To systematically review the current demographics, treatment and mortality rate associated with xanthogranulomatous pyelonephritis (XGP) and to test the hypothesis that the weighted pooled peri-operative mortality rate will be <10%.

Methods

Searches were performed of the Cochrane, Embase and Medline databases and the grey literature for studies published during the period 1 January 2000 to 30 August 2021. Eligible studies reported cohorts of ≥10 predominantly adult patients with XGP and described either average patient age or mortality rate.

Results

In total, 40 eligible studies were identified, representing 1139 patients with XGP. There were 18 deaths, with a weighted pooled peri-operative mortality rate of 1436 per 100 000 patients. The mean age was 49 years, 70% of patients were female and 28% had diabetes mellitus. The left kidney was more commonly affected (60%). Four patients had bilateral XGP, and all of whom survived. Renal or ureteric stones were present in 69% of patients, including 48% with staghorn calculi. Urine culture was positive in 59% of cases. Fistulae were present in 8%. Correct preoperative diagnosis occurred in only 45% of patients. Standard treatment continues to comprise a short cause of antibiotics and open radical (total) nephrectomy. Preoperative decompression occurred in 56% of patients. When considered at all, laparoscopic nephrectomy was performed in 34% of patients. Partial nephrectomy was conducted in 2% of patients.

Conclusions

Xanthogranulomatous pyelonephritis has a lower mortality rate than historically reported. A typical patient is a woman in her fifth or sixth decade of life with urolithiasis. While open radical nephrectomy remains the most common treatment method, laparoscopic, and to a lesser degree partial nephrectomy, are feasible in well selected patients.

Introduction

Xanthogranulomatous pyelonephritis (XGP) is a rare severe form of chronic bacterial renal infection. Most cases are unilateral, with obstructing renal calculi and granulomatous inflammation resulting in a non-functioning, hydronephrotic, enlarged kidney with diffuse parenchymal destruction. Its peak incidence is at age 50–70 years, with a 2:1 female to male preponderance. Its population incidence is 1.4 cases per 100 000 per annum [1]. However, amongst patients with chronic pyelonephritis, XGP comprises 0.6–1.0% of cases and 19% of those requiring nephrectomy [2, 3]. At least 15% of patients require intensive care unit admission [4, 5] and almost all undergo unilateral radical (total) nephrectomy [3, 6].

Xanthogranulomatous pyelonephritis is considered life-threatening and peri-operative mortality has been reported to be as high as 40% [6, 7]. However, the modern mortality rate is unknown. There have been no systematic reviews, with the literature limited to case reports and case series. The aim of this study therefore was to analyse systematically the modern mortality rate of patients with XGP, which we hypothesized would be <10%. Our secondary aim was to summarize the demographics and treatment patterns associated with this disease.

Methods

Search Strategy

Systematic searches were performed on 4 September 2021 of the medical databases Embase, Medline and the Cochrane Central Register of Controlled Trials. Searches were conducted by title or abstract, applying keywords and Boolean operators as follows: (xanthogranulomatous pyelonephritis) AND (cases OR patients). The grey literature was also searched. Given the rarity of XGP, experts in the field were not sought to guide the methodological approach. Our method for identifying and evaluating data complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (Appendix 1 and Fig. 1). This included pre-publication of our proposed analysis on PROSPERO (ID 278342). Identified studies were screened by title and abstract, followed by full-text appraisal. Articles then advanced to data extraction, including review of references. Two independent authors (F.H., N.K.) performed study screening and data extraction, using a predefined form (Appendix 2).

Details are in the caption following the image — **Fig. 1**
Open in figure viewer PowerPoint

Preferred Reporting Items for Systematic Reviews and Meta-analyses flow diagram.

Study Eligibility

Study eligibility was established based on the PICOS method: patient population (P), intervention (I), comparator (C), outcome (O) and study (S) [8]; eligible studies reported on cohorts or subcohorts containing predominantly adult patients with XGP (P) treated with curative intent (I), were not required to have a comparator cohort (C) and stated either mortality rate or average patient age (O). Eligible articles were original full-length articles or conference abstracts, published in English between 1 January 2000 and 30 August 2021 (S).

Intended Analyses

The primary outcome was 1-year mortality rate for patients with XGP. Secondary outcomes were pooled mean patient age, gender, prevalence of diabetes, disease site, mortality of bilateral disease, predominant bacteria and rates of each management modality. Qualitative summary was intended for all data. Quantitative analyses were planned to assess the pooled incidence of mortality and mean age at diagnosis. Meta-analysis was conducted using the package meta in R [9], with incidence reported per 100 000 procedures because of the low incidence of these events. Random-effects models were used throughout and the I² metric was used to assess statistical heterogeneity. If significant heterogeneity was found, manual comparison of study characteristics (sample size, median age, developed/ developing nation etc.) was planned between the (smaller) group of outlier studies that reported an over-five-times-higher mortality rate and the remaining studies.

Risk of Bias

Randomized controlled trials were not expected. Subsequently, risk of bias was assessed with the ROBINS-I template, in accordance with the Cochrane Handbook [10, 11]. Studies were assessed independently by two authors (F.H., N.K.). Differences were resolved by consensus. Risk of bias was not used to exclude studies. However, weighted pooled analysis was intended to be repeated for the subgroup of studies at only low or medium risk of bias.

Results

Initial database searches returned 693 publications. After removing 206 duplicates, 387 articles were screened by title and abstract, with 43 then retrieved for full-text review (Appendix 3). Three studies were excluded, with all three having both unclear mean/median patient age and failure to state number of deaths [12-14]. Finally, 40 eligible studies were identified, comprising 1139 patients with XGP from 20 nations [3-6, 15-50] (Table 1). All studies were retrospective, and only five were multicentre [20, 21, 29, 37, 50].

Table 1. Eligible studies.

Year	1st author	Nation	Abstract or full text	Patients, n	Mean age, years	Female, n	Left side, n	Diabetes, n	Inclusion criteria	Deaths, n	Mortality follow-up, days	Lap. nephx, n	HAL nephx, n	Lap. convert to open nephx, n	Open nephx, n
2000	Huang [15]	China	Abstract^*	28	n.s.	n.s.	n.s.	n.s.	Clinical diagnosis	0	n.s.	n.s.	n.s.	n.s.	n.s.
2000	MattaceRaso [16]	Italy	Abstract^*	10	n.s.	n.s.	4	n.s.	Histol. dx post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2001	Fallatah [17]	Saudi Arabia	Full text	10	45	3	6	1	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2003	Zorzos [18]	Greece	Full text	39	57	25	n.s.	4	Histol. dx. post nephx	1	n.s.	0	0	0	39
2004	Saavedra Jo [19]	Peru	Abstract^*	11	n.s.	8	n.s.	n.s.	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2005	Khaira [20]	USA	Full text	11	51	n.s.	n.s.	n.s.	Histol. dx. post nephx	0	n.s.	2	0	1	8
2006	Al-Ghazo [21]	China	Full text	18	50	13	16	4	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2006	Dwivedi [22]	India	Full text	26	42^*	16	20	n.s.	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	26
2006	Kapoor [23]	India	Full text	25	48	8	n.s.	6	Histol. dx. post nephx	2	n.s.	8	0	2	25
2006	Rosoff [24]	ISA	Full text	11	51	6	6	4	Histol. dx. post lap. Nephx	0	n.s.	7	4	0	0
2007	Afgan [25]	Pakistan	Full text	11	48	10	10	7	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2007	Loffroy [26]	France	Full text	13	55	10	6	1	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2007	Vanderbrink [27]	USA	Full text	12	50	11	6	n.s.	Histol. dx. post nephx	1	n.s.	3	2	1	6
2008	Korkes [25]	Brazil	Full text	41	47	35	n.s.	n.s.	Histol. dx. post nephx	2	n.s.	1	n.s.	1	39
2009	Guzzo [26]	USA	Abstract^†	26	44	n.s.	n.s.	n.s.	Histol. dx. post nephx	1	n.s.	14	n.s.	n.s.	12
2009	Leoni [27]	Argentina	Abstract^*	10	50	8	n.s.	n.s.	Histol. dx. post nephx	1	n.s.	n.s.	n.s.	n.s.	n.s.
2011	Arvind [3]	India	Full text	19	38	n.s.	n.s.	7	Histol. dx. post lap. Nephx	1	n.s.	14	0	5	NA
2011	Kuo [28]	Taiwan	Full text	30	55	25	18	12	Histol. dx. post nephx	n.s.	NA	3	n.s.	n.s.	27
2011	Shah [29]	India	Full text	37	42	17	16	4	Histol. dx. post nephx	1	n.s.	16	0	1	20
2011	Siddappa [30]	India	Full text	16	52	10	9	n.s.	Histol. dx. post nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2012	Lima [31]	Brazil	Full text	66	42	39	34	n.s.	Histol. dx. post lap. Nephx	0	n.s.	58	0	8	NA
2013	Fugita [32]	Brazil	Abstract^†	41	43	n.s.	n.s.	n.s.	Histol. dx. post lap. Nephx	1	n.s.	37	n.s.	4	NA
2013	Kim [33]	South Korea	Full text	21	52	15	16	11	Histol. dx. post nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2013	Qi-chao [34]	China	Abstract^‡	13	40	10	n.s.	n.s.	Histol. dx. post nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2014	Datta [35]	India	Abstract^‡	18	n.s.	13	15	2	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2014	Srivastava [36]	India	Abstract^†	65	42	40	n.s.	46	Histol. dx. post nephx	n.s.	NA	28	0	7	30
2015	Addison [37]	New Zealand	Full text	35	47	32	n.s.	11	Histol. dx. post nephx	2	30^¶	1	0	0	33
2016	Caliskan [38]	Turkey	Full text	13	56	6	9	3	Histol. dx. post nephx	0	n.s.	0	0	0	13
2016	Danilovic [39]	Brazil	Abstract^†	80	44	65	31	n.s.	Histol. dx. post nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2017	Canvasser [6]	USA	Abstract^†	11	39	10	n.s.	6	PCNL for XGP	0	1171^§	n.s.	n.s.	n.s.	n.s.
2018	Campanario-Perez [40]	Spain	Full text	17	60	10	8	2	Histol. dx. post lap. Nephx	1	n.s.	15	n.s.	2	NA
2018	Ichaoui [41]	Tunisia	Abstract^*	42	50	n.s.	n.s.	n.s.	Histol. dx. post lap. Nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2019	Asali [42]	Israel	Full text	27	61	22	n.s.	n.s.	Histol. dx. post lap. Nephx	0	n.s.	26	0	1	NA
2019	Kisa [43]	Turkey	Full text	22	51	12	10	6	Histol. dx. post nephx	n.s.	NA	3	0	0	19
2019	Kundu [44]	India	Full text	40	40	26	25	n.s.	Histol. dx. post nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2019	Zhuo [45]	China	Abstract^‡	41	57	24	19	n.s.	Histol. dx. post nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2020	Chiba [46]	Tunisia	Abstract^†	10	47^§	n.s.	n.s.	n.s.	Histol. dx. post nephx	0	n.s.	n.s.	n.s.	n.s.	n.s.
2021	Aviles-Ibarra [47]	Mexico	Abstract^*	72	50	60	n.s.	n.s.	Histol. dx. post nephx	n.s.	NA	n.s.	n.s.	n.s.	n.s.
2021	Barboza [48]	USA	Full text	40	54	n.s.	23	6	Histol. dx. post nephx	2	n.s.	12	5	3	20
2021	Xie [49]	USA	Full text	61	50	51	n.s.	n.s.	Histol. dx. post nephx	2	n.s.	40	0	0	21

HAL, hand-assisted laparoscopy; Histol. dx., histological diagnosis; Lap., laparoscopic; n.s., not stated; n, number; NA, follow-up duration not applicable as peri-operative mortality not stated; Nephx, nephrectomy.
^* Article in language other than English.
^† Conference proceedings.
^‡ Unable to source full-text article.
^§ Median.
^¶ Strict peri-operative mortality time limit.

Primary Outcome: Mortality

The presence or absence of XGP-related mortality was stated by 27 studies, comprising 630 patients [4, 6, 15-27, 29, 30, 32, 34, 35, 38, 40, 42, 43, 45, 49, 50]. In total there were 18 deaths within 1 year of diagnosis, resulting in a weighted proportion of 1436 deaths per 100 000 patients (95% CI 292–2579; Fig. 2). The heterogeneity of this analysis was low (I² = 0%).

Secondary Outcomes

Demographics

The weighted mean patient age was 48.9 years (95% CI 46.1–51.7; I² 83.6%), with 70% of the patients being female (95% CI 65–76%) and 28% having diabetes (95% CI 19–38%). Slightly more cases occurred in the left kidney (60%) than the right, which was statistically significant (95% CI 52–68%). Four patients had bilateral XGP, all of whom survived [4, 40, 42]. When stated, the correct preoperative diagnosis of XGP was made in only 183 of 408 patients (45%).

Associated Conditions

Where reported, upper urinary tract stones were present in 545 of 788 patients (69%) [3, 5, 6, 16-18, 20-24, 26, 27, 30, 31, 33, 36, 38-44, 46, 47, 49, 50]. This included 214 of 450 patients (48%) with staghorn calculi. In four patients, concurrent renal tumour was found [17, 30, 33].

Microbiology

When available preoperatively, 370 of 625 patients (59%) had positive voided urine culture. Twenty articles reported the relative frequency of different micro-organisms [3, 4, 6, 16, 19, 21-23, 25, 26, 28, 31, 33, 36, 40, 43, 44, 46, 47, 49]. The most commonly cultured were Escherichia coli (16 studies) and Proteus species (four). These two pathogens occupied the most common position in 19 studies. One work observed Candida species as the second most common organism [43]. There was a wide range of less common bacteria, including species Klebsiella, Enterobacter, Streptococcus, Corynebacterium, Morganella and Pseudomonas aeruginosa [4].

Treatment

All patients received antibiotics. Where described, 161 of 286 cases (56%) underwent initial upper urinary tract decompression, with either a percutaneous nephrostomy (vast majority), or rarely, a ureteric stent. Thirty-eight of the 40 eligible studies enrolled only patients with a histological diagnosis of XGP after undergoing radical or partial nephrectomy [3, 5, 4, 6, 16-41, 43-50]. Only one study enrolled patients based on clinical diagnosis, and presented a spectrum of treatment. In this case series, Huang et al. reported 28 patients with XGP, of whom 20 underwent radical nephrectomy and eight were successfully managed with antibiotics alone [15]. A separate single series identified 11 patients with XGP managed with percutaneous nephrolithomy, with no deaths and only one treatment failure requiring nephrectomy [42].

Surgical Technique

Fourteen studies enrolled patients with XGP undergoing nephrectomy via either a laparoscopic or an open approach [3, 4, 6, 18, 20, 23, 27, 28, 31, 32, 39, 40, 46, 50]. In this subgroup, most patients received open nephrectomy, while 138 of 405 patients (34%) underwent laparoscopic nephrectomy. There was no clear trend of changing surgical approach over time (Fig. 3). Eighteen case series enrolled patients (462 total) undergoing nephrectomy via an unspecified approach [5, 16, 17, 19, 21, 22, 25, 26, 29, 33, 36-38, 41, 44, 47-50], and another six works enrolled only patients (181 total) managed with laparoscopic nephrectomy [24, 30, 34, 35, 43, 45]. When a laparoscopic approach was chosen and rates of intra-operative conversion to an open approach were reported, this occurred in 36 of 282 patients (13%). Separate to surgical approach, the vast majority of patients undergoing renal resection received radical nephrectomy, with only 14 instances across seven cohorts of partial nephrectomy [4, 26, 36, 40, 47-49].

Fistulae

When measured, fistulae were observed in 23 of 291 patients (8%) [3, 6, 17, 18, 20, 21, 23, 26, 27, 31, 33, 43, 47]. This included 12 nephro-cutaneous, seven nephro-colic, two duodenal, one pancreatic and one entero-cutaneous fistula. Survival data were available for 15 of these patients, with a death occurring in four (27%) [18, 23, 27, 43].

Assessment of Bias

The ROBINS-I template suggested that risk of bias was unassessable (two studies), moderate (28 studies), or serious (10) for the identified 40 works (Appendix 4). When studies with serious or unassessable risk of bias were excluded, the weighted pooled mortality rate was similar (1101 deaths per 100 000 patients). Publication bias was not assessed.

Discussion

Xanthogranulomatous pyelonephritis is a multiforme disease, ‘known to imitate almost every other inflammatory disease of the kidney’ [51]. Patients commonly present with flank pain, fever, rigours and elevated inflammatory markers. Urine culture is variably positive, often due to pre-treatment with antibiotics. Serum investigations typically reveal anaemia and leucocytosis, as well as hepatic dysfunction in 50% of patients [52]. CT usually demonstrates a large heterogenous renal mass and calyceal dilatation secondary to obstructing calculi. Some have dubbed this the ‘bear paw sign’ [22, 24]. The inflammatory process often extends into the retroperitoneum beyond Gerota's fascia, and may include peri-nephric abscess. However, wide variation in clinical and radiological presentation occurs. Our findings support this difficulty, with correct preoperative diagnosis occurring in fewer than half the identified patients. This uncertainty regarding clinical and radiological information probably explains why 38 of the 40 eligible studies enrolled only patients with postoperative histological confirmation. The characteristic microscopic finding is foamy lipid-laden histiocytes amid severe inflammation causing destruction of renal parenchyma. The frequency of incorrect diagnosis is the primary obstacle to treatment [51].

This represents the largest systematic review of XGP to date. The pooling of 1139 cases of this uncommon disease allows patterns to be drawn that are typically invisible in the observed small samples. The weighted pooled mortality was 1436 deaths per 100 000 patients. As hypothesized, this is much lower than the previously stated figures of <40% [6, 7]. These lower mortality rates may be related to multifactorial improvements in care, including broader antibiotic options, wider availability of CT scanning allowing earlier diagnosis, and superior intensive care cardiorespiratory capabilities. Although the Malek and Elder staging scale exists for XGP, this was rarely used by the 40 identified studies, and no correlation can be made between stage and mortality rate [43, 52]. Similarly, while previous authors have held that ‘bilateral XGP is usually fatal’ [53], in this review none of the four identified such cases died. These patients were presented within three separate single-centre studies published in the past 5 years from centres in either Turkey or the USA [4, 40, 42].

The observed patient demographics and microbiology were mostly in keeping with that previously reported. Sources such as the seminal textbook Campbell-Walsh-Wein Urology [51], and the largest cohort to date, reported by Parsons et al. in 1983 [1], agree on many factors. These include peak age of incidence in the sixth decade, women outnumbering men 2:1, diabetes as a weak risk factor, and the bacterial dominance of E. coli and Proteus species. Our findings support most of these tenets. However, the weighted pooled mean age was 48 years. While the cause for this mild shift towards younger patients is unclear, it may be attributable to globally rising rates of diabetes amongst younger adults, which is the leading modifiable risk factor for XGP. The mild preponderance of left-sided XGP was unexpected. While potentially attributable to sampling error, the authors believe this is most likely a true finding, relating to the poorly understood slightly higher rate of urolithiasis in the left rather than right kidney [54, 55]. Fistulae were relatively common, present in 8% of XGP patients. This risk may not have been adequately appreciated from the typical small case series to date. Fistulae require careful multidisciplinary management and often complex reconstruction. In this review over one-quarter of patients with fistulae died.

What constitutes adequate treatment continues to be debated. Typical treatment comprises antibiotics followed by open radical nephrectomy. Over 50% of patients will present with an infected obstructed upper tract and require preoperative decompression with either a nephrostomy (most) or ureteric stent. The requirement for a definitive surgical approach stems from the disease's obliteration of tissue planes, which is well known to make dissection technically very challenging. However, for well-selected patients, several variations exist. A longer course (4 weeks or more) of preoperative antibiotics appears to improve outcomes [50]. There are rare reports of successful treatment with antibiotics alone in patients with focal disease and no urinary tract obstruction [15]. Laparoscopic nephrectomy appears possible for a third of patients, although >10% will require conversion to open surgery [24, 30, 34, 35, 43, 45]. Lastly, <2% of cases may be amenable to partial nephrectomy. In all cases, this uncommon nephron-sparing approach was chosen when the inflammatory process was particularly focal, and limited to a pole (e.g., not interpolar).

This review is limited by its inclusion of only non-randomized retrospective cohorts of predominantly adult patients. Non-randomized studies are more prone to selection bias, with authors potentially less likely to publish cohorts of patients who experienced high morbidity or mortality at their centre. All but five works were single-centre studies. The median study size was small at 23 patients. XGP is well documented in paediatric patients [56], but was not the focus of this review. Additionally, all but two of the identified studies enrolled only patients based on postoperative histological diagnosis. Hence, cohorts are likely to omit patients with XGP who were managed conservatively.

Duration of follow-up for mortality was undefined in 38 of 40 studies. Given that death following complications related to nephrectomy for XGP was reported >90 days postoperatively in two patients [28, 30], it is likely that lack of disciplined data capture may have missed some events. Hence, these results should be interpreted with caution. Furthermore, complication reporting was poorly performed, for example, the incidence of death or of fistulae was reported by only 29 and 13 studies, respectively. The authors recommend routine use of the new urology-specific CAMUS approach for complication reporting, for both in-house audit and peer-reviewed publication [57]. Lastly, governance and impartiality information were commonly absent, including ethics approval (unstated or consciously not obtained in 35 studies), conflict of interest (missing in 32 studies) and funding (missing in 34 studies).

In conclusion, current patients with XGP experience a lower mortality rate than historically reported. The typical patient is a woman in her fifth or sixth decade of life with urolithiasis and often diabetes. Standard treatment continues to comprise a short cause of antibiotics, percutaneous decompression in just over 50% of patients, and open radical nephrectomy. Laparoscopic, and to a lesser degree, partial nephrectomy are feasible in well selected patients.

Author Contributions

FH and NK created the concept, acquired and analysed the data and wrote the initial manuscript. MOC performed the statistical analyses. All authors refined the final manuscript, and agree to be accountable for all aspects of the work.

Acknowledgement

Open access publishing facilitated by The University of Adelaide, as part of the Wiley - The University of Adelaide agreement via the Council of Australian University Librarians.

Disclosure of Interests

The authors declare that they have no disclosure of interest.

Funding

No funding was received in relation to this work.

Appendix 1: Preferred reporting items for systematic reviews and meta-analyses checklist

Section/topic	#	Checklist item	Reported on page #
TITLE
Title	1	Identify the report as a systematic review, meta-analysis, or both	Title page
ABSTRACT
Structured summary	2	Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number	1
INTRODUCTION
Rationale	3	Describe the rationale for the review in the context of what is already known	2
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS)	2
METHODS
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number	2
Eligibility criteria	6	Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale	3
Information sources	7	Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched	2
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated	2
Study selection	9	State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis)	2
Data collection process	10	Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators	4
Data items	11	List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made	Appx 2
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis	3
Summary measures	13	State the principal summary measures (e.g., risk ratio, difference in means)	3
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis	3
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies)	3
Additional analyses	16	Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were prespecified	3
RESULTS
Study selection	17	Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram	3
Study characteristics	18	For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations	Table 1
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12)	Appx 4
Results of individual studies	20	For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot	Table 1
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency	4
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies (see Item 15)	6
Additional analysis	23	Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16])	5
DISCUSSION
Summary of evidence	24	Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers)	6
Limitations	25	Discuss limitations at study and outcome level (e.g., risk of bias), and at review level (e.g., incomplete retrieval of identified research, reporting bias)	8
Conclusions	26	Provide a general interpretation of the results in the context of other evidence, and implications for future research	8
FUNDING
Funding	27	Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review	9

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097. https://doi.org/10.1371/journal.pmed1000097. For more information, visit: www.prisma-statement.org.

Appendix 2: Data extraction pro-forma

Appendix 3: Studies retrieved for full-text review

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Appendix 4: Risk of bias for identified studies, using the ROBINS-I tool

Year	First author	Bias due to confounding	Bias in selection of participants into the study	Bias in classification of interventions	Bias due to deviations from intended interventions	Bias due to missing data	Bias in measurement of outcomes	Bias in selection of the reported result	Overall bias
2000	Huang [12]	Not stated	Moderate	Low	Not stated	Not stated	Moderate	Not stated	Unassessable
2000	MattaceRaso [13]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2001	Fallatah [14]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2003	Zorzos [15]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2004	Saavedra Jo [16]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2005	Khaira [17]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2006	Al-Ghazo [18]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2006	Dwivedi [19]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2006	Kapoor [20]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2006	Rosoff [21]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2007	Afgan [22]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2007	Loffroy [23]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2007	Vanderbrink [24]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2008	Korkes [25]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2009	Guzzo [26]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2009	Leoni [27]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2011	Arvind [3]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2011	Kuo [28]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2011	Shah [29]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2011	Siddappa [30]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2012	Lima [31]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2013	Fugita [32]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2013	Kim [33]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2013	Qi-chao [34]	Not stated	Moderate	Low	Not stated	Low	Moderate	Not stated	Unassessable
2014	Datta [35]	Not stated	Moderate	Low	Not stated	Low	Moderate	Low	Moderate
2014	Srivastava [36]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2015	Addison [37]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2016	Caliskan [38]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2016	Danilovic [39]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2017	Canvasser [6]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2018	Campanario-Perez [40]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2018	Ichaoui [41]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2019	Asali [42]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2019	Kisa [43]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2019	Kundu [44]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2019	Zhuo [45]	Low	Moderate	Low	Low	Low	Moderate	Low	Moderate
2020	Chiba [46]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2021	Aviles-Ibarra [47]	Not stated	Moderate	Low	Low	Low	Moderate	Low	Not stated
2021	Barboza [48]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious
2021	Xie [49]	Moderate	Moderate	Low	Low	Low	Moderate	Low	Serious

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Abbreviation

XGP: xanthogranulomatous pyelonephritis

Citing Literature

Volume131, Issue4

April 2023

Pages 395-407

Xanthogranulomatous pyelonephritis: a systematic review of treatment and mortality in more than 1000 cases

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Methods

Search Strategy

Study Eligibility

Intended Analyses

Risk of Bias

Results

Primary Outcome: Mortality

Secondary Outcomes

Demographics

Associated Conditions

Microbiology

Treatment

Surgical Technique

Fistulae

Assessment of Bias

Discussion

Author Contributions

Acknowledgement

Disclosure of Interests

Funding

Appendix 1: Preferred reporting items for systematic reviews and meta-analyses checklist

Appendix 2: Data extraction pro-forma

Appendix 3: Studies retrieved for full-text review

References

Appendix 4: Risk of bias for identified studies, using the ROBINS-I tool

References

Abbreviation

Citing Literature

Figures

References

Related

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