Transperitoneal, Hand-Assisted Laparoscopic Donor Nephrectomy: Surveillance of Renal Function by Immune Monitoring

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ransperitoneal, Hand-Assisted Laparoscopic Donor Nephrectomy:urveillance of Renal Function by Immune Monitoring

. Hamza, S. Wagner, K. Weigand, H. Loertzer, O. Rettkowski, A. Jurzcok, K. Fischer, and P. Fornara

ABSTRACT

The history of living donor nephrectomy has undergone several development phases withrespect to medical, immunologic, and operative aspects. Due to the shortage of postmor-tem organ donations and the rising number of patients with terminal renal insufficiencywho are awaiting kidney transplantation, living kidney donation has become increasinglyimportant during recent years.

Methods. From December 2004 to May 2005, we performed hand-assisted laparoscopicdonor nephrectomies on 15 female and 9 male patients of median age 37 years. Ourimmunosuppressive regimen included tacrolimus, mycophenolate mofetil, methylpred-nisolone, and a monoclonal antibody.

Results. The median operative time was 138 minutes (113–180 minutes), and the medianwarm ischemia time was 87 seconds (63–150 seconds); results comparable to those of opendonor nephrectomy. The hospitalization periods of the donors were between 5 and 7 days.The renal function and acute-phase parameters showed a transient increase during andafter the operation. Most of the patients reached baseline levels by postoperative day3 or 4.

Conclusion. Together with the clinical data, these findings confirmed the efficacy andminimal invasiveness of laparoscopic donor nephrectomy. It is thus possible that in the

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HE FIRST SUCCESSFUL KIDNEY TRANSPLAN-TATION took place in Boston, Massachusetts in 1954

n identical twins, using a living donor. Thereafter, theesire has existed to perform living donor transplantation,ot just between close relatives, but also between husbandsnd wives or close friends. The shortage of postmortemrgan donations and the increased number of patients witherminal renal insufficiency awaiting transplantation ac-ounts for the increased importance of living donor kidneyransplantation.1–3

The rapid development in the last few years of laparo-copic surgical techniques using minimally invasive methodsas led to laparoscopy being used in urology as well as inrgan transplantation. The utilization of laparoscopy in

iving donor transplantation has gained increasing accep-ance among both donors and recipients in the last few

2008 by Elsevier Inc. All rights reserved.60 Park Avenue South, New York, NY 10010-1710

ransplantation Proceedings, 40, 895–901 (2008)

The German Transplant Act of 1997 defined the judicial,egal, and human rights bases for living donor transplanta-ion and also set out preconditions and restrictions. Theeasons for the rise in the number of living donor trans-lantations in Germany and other European countries ares follows: (1) decline in the number of available deceasedonor kidneys with a consequent shortage of organs; (2)

ncreased waiting times for dialysis-dependent patients

From the Clinic of Urology and Kidney Transplantation Centre,A.H., S.W., K.W., H.L., A.J., K.F., P.F.) and Clinic of Interne

edicine (O.R.), Martin-Luther-University Halle-Wittenberg,alle, Germany.Address reprint requests to OA Dr. med. Hamza, Clinic ofrology and Center of Kidney Transplantation, Martin-Luther-niversity Halle-Wittenberg, Ernst-Grube-Street 40, 06120 Halle

Saale), Germany. E-mail: [email protected]

0041-1345/08/$–see front matterdoi:10.1016/j.transproceed.2008.03.079

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waiting a kidney; and the population is increasingly readyo help a partner by means of a living organ donation.2,4

Analysis of the development of living donor nephrecto-ies between 1991 and 2005 by comparing the percentage

f living donors with deceased donor kidneys revealed anncrease from 2.6% in 1991 to 16.3% in 2001 and to 23.8%n 2005 (Fig 1).

On the basis of a large sample of patients with renalransplants the Collaborative Transplant Study showed thathe 5-year survival rate for living donor transplants was0 % higher than for deceased donor transplants.The advantages of living donor transplants compared

ith deceased donor transplants are based on the follow-ng factors2,5–7: (1) reduced waiting times and reduceduration of dialysis; (2) reduced cold ischemia time; (3)

mproved organ quality through planned nephrectomy;4) optimum timing for renal transplantation; and (5)lanned perioperative and postoperative immunosup-ression.Laparoscopic nephrectomy, which was first successfully

erformed in 1991 by Clayman, has become standardractice. The first laparoscopic donor nephrectomy tooklace in 1996, and the first hand-assisted laparoscopiconor nephrectomy was performed in 1998. Demonstra-ion of the minimal invasiveness of laparoscopic tech-iques was provided by Fornara in 2003.8 Since then

aparoscopic techniques have been shown to have a lowerostoperative acute phase reaction compared to openperative techniques.8,9 The long warm ischemia time in

aparoscopic donor nephrectomy led to the development

Table 1. Hand-Assisted Living Donor Nephrectomies

Men Women

umber of patients � 24 9 15edian age � 37ecipient 6 � spouse 11 � spouse

1 � friend

f hand-assisted donor nephrectomy in 1998 and thus to ainimal warm ischemia time of the removed kidneys.9

The Transplant Act specifies that the donor must beealthy and that all risks to the donor should be eliminatedefore donation. The evaluation of the living donor is an

ntensive process that is taken seriously. The preparation ofhe patient takes place in close collaboration betweenrologists, nephrologists, anesthetists, and immunologists.n addition to the extensive dialogue with the donor and theecipient, a preparatory program is performed; the medicalequirements for living donor nephrectomy consist primar-ly of two minimum requisites: Blood group compatabilitynd Negative cross-matching.

Subsequently, all invasive, internal, urologic, and radio-ogic diagnostics take place. When the findings are com-lete, the documents are submitted to the Ethics Commis-ion. The living donor nephrectomy and renal transplantre performed when the Ethics Commission has respondedositively.2,4

In selecting the operative method (ie, open or laparo-copic), several factors must be taken into account: arterialupply to the kidneys; patient’s preoperative history; andatient’s wishes.

Fig 1. Living Donor nephrec-tomy in Germany 1991–2005.pm. don. � postmortem donornephrectomy; LDN � living do-nor nephrectomy.

Fig 2. Position of patient and trocar placement.

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LAPAROSCOPIC DONOR NEPHRECTOMY 897

The decision regarding whether to remove the left oright kidney depends on the overall medical findings. Arinciple based on medical and legal precepts is applied:amely, the donor retains the better kidney unless theecipient would be at less risk due to the superior arterialupply.10–13

ATIENTS AND METHODS

ighty-three renal transplants were performed from December 15,004 through May 31, 2006. The indications for hand-assisted,aparoscopic living donor nephrectomy were observed in 24 livingonors: 15 women and 9 men. Their median age was 37 yearsTable 1). A preoperative history of abdominal hysterectomy (n �) and laparoscopic cholecystectomy (n � 1) was confirmed. Thelood group was compatible for all patients, and a negativeross-match fulfilled the preconditions for transplantation. In ad-

Fig 3. Aspect of isolated vessels (intraoperative).

ig 4. The sac to envelope the

ition, we identified HLA typings as well as current and pastntibodies in the recipients.

Immunosuppression included tacrolimus, mycophenolate mofe-il, methylprednisolone, and monoclonal antibodies. The recipientseceived the first dose (one-half dose) of tacrolimus 3 days beforehe renal transplantation.6

The following clinical and laboratory parameters were deter-ined postoperatively using a fixed formula: operation time,

ospitalization period, complications; warm ischemia time; andenal vascular quality.

The renal function parameters were serum creatinine (S-Crea),�mol/L), serum cystatin C (C-Cys), (mg/L), urine total proteinU-Prot; g/L), urine immunoglobulin G (U-IgG; mg/L), urinelbumin (U-Alb), (mg/L), urine transferrin (U-Tf), (mg/L), tubuleunction/tubule integrity, (mg/L), urine retinol-binding proteinU-RbP; mg/L), urine �1-microglobulin (U-�1M; mg/L), urine2-microglobulin (U-ß2M; mg/L), urine alanine aminopeptidaseU-AAP; U/L), and urine N-acetyl-beta-glucosaminidase (U-NAG;U/L).

Fig 5. The surgeon’s hand in the sac to control the kidney.

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The parameters in the acute phase included Serum interleukin(S-IL 6; pg/L), Serum C-reactive protein (S-CRP; mg/L),

erum amyloid A (SAA; mg/L), Urine interleukin 6 (U-IL 6;g/mL), Urine interleukin 8 (U-IL 8; pg/mL), Urine myelo-eroxidase (U-MPO; �g/mL), Urine C-reactive protein (U-RP; mg/L), and Urine �2 – macroglobulin in urine (U-�2M;g/L).Blood and urine samples were obtained preoperatively (T0);

uring the surgical procedure T1 after trocar insertion and T2

fter disconnection of the hilar vessels; and also at 6, 12, 24, 48,2, and 96 hours after the operation (T3–T8, respectively).

perative Technique

fter extensive explanation of the operative risks and preparationf the patients, and after inquires to Eurotransplant regardingotential kidneys becoming available for the recipient, both donornd recipient were taken into the operating theatre. The laparo-copic, hand-assisted donor nephrectomy began first after theatient was placed in the thoracoabdominal position. After cre-tion of the pneumoperitoneum by insertion of a 10-mm trocarbove the umbilicus, four additional working trocars were intro-uced (Fig 2). Depending on the side from which the kidney was toe removed, the peritoneum was opened laterocolically and theolon mobilized medially. This maneuver was followed by inspec-ion and subsequent depiction of the psoas muscle and the ureter.reparation followed along the ureter and the adnexal vessels to

he renal hilum, where the vessels were identified. After complete

Fig 6. Postoperative check of the patient.

Table 2. Operat

Open

ouglas et al. 1999 (P � .05) —uiz-Deya et al. 200121 (P � .05) —tiefelmann et al. 200119 265 � 50 (n � 23)olf et al. 200022 (P � .001) 94.8 � 21 (n � 40)ercher 200116 —olf et al. 200123 (P � .0001) 125 � 36 (n � 27)emelmann et al. 200010 —toffel 2002 (P � .01)9 —

xposure of the kidney and vessels with ligation of the sideranches of the renal vein, the vena cava and the abdominal aortaere isolated. Thereafter, the hand port was placed via a median

aparotomy. The vessels were further prepared under digital con-rol, and after intravenous administration of heparin, the ureteras cut between two clips at the transition to the pelvis minor. The

enal artery was occluded by means of clips, and cut, with two clipset proximal to the aorta. The vein was closed by a row of Endo-TAtaples. Immediately after extirpation of the kidney, perfusion withTK solution was carried out. The recipient was being prepared

imultaneously in the neighboring operating theatre (Figs 3–6).his resulted in a reduction of the cold ischemia time to under 30inutes.14–19

ESULTS

ighty-three kidney transplantations were performed fromecember 15, 2004 to May 31, 2006 including 24 from

and-assisted, laparoscopic donor nephrectomies. In sixases, the kidney donation was from a first-degree relativend in 17 cases from the spouse. The operative time was onverage 138 minutes (113–180). The warm ischemia timeas reduced to an average of 87 seconds (63–150; Tables 2nd 3). All procedures were performed by hand-assistedaparoscopy. The average hospitalization period of theonors was 5 days (4–7).The serum markers of the glomerular filtration rate for

he donor (S-Crea and S-Cys; Figs 7 and 8) rose duringnd after the donor nephrectomy. On postoperative daythey remained significantly elevated above the initial

alues. The reduced glomerular filtration rate resultedrom the loss of the donated kidney. How far and whenhe single kidney compensated for the loss can only bescertained when data from long-term observation be-omes available.

The urine markers of kidney glomerular and tubularunction showed a relevant increase between 12 and 18ours after donor nephrectomy. The time of the increaseiffered slightly between the individual parameters. How-ver, at 4 days after the procedure there was no statisticallyignificant difference between the initial and the final valuesFig 9). The sole exception was U-�1M, in which theifference between preoperative and postoperative valuesas still statistically significant at 4 days after donor ne-

ime in Minutes

Laparoscopic Hand-Assisted Laparoscopic

187 � 22 (n � 10) 121 � 26 (n � 12)215 � 12 (n � 11) 165 � 12 (n � 24)

— 240 � 88 (n � 66)— 215 � 51 (n � 10)— 275 (193–360) (n � 29)— 204 � 32 (n � 23)— 140 (120–400) (n � 10)

230 � 19 (n � 14) 180 � 26 (n � 33)

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138 (113–180) (n � 24)

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hrectomy, indicating impaired tubular function. This pos-ibly represented a result of functional overload of theemaining kidney (Fig 10).

The systemic reaction to the operative trauma was sig-ificant. S-IL6 returned to approximate initial values at 3ays after the procedure, while acute phase proteinshowed a significant difference between preoperative andostoperative values 4 days after donor nephrectomy (Figs1 and 12).The urine interleukins, IL6 and IL8 (ie, the urinearkers of renal function) showed significant increases at

4 and 12 hours after the procedure, respectively, as didhe granulocyte marker, U-MPO, suggesting an inflam-atory reaction to the operative trauma (Fig 13). U-CRP

nd U-�2M were not observed in the urine at any time,hich may be construed as a sign of lack of admixedlood. Alternatively, it can be postulated that the tubularunction of the remaining kidney was sufficient to preventhe excretion of detectable amounts of CRP into therine.

omplications

wo donors experienced retroperitoneal hematomas post-peratively, which required a blood transfusion; surgicalevision was not required, however. One recipient, who wasnown to have chronic heart disease that was stable at theime of the operation, suffered a fatal acute myocardial

ig 7. Levels of S-creatinine at determined postoperative times

Table 3. Warm Isch

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ouglas et al. 1999 [13] (P � .05) —uiz-Deya et al. 2001 (P � .05)21 —tiefelman et al. 200119 —olf et al. 2000 (P � .001)22 —ercher 200110 —olf et al. 2001 (P � .0001)23 96 � 57 (n � 27)emelman et al. 200010 —toffel et al. 20029 —wn results

T0–T8). (

nfarction on postoperative day 3. A second recipientxperienced an unexplained venous thrombosis that causedcclusion of the kidney despite repeated revision. Fourases of lymphocoel formation were observed: two patientsad to be laparoscopically windowed, while the other twoatients remained asymptomatic. Ureteral leakage necessi-ated revision and reattachment of the ureter in one patientTable 4).

ISCUSSION

he increased interest in living donor kidney transplanta-ion arises from the following causes: shortage of organsrom deceased donors, long waiting times for a kidney, thenhanced results and survival rates with living donor kidneyransplantation, and establishment of laparoscopic ne-hrectomy and the resulting reduced strain on the donor.Our results showed that more female spouses donated

idneys for their male partners than vice versa. Thisirrors the women’s emotional attachment to their part-

ers. The increased warm ischemia time of 3 to 5 minutesfter laparoscopic nephrectomies is a main focus ofriticism in the literature.20,21 The development of hand-ssisted, laparoscopic living donor nephrectomy reduceshe warm ischemia time rendering it comparable to theecorded times for open nephrectomies. Our resultshowed that, with the use of a hand port and goodrganization of the nephrectomy and transplantationeams, an average warm ischemia time of 98 seconds is

ig 8. Levels of S-cystatin C at determined postoperative times

Time in Seconds

Laparoscopic Hand-Assisted Laparoscopic

235 � 32 (n � 12) 74 � 32 (n � 10)234 � 18 (n � 24) 96 � 12 (n � 11)

— 121 � 39 (n � 60)— 174 � 78 (n � 10)— 73 (30–165) (n � 29)— 183 � 124 (n � 23)— 150 (60–270) (n � 10)

450 � 104 (n � 14) 144 � 66 (n � 33)87 (63–150) (n � 24)

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chievable. We observed reduced renal blood flow arisingrom increased abdominal pressure, with the resultingransient impairment of function in the donor kidney, asvidenced by laboratory parameters, only up to postop-rative day 4. The other tests performed postoperativelynd during after treatment indicated normal renal func-ion. During the establishment and development phase, aew operative method requires the accumulation ofxperience by the surgeons who normally require longernitial training times and can cause more complications.he high complication rate in the 1990s during thestablishment phase of laparoscopic living donor ne-hrectomy, namely, ureteral injuries and loss of organs asresult of the laparoscopic extraction, has been reduced

o a low level today.9,14 The complications among ourample of patients did not endanger the donors. Theyere comparable to those after open nephrectomy and

ubsequent transplantation. The marked shortening ofhe warm ischemia time through hand-assisted laparo-copic living donor nephrectomy has led to an improve-ent in renal function. In three recipients increased

unction was observed on postoperative day 3 or 4, andhe patients have been dialysis-free since then. Theemaining patients had primary renal function. Creati-ine values measured at 3 and 6 months showed stableenal function. Degradation of renal function was ob-erved in one patient only, as a result of three rejectionpisodes. Recovery times for patients operated on lapa-

ig 9. Levels of U-ß2M at determined postoperative timesT0–T8).

ig 10. Levels of U-a1M at determined postoperative times

oscopically was clearly faster and better. Our resultsorresponded with those in the literature.15,21–23 Weischarged the donors between days 5 and 7 after therocedure. As far as pain therapy is concerned, webserved that the patients needed a similar amount ofnalgesic on day 1 after the procedure as those who hadpen surgery, but significantly less on days 2 and 3.In conclusion, the rising numbers of renal insufficiency

atients, long waiting times for kidney transplantation, andrgan shortages have together combined to lead to an

ncreased proportion of living donor nephrectomies inermany and central Europe. The establishment and intro-

uction of hand-assisted living donor nephrectomy hasinimized the disadvantages of laparoscopic nephrectomy.perative and warm ischemia times in hand-assisted living

onor nephrectomy are dependent on experienced sur-eons and good organization. The various laboratory pa-ameters obtained from our sample of patients did not showisadvantages with respect to renal function of the trans-lanted kidney. The reduced hospitalization periods al-

owed costs to be reduced and also quicker return to work.he risks of the procedure must be explained to the donor.he preparation of the donor for the procedure must beptimised, and strict indicators to decide in favor of eitherlaparoscopic or open nephrectomy must be adhered to. Aell-established kidney transplant center must have mas-

ery over both operative techniques and be able to offeroth to patients.

ig 11. Levels of S-IL6 at determined postoperative timesT0–T8).

ig 12. Levels of S-CRP at determined postoperative times

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LAPAROSCOPIC DONOR NEPHRECTOMY 901

EFERENCES

1. Fornara P: Trotz Gegenwindes machen sich Operateure fürrossover-Transplantation stark. Urologische Nachrichten 3:6,0012. Hamza A, Rettkowski O, Osten B, et al: Lebendspende für

ie Nierentransplantation. Urologe A 42:961, 20033. Tullius SG, Pfitzman R, Neuhaus P: Nierentransplantation.

e Gruyter, Berlin, S. p. 181, 20014. Sengler H: Stellungnahme zu rechtlichen Aspekten aus Sicht

es Bundes-gesundheitsministeriums Nieren-Lebendspende, G.irste, Pabst-Verlag 20005. Dreikom K: Stein der Weisen oder doch ein Akt der Inhu-anität? Urologische Nachrichten 98:6, 20026. Lenhard V, Dreikorn K, Opelz G: Aktuelle immunologischespekte der Nierentransplantation. Urologe A 21:280, 19827. Sasaki TM, Finelli F, Bugarin E, et al: Is laparoscopic donor

ephrectomy the new criterion standard? Arch Surg 135:943, 20028. Fornara P, Zacharias M, Steinacker M, et al: Laparosko-

ische vs. offene Nephrektomie. Urologe A 42:197, 20039. Stoffel F, Forster TH, Steiger J, et al: Handassistierte lapa-

oskopische Spendernephrektomie. Urologe A 41:258, 200210. Bemelman WA, van Doorn RC, de Wit LT, et al: Handas-

isted laparoscopic donornephrectomy. Ascending the learningurve. Surg Endosc 15:442, 2001

11. Ebeling V, Türk I, Deger S, et al: Laparoskopische Donor-ephrektomie. Pro und Contra. Transplant Linc Nierentransplan-ation 1:101, 2002

12. Giessing M, Deger S, Ebeling V, et al: Multipleierengefäße bei der laparoskopischen Lebendnierenspende. Uro-

oge A 42:225, 200313. Wolf S, Tchetgen M, Merion R: Handassisted laparoscopic

ive donor nephrectomy. Urology 52: 885, 199814. Fahlenkamp D, Rassweiler J, Fornara P, et al: Complica-

ions of laparoscopic procedures in urology: experience with 2,407rocedures at 4 German centres. J Urol 162:765, 199915. Forster TH, Stoffel F, Gasser TC: Laparoscopic versus open

ive donornephrectomy a comparison of pain and need for narcot-cs. Eur Urol 39:6, 2001

16. Kercher K, Dahl D, Harland R, et al: Handassisted laparo-copic donor nephrectomy minimizes warm ischemia. Urology8:152, 200117. Odland MD, Ney AL, Jacobs DM, et al: Initial experience

ith laparoscopic live donornephrectomy. Surgery 126:603, 199918. Rassweiler J, Fornara P, Weber M, et al: Laparoscopic

ephrectomy: the experience of the laparoscopy working group ofhe German Urologie Association. J Urol 160:18, 1998

19. Stifelman MD, Hull D, Sosa RE, et al: Handassisted lapa-oscopic donornephrectomy: a comparison with the open ap-roach. J Urol 166:444, 200120. Slakey DP, Wood JC, Hender D, et al: Laparoscopic living

onor nephrectomy: advantages of the handassisted method.ransplantation 68:581, 199921. Ruiz-Deya G, Cheng P, Palmer E, et al: Open donor,

aparoscopic donor and handassisted laparoscopic donor ne-hrectomy: a comparison of outcomes. J Urol 166:1270, 200122. Wolf JS, Marcovich R, Merion RM, et al: Prospective, caseatched comparison of handassisted laparoscopic and open surgi-

al live donornephrectomy. J Urol 163:1650, 200023. Wolf JS, Merion RM, Leichtman AB, et al: Randomized

ig 13. Levels of U-IL 8 at determined postoperative times

Table 4. Complications in Hand-Assisted LivingDonor Nephrectomy

Complication

ouglas et al. 1999 (P � .05) Conversion 1/23Postoperative ileus 2/23

tiefelman et al. 200119 No complications in kidneydonor

1/40 Delayed transplantedkidney function

1/40 Urethra complicationsercher 200110 1/29 Wound infection

1/29 Subcutaneousemphysema

1/30 Conversion2/29 Atelectasis with

transient fever1/29 Urinary retention

olf et al. 200123 (P � .0001) 1/23 Urinary retention1/23 Fascial defect without

herniation1/23 Wound infection

toffel 20029 (n � 33) 1/33 Damage to lumbar veinTreatment with paracentesis,

substitution of packederythrocytes necessarypostoperatively

2/33 Decapsulation of thesuperior pole of the kidney

2/33 Wound seromas1/33 Wound haematomas

urrent study results 2/24 Retroperitonealhaematomas

1/24 Myocardial infarction1/24 Venous thrombosis and

transplantectomy4/24 Lymphoceleformation

ontrolled trial of hand-assisted laparoscopic versus open surgicalive donor nephrectomy. Transplantation 72:284, 2001