- Email: [email protected]
Comparison of Native Ureteral Ligation and Open Nephrectomy for Pediatric Renal Transplantation
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
Comparison of Native Ureteral Ligation and Open Nephrectomy in Pediatric Renal Transplant G. Torino, M. Innocenzi,* E. Mele, S. Gerocarni Nappo and N. Capozza Children’s Hospital, IRCCS, and Department of From the Division of Pediatric Urology, Bambino Gesu Obstetric-Gynecological Sciences and Urological Sciences, University of Rome Sapienza (MI), Rome, Italy
Purpose: In pediatric renal recipients there are some indications for native nephrectomy, which can be performed before, during or after transplantation. Indications include massive proteinuria resistant to therapy, intractable hypertension, polyuria and chronic or recurrent kidney infections. Several scientific studies of adults have demonstrated a minimally invasive alternative to native nephrectomy, which consists of ligation of the native ureter without removing the kidney. We evaluated the safety and efficacy of this minimally invasive technique in pediatric recipients of renal transplantation. Materials and Methods: A total of 29 pediatric kidney transplant recipients underwent unilateral native ureteral ligation during renal transplantation between 2009 and 2013 (group A). In addition, a control group of 21 pediatric renal transplant recipients was enrolled who had undergone unilateral native nephrectomy between January 2005 and December 2008 (group B). Both groups were evaluated preoperatively by Doppler ultrasound of the native kidneys. Results: Statistical analysis of the 2 groups for the 3 main variables considered (surgical time, intraoperative blood loss and length of surgical scar) revealed a significant difference (Mann-Whitney U test, p <0.001). This finding confirmed the hypothesis that during renal transplantation ligation of the native ureter is less invasive than native nephrectomy. Conclusions: Ligation of the native ureter without removal of the ipsilateral kidney is a feasible procedure in pediatric renal transplant recipients. This method is easy to perform and significantly less invasive than surgical nephrectomy.
Abbreviations and Acronyms NK ¼ native kidney NN ¼ native nephrectomy NUL ¼ native ureteral ligation Accepted for publication April 23, 2016. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Correspondence: Department of ObstetricGynecological Sciences and Urological Sciences, University of Rome Sapienza, Piazza S. Onofrio, 4-00165 Rome, Italy (e-mail: innocenzi. [email protected]).
Key Words: kidney transplantation, ligation, minimally invasive surgical procedures, nephrectomy, ureter
IN pediatric renal recipients indications for native nephrectomy include massive proteinuria resistant to therapy, intractable hypertension, polyuria, chronic or recurrent kidney infections and need to use the native ureter for reconstruction of the urinary tract of the graft.1,2 Native nephrectomy can be performed before, during or after transplantation, and can be done using open surgery or
mini-invasive surgical techniques. Minimally invasive techniques have an advantage over open surgery in terms of postoperative pain and hospital stay.3,4 However, open and minimally invasive surgical techniques can involve significant morbidity and complications.5 The most important complications related to native nephrectomy are bleeding, infection, intestinal/liver/splenic lesions and
0022-5347/16/1963-0001/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
Dochead: Pediatric Urology
http://dx.doi.org/10.1016/j.juro.2016.04.078 Vol. 196, 1-6, September 2016 Printed in U.S.A.
www.jurology.com
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
j
1
58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114
2
115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 ½F1 165 166 167 168 169 170 171
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
pneumothorax.1 For bilateral pre-transplant native nephrectomy morbidity and mortality rates of 40% to 50% and 3% to 11%, respectively, have been reported.6 However, more recently a mortality rate of less than 1% and a complication rate of about 6% have been reported for surgical native nephrectomy.7,8 NUL has been applied in adults to use the native ureter to reconstruct the urinary tract of the graft.9,10 These studies have resulted in a complication rate of approximately 2% with subsequent need to remove the kidney subjected to ligation.9,11 The main complications reported are linked to infection and late onset of flank pain from 7 to 82 months postoperatively. This pain is thought to be due to the underlying renal disease rather than NUL.9 In the literature there are only 2 known clinical studies describing NUL as an alternative to NN to deal with massive proteinuria (17 patients) and vesicoureteral reflux in the native kidneys (12).12,13 These studies show the absence of complications and postoperative symptoms related to NUL. Only 2 cases of NUL have been described in pediatric recipients, which were performed during kidney transplantation as an alternative to NN.13 In both of these patients the indication for NUL was vesicoureteral reflux in the NK. The authors did not report symptoms or complications. The present study is novel because 1) we routinely applied NUL in pediatric renal transplantation and 2) the technique was used not only to reconstruct the urinary tract of the graft (as described in the literature), but also in all cases where there was any indication for NN (excluding conditions of premalignant/malignant or polycystic kidneys). We evaluate the safety and efficacy of this minimally invasive technique in pediatric recipients of renal transplantation.
MATERIALS AND METHODS We prospectively recruited patients attending Bambino Ges u Children’s Hospital from 2009 to 2013. During this period all pediatric candidates for kidney transplantation with an indication for nephrectomy underwent unilateral NUL without excision of the ipsilateral kidney during renal transplantation. Ligation of the ureter was performed with a 2-zero nonabsorbable suture, mainly just below the ureteropelvic junction (fig. 1). Indications for NN were polyuria, massive proteinuria resistant to therapy, intractable hypertension, recurrent urinary tract infections and need to use the native ureter for reconstruction of the urinary tract of the graft. Polyuria, given the absence of an internationally established definition,2 was defined as urine output greater than 48 ml/kg per day, while proteinuria was considered to be massive at values greater than 3 gm/1.73 m2 per 24 hours.14 Dochead: Pediatric Urology
Figure 1. Ureteral ligation during renal transplant.
Recipients with malignant renal lesions, conditions predisposing to malignancy of NK or polycystic kidneys were excluded from the study. Those awaiting kidney transplantation who underwent pre-transplant NN were also excluded. Between 2009 and 2013 we recruited 29 candidates for kidney transplant who also needed to undergo unilateral NUL during renal transplantation as an alternative to NN (group A). In addition, we enrolled a control group of 21 pediatric recipients who had undergone unilateral NN between January 2005 and December 2008 for the same indications (group B, table 1). Operative time, intraoperative blood loss and length of surgical scar were evaluated in the 2 patient groups to compare the invasiveness of NUL vs nephrectomy. Antibiotic prophylaxis was used for 1 month in both groups. Perioperative complications were also compared in the 2 groups. Postoperative followup consisted of systematic laboratory tests, Doppler ultrasound and regular assessments of pain, blood pressure, infections and possible complications. Mann-Whitney U test was used to analyze continuous variables and Fisher exact test to analyze dichotomous variables. A p value of less than 0.05 was considered statistically significant in both tests. Median followup was 28 months (range 1 to 49) in group A and 84 months (66 to 102) in group B.
RESULTS Although a preponderance of males was observed in the 2 patient groups, with a male-to-female Table 1. Indications for native nephrectomy
No. No. No. No. No. No.
intractable hypertension polyuria intractable proteinuria urinary tract reconstruction recurrent pyelonephritis due to vesicoureteral reflux recurrent pyelonephritis due to obstructive hydronephrosis Totals
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
Group A
Group B
2 17 6 2 1 1
4 9 6 1 1 0
29
21
½T1
172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
3
286 229 to remove the graft due to rejection, we simultaratio of 3.1:1 in group A and 1.3:1 in group B, the 287 230 neously performed NN less than 1 month after the difference was not statistically significant (Fisher 288 231 embolization. exact test, p ¼ 0.22). Median patient age was 289 232 The other patient with a late complication was a 10.5 years (range 2 to 18) in group A and 9.3 years 290 233 14-year-old girl suffering from nephronophthisis (2 to 18) in group B. Any difference between the 291 234 who underwent NUL for polyuria. Postoperative 2 groups regarding age was not statistically signif292 235 ½T2 icant (Mann-Whitney U test, p ¼ 0.85; table 2). ultrasound documented progressive hydronephrosis 293 236 of the native kidney in the absence of symptoms. All patients in both groups underwent ureteral 294 237 At 28 months after the NUL procedure the patient ligation or nephrectomy unilaterally. The predomi295 238 presented with flank pain and hydronephrosis nant side involved was the right side (90% in group 296 239 (about 10 cm in anteroposterior diameter) of the A and 81% in group B, Fisher exact test, p ¼ 0.43). 297 240 NK. She subsequently underwent percutaneous Statistical analysis between the 2 groups for the 298 241 drainage and nephrostomy tube placement. 99mTc3 main variables considered (surgical time, intra299 242 operative blood loss and length of surgical scar) mercaptoacetyltriglycine scintigraphy performed 300 243 demonstrated a significant difference (Mannwith the nephrostomy on site documented some 244 Whitney U test, p <0.001), confirming the hypothactivity of the NK (fig. 2). Given the production of ½F2301 302 245 esis that during renal transplantation NUL is about 70 ml per day of urine from the nephrostomy, 303 246 less invasive than NN (table 2). we performed alcoholization of the residual cavity 304 247 In group A Doppler analysis after NUL revealed through the nephrostomy. Followup ultrasound at 305 248 that the native kidney underwent gradual decrease 10 months demonstrated persistent hydronephrosis 306 249 of the blood supply and progressive reduction of with unchanged diameters but without symptoms. 307 250 the renal parenchyma leading to atrophy. At folCurrently the patient is being followed using a 308 251 lowup no patient in group A had postoperative conservative approach. To date, the hydronephrosis 309 252 infection of the kidney or hypertension. In addition, is stable and the patient has no symptoms. 310 253 no patient presented with early postoperative No patient in group B presented with complica311 254 pain. Finally, no perioperative complications were tions related to surgical nephrectomy. The 4 patients 312 255 seen in group A. in group B with hypertension as the indication for 313 256 Only 2 patients (6.8%) in group A had a late NN had normal blood pressure at postoperative 314 257 complication (flank pain/discomfort from massive followup. 315 258 hydronephrosis of the ligated kidney) that required Flank pain/discomfort from massive hydro316 259 a subsequent procedure. One patient, a 13-year-old nephrosis (seen in 2 patients in group A) was not 317 260 boy with nephronophthisis as the underlying disstatistically significant. Other than 1 patient in 318 261 ease, had normal preligation urine output (15 ml/kg group A, all patients in both groups had a func319 262 per day). This patient underwent NUL for arterial tioning graft. No patient in either group currently 320 263 hypertension and postoperative ultrasound docuhas significant proteinuria. 321 264 mented progressive hydronephrosis. At 25 months 322 265 postoperatively the patient presented with flank 323 266 pain/discomfort from a massive hydronephrosis DISCUSSION 324 267 (about 10 cm in anteroposterior diameter) of the The current trend in pediatric renal transplantation 325 268 NK, which was treated with drainage and percutais to reserve NN for carefully selected recipients 326 269 neous instillation of the renal pelvis with tetracyand for a smaller number than in the past.14,15 327 270 cline. One month later, owing to the persistence of NN is now performed in 10% to 50% of pediatric 328 271 about 50 ml per day urine drainage, we performed renal transplant recipients.1,2,16 329 272 percutaneous embolization of the NK. Two weeks In our 2 groups of patients the main indications 330 273 later, although the patient was asymptomatic, for NN were polyuria and intractable massive pro331 274 Doppler ultrasound showed poor persistent vascuteinuria. Polyuria is associated with an increased 332 275 larization in the residual parenchyma. The patient risk of vascular thrombosis of the graft in pediatric 333 276 also had hydronephrosis. Since it was necessary recipients, since it can complicate the management 334 277 Table 2. Patient characteristics 335 278 336 279 Ureteral Ligation Surgical Nephrectomy Overall p Value 337 280 Median yrs age (IQR) 10.5 (9.1e12.9) 9.3 (6.0e16.7) 10.5 (6.4e13.3) 0.85 338 281 Median mins operative time (IQR) 8 (7e10) 34 (28e47) 11 (8e30) <0.001 339 282 Median ml perioperative blood loss (IQR) 0 (0e5) 15 (4e51) 5 (0e11) <0.001 Median cm scar length (IQR) 17 (15e18) 22 (20e24) 18 (16e22) <0.001 340 283 341 284 All variables were analyzed using the Kolmogorov-Smirnov test to assess distribution. In all cases variables showed nonparametric distribution (p <0.001). Consequently 342 285 comparison between the 2 treatment groups was carried out using the Mann-Whitney U test. A p value of less than <0.05 was considered statistically significant. Dochead: Pediatric Urology
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
4
343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
400 with an increased risk of vascular thrombosis and 401 thromboembolism.20e23 402 In our study NUL was systematically performed 403 in patients in group A as an alternative to surgical 404 nephrectomy (in all instances in which the latter 405 was indicated). By blocking the excretory function 406 of the kidney NUL leads to atrophy of the renal 407 parenchyma, thereby achieving functional nephrectomy (fig. 3). NUL failed in only 2 patients ½F3 408 409 (6.8%) in group A. In fact, in these 2 patients 410 we documented residual diuresis from the neph411 rostomy of 50 ml per day in 1 patient and 70 ml per 412 day in 1. 413 NUL is a simple and noninvasive procedure. As 414 documented in this study involving pediatric renal 415 transplantation, NUL is faster to perform than ne416 phrectomy. There is also less risk of bleeding and 417 the procedure requires a smaller surgical incision 418 (table 2). In addition, in certain instances, such as 99m Figure 2. Tc-mercaptoacetyltriglycine renal scintigraphy 419 when patients have undergone previous surgery, reveals some activities of native kidney. 420 NN can only be performed with considerable diffi421 culty and additional risk. Therefore, in these situ422 ations simple NUL may be considered a preferable 423 alternative. of fluids in the post-transplant period.4,17 Such dif424 No patient in group A needed greater analgesic ficulties in the management of postoperative 425 therapy than those in group B. These data are fluid may lead to hemodynamic imbalances and 426 surprising, especially when compared with partial then to vascular thrombosis of the graft, as well as 427 and transient ureteral obstruction (such as ureteral to other types of damage such as acute tubular 428 stones), which is instead a pathology associated necrosis. Moreover, persistence of native polyuria 429 with typical flank pain. Analysis of the pathophysin the post-transplant period may cause chronic 430 iology of pain from ureteral obstruction suggests hypoperfusion of the graft, especially in pediatric 431 that it derives from distention of the wall of the recipients who receive grafts from adult donors, 9,12 432 urinary collecting system. In total and permaand this condition could lead to acceleration of 433 nent ureteral obstruction the pressure within the chronic fibrosis of the graft and increased nephro434 toxicity of certain drugs such as cyclosporine.2 urinary collecting system sharply increases for up 435 to about 5 hours, then gradually decreases.24 In However, some do not consider polyuria to be an 436 absolute indication for NN in these recipients.18,19 addition, any pain potentially caused by NUL in 437 patients in group A may have been masked by Intractable massive proteinuria is also associated 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 Figure 3. Two months after ureteral ligation. A, histology shows glomerular atrophy in kidney. H&E, reduced from 40. B, histology 455 demonstrates tubular atrophy in kidney. H&E, reduced from 5. 456 Dochead: Pediatric Urology
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513
use of analgesic drugs given anyway in the posttransplant period. During followup no patient in group A had episodes of infection in the NK, including the 2 patients who underwent NUL for recurrent pyelonephritis due to vesicoureteral reflux and obstructive hydroureteronephrosis. In the past removal of the NK was preferred to NUL to prevent infectious complications related to the obstructed NK in immunosuppressed recipients at risk for infection.25,26 Subsequently two groups reported series of NUL in adult renal transplant recipients with no infectious complications.9,27 One possible explanation is that pyelonephritis is frequently the result of infection ascending from the lower urinary tract.12 Therefore, NUL would prevent this pathogenetic mechanism. Finally, it is noteworthy that the 2 recipients in our series with recurrent pyelonephritis are the first cases described in the literature managed by NUL for this specific indication. No patient in group A presented with hypertension during followup. In addition, 2 patients in group A with hypertension as the indication for NUL had marked improvement at postoperative followup. To date, NUL has not been described as an alternative to NN when hypertension is the specific indication for treatment. On the contrary, NN rather than ureteral ligation is recommended in recipients with hypertension.9e23 Therefore, our decision to use NUL as an alternative to NN in cases of hypertension represents an innovation, although its efficacy needs to be verified through studies with a larger number of patients. Only 2 patients in group A (6.8%) had complications related to NUL, while no patient in group B presented with complications related to NN. The
5
difference was not significant (Fisher exact test, p ¼ 0.50). However, the complication (flank pain/ discomfort from massive hydronephrosis) suffered by the 2 patients in group A could be defined as grade IIIa according to the Dindo-Clavien scale, as it did not affect the renal graft or patient survival. Moreover, treatment of this complication in both patients was mini-invasive (drainage with alcoholization with or without embolization of the native kidney). Following the mini-invasive procedure 1 patient required nephrectomy, not for an absolute indication, but because the graft had to be removed due to rejection. These observations regarding complications confirm that NUL is a safe procedure. Furthermore, NUL does not expose recipients to additional postoperative risks compared to NN. The main limitation of our series is the comparison between a prospective study group (group A) and a retrospective control group (group B). However, this factor did not affect our results in terms of the efficacy and safety of the procedure, which were the main parameters of interest in the study. Other limitations are the relatively short followup and the small sample size.
CONCLUSIONS NUL without removal of the ipsilateral kidney is a feasible procedure in pediatric renal transplant recipients. This method is easy to perform and significantly less invasive than surgical nephrectomy. Ligation of the ureter is a safe procedure during renal transplantation regardless of the type of indication, with the exception of premalignant/ malignant renal lesions and polycystic kidneys.
REFERENCES 1. Fraser N, Lyon PC, Williams AR et al: Native nephrectomy in pediatric transplantationdless is more! J Pediatr Urol 2013; 9: 84.
peritoneal dialysis: a new management for end-stage renal disease in children. BJU Int 2007; 99: 904.
2. Ghane Sharbaf F, Bitzan M, Szymanski KM et al: Native nephrectomy prior to pediatric kidney transplantation: biological and clinical aspects. Pediatr Nephrol 2012; 27: 1179.
6. Yarimizu SN, Susan LP, Straffon RA et al: Mortality and morbidity in pretransplant bilateral nephrectomy: analysis of 305 cases. Urology 1978; 12: 55.
3. Hamilton BD, Gatti JM, Cartwright PC et al: Comparison of laparoscopic versus open nephrectomy in the pediatric population. J Urol 2000; 163: 937.
7. Nahas WC, Mazzucchi E, Pinheiro MS et al: Role of native nephrectomy in renal transplant recipients. Transplant Proc 2002; 34: 717.
4. Kravarusic D, Sigalet DL, Hamiwka LA et al: Persistent post-transplant polyuria managed by bilateral native-kidney laparoscopic nephrectomy. Pediatr Nephrol 2006; 21: 880.
8. Shoma AM, Eraky I and El-Kappany HA: Pretransplant native nephrectomy in patients with end-stage renal failure: assessment of the role of laparoscopy. Urology 2003; 61: 915.
5. Gundeti MS, Taghizaedh A and Mushtaq I: Bilateral synchronous posterior prone retroperitoneoscopic nephrectomy with simultaneous
9. Gallentine ML and Wright FH Jr: Ligation of the native ureter in renal transplantation. J Urol 2002; 167: 29.
Dochead: Pediatric Urology
10. Nie Z, Zhang K, Huo W et al: Comparison of urological complications with primary ureteroureterostomy versus conventional ureteroneocystostomy. Clin Transplant 2010; 24: 615. 11. Guiter J, Cuenant E, Mourad G et al: Reestablishment of urinary continuity by ureteroureterostomy in renal transplantation. Apropos of 135 cases. J Urol (Paris) 1985; 91: 27. 12. Goh BK, Dean PG, Cosio FG et al: Bilateral native ureteral ligation without nephrectomy in the management of kidney transplant recipients with native proteinuria. Am J Transplant 2011; 11: 2747. 13. Guzman JA: Intravesical ligation as a new technique to manage a refluxing native ureter without simultaneous nephrectomy in renal transplantation. Transplant Proc 2012; 44: 2940.
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570
6
571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
14. Vincenti FG: Recurrent focal segmental glomerulosclerosis in the renal allograft: current concepts of pathogenesis, diagnosis, and management. NephSAP 2005; 4: 1. 15. Schr€oder A and Koyle M: Editorial comment. J Pediatr Urol 2013; 9: 89. 16. Harper L, Michel JL and Dunand O: Editorial comment. J Pediatr Urol 2013; 9: 90.
19. Matas AJ, Chavers BM, Nevins TE et al: Recipient evaluation, preparation, and care in pediatric transplantation: the University of Minnesota protocols. Kidney Int Suppl 1996; 53: S99. 20. Lau SO, Tkachuck JY, Hasegawa DK et al: Plasminogen and antithrombin III deficiencies in the childhood nephrotic syndrome associated with plasminogenuria and antithrombinuria. J Pediatr 1980; 96: 390.
17. Singh A, Stablein D and Tejani A: Risk factors for vascular thrombosis in pediatric renal transplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. Transplantation 1997; 63: 1263.
21. Barbour SJ, Greenwald A, Djurdjev O et al: Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int 2012; 81: 190.
18. Langlois V, Geary D, Murray L et al: Polyuria and proteinuria in cystinosis have no impact on renal transplantation. A report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 2000; 15: 7.
22. Singhal R and Brimble KS: Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 2006; 118: 397.
Dochead: Pediatric Urology
23. Bramham K, Hunt BJ and Goldsmith D: Thrombophilia of nephrotic syndrome in adults. Clin Adv Hematol Oncol 2009; 7: 368. 24. Gulmi FA, Felsen D and Vaughan ED Jr: Pathophysiology of urinary tract obstruction. In: Campbell’s Urology, 7th ed. Edited by PC Walsh, AB Retik, ED Vaughan Jr et al. Philadelphia: WB Saunders 1997; chapt 9, p 350. 25. Greenberg SH, Wein AJ, Perloff LJ et al: Ureteropyelostomy and ureteroneocystostomy in renal transplantation: postoperative urological complications. J Urol 1977; 118: 17. 26. Jaffers GJ, Cosimi AB, Delmonico FL et al: Experience with pyeloureterostomy in renal transplantation. Ann Surg 1982; 196: 588. 27. Lord RH, Pepera T and Williams G: Ureteroureterostomy and pyeloureterostomy without native nephrectomy in renal transplantation. Br J Urol 1991; 67: 349.
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614
Comparison of Native Ureteral Ligation and Open Nephrectomy in Pediatric Renal Transplant G. Torino, M. Innocenzi,* E. Mele, S. Gerocarni Nappo and N. Capozza Children’s Hospital, IRCCS, and Department of From the Division of Pediatric Urology, Bambino Gesu Obstetric-Gynecological Sciences and Urological Sciences, University of Rome Sapienza (MI), Rome, Italy
Purpose: In pediatric renal recipients there are some indications for native nephrectomy, which can be performed before, during or after transplantation. Indications include massive proteinuria resistant to therapy, intractable hypertension, polyuria and chronic or recurrent kidney infections. Several scientific studies of adults have demonstrated a minimally invasive alternative to native nephrectomy, which consists of ligation of the native ureter without removing the kidney. We evaluated the safety and efficacy of this minimally invasive technique in pediatric recipients of renal transplantation. Materials and Methods: A total of 29 pediatric kidney transplant recipients underwent unilateral native ureteral ligation during renal transplantation between 2009 and 2013 (group A). In addition, a control group of 21 pediatric renal transplant recipients was enrolled who had undergone unilateral native nephrectomy between January 2005 and December 2008 (group B). Both groups were evaluated preoperatively by Doppler ultrasound of the native kidneys. Results: Statistical analysis of the 2 groups for the 3 main variables considered (surgical time, intraoperative blood loss and length of surgical scar) revealed a significant difference (Mann-Whitney U test, p <0.001). This finding confirmed the hypothesis that during renal transplantation ligation of the native ureter is less invasive than native nephrectomy. Conclusions: Ligation of the native ureter without removal of the ipsilateral kidney is a feasible procedure in pediatric renal transplant recipients. This method is easy to perform and significantly less invasive than surgical nephrectomy.
Abbreviations and Acronyms NK ¼ native kidney NN ¼ native nephrectomy NUL ¼ native ureteral ligation Accepted for publication April 23, 2016. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Correspondence: Department of ObstetricGynecological Sciences and Urological Sciences, University of Rome Sapienza, Piazza S. Onofrio, 4-00165 Rome, Italy (e-mail: innocenzi. [email protected]).
Key Words: kidney transplantation, ligation, minimally invasive surgical procedures, nephrectomy, ureter
IN pediatric renal recipients indications for native nephrectomy include massive proteinuria resistant to therapy, intractable hypertension, polyuria, chronic or recurrent kidney infections and need to use the native ureter for reconstruction of the urinary tract of the graft.1,2 Native nephrectomy can be performed before, during or after transplantation, and can be done using open surgery or
mini-invasive surgical techniques. Minimally invasive techniques have an advantage over open surgery in terms of postoperative pain and hospital stay.3,4 However, open and minimally invasive surgical techniques can involve significant morbidity and complications.5 The most important complications related to native nephrectomy are bleeding, infection, intestinal/liver/splenic lesions and
0022-5347/16/1963-0001/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
Dochead: Pediatric Urology
http://dx.doi.org/10.1016/j.juro.2016.04.078 Vol. 196, 1-6, September 2016 Printed in U.S.A.
www.jurology.com
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
j
1
58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114
2
115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 ½F1 165 166 167 168 169 170 171
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
pneumothorax.1 For bilateral pre-transplant native nephrectomy morbidity and mortality rates of 40% to 50% and 3% to 11%, respectively, have been reported.6 However, more recently a mortality rate of less than 1% and a complication rate of about 6% have been reported for surgical native nephrectomy.7,8 NUL has been applied in adults to use the native ureter to reconstruct the urinary tract of the graft.9,10 These studies have resulted in a complication rate of approximately 2% with subsequent need to remove the kidney subjected to ligation.9,11 The main complications reported are linked to infection and late onset of flank pain from 7 to 82 months postoperatively. This pain is thought to be due to the underlying renal disease rather than NUL.9 In the literature there are only 2 known clinical studies describing NUL as an alternative to NN to deal with massive proteinuria (17 patients) and vesicoureteral reflux in the native kidneys (12).12,13 These studies show the absence of complications and postoperative symptoms related to NUL. Only 2 cases of NUL have been described in pediatric recipients, which were performed during kidney transplantation as an alternative to NN.13 In both of these patients the indication for NUL was vesicoureteral reflux in the NK. The authors did not report symptoms or complications. The present study is novel because 1) we routinely applied NUL in pediatric renal transplantation and 2) the technique was used not only to reconstruct the urinary tract of the graft (as described in the literature), but also in all cases where there was any indication for NN (excluding conditions of premalignant/malignant or polycystic kidneys). We evaluate the safety and efficacy of this minimally invasive technique in pediatric recipients of renal transplantation.
MATERIALS AND METHODS We prospectively recruited patients attending Bambino Ges u Children’s Hospital from 2009 to 2013. During this period all pediatric candidates for kidney transplantation with an indication for nephrectomy underwent unilateral NUL without excision of the ipsilateral kidney during renal transplantation. Ligation of the ureter was performed with a 2-zero nonabsorbable suture, mainly just below the ureteropelvic junction (fig. 1). Indications for NN were polyuria, massive proteinuria resistant to therapy, intractable hypertension, recurrent urinary tract infections and need to use the native ureter for reconstruction of the urinary tract of the graft. Polyuria, given the absence of an internationally established definition,2 was defined as urine output greater than 48 ml/kg per day, while proteinuria was considered to be massive at values greater than 3 gm/1.73 m2 per 24 hours.14 Dochead: Pediatric Urology
Figure 1. Ureteral ligation during renal transplant.
Recipients with malignant renal lesions, conditions predisposing to malignancy of NK or polycystic kidneys were excluded from the study. Those awaiting kidney transplantation who underwent pre-transplant NN were also excluded. Between 2009 and 2013 we recruited 29 candidates for kidney transplant who also needed to undergo unilateral NUL during renal transplantation as an alternative to NN (group A). In addition, we enrolled a control group of 21 pediatric recipients who had undergone unilateral NN between January 2005 and December 2008 for the same indications (group B, table 1). Operative time, intraoperative blood loss and length of surgical scar were evaluated in the 2 patient groups to compare the invasiveness of NUL vs nephrectomy. Antibiotic prophylaxis was used for 1 month in both groups. Perioperative complications were also compared in the 2 groups. Postoperative followup consisted of systematic laboratory tests, Doppler ultrasound and regular assessments of pain, blood pressure, infections and possible complications. Mann-Whitney U test was used to analyze continuous variables and Fisher exact test to analyze dichotomous variables. A p value of less than 0.05 was considered statistically significant in both tests. Median followup was 28 months (range 1 to 49) in group A and 84 months (66 to 102) in group B.
RESULTS Although a preponderance of males was observed in the 2 patient groups, with a male-to-female Table 1. Indications for native nephrectomy
No. No. No. No. No. No.
intractable hypertension polyuria intractable proteinuria urinary tract reconstruction recurrent pyelonephritis due to vesicoureteral reflux recurrent pyelonephritis due to obstructive hydronephrosis Totals
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
Group A
Group B
2 17 6 2 1 1
4 9 6 1 1 0
29
21
½T1
172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
3
286 229 to remove the graft due to rejection, we simultaratio of 3.1:1 in group A and 1.3:1 in group B, the 287 230 neously performed NN less than 1 month after the difference was not statistically significant (Fisher 288 231 embolization. exact test, p ¼ 0.22). Median patient age was 289 232 The other patient with a late complication was a 10.5 years (range 2 to 18) in group A and 9.3 years 290 233 14-year-old girl suffering from nephronophthisis (2 to 18) in group B. Any difference between the 291 234 who underwent NUL for polyuria. Postoperative 2 groups regarding age was not statistically signif292 235 ½T2 icant (Mann-Whitney U test, p ¼ 0.85; table 2). ultrasound documented progressive hydronephrosis 293 236 of the native kidney in the absence of symptoms. All patients in both groups underwent ureteral 294 237 At 28 months after the NUL procedure the patient ligation or nephrectomy unilaterally. The predomi295 238 presented with flank pain and hydronephrosis nant side involved was the right side (90% in group 296 239 (about 10 cm in anteroposterior diameter) of the A and 81% in group B, Fisher exact test, p ¼ 0.43). 297 240 NK. She subsequently underwent percutaneous Statistical analysis between the 2 groups for the 298 241 drainage and nephrostomy tube placement. 99mTc3 main variables considered (surgical time, intra299 242 operative blood loss and length of surgical scar) mercaptoacetyltriglycine scintigraphy performed 300 243 demonstrated a significant difference (Mannwith the nephrostomy on site documented some 244 Whitney U test, p <0.001), confirming the hypothactivity of the NK (fig. 2). Given the production of ½F2301 302 245 esis that during renal transplantation NUL is about 70 ml per day of urine from the nephrostomy, 303 246 less invasive than NN (table 2). we performed alcoholization of the residual cavity 304 247 In group A Doppler analysis after NUL revealed through the nephrostomy. Followup ultrasound at 305 248 that the native kidney underwent gradual decrease 10 months demonstrated persistent hydronephrosis 306 249 of the blood supply and progressive reduction of with unchanged diameters but without symptoms. 307 250 the renal parenchyma leading to atrophy. At folCurrently the patient is being followed using a 308 251 lowup no patient in group A had postoperative conservative approach. To date, the hydronephrosis 309 252 infection of the kidney or hypertension. In addition, is stable and the patient has no symptoms. 310 253 no patient presented with early postoperative No patient in group B presented with complica311 254 pain. Finally, no perioperative complications were tions related to surgical nephrectomy. The 4 patients 312 255 seen in group A. in group B with hypertension as the indication for 313 256 Only 2 patients (6.8%) in group A had a late NN had normal blood pressure at postoperative 314 257 complication (flank pain/discomfort from massive followup. 315 258 hydronephrosis of the ligated kidney) that required Flank pain/discomfort from massive hydro316 259 a subsequent procedure. One patient, a 13-year-old nephrosis (seen in 2 patients in group A) was not 317 260 boy with nephronophthisis as the underlying disstatistically significant. Other than 1 patient in 318 261 ease, had normal preligation urine output (15 ml/kg group A, all patients in both groups had a func319 262 per day). This patient underwent NUL for arterial tioning graft. No patient in either group currently 320 263 hypertension and postoperative ultrasound docuhas significant proteinuria. 321 264 mented progressive hydronephrosis. At 25 months 322 265 postoperatively the patient presented with flank 323 266 pain/discomfort from a massive hydronephrosis DISCUSSION 324 267 (about 10 cm in anteroposterior diameter) of the The current trend in pediatric renal transplantation 325 268 NK, which was treated with drainage and percutais to reserve NN for carefully selected recipients 326 269 neous instillation of the renal pelvis with tetracyand for a smaller number than in the past.14,15 327 270 cline. One month later, owing to the persistence of NN is now performed in 10% to 50% of pediatric 328 271 about 50 ml per day urine drainage, we performed renal transplant recipients.1,2,16 329 272 percutaneous embolization of the NK. Two weeks In our 2 groups of patients the main indications 330 273 later, although the patient was asymptomatic, for NN were polyuria and intractable massive pro331 274 Doppler ultrasound showed poor persistent vascuteinuria. Polyuria is associated with an increased 332 275 larization in the residual parenchyma. The patient risk of vascular thrombosis of the graft in pediatric 333 276 also had hydronephrosis. Since it was necessary recipients, since it can complicate the management 334 277 Table 2. Patient characteristics 335 278 336 279 Ureteral Ligation Surgical Nephrectomy Overall p Value 337 280 Median yrs age (IQR) 10.5 (9.1e12.9) 9.3 (6.0e16.7) 10.5 (6.4e13.3) 0.85 338 281 Median mins operative time (IQR) 8 (7e10) 34 (28e47) 11 (8e30) <0.001 339 282 Median ml perioperative blood loss (IQR) 0 (0e5) 15 (4e51) 5 (0e11) <0.001 Median cm scar length (IQR) 17 (15e18) 22 (20e24) 18 (16e22) <0.001 340 283 341 284 All variables were analyzed using the Kolmogorov-Smirnov test to assess distribution. In all cases variables showed nonparametric distribution (p <0.001). Consequently 342 285 comparison between the 2 treatment groups was carried out using the Mann-Whitney U test. A p value of less than <0.05 was considered statistically significant. Dochead: Pediatric Urology
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
4
343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
400 with an increased risk of vascular thrombosis and 401 thromboembolism.20e23 402 In our study NUL was systematically performed 403 in patients in group A as an alternative to surgical 404 nephrectomy (in all instances in which the latter 405 was indicated). By blocking the excretory function 406 of the kidney NUL leads to atrophy of the renal 407 parenchyma, thereby achieving functional nephrectomy (fig. 3). NUL failed in only 2 patients ½F3 408 409 (6.8%) in group A. In fact, in these 2 patients 410 we documented residual diuresis from the neph411 rostomy of 50 ml per day in 1 patient and 70 ml per 412 day in 1. 413 NUL is a simple and noninvasive procedure. As 414 documented in this study involving pediatric renal 415 transplantation, NUL is faster to perform than ne416 phrectomy. There is also less risk of bleeding and 417 the procedure requires a smaller surgical incision 418 (table 2). In addition, in certain instances, such as 99m Figure 2. Tc-mercaptoacetyltriglycine renal scintigraphy 419 when patients have undergone previous surgery, reveals some activities of native kidney. 420 NN can only be performed with considerable diffi421 culty and additional risk. Therefore, in these situ422 ations simple NUL may be considered a preferable 423 alternative. of fluids in the post-transplant period.4,17 Such dif424 No patient in group A needed greater analgesic ficulties in the management of postoperative 425 therapy than those in group B. These data are fluid may lead to hemodynamic imbalances and 426 surprising, especially when compared with partial then to vascular thrombosis of the graft, as well as 427 and transient ureteral obstruction (such as ureteral to other types of damage such as acute tubular 428 stones), which is instead a pathology associated necrosis. Moreover, persistence of native polyuria 429 with typical flank pain. Analysis of the pathophysin the post-transplant period may cause chronic 430 iology of pain from ureteral obstruction suggests hypoperfusion of the graft, especially in pediatric 431 that it derives from distention of the wall of the recipients who receive grafts from adult donors, 9,12 432 urinary collecting system. In total and permaand this condition could lead to acceleration of 433 nent ureteral obstruction the pressure within the chronic fibrosis of the graft and increased nephro434 toxicity of certain drugs such as cyclosporine.2 urinary collecting system sharply increases for up 435 to about 5 hours, then gradually decreases.24 In However, some do not consider polyuria to be an 436 absolute indication for NN in these recipients.18,19 addition, any pain potentially caused by NUL in 437 patients in group A may have been masked by Intractable massive proteinuria is also associated 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 Figure 3. Two months after ureteral ligation. A, histology shows glomerular atrophy in kidney. H&E, reduced from 40. B, histology 455 demonstrates tubular atrophy in kidney. H&E, reduced from 5. 456 Dochead: Pediatric Urology
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513
use of analgesic drugs given anyway in the posttransplant period. During followup no patient in group A had episodes of infection in the NK, including the 2 patients who underwent NUL for recurrent pyelonephritis due to vesicoureteral reflux and obstructive hydroureteronephrosis. In the past removal of the NK was preferred to NUL to prevent infectious complications related to the obstructed NK in immunosuppressed recipients at risk for infection.25,26 Subsequently two groups reported series of NUL in adult renal transplant recipients with no infectious complications.9,27 One possible explanation is that pyelonephritis is frequently the result of infection ascending from the lower urinary tract.12 Therefore, NUL would prevent this pathogenetic mechanism. Finally, it is noteworthy that the 2 recipients in our series with recurrent pyelonephritis are the first cases described in the literature managed by NUL for this specific indication. No patient in group A presented with hypertension during followup. In addition, 2 patients in group A with hypertension as the indication for NUL had marked improvement at postoperative followup. To date, NUL has not been described as an alternative to NN when hypertension is the specific indication for treatment. On the contrary, NN rather than ureteral ligation is recommended in recipients with hypertension.9e23 Therefore, our decision to use NUL as an alternative to NN in cases of hypertension represents an innovation, although its efficacy needs to be verified through studies with a larger number of patients. Only 2 patients in group A (6.8%) had complications related to NUL, while no patient in group B presented with complications related to NN. The
5
difference was not significant (Fisher exact test, p ¼ 0.50). However, the complication (flank pain/ discomfort from massive hydronephrosis) suffered by the 2 patients in group A could be defined as grade IIIa according to the Dindo-Clavien scale, as it did not affect the renal graft or patient survival. Moreover, treatment of this complication in both patients was mini-invasive (drainage with alcoholization with or without embolization of the native kidney). Following the mini-invasive procedure 1 patient required nephrectomy, not for an absolute indication, but because the graft had to be removed due to rejection. These observations regarding complications confirm that NUL is a safe procedure. Furthermore, NUL does not expose recipients to additional postoperative risks compared to NN. The main limitation of our series is the comparison between a prospective study group (group A) and a retrospective control group (group B). However, this factor did not affect our results in terms of the efficacy and safety of the procedure, which were the main parameters of interest in the study. Other limitations are the relatively short followup and the small sample size.
CONCLUSIONS NUL without removal of the ipsilateral kidney is a feasible procedure in pediatric renal transplant recipients. This method is easy to perform and significantly less invasive than surgical nephrectomy. Ligation of the ureter is a safe procedure during renal transplantation regardless of the type of indication, with the exception of premalignant/ malignant renal lesions and polycystic kidneys.
REFERENCES 1. Fraser N, Lyon PC, Williams AR et al: Native nephrectomy in pediatric transplantationdless is more! J Pediatr Urol 2013; 9: 84.
peritoneal dialysis: a new management for end-stage renal disease in children. BJU Int 2007; 99: 904.
2. Ghane Sharbaf F, Bitzan M, Szymanski KM et al: Native nephrectomy prior to pediatric kidney transplantation: biological and clinical aspects. Pediatr Nephrol 2012; 27: 1179.
6. Yarimizu SN, Susan LP, Straffon RA et al: Mortality and morbidity in pretransplant bilateral nephrectomy: analysis of 305 cases. Urology 1978; 12: 55.
3. Hamilton BD, Gatti JM, Cartwright PC et al: Comparison of laparoscopic versus open nephrectomy in the pediatric population. J Urol 2000; 163: 937.
7. Nahas WC, Mazzucchi E, Pinheiro MS et al: Role of native nephrectomy in renal transplant recipients. Transplant Proc 2002; 34: 717.
4. Kravarusic D, Sigalet DL, Hamiwka LA et al: Persistent post-transplant polyuria managed by bilateral native-kidney laparoscopic nephrectomy. Pediatr Nephrol 2006; 21: 880.
8. Shoma AM, Eraky I and El-Kappany HA: Pretransplant native nephrectomy in patients with end-stage renal failure: assessment of the role of laparoscopy. Urology 2003; 61: 915.
5. Gundeti MS, Taghizaedh A and Mushtaq I: Bilateral synchronous posterior prone retroperitoneoscopic nephrectomy with simultaneous
9. Gallentine ML and Wright FH Jr: Ligation of the native ureter in renal transplantation. J Urol 2002; 167: 29.
Dochead: Pediatric Urology
10. Nie Z, Zhang K, Huo W et al: Comparison of urological complications with primary ureteroureterostomy versus conventional ureteroneocystostomy. Clin Transplant 2010; 24: 615. 11. Guiter J, Cuenant E, Mourad G et al: Reestablishment of urinary continuity by ureteroureterostomy in renal transplantation. Apropos of 135 cases. J Urol (Paris) 1985; 91: 27. 12. Goh BK, Dean PG, Cosio FG et al: Bilateral native ureteral ligation without nephrectomy in the management of kidney transplant recipients with native proteinuria. Am J Transplant 2011; 11: 2747. 13. Guzman JA: Intravesical ligation as a new technique to manage a refluxing native ureter without simultaneous nephrectomy in renal transplantation. Transplant Proc 2012; 44: 2940.
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570
6
571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592
NATIVE URETERAL LIGATION AND OPEN NEPHRECTOMY IN KIDNEY TRANSPLANT
14. Vincenti FG: Recurrent focal segmental glomerulosclerosis in the renal allograft: current concepts of pathogenesis, diagnosis, and management. NephSAP 2005; 4: 1. 15. Schr€oder A and Koyle M: Editorial comment. J Pediatr Urol 2013; 9: 89. 16. Harper L, Michel JL and Dunand O: Editorial comment. J Pediatr Urol 2013; 9: 90.
19. Matas AJ, Chavers BM, Nevins TE et al: Recipient evaluation, preparation, and care in pediatric transplantation: the University of Minnesota protocols. Kidney Int Suppl 1996; 53: S99. 20. Lau SO, Tkachuck JY, Hasegawa DK et al: Plasminogen and antithrombin III deficiencies in the childhood nephrotic syndrome associated with plasminogenuria and antithrombinuria. J Pediatr 1980; 96: 390.
17. Singh A, Stablein D and Tejani A: Risk factors for vascular thrombosis in pediatric renal transplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. Transplantation 1997; 63: 1263.
21. Barbour SJ, Greenwald A, Djurdjev O et al: Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int 2012; 81: 190.
18. Langlois V, Geary D, Murray L et al: Polyuria and proteinuria in cystinosis have no impact on renal transplantation. A report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 2000; 15: 7.
22. Singhal R and Brimble KS: Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 2006; 118: 397.
Dochead: Pediatric Urology
23. Bramham K, Hunt BJ and Goldsmith D: Thrombophilia of nephrotic syndrome in adults. Clin Adv Hematol Oncol 2009; 7: 368. 24. Gulmi FA, Felsen D and Vaughan ED Jr: Pathophysiology of urinary tract obstruction. In: Campbell’s Urology, 7th ed. Edited by PC Walsh, AB Retik, ED Vaughan Jr et al. Philadelphia: WB Saunders 1997; chapt 9, p 350. 25. Greenberg SH, Wein AJ, Perloff LJ et al: Ureteropyelostomy and ureteroneocystostomy in renal transplantation: postoperative urological complications. J Urol 1977; 118: 17. 26. Jaffers GJ, Cosimi AB, Delmonico FL et al: Experience with pyeloureterostomy in renal transplantation. Ann Surg 1982; 196: 588. 27. Lord RH, Pepera T and Williams G: Ureteroureterostomy and pyeloureterostomy without native nephrectomy in renal transplantation. Br J Urol 1991; 67: 349.
FLA 5.4.0 DTD JURO13688_proof 1 June 2016 5:48 pm EO: JU-16-129
593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614