Urological complications after living-donor renal transplantation

Transcription

1 BJU Interntionl (2001), 87, 295±306 Urologicl complictions fter living-donor renl trnsplnttion M. EL-MEKRESH, Y. OSMAN, B. ALI-EL-DEIN, T. EL-DIASTY nd M.A. GHONEIM The Urology & Nephrology Centre, Mnsour, Egypt Ojective To determine the incidence nd mngement of urologicl complictions fter 1200 consecutive livedonor renl trnsplnttions, ll of which were crried out in one centre; the possile risk fctors nd the effect on ptient nd grft survivl were lso ssessed. Ptients nd methods Dt were retrieved from n electronic dtse; the incidence of urologicl complictions ws determined, nd correlted with relevnt risk fctors y univrite nd multivrite nlysis. The effect on ptient nd grft survivl ws ssessed using Kpln±Meier sttistics. Results There were 100 complictions in 96 ptients (8%); urinry leks occurred in 37, ureteric strictures in 23 nd lymphoceles cusing ureteric ostruction in 17. Percutneous needle iopsy ws complicted y hemturi nd clot nuri in six ptients. Lte complictions included 11 cses of stones, four of ldder mlignncy nd two of hemorrhgic cystitis. There ws evidence tht the ge of the recipients (<10 yers), method of estlishing urinry continuity (uretero-ureteric nstomosis) nd high dose of steroids hd n independent positive effect on the incidence of urologicl complictions. However, their development did not in uence grft or ptient survivl. Conclusion When there is meticulous ttention to the technicl detils, renl trnsplnttion should incur few urologicl complictions. Erly intervention with percutneous dringe reduces moridity nd the likelihood loss of grft function. Proper nd prompt mngement should not ffect the grft nd/or the ptient's survivl. Keywords urologicl complictions, kidney, trnsplnttion Introduction The urologicl complictions fter renl trnsplnttion hve een ddressed in mny reports. With current improvements in grft survivl concomitnt with etter immunosuppression, it would e uncceptle to lose ptient or grft s result of technicl issues. This is prticulrly importnt when deling with living donors. In this contriution, the urologicl complictions encountered fter 1200 consecutive live-donor renl trnsplnttions re descried, with n nlysis of the possile predictors nd the different methods dopted in their mngement. Ptients nd methods Between 1976 nd 1999, 1200 consecutive living-donor renl trnsplnts were crried out for 892 mle nd 308 femle ptients (men ge 29.8 yers SD 10.2, rnge 5±62; donors 34.9 yers, SD 9.9, rnge 17±69). There were 1152 rst, 46 second nd two third trnsplnts. Accepted for puliction 18 Decemer 2000 The grft ws revsculrized in stndrd wy; the renl vein ws nstomosed to the side of the externl ilic vein in most cses nd the common ilic vein or inferior ven cv were used in children. For the renl rtery, n end-to-end nstomosis with the internl ilic rtery, or n end-to-side with the externl or common ilic rteries were used. The methods used for estlishing urinry continuity were ureteroneocystostomy (Lich-Gregoire method in 999 nd Politno-Ledetter in 170), uretero-ureteric nstomosis in 25, pelvi-ureteric in three nd n ilel conduit in three; ureteric stents were not used routinely. Their plcement ws indicted in cses with dif cult nstomosis nd/or unhelthy ldder wll, usully seen in defunctionlized ldders. A Foley ctheter ws left in the ldder for 4±6 dys. Suction drins were used routinely nd removed within 72 h. Severl immunosuppressive regimens were used throughout the period of the study; initilly they were zthioprine-sed regimens (300 ptients) nd susequently cyclosporin-sed protocols (172 ptients) ut currently triple-therpy pproch is given (728 ptients). # 2001 BJU Interntionl 295

2 296 M. EL-MEKRESH et l. After surgery ptients were monitored cliniclly, iochemiclly nd rdiologiclly. Different modlities were used to dignose urologicl compliction; conventionl ultrsonogrphy, 99m Tc-DTPA dynmic renl scintigrphy nd spirtion of peri-grft collections, with determintion of its cretinine content. Percutneous nephrostomy with ntegrde urogrphy ws crried out if indicted. Recently, newer imging modlities (CT nd MR urogrphy) were lso used. Further dignostic nd therpeutic procedures were dependent on the ndings nd the clinicl course. The dt were stored in n electronic dtse. To determine the sttisticl signi cnce of differences, the Person nd chi-squre tests were used. The survivl of the grft nd ptients ws computed using the Kpln- Meier technique [1], with differences in survivl clculted y the log-rnk test [2], with P<0.05 considered to indicte signi cnce. Stepwise logistic regression ws used for the multivrite nlysis [3]. Results Overll, there were 100 complictions in 96 ptients, n incidence of 8% (Tle 1); 60 intrinsic urologicl complictions were recorded, presumly cused y the reimplnttion procedures. There ws extrmurl compression y lymphocele in 17 ptients nd clot nuri fter needle iopsy in six. Lte complictions (>6 months fter surgery) occurred in 17 ptients, 11 from stone formtion, four from the development of ldder mlignncy nd two ptients with hemorrhgic cystitis. Tle 1 Urologicl complictions from 1200 renl trnsplnttions Compliction No. of complictions Intrinsic: Lekge vesicl 09 ureteric 10 vesico-ureteric 17 uretero-ilel 01 Strictures pelvi-ureteric 02 ureteric 03 ureterovesicl 18 Clot nuri (fter needle iopsy) 06 Ostructing lymphocele 17 Lte (>6 months): Stones ldder 04 ureter 04 kidney 03 Bldder mlignncy 04 Hemorrhgic cystitis 02 Fig. 1., PCN nd n ntegrde study show urinry lek t the VUJ;, the sme study 10 dys lter shows complete heling.

3 COMPLICATIONS AFTER RENAL TRANSPLANTATION 297 Tle 2 The mngement of intrinsic ureteric ostruction Mngement No. of strictures Endourologicl: PCNt stent 7 Open surgery: Bori p ureteroneocystostomy 3 Replcement y n ilel ureter 3 Uretero-ureteric nstomosis 3 Direct vesico-ureteric reimplnttion 3 Resection/nstomosis of PUJ 2 Trnsvesicl metotomy 1 Pyelovesicl nstomosis 1 There were 37 cses of urinry lekge (Tle 1); the conservtive mngement of vesicl leks y prolonged ctheter dringe ws successful in six ptients. Three ptients (with ureters reimplnted y the Politno- Ledetter technique) required open repir nd closure in two lyers. Severl methods were used to mnge ureteric leks. For minor leks t the VUJ, de nitive tretment y percutneous nephrostomy (PCN) dringe ws ttempted in 14 ptients (Fig. 1). Two ptients Fig. 2., An ntegrde study shows stricture involving the distl ureter;, the result fter ureteroureterostomy. Fig. 3., An ostruction t the level of the PUJ nd, the result fter resection nd nstomosis.

4 298 M. EL-MEKRESH et l. Fig. 4., An extensive stricture involving the whole ureter, with, the replcement of the ureter y ileum. Fig. 5., A clot nuri developing fter renl iopsy nd treted y PCN dringe;, complete dissolution of the clots nd ptent system 7 dys lter.

5 Tle 3 The univrite nlysis of possile risk fctors for urologicl complictions COMPLICATIONS AFTER RENAL TRANSPLANTATION 299 Vrile No. of ptients No. (%) of complictions P Age (yers) < (24.1) 10± (8.9) 21± (6.1) 31± (9.5) 41± (6.8) > (17) 0.03 Sex mle (9.3) femle (5.5) 0.05 No. of renl rteries Single (8.3) multiple (8.8) 0.85 Site of nstomosis (the min renl rtery) Internl ilic (8.1) Externl ilic (7.8) Common ilic (12.5) Aort Lterlity of hrvested kidney Right (9.9) Left (7.2) 0.09 Acute rejection No (6.9) Yes (9.3) 0.18 Bilhrzisis No (7.4) Yes (10) Primry urinry continuity Politno-Ledetter (15.3) Lich-Gregoire (6.6) Uretero-ureteric (28) Pelvi-ureteric Ilel conduit <0.01 Immunosuppression Az or CsA* + high-dose steroids (17.1) Az or CsA + low-dose steroids (8.1) Triple therpy (6.6) <0.01 * Azthioprine or cyclosporin A. required susequent reconstructive procedures. Open surgicl revision ws required in 16 ptients. For distl pthologies, uretero-vesicl reimplnttion ws possile. Leks resulting from more ischemic dmge of the ureter required either uretero-ureteric nstomosis ( ve) (Fig. 2), Bori p ureteroneocystostomy (two) or n nstomosis etween the renl pelvis of the donor's kidney nd the ureter of the recipient (one ptient). In one ptient with totl necrosis of the ureter, interposition of segment of ileum etween the renl pelvis nd the ldder ws necessry. There were 23 cses of intrinsic ureteric ostruction; the site of ostruction ws t the PUJ (two), middle ureter (three) nd t the VUJ (18). Endourologicl mngement in the form of percutneous dringe, ntegrde dilttion nd stenting ws effective in three of seven ptients for whom such n pproch ws used. However, for de nitive mngement, open surgery ws required in most (Tle 2). A ureteroneocystostomy or Bori p ws successful in six cses. Uretero-ureteric nstomosis ws fesile in three ptients. Resection nstomosis of the PUJ ws used in two ptients with PUJ ostruction (Fig. 3). Extensive strictures involving the whole ureter were treted y n ilel replcement in three ptients (Fig. 4) or y pyelovesicl nstomosis in one. There were six episodes of nuri fter needle iopsy of the grfts; these were the result of hemturi nd clot ostruction of the ureter. These were ll treted successfully y temporry PCN dringe (Fig. 5). Using conventionl ultrsonogrphy, dignosis of

6 300 M. EL-MEKRESH et l. c d Fig. 6. A lymphocele leding to ureteric ostruction visile on;, ultrsonogrphy,, CT fter contrst medium nd c, MR urogrphy; d, the result fter mrsupiliztion. Tle 4 The multivrite nlysis of possile risk fctors for urologicl complictions Vrile Regression estimte (B) SEM Exp (B) P Recipient's ge (yers) < ±20 x ±30 x ±40 x ±50 x > Primry urinry continuity Uretero-ureteric Politno-Ledetter x Lich-Gregoire x Immunosuppression Low-dose steroids High-dose steroids peri-grft collection ws estlished in 291 ptients (24.3%). Of these, only 17 were lrge enough to cuse extrmurl ostruction of the ureter. Initilly spirtion with or without sclerotherpy using tetrcycline ws tried for ll cses. De nitive tretment y mrsupiliztion ws required in 10 (Fig. 6). There were 11 cses of stones; three were in the kidney, four in the ureter nd four in the ldder. Notly ll the vesicl stones followed reimplnttion y the Politno-Ledetter procedure; of these, two were treted y endoscopic litholpxy nd two required cystolithotomy. Renl stones were treted y ESWL nd one cse required djuvnt ntegrde ureteroscopy. Three ptients pssed their ureteric stones spontneously nd one required ntegrde ureteroscopy (Fig. 7). One ptient developed crcinom in situ of the ldder

7 COMPLICATIONS AFTER RENAL TRANSPLANTATION 301 Fig. 7., An ntegrde study showing lling defect cused y stone in the ureter;, tretment y ntegrde ureteroscopy. Fig. 8. IVU showing, good grft function nd lling defect on the left side of the ldder; nd, the result fter cystectomy nd orthotopic ldder sustitution.

8 302 M. EL-MEKRESH et l. Percent surviving Percent surviving nd ws treted y intrvesicl chemotherpy. Three ptients hd in ltrting ldder tumours nd required cystectomy nd orthotopic ldder sustitution (Fig. 8). Unfortuntely, within 2 yers of the cystectomy, they ll died from distnt metstsis. Anlysis of risk fctors Time (yers) Time (yers) Fig. 9. Survivl mong, ptients nd, grfts with (green) nd without (red) urologicl complictions; the log-rnk test vlues were 0.83 nd 0.16, respectively. The incidence of urologicl complictions ws correlted with severl potentil risk fctors (Tle 3). Three fctors were signi cnt; the ptient's ge, the method used to restore primry urinry continuity nd the regimens of immunosuppression. The highest incidence of complictions reltive to ge occurred mong recipients who were <10 yers old. Uretero-ureteric nstomosis ws ssocited with the highest incidence of urologicl complictions, most of which were cused y urinry lekge (28%). Agin, initil regimens of immunosuppression in which high doses of steroids were used were ssocited with the highest rte of complictions (17.1%). These oservtions were con rmed y the multivrite nlysis (Tle 4). Recipients ged <10 yers, use of ureteroureteric nstomosis nd the use of high dose of steroids supported their signi cnce s independent risk fctors. In generl, there ws no effect of the vriles ssessed on grft or ptient survivl (Fig. 9). No grft loss ws identi ed tht resulted directly from urologicl compliction or from its mngement. However, longterm survivl could not e chieved in the three ptients who developed in ltrting ldder tumours. Discussion The potentil vlue of the present series is tht it included mny ptients, ll of whom received kidneys from living donors nd underwent trnsplnttion in one centre. The reported incidence of urologicl complictions in lrge series is 2.6±15% [4±13]. This wide rnge proly re ects the method of reporting; some uthors do not include lymphoceles s urologicl compliction [10±13], nd others include UTI [6]. Furthermore, the compliction rte ws slightly higher in ptients who received kidneys from living donors thn in those who received orgns from cdvers [8,14]. This is presumly result of more extensive hilr dissection required during hrvesting from the living donor, with the ttendnt risks of injury to the lood supply of the ureter. The most commonly reported urologicl complictions re urinry lekge nd/or ureteric ostruction; the reported incidence of the former is 1.2% [6,7] to 8.9% [8]. In the present series, the incidence ws 3.1%. Lekge from the urinry ldder ws usully esily treted y prolonged ctheter dringe. Almost hlf of the ureteric leks were mnged y percutneous techniques. This is currently used s the initil mngement in ll cses; open surgicl revision cn e used susequently if this fils. The choice of the reconstructive procedure depends on the opertive ndings. Distl pthologies cn e corrected y uretero-vesicl reimplnttion or ureteroureteric re-nstomosis. For more proximl lesions pelvi-ureteric or Bori tue cn e used. In the present experience, the highest incidence of urinry leks followed primry uretero-ureteric nstomosis, proly ecuse the suture line could not withstnd the stresses resulting from the signi cnt diuresis encountered in some cses. This oservtion ws lso reported y others [15]; the recipient's ureter should e reserved for secondry procedures only. The reported incidence of ostruction y intrinsic lesions of the ureter is 1.3% [6] to 10.2% [11]; in the present series, the incidence ws 1.9%. Most of the ostructions involved the distl ureter or the VUJ. Vrious cuses re possile in the pthogenesis of this compliction. Ischemi of the ureter [11], urinry leks with peri-ureteric rosis [11], technicl prolems [6,12] nd ureteritis resulting from

9 COMPLICATIONS AFTER RENAL TRANSPLANTATION 303 cute rejection episodes [16,17] were ll implicted. Percutneous dringe with ntegrde dilttion nd stenting cn e ttempted initilly ut for filures, open surgicl revision is necessry. Imging techniques usully underestimte the extent of the pthology. Open surgicl repir should involve the use of helthy well-vsculrized proximl segment. The choice of re-estlishing the urinry continuity depends on the opertive ndings. Uretero-ureteric, pelvi-ureteric nd pyelovesicl nstomosis cn ll e used. The replcement of the ureter y n isolted ilel segment ws successfully used in three ptients in whom there ws extensive ischemic dmge of the ureter. The development of peri-grft lymphtic collections is not uncommon; Khuli et l. [18] reported n incidence of 36%, most of which were smll nd resolved spontneously. The source of lymph production is either the perivsculr lymphtics of the recipient or the renl hilr lymphtics of the donor. These lymphtic chnnels must e voided or meticulously controlled to minimize the possiility of developing such compliction. Active mngement of lymphoceles is only indicted if they re lrge enough to ecome symptomtic or cuse n ostruction of the ureter. Percutneous dringe with sclerotherpy cn e tried initilly, ut if these mesures re not suf cient, mrsupiliztion y n open or lproscopic procedure is then necessry. Severl studies hve compred the incidence of complictions reltive to the technique of ureteroneocystostomy. In retrospective study, Hkim et l. [19] found no dvntge with ny speci c technique. Other retrospective studies suggested n dvntge for the Lich- Gregoire over the Politno-Ledetter procedure [20±22]. In prospective rndomized studies, Wltke et l. [23] reported higher incidence of ureteric ostruction with the end-to-side technique thn with the Politno-Ledetter method. Anlysis of the dt from Pless et l. [24] suggests tht there is no difference in the incidence of mjor complictions etween the extrvesicl (Lich-Gregoire) nd Politno-Ledetter techniques. In the present experience, the rte of urologicl complictions fter the Politno-Ledetter ws 15.3% nd ws 6.6% fter the Lich-Gregoire technique. Nevertheless, the difference ws not signi cnt in the multivrite nlysis. It ws oserved tht n importnt numer of complictions following Politno±Ledetter method ws due to vesicl leks. The highest rte of complictions occurred following ureteroureteric nstomosis. The volume of urine produced soon fter surgery is unpredictle; if these re lrge the fresh suture line cnnot withstnd such diuretic lod nd this cn result in urine lekge. If this method is chosen, stent or nephrostomy dringe must e plced. The ptient's ureter should not e used during primry surgery ut e sved for secondry procedure if required. Severl uthors dvocte the routine use of ureteric stents nd mintin tht this would result in lower incidence of urologicl complictions, prticulrly urinry leks nd erly postopertive ostruction [25±27]. This ws con rmed in rndomized study y Benoit et l. [28] ut the use of stents is not without potentil hzrds. Degrdtion of the polyurethne stents, encrusttion, migrtion nd incresed incidence of UTI re reported [27]. A meticulously performed Lich-Gregoire nstomosis does not require stenting; stents were used springly nd were inserted only if dif cult vesicoureteric reimplnttion ws encountered. This usully occurs when ureters re reimplnted into ldder which ws defunctionlized for long time. We lso dvocte the use of routine stenting if uretero-ureteric or pelvi-ureteric nstomosis is used s primry procedure, to decrese the incidence of urinry leks. There is correltion etween the rte of urologicl complictions nd the steroid dose of immunosuppression [9]. Furthermore, the rte of these complictions ws reduced when recent protocols with low-dose steroids were introduced [12]. The present study con rmed these oservtions. Evidence ws provided tht the use of high doses of steroids cn ct s n independent fctor in the pthogenesis of urologicl complictions. The potentil impct of urinry ilhrzisis hs een ddressed y severl studies [29±33] with controversil conclusions. In the present series the rte of complictions mong ptients with evidence of ilhrzisis ws 10%, while tht mong ptients with no evidence ws 7.4%; this difference ws not sttisticlly signi cnt in the univrite nlysis. All our trnsplnt recipients re surveyed cliniclly nd serologiclly for evidence of ilhrzisis nd if positive ptients received one or more courses of prziquntel. The incidence of urologicl complictions in peditric renl trnsplnttion is reltively high [34]. The high lumr position of the trnsplnted kidney often dicttes the use of uretero-ureteric or pelvi-ureteric nstomosis. These procedures re usully ssocited with higher incidence of urinry leks, s noted previously. In ddition, the lood supply to the donor kidney, otined from n dult, is reltively disproportionte. As result, the lood supply to the ureter my e compromised. Furthermore, ureters re often reimplnted into neuropthic or pthologicl ldders with history of PUV. Under such circumstnces, ldder ugmenttion, if required, is crried out 8±12 weeks efore the trnsplnttion. The ugmenttion is constructed from segment of ileum rrnged in `W' con gurtion. The ntive ureter is implnted during the initil procedure using serous-lined tunnel to provide the future ntire ux mechnism [35]. During trnsplnttion the ntive

10 304 M. EL-MEKRESH et l. kidney is removed nd its ureter, which ws lredy reimplnted, is nstomosed to the donor's ureter. The present incidence of urinry clculi ws 0.9%, which is within the rnge reported previously [36,37]. The incidence of urinry stone disese ppers to e the sme in trnsplnt recipients s in the generl popultion. Motyne et l. [38] reported n incidence of 6.3%, ut this could e explined y the use of stpled ureteroureteric nstomosis; the stples ct s nidus for stone formtion. There is n incresed incidence of ldder clculi in pncres/renl trnsplnt recipients through the use of nonsorle suture in the pncres-toldder nstomosis [37]. There were erly suggestions tht trnsplnting kidney with multiple rteries is ssocited with n incresed risk of urologicl complictions such s clycel or ureteric stule [39,40]; these reports were not con rmed in more recent studies [41]. The present results con rmed tht the incidence of urologicl complictions hs no reltion with the numer of renl rteries. Nevertheless, the use of kidney with single rtery is generlly preferred, with the condition tht renl function is similr or nerly so on either side. If there is n importnt difference in clernce vlues, s determined y rdioisotope renogrphy, the kidney with the lower clernce is hrvested irrespective of the ntomicl ndings [42]. The incresed risk of neoplsi mong renl trnsplnt recipients hs long een recognized [43]. Penn reported tht of ll newly dignosed tumours mong orgn llogrft recipients, 2% will originte in the lower urinry trct [44]. GutieÁrrez et l. [45] reported three cses of ldder tumour in 57 ptients who developed neoplsi fter trnsplnttion. Buzzeo et l. [46] reported six cses of ldder cncer; they clculted tht renl trnsplnt recipients hve reltive risk of 3.3 of developing ldder cncer, compred with similr cohort of the norml popultion. A higher incidence ws lso reported mong the supopultion of ptients who hd kidney trnsplnt s result of nlgesic nephropthy [47]; mong 65 such kidney trnsplnt ptients, 10 (15%) hd trnsitionl ppillry crcinom of the renl pelvis, ureter nd ldder. Four of the present ptients (0.3%) developed ldder urothelil crcinom; one hd crcinom in situ nd three were in ltrting. The crcinom in situ ws treted y intrvesicl chemotherpy instilltion nd the remining three y cystectomy nd orthotopic ldder sustitution using urethrl Kock pouch in one nd n ilel-`w' neoldder with serouslined extrmurl tunnel in two. In generl, the results were unfvourle nd none survived in the long term. Although the incidence of hemturi fter percutneous needle iopsy of renl llogrfts is rre (through the use of trumtic ultrsound-guided techniques) it my still occur. Rrely, the extent of leeding will led to the formtion of lood clots which ll the renl pelvis nd ureter, leding to ostructive nuri. To mnge this sitution PCN dringe of the kidney is the sfest pproch. The PCN tue is left until the clot is completely dissolved, s shown y the free pssge of dye. Hemorrhgic cystitis is known compliction of the long-term use of cyclophosphmide. In the erly prt of the present experience, cyclophosphmide ws used in ptients who developed heptotoxicity s result of zthioprine immunosuppression. These ptient were converted lter to cyclosporin-sed regimen nd more recently to mycophenolte mofetil. In conclusion, renl trnsplnttion should incur few urologicl complictions. If there is meticulous ttention to the technicl detils during the ench preprtion nd/or the implnttion procedure, with preservtion of the ureteric vsculture, mny importnt prolems cn e voided. Stents cn e used prophylcticlly in dif cult procedures. Erly intervention with percutneous dringe of the kidney reduces moridity, sepsis nd the risk of losing grft function [48±50]. 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12 306 M. EL-MEKRESH et l. trnsplnt ptients with end-stge nlgesic nephropthy. World J Urol 1995; 13: 254±61 48 Shokeir AA, el-disty TA, Bkr MA, Erky I, Shm MA, Ghoneim MA. Ureteric complictions of renl trnsplnttion. The role of percutneous techniques. Trnsplnt Proc 1993; 25: 2303±4 49 Streem SB, Novick AC, Steinmuller DR, Musselmn PW. Percutneous techniques for the mngement of urologicl renl trnsplnt complictions. J Urol 1986; 135: 456±9 50 Swierzewski SJ, Konnk JW, Ellis JH. Tretment of renl trnsplnt ureterl complictions y percutneous techniques. J Urol 1993; 149: 986±7 Authors M. El-Mekresh, MD. Y. Osmn, MD. B. Ali-El-Dein, MD. T. El-Disty, MD. M. A. Ghoneim, MD, MD(Hon), Professor, Director. Correspondence: Prof. M.A. Ghoneim, Urology & Nephrology Center, Mnsour, Egypt.