Reconstructive versus palliative management of ureteral stenosis after kidney transplant: an EAU‑YAU kidney transplantation working group collaboration

doi:10.21203/rs.3.rs-4933012/v1

Introduction

The gold standard for treatment of ureteral stenosis after kidney transplantation is surgical redo of the anastomosis, although some patients may only be candidates for palliative treatment by permanent urinary catheterization. We aimed to compare the functional results of these two approaches.

Methods

A retrospective comparative analysis was carried out to compare the groups. The outcomes of each procedure and factors associated with success of reconstruction, graft failure and GFR variation were analyzed by means of descriptive statistics.

Results

30 (54.5%) and 24 (44.5%) patients underwent surgical and palliative treatment, respectively. Distal/ureterovesical location was most frequently observed (81.1%, p < 0.0001). Reconstruction consisted of ureterovesical reimplantation, pyeloureterostomy and ureteroureterostomy in 11 (36.6%), 13 (43.3%) and 3 (10.0%) cases, respectively. Intestinal segment interposition was employed in 2 (6.7%) cases. We observed 4 (13.3%) cases of failure after surgery and ureterovesical reimplantation was significantly associated with stricture recurrence (p = 0.018). A significant variation of GFR from post treatment baseline to last follow-up was observed in the palliative group (43.5 to 32.0, p < 0.001), although graft survival was similar (9.1% vs. 10.0%, p = 0.65).

Conclusion

Surgical reconstruction can attain definitive treatment of post KT US in almost nine out of ten patients with a satisfactory safety profile. On the other hand, palliative treatment seems to be associated with GFR degradation.

renal transplant

stenosis

reconstruction

renal function

pyeloureterostomy

Ureteral stenosis (US) is the most frequent surgically-related kidney transplant (KT) complication. While early occurring stenoses are mainly related to perioperative problems such as technical error or ureteral ischemia, late ones have a more complex etiology comprising infection, fibrosis and chronic vascular disease (1). Primary care mainly relies on urgent urinary drainage by means of a nephrostomy tube or double J stent placement, whereas long-term management may involve active strategies or a palliative approach by periodical tube exchange. Endoscopic procedures may be adopted as first-line treatment, although they may be less effective in long (> 3 cm) and late occurring strictures (2). On the other hand, refection of the anastomosis may be offered to fit patients, either as a first-line option or after failure of endoscopic management (3). Finally, palliative management by urinary tube exchange may be reserved for frail or comorbid patients. However, it poses a higher risk of recurrent urinary tract infection and may contribute to renal function degradation over time (4). The purpose of this paper was to describe the long-term outcomes of surgical management of post-transplant ureteral strictures and compare them with palliative management in terms of renal function preservation and graft survival.

This was a multicenter study conducted by three referral centers in France (La Conception University Hospital in Marseille and Toulouse University Hospital) and Italy (Azienda Ospedaliero-Universitaria Careggi, Florence). Data regarding patients > 18 years old presenting ureteral stricture of kidney transplant between 2012 and 2022 were retrospectively collected. Cases managed by endoscopic procedures only were excluded. Patients were allocated to palliative or surgical management based on their surgeon’s clinical judgement and patient preferences. Baseline characteristics included patient demographics and comorbidities (diabetes, hypertension and Charlson Comorbidity Index, CCI), allograft description (side, number of arteries and veins, type of urinary anastomosis), stricture characteristics (clinical presentation and time, location, length) and initial management (type of primary drainage and previous endoscopic procedures) were recorded for each group. For the surgical group, treatment variables included surgical technique, operative time (OT), estimated blood loss (EBL), postoperative complications (up to 90 postoperative days according to the Clavien-Dindo Classification), and long-term success (i.e., recurrence of stricture requiring permanent urinary drainage). Type of urinary drainage (nephrostomy or stent) and periodicity of exchanges were recorded in the palliative arm. Follow-ups were scheduled at 6 and 12 months, and then yearly. Long-term outcomes included glomerular filtration rate (GFR, estimated by the CKD EPI formula) and graft survival.

Statistical analysis

Normality of data was tested with the Shapiro-Wilk test. Descriptive statistics of categorical variables focused on frequencies and proportions. Medians and interquartile ranges (IQR) were reported for continuously coded variables. The Mann-Whitney and Fisher exact tests were used to compare clinical variables between the surgical and palliative groups and to investigate the association between variables and treatment outcomes. Student’s t-test was employed to evaluate variations of continuous variables within the same group. Statistical tests were performed using SPSS v.28 (IBM Corp., Armonk, NY). All tests were 2-sided, with a significance level set at 0.05.

Baseline features of the two cohorts are outlined in Tables 1 (patients and grafts) and 2 (strictures). Groups were comparable in terms of comorbidities and allograft characteristics, although renal function on diagnosis was significantly better in the reconstructive group (32 vs. 22 ml/ min, p=0.011). Lich Gregoir and ureteropyelostomy were the two most commonly performed urinary anastomoses, with the latter being more frequently observed in the palliative group (6.7% vs. 26.1%, p=0.034). Distal/ intravesical strictures were the most frequent with a non-significant difference between the groups (90.0% vs. 72.7%, p=0.085). 85.5% of strictures were diagnosed secondary to acute kidney injury (AKI) at a median of 1.5 (IQR 1-5) months and with comparable rates of early and late-presenting strictures between groups (p= 0.573). Five (16.7%) and 2 (8.0%) patients were primarily treated by means of minimally invasive endoscopic approaches in the reconstructive and palliative groups, respectively.

Outcomes regarding the reconstruction group are displayed in Table 3. Median diagnosis-to-surgery time was 9.8 (5.5–25.5) months. All procedures were performed through an open approach with a median OT of 120 (100-180) min. and an EBL of 100 (75-125) cc. No major intraoperative complications were reported. Median times of bladder catheterization, hospital stay, and double J stent removal were 7 (5-10), 8 (6-11) and 42 (33-72) days, respectively. The overall complication rate was 23.3%. Four (13.3%) patients presented acute obstructive kidney injury which required placement of a double stent (Clavien-Dindo 3a). Other complications consisted of postoperative transfusions (3, 10.0%)

In the palliative group, 24 (96.0%) patients were managed by indwelling double J stent, whereas one (4.0%) was managed by single J stent in an ileal conduit. The periodicity of changes was 6 (6-9) and 1.5 months for double and single J stents, respectively. At a median follow up of 64 months, we estimated a median number of 7.9 (6.0–10.2) stent replacements per patient.

Median follow-up was 70 (28-98) and 64 (33-84) months after reconstruction and the beginning of drainage, respectively. We observed no differences in graft survival (90.0% vs. 90.9%, p= 0.341) or GFR distribution (median: 40.2 vs 34.0, p= 0.536) between groups at last follow-up. However, within group analysis showed a significant reduction in GFR in the palliative group at last follow-up (41.0 to 40.25, p= 0.83 vs. 43.5 to 32.0, p=0.028), but not at the 6-, 12- and 24-month marks. The results are displayed in Tables 4 and 5.

Four (13.3%) patients in the surgical cohort presented stricture recurrence, all within 3 months of the procedure. Baseline patient and stricture characteristics were not associated with risk of re-stenosis. On the other hand, we observed a lower incidence of re-stenosis for patients undergoing reconstruction with native ureter (0% vs 30.8%, p=0.026), while all stricture recurrences occurred after redo ureteral reimplantation (p=0.018). Moreover, all patients who experienced early ureteral obstruction after reconstruction had long-term failure of the reconstruction (100%, p=0.009). The results are outlined in Table 6.

Ureteral stricture is the most common urological complication of renal transplantation with an estimated incidence of 0.6–10.5% over time (5) and a significant risk of morbidity in terms of renal function degradation and urinary tract infections. In this study, we analyzed the outcomes of patients managed by means of active surgical treatment or indwelling ureteral stent.

There is paucity of data regarding comparative outcomes of urinary obstruction after renal transplantation. Patients were comparable in terms of baseline characteristics although we observed a tendency for a lower median age in the reconstructive group. Renal function on diagnosis was better in the reconstructive group. However, the observation may be linked to the acute event since no difference in GFR was observed at 6 months follow-up. We observed a significantly higher prevalence of primary pyeloureterostomies (PU) in the palliative group which may have influenced treatment allocation. In this regard, Neto et. al reported a 90% rate of palliative management for patients presenting this type of anastomosis (6), suggesting that adherences and tissue loss frequently make reconstruction challenging in these cases. In fact, both PU strictures allocated to surgical treatment required more complex reconstructions by means of intestinal segment interposition.

Pyeloureterostomy (PU) and ureteroneocystostomy (UC) redo, the latter with a psoas hitch if necessary, were the most commonly performed reconstructive surgeries in our series. Overall, we found reconstruction by means of native ureter to be significantly associated with treatment success, whereas all recurrences were observed after UC, possibly due to a residual stenosis in the allograft’s ureter. On this subject, Lehmann et al. reported comparable rates of success although with a higher frequency of pyelonephritis after UC (7). On the other hand, a smaller retrospective series indeed showed better outcomes for PU in terms of stenosis recurrence (8). Ureteroureterostomy (UU) was successfully performed for 3 patients – all from the same center – with no recurrence observed. In a metanalysis by Suttle et al., ureteroneocystostomy presented a lower risk of stricture compared with ureteroureterostomy (HR 0.63), although the authors did not distinguish between primary and salvage procedures (9). It should be noted that previous minimally invasive treatments such as balloon dilatation and/or laser incision were not associated with failure of reconstructive surgery. Given that, endoscopic treatment should still be offered as a primary option when appropriate (i.e. short and early occurring stenoses) (2)(3)(10).

Regarding functional outcomes, we observed a significant decline in renal function from baseline to last follow-up in the palliative group, whereas GFR was stable over time after surgery. The finding is consistent with imaging studies carried out on patients with indwelling ureteral stents as was the case for all of our patients allocated to palliative management. Toyota et al. found indwelling ureteral stents but not nephrostomy tubes to be associated with a long-term reduction in renal parenchymal thickness and GFR (11). Similarly, Kim et al. observed a time-dependent correlation between duration of indwelled ureteral stent and renal parenchymal width (12).

Our study carries the intrinsic limitations of retrospective analysis which did not enable us to control for confounding factors related to treatment allocation and individual patient characteristics. Likewise, each center’s experience may have influenced the choice of surgical technique which meant that the most appropriate approach was not necessarily performed for each type of stenosis. Finally, the reduced number of events regarding stenosis recurrence did not enable regression analysis to be carried out. All of the cases in our series were performed by open surgery, either because of lack of access to a robotic platform during the less recent cases or the surgeon’s individual choice. In this regard, Heidenberg et al. recently reported a 100% rate of early success (13) of robot-assisted transplant ureteral repair (RATUR), still with an acceptable profile risk. RATUR is currently being implemented at each study center.

Ureteral stenosis after renal transplantation can be managed by either palliative or active treatment. In this context, reconstructive surgery can attain long-term success in approximately 90% of patients with an acceptable risk profile. Utilization of native ureter appears to provide better results although the paucity of our data does not enable us to draw definitive conclusions. On the other hand, palliative treatment by indwelling ureteral stent was associated with renal function degradation which should encourage surgeons to pursue active treatment when possible.

US: Ureteral stenose; KT kidney transplant; CCI Charlson Comorbidity Index; OT operative time; EBL estimated blood loss; GFR glomerular filtration rate; ;IQR interquartile range; AKI acute kidney injury; PU pyeloureterostomy; UC ureteroneocystostomy; UU Ureteroureterostomy; RATUR robot assisted transplant ureteral repair.

Funding: This research received no external funding.

Competing interests: The authors have no competing interests to declare that are relevant to the content of this article.

Data collection: data collection followed the principles outlined in the Declaration of Helsinki. Consent: All patients signed an informed consent form agreeing to share their own anonymous information for future studies.

Ethical approval: ethical was waived by the local Ethics Committee in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

Data Availability Statement: Data are available on request due to restrictions, e.g., privacy or ethical reasons

Authors’ contributions

Protocol/project development: R Boissier, G Lucignani, A Rivetti, R Boissier, T Prudhomme, A. Pecoraro, B. Bañuelos Marco, A. Piana, A. López-Abad, M.I.Dönmez, H.B. Haberal A. Territo

Data collection or management: C.L. Catucci, G Lucignani, T Prudhomme, A Rivetti

Data analysis: G Lucignani

Manuscript writing/editing: G Lucignani, R Boissier

Manuscript reviewing: R Boissier, T Prudhomme, A. Pecoraro, B. Bañuelos Marco, A. Piana, A. López-Abad, M.I.Dönmez, H.B. Haberal A. Territo

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Table 1: Baseline characteristics

	Reconstructive (n=30)	Palliative (n=24)	p value
Age	56 (48.25 - 66.75)	64 (58-70)	0.085
Gender n (%) - Male - Female	15 (50.0) 15 (50.0)	16 (69.6) 8 (30.4)	0.173
BMI, median (IQR)	25.75 (23.8-29.4)	26.8 (23.9-31.9)	0.382
Diabetes n (%)	6 (16.7)	3 (13.0)	0.443
Hypertension n (%)	6 (20.0)	7 (30.4)	0.522
Charlson, median (IQR)	3 (2-5)	4 (2-7)	0.118
Living donor n (%)	3 (10.0)	3 (12.0)	1.000
Previous transplantation n (%)	4 (13.3)	3 (12.0)	1.000
eGFR on diagnosis, median (IQR)	32 (25-40)	22 (16-27)	0.011
Number of arteries n (%) - 1 - > 1	27 (90.0) 3 (10.0)	21 (84.0) 4 (16.0)	0.687
Inferior polar artery n (%)	3 (10.0)	3 (12.0)	0.651
Number of veins n (%) - 1 - > 1	27 (90.0) 3 (10.0)	21 (84.0) 4 (16.0)	0.687
Number of ureters n (%) - 1 - > 1	30 (100) 0 (0)	23 (92) 2 (8)	0.453
Kidney side n (%) - Left - Right	15 (50.0) 15 (50.0)	17 (68.0) 8 (33.3)	0.274
Implantation side n (%) - Left - Right	18 (60.0) 12 (40.0)	17 (68.0) 8 (33.3)	0.467
Type of anastomosis n (%) - Lich Gregoir Ureterovesical - Ureteropyelostomy - Ureteroileostomy	27 (90.0%) 2 (6.7 %) 1 (3.3 %)	18 (72.0%) 6 (26.1%) 1 (4.3%)	0.014 0.034 0.879

Key: BMI: body mass index; IQR: interquartile range; eGFR: estimated glomerular filtration rate.

Table 2 Stricture characteristics

	Whole group
		Reconstructive	Palliative	p value
Clinical presentation, n (%) - Incidental - AKI - Infection	2 (3.6) 47 (85.5) 6 (10.9)	2 (6.7) 25 (83.3) 3 (10.0)	0 (0) 22 (88.0) 3 (12.0)	0.189
Onset (months), median (IQR)	2 (1.5 – 5)	3 (2 - 5)	5 (1 - 12)	0.275
Onset. n (%) - Early - Late	25 (45.5) 30 (55.5)	16 (53.3) 14 (46.7)	9 (36.0) 16 (64)	0.573
Location of the stricture, n (%) - Ureteropelvic junction - Proximal - Middle - Distal/ ureterovesical	5 (9.1) 2 (3.6) 3 (5.5) 45 (81.8)	1 (3.3) 0 (0) 2 (6.7) 27 (90)	4 (16) 2 (9.1) 1 (4.5) 18 (72.7)	0.212 0.184 1.000 0.082
Previous minimally invasive treatment, n (%)	7 (12.7)	5 (16.7)	2 (8.0)	0.436

Key IQR: interquartile range

Table 3 Reconstruction characteristics and outcomes


Time stenosis to reconstruction (months), median (IQR)	9.8 (5.5-25.5)
Type of reconstruction, n (%) - Ureterovesical reimplantation - Pyeloureterostomy - Ureteroureterostomy - Appendiceal onlay flap - Ureteropyeloplasty	12 (36.6) 13 (43.3) 3 (10.0) 1 (0.3) 1 (0.3)
Surgical time (minutes), median (IQR)	120 (100–180)
Blood loss (ml), median (IQR)	100 (75-125)
Bladder catheter (days), median (IQR)	7 (5-10)
Double J stent (days), median (IQR)	42 (33-72)
Hospital stay (days), median (IQR)	8 (6-11)
Postoperative complications n (%) Minor complications - Transfusion Major complications - Ureteral obstruction	7 (23.3) - 3 (10.0) - 4 (13.3)

Key: IQR: interquartile range, AKI: acute kidney injury.

Table 4 Long-term outcomes

Reconstructive

Palliative

p value

Follow-up months), median (IQR)

70 (28-98)

64 (33-84)

0.462

Graft survival, n (%)

- 6 months

- 1 year

- 2 years

- Last follow-up

30 (100.0)

29 (96.7)

27 (90.0)

25 100.0)

25 (100.0)

23 (90.9)

1.000

0.426

0.341

Re-stenosis, n (%)

- 6 months

- Last follow-up

13.3 (4)

GFR (ml/min), median (IQR)

- 6 months

- 1 year

- 2 years

- Last follow-up

41 (28.5-61)

45 (31.5-59.5)

50 (40-66)

40.25 (30.25-55.5)

44 (27.8-53.5)

44 (29–65)

40 (28-55)

34 (22-50.5)

0.568

0.991

0.178

0.536

Key: IQR: interquartile range; eGFR: estimated glomerular filtration rate.

Table 5 GFR variation on follow-up within each group.

GFR variation	Whole group		Reconstructive		Palliative
6 months - 1 year	-9.3 (-20.7-2.1)	0.103	0.5 (-2.1–3.3)	0.688	-3.2 (-8.1–1.7)	0.195
6 months - 2 years	-1.1 (-4.8–2.6)	0.535	-0.4 (-3.6–2.8)	0.823	-0.7 (-3.0–1.7)	0.579
6 months- last follow up	4.4 (-0.39–9.2)	0.070	2.7 (-2.1–7.6)	0.129	3.8 (0.4–7.2)	0.028

eGFR: estimated glomerular filtration rate.

Table 6 Association between preoperative features and failure of reconstruction

	Success	Failure	p value
Early stenosis	15 (57.7)	1 (25.0)	0.249
Stricture location - Proximal - Middle - Distal	1 (3.8) 2 (6.7) 23 (88.9)	0 (0.0) 0 (0.0) 4 (100.0)	0.867 0.747 0.640
Nephrostomy tube	14 (53.8)	2 (50.0)	0.648
Previous minimally invasive treatment	5 (16.7)	0 (0)	0.548
Type of reconstruction - Ureterovesical reimplantation - Pyeloureterostomy - Ureteroureterostomy - Use of native ureter - Use of intestinal segment	8 (30.7) 13 (53.8) 3 (11.5) 14 (65.7) 2 (6.7)	4 (100) 0 (0) 0 (0) 0 (0) 0 (0)	0.018 0.066 0.72 0.026 0.75
Early obstructive IRA	0 (0)	4 (100.0)	0.009

No competing interests reported.

Reconstructive versus palliative management of ureteral stenosis after kidney transplant: an EAU‑YAU kidney transplantation working group collaboration

Status:

Version 1

Abstract

INTRODUCTION

MATERIALS AND METHODS

Statistical analysis

RESULTS

DISCUSSION

CONCLUSION

Abbreviations

Declarations

References

Tables

Additional Declarations

Status:

Version 1