominantlyaffecting middle-aged women. A long-standing renal stone,

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Figure 2 Contrast CT of the abdomen showing poor contrastuptake and swelling of the left kidney.

356 S. Gupta et al.

obstruction and infection lead to subsequent infiltration bylipid-laden macrophages (xanthomas; hence xanthogranu-lomatous) and a significant drop in renal function by unknownmechanisms. XPN is often mistaken for renal malignancy andprompts surgical exploration and removal of the affectedrenal unit.

The diagnosis of XPN was often based on pathologicassessment, after nephrectomy. However, increasinglysensitive radiologic investigations (sonography, four-phaseCT) in combination with clinical suspicion have made itspreoperative diagnosis possible, providing the option ofconservative management without nephrectomy. Thepurpose of this article is to report a case of XPN in whichconservative management was attempted, and to reviewthe literature on conservative management of this rela-tively uncommon disease in children.

Case report

A 17-year-old female presented with left abdominal pain of2 months’ duration, low-grade intermittent fever,increased urinary frequency and dysuria. The patient hadno history of gross hematuria, prior established UTI orunexplained fever as a young child. The family history wasnon-contributory. At presentation she was afebrile andphysical examination revealed tenderness over her leftabdomen and lower left back with no palpable mass.

Urinalysis showed a pH of 6.5, a specific gravity of 1.020with trace leukocyte esterase and 32 white blood cells perhigh-power field on microscopic examination. Blood andnitrites were negative on urine dipstick. The urine culturegrew mixed gram-positive flora. The inflammatory markerswere elevated with an erythrocyte sedimentation rate of101 mm/h and C-reactive protein of 88 mg/L. Completeblood count, electrolytes and renal functions were normal.

A plain X-ray of the abdomen showed a left staghorncalculus (Fig. 1). A CT scan of the abdomen with contrastshowed poor uptake of the contrast by the left kidney anda large staghorn calculus in the renal pelvis (Fig. 2). At the

Figure 1 Plain X-ray of the abdomen showing a left staghorncalculus.

time of presentation a DMSA nuclear scan showed that theaffected kidney contributed to only 18% of differentialfunction (Figs. 3 and 4).

Parenteral antibiotic therapy with ampicillin andgentamicin was initiated. After 4 days of antibiotic therapyand in an attempt to salvage the kidney and avoidnephrectomy, the patient underwent placement of apercutaneous nephrostomy tube. Drainage fluid from thenephrostomy tube grew Proteus mirabilis which was sensi-tive to ampicillin, gentamicin and ciprofloxacin. The patientwas sent home on oral ciprofloxacin. Her abdominal painimproved and she continued to be afebrile. However, after 7weeks of antibiotics, a follow-up renal nuclear scan showedonly marginal improvement in the differential function(from 18% to 23%) on the left side implying irreversibleparenchymal damage. Subsequent urine cultures continuedto be persistently positive for P. mirabilis. For these tworeasons, the patient was considered to have failed

Figure 3 DMSA scan showing good uptake in normal rightkidney and poor renal uptake on the left side.

Figure 4 DMSA scan flow curve showing poor renal uptakeand function of the left kidney (circles) as compared to theright kidney (diamonds) or aorta (squares).

Xanthogranulomatous pyelonephritis 357

conservative therapy and underwent a left nephrectomy.Surgically removing the stone was not considered toimprove the outcome, since the obstruction was relievedpreviously with the nephrostomy tube placement.

The removed kidney had global cortical atrophy,weighing 78 g with cortical thickness of 0.6 cm. There wereno gross developmental abnormalities of the kidney.Review of the renal histology demonstrated that theglomeruli were present in the usual numbers. However,there were areas of extensive glomerulosclerosis associ-ated with a dense chronic inflammatory cell infiltrate thatwas centered in the medulla of the kidney. The inflamma-tory infiltrate consisted of acute and chronic inflammatorycells with focal areas of necrosis lined by multinucleatedforeign-body-type giant cells. Numerous foamy histiocyteswere also present. The staghorn calculus found in the renalpelvis was composed predominantly of magnesium ammo-nium phosphate.

Discussion

The first descriptions of the distinctive gross and macro-scopic features of XPN were made by Schlagenhaufer in1916. In 1935, Oberling introduced the term ‘xanthogra-nulomatous pyelonephritis’. Although several investigatorsreported their findings regarding this uncommon condition,it was not until 1978 that Malek and Elder coined a stagingclassification of the disease, to distinguish the most suitablesurgical approach for each patient [5]. XPN is an uncommoninflammation of the renal parenchyma that occurs usuallyin the presence of chronic obstruction and suppuration. Itcan be seen at any pediatric age, including neonates,indicating the possibility of prenatal origin [6]. A review ofliterature done by Marteinsson et al. in 1996 reported 197pediatric cases of XPN [7]. Our review of the literaturerevealed that approximately 40 more pediatric cases of XPNhave been reported since 1996. We could not find anydifferentiating clinical features in children compared toadults.

It is unclear why the initial UTI and large staghorn stoneremain asymptomatic over a long period of time. Aninfection with low-virulence organisms and the presence ofa low-grade and partial obstruction could explain thechronic and relatively silent clinical presentation. Theisolation of the causal organism has been variable anddocumented in 50%e75% of XPN cases with Escherichia coli

and Proteus species being the most commonly implicatedorganisms (59%e95%) (2, 8e10). In one series, 33% of thecases had polymicrobial infections [8].

Obstruction due to renal stone occurs frequently and hasbeen reported in up to 83% of XPN cases. One third to halfof calculi are of the staghorn variety [2,3,5,8]. Lessfrequently, urinary tract obstruction as a result of UPJobstruction, severe VUR and tumors (e.g. renal cell carci-noma, ureteral carcinoma, bladder carcinoma) has beendescribed [2,9]. However, even in the absence of anatom-ical obstruction, physiological obstruction is often present.Obstruction is primarily seen in children with diffuse XPNcases and has never been described in focal XPN [11].

The reason why xanthogranulomatous inflammationoccurs is still unclear. However, the combination ofobstruction of the urinary tract and infection are the twomost consistently associated factors that predispose to thedevelopment of XPN. This observation is supported by studiesin rats in which ureteral ligation followed by E. coli infectiondemonstrated xanthogranulomatous inflammation [12,13].

Many other factors thought to be involved in the path-ogenesis of XPN have been suggested. Anhalt et al.proposed three potential mechanisms. The first was thatthe initial infection caused tissue damage with release oflipid material initiating the XPN. He also proposed that theprocess could be primarily a metabolic phenomenon witha secondary inflammatory reaction. Lastly, the investiga-tors proposed a combination of the above two mechanismsin association with vascular insufficiency and obstruction[14]. Malnutrition, which may lead to a state of immunecompromise, has also been observed in patients with XPN[15]. However, the lack of other evidence of systemicimmune deficiency and the successful treatment of XPN bynephrectomy lead to the conclusion that the presence of anunderlying immunological defect is unlikely. The malnutri-tion in these patients may be an end result of the XPN,rather than its cause. Still, the sequence of events involvedin the pathogenesis of XPN is not clear.

It is puzzling that XPN has been observed in neonatesand infants [6,16]. These observations suggest thatobstruction plays the main role in the pathogenesis ratherthan chronic infection. In experimental models, the xan-thogranulomatous foci usually began to develop in thekidney as early as 1 month after the insult [12].

XPN can be invasive and can affect the tissues sur-rounding the kidney. Moreover, there is always the concernof sepsis and associated malignancy with XPN. Hence,nephrectomy has been the treatment of choice. However,malignancy is rarely associated with XPN [17,18]. Tasi et al.reported an adult case with bilateral diffuse XPN with nofever, who was managed with supportive care without renalreplacement therapy. The 18 months of follow up wereuneventful with relatively stable renal function (serumcreatinine 10.6 mg/dl). So, it was suggested that fever maybe used as an indicator for nephrectomy [19].

In pediatric patients, there have been case reports ofsuccessful medical management of focal XPN. Brown et al.reported a case of a 27-month-old boy with focal XPN whowas successfully treated with 3 weeks of intravenous (i/v)antibiotics [20]. Hughes et al. used a course of 3 weeks ofnetilmicin to treat a case of multifocal XPN with success[21]. Rasoulpour et al. used 2 weeks of i/v followed by 8

358 S. Gupta et al.

weeks of oral antibiotic to treat a case of focal XPN [10].Moreover, there have been case reports of XPN in renalallograft, treated successfully with antibiotics [22,23]. Thepatients who were medically managed were followed withrenal ultrasound, i/v pyelography, CT scan and renalnuclear studies. All of these reports are related to focalXPN. In contrast, there are virtually no data on theconservative management of diffuse XPN. It is difficult toidentify the cases of XPN in which conservative manage-ment may be tried without putting the patient at a signifi-cant risk.

The indications for nephrectomy in XPN cases are notalways straightforward. A review of the literature foundthat there is no published evidence to suggest whetherdifferential function can be used to guide the treatment ofXPN. Differential function of near 20% is a grey zone as faras recommendation for nephrectomy is concerned.

Our patient had a differential function of 18% initially onthe affected side with no obvious evidence of obstruction.We decided to try conservative management initially sinceshe was afebrile, clinically stable and had a borderlinedifferential function on the initial DMSA scan. The therapywas targeted towards two important etiological factors:obstruction and infection. In this case, the failure toimprove with conservative management could be explainedby the irreversible nature of the inflammation with diffusekidney involvement and difficult-to-eradicate infection.Also, our patient had been symptomatic for several monthsprior to establishing the diagnosis or receiving any form oftherapy. It is also unclear if a longer course of antibiotictherapy would have changed the outcome in our patient.Without any clear guidelines on the management of XPN,conservative and surgical treatments should be consideredfor each individual case.

XPN, though puzzling in etiology, should be suspectedwhen there is a history of recurrent or therapy-resistantpyelonephritis, renal calculi, flank tenderness or mass.Early diagnosis with newer imaging techniques may changethe natural history, particularly in focal XPN, and helpsalvage the affected kidney.

Conflict of interest

None.

Role of the funding source

None.

Ethical approval

Not required.

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