Vassilios Papalois

Laparoscopic Versus Open Live Donor Nephrectomy in Renal Transplantation : A Meta-Analysis

Objective:The aim of this study was to compare laparoscopic versus open live donor nephrectomy using meta-analytical techniques. Summary Background Data:Laparoscopic live donor nephrectomy has gained widespread acceptance and is increasingly performed. The body of evidence assessing the safety and efficacy of laparoscopic compared with established open techniques is growing; however, very few randomized control trials exist and individual studies often have small patient numbers with varying results. We combined the available raw data to strengthen the current literature in comparing these techniques. Methods:A literature search was performed and comparative studies published between 1997 and 2006 of open versus laparoscopic donor nephrectomy were included. Outcomes evaluated were operative and warm ischemia times, blood loss, donor complications, length of hospital stay, time to return to work, and delayed graft function. Results:Seventy-three studies matched the selection criteria and included 6594 patients, 3751 (57%) had undergone laparoscopic surgery and 2843 (43%) open nephrectomy. The open nephrectomy group had shorter operative and warm ischemia times by 52 minutes (P < 0.001) and 102 seconds (P < 0.001), respectively. This did not translate into higher delayed graft function or graft loss rates between the 2 groups. Patients in the laparoscopic group had a shorter hospital stay and a faster return to work by 1.58 days (P < 0.001) and 2.38 weeks (P < 0.001), respectively. There was a significantly higher rate of overall donor complications in the open group (P = 0.007), a finding not reproduced in any subsequent sensitivity analyses. When only randomized control trials were considered, there were shorter operative times (P = 0.002) for the open group but nonsignificantly different warm ischemia times. In contrast to the main analysis there were no differences in the overall complication rate, postoperative analgesia, hospital stay, or time taken to return to work. Conclusions:Laparoscopic nephrectomy in live donor transplantation is a safe alternative to the open technique. Although open nephrectomy may be associated with shorter operative and warm ischemia times, patients undergoing laparoscopic nephrectomy may benefit from a shorter hospital stay and faster return to work without compromising graft function.

Pre-emptive transplants for patients with renal failure: an argument against waiting until dialysis.

Background. Pre-emptive kidney transplants have not been favored in some centers because of concern about possible increased noncompliance and allegedly inferior long-term results. We analyzed our experience with pre-emptive kidney transplants to determine whether such concerns are justified. Patients and Methods. Between January 1, 1984, and June 30, 1998, we performed 1849 adult primary kidney transplants: 385 pre-emptive (recipients not undergoing dialysis, ND) and 1464 non-pre-emptive (recipients undergoing dialysis, D). Results were subdivided by donor source: cadaver (CAD) and living donor (LD). ND recipients tended to be younger, but otherwise, the two groups were similar. Posttransplantation quality of life in recipients was evaluated using the nationally standardized Short Form Health Survey (SF-36). The posttransplantation employment status of the recipients was also evaluated. Results. The patient survival rate 5 years posttransplantation was significantly better for ND (vs. D) recipients for both CAD (92.6% vs. 76.6%, P =0.001) and LD (93.3% vs. 89.5%, P =0.02) transplants. The 5-year patient survival rate was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1–2, and > 2 years pretransplantation for both CAD (P =0.0005) and LD (P =0.0001) transplants. The graft survival rate 5 years posttransplantation was similar between ND and D recipients for CAD transplants, but significantly better for ND (vs. D) recipients of LD transplants (92.3% vs. 84.8%, P =0.006). For CAD transplants, the 5-year graft survival rate was not different when ND recipients were compared with recipients undergoing dialysis for < 1, 1–2, and > 2 years pretransplantation; for LD transplants it was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1–2, and > 2 years pretransplantation (P =0.04). The incidence of acute and chronic rejection was no different between ND and D recipients for either CAD or LD transplants, and it was also not affected by the pretransplantation time undergoing dialysis. Graft loss secondary to the recipient’s discontinuation of immunosuppressive therapy (a crude estimate of compliance) was similar between ND and D recipients. Five years posttransplantation, the SF-36 scores regarding the recipient’s quality of life and the employment status were similar for ND compared with D recipients, regardless of donor source. Conclusions. ND recipients do not seem to have higher rates of noncompliance than D recipients. Results for ND recipients seem to be superior than for D recipients, supporting the contention that renal failure patients should, if possible, undergo transplantation before dialysis.

Comparison of Laparoscopic Versus Hand-assisted Live Donor Nephrectomy

Background. The aim of the present study was to compare hand-assisted laparoscopic live donor nephrectomy with the classic laparoscopic method, using meta-analytical techniques. Methods. A literature search was performed for studies comparing hand-assisted laparoscopic nephrectomy with classic laparoscopic nephrectomy for live kidney donation between 1999 and 2005. The following end points were evaluated: operative time, warm ischemia time, intraoperative adverse events, donor and recipient postoperative complications, and length of hospital stay. Results. Nine comparative studies matched the selection criteria, reporting on 376 patients, of whom 202 (53.7%) had hand-assisted laparoscopic nephrectomy and 174 (46.3%) had the classic laparoscopic technique. Conversion to open surgery was 2.97% in the hand-assisted group and 4.60% in the laparoscopic group (P=0.35). Total operative and warm ischemia times were significantly shorter for hand-assisted laparoscopy by 30.03 minutes (P=0.02) and 1.14 minutes (P<0.001), respectively. The intraoperative blood loss was less for the hand-assisted laparoscopy group by 34.16 mL (P=0.008), although intraoperative (3.46% vs. 7.47%; P=0.24) and postoperative (5.94% vs. 10.34%; P=0.30) donor complications and recipient complications (including delayed graft function and primary nonfunction, 8.41% vs. 7.42%; P=0.32) were similar between the hand-assisted and laparoscopic groups. Conclusion. Hand-assisted laparoscopic nephrectomy appeared to have the same donor and recipient complication rate with standard laparoscopy but offered substantial advantages in terms of shortened operative and warm ischemia time as well as decreased intraoperative bleeding.

Determinants of mycophenolic acid levels after renal transplantation.

There are data suggesting an association between mycophenolic acid (MPA) levels and acute rejection and toxicity in renal transplant recipients treated with mycophenolate mofetil (MMF), and therefore, knowledge of factors determining MPA levels may aid in accurate adjustment of MMF dosage. A total of 4970 samples taken 12 hours postdose were analyzed for MPA by immunoassay at regular intervals from the first week posttransplantation in 117 renal transplant patients immunosuppressed with MMF and tacrolimus in a steroid-sparing regimen (prednisolone for the first 7 days only). MPA levels rose in the first 3 months and stabilized thereafter; dose-normalized MPA levels rose throughout the first 12 months and subsequently stabilized. Multivariate analysis by means of a population-averaged linear regression showed positive associations between MPA level and total daily dose (P < 0.001) but not individual dose or total daily dose corrected for body weight. Positive associations were also seen with serum albumin (P = 0.01), tacrolimus trough level (P = 0.01), and female gender (P = 0.002). The association with tacrolimus levels diminished with time. Negative associations were seen between MPA level and higher estimated creatinine clearance (P < 0.001), and also with increasing alanine transaminase levels (P = 0.002), the use of oral antibiotics (P < 0.001), and infective diarrhea (P < 0.001). The latter findings may be related to changes in enterohepatic recirculation of MPA. Many clinical variables show associations with trough MPA levels. An understanding of these factors may aid therapeutic monitoring of MMF.

Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy—an Open Label, Randomized Trial

Background. Immunosuppressive regimens for kidney transplantation which reduce the long-term burden of immunosuppression are attractive, but little data are available to judge the safety and efficacy of the different strategies used. We tested the hypothesis that the simple, cheap, regimen of alemtuzumab induction combined with tacrolimus monotherapy maintenance provided equivalent outcomes to the more commonly used combination of interleukin-2 receptor monoclonal antibody induction with tacrolimus and mycophenolate mofetil combination maintenance, both regimens using steroid withdrawal after 7 days. Methods. One hundred twenty-three live or deceased donor renal transplant recipients were randomized 2:1 to receive alemtuzumab/tacrolimus or daclizumab/tacrolimus/mycophenolate. The primary endpoint was survival with a functioning graft at 1 year. Results. Both regimens produced equivalent, excellent outcomes with the primary outcome measure of 97.6% in the alemtuzumab arm and 95.1% in the daclizumab arm at 1 year (95% confidence interval of difference 6.9% to −1.7%) and at 2 years 92.6% and 95.1%. Rejection was less frequent in the alemtuzumab arm with 1- and 2-year rejection-free survival of 91.2% and 89.9% compared with 82.3% and 82.3% in the daclizumab arm. There were no significant differences in terms of the occurrence of opportunistic infections. Conclusion. Alemtuzumab induction with tacrolimus maintenance monotherapy and short-course steroid use provides a simple, safe, and effective immunosuppressive regimen for renal transplantation.

A meta‐analysis of mini‐open versus standard open and laparoscopic living donor nephrectomy

Mini‐open donor nephrectomy (MODN) potentially combines advantages of standard open (SODN) and laparoscopic techniques (LDN). This article is a comparison of these techniques. A literature search was performed for studies comparing MODN with SODN or LDN. Nine studies met our selection criteria. Of the 1038 patients, 433 (42%) underwent MODN, 389 (37%) SODN and 216 (21%) LDN. MODN versus SODN: Operative time (P = 0.17), warm ischemia time (P = 0.20) and blood loss (P = 0.30) were not significantly different. Hospital stay and time to return to work were shorter for MODN by 1.67 days (P < 0.001) and 5 weeks (P = 0.03). Analgesia requirement and overall complications were less in the MODN group (P < 0.001) and (P = 0.03). Ureteric complications (P = 0.21) and 1‐year graft survival (P = 0.28) were not significantly different. MODN versus LDN: Operative and warm ischemia times were significantly shorter for the MODN by 55 min (P = 0.005) and 147 s (P < 0.001). Analgesia requirement was greater for the MODN group by 9.62 mEq morphine (P = 0.04). No significant differences were found for blood loss (P = 0.8), hospital stay (P = 0.35), donor complications (P = 0.40) or ureteric complications (P = 0.83). MODN appears to provide advantages for the donor in comparison to SODN and also has a shorter operative time when compared with the LDN.

ABO incompatible living renal transplantation with a steroid sparing protocol.

Background. ABO incompatible (ABOi) live-donor renal transplantation is a successful and accepted form of treatment for patients with renal failure. Although there is significant controversy as to how antiblood group antibodies should be removed and their resynthesis prevented, subsequent immunosuppressive regimes have all involved steroids. We and other groups have successfully used steroid sparing regimes for conventional ABO compatible transplantation and this study describes the use of our steroid sparing protocol in ABOi transplantation. Methods. We have transplanted 10 ABOi patients using 1 week of steroids (prednisolone 1 mg/kg for 4 days, 0.5 mg/kg for 3 days and then stopped), tacrolimus and mycophenolate mofetil. Steroids were reintroduced in the event of rejection. Results. Patient- and allograft-survival 1 year posttransplantation is 100%. Three patients experienced antibody-mediated rejection within 2 weeks of transplantation, which was successfully reversed. There has been no late rejection. Allograft function was similar to our live-donor ABO compatible transplant patients receiving a similar steroid sparing regime (12-month mean creatinine 131±15 &mgr;mol/L vs. 138±48 &mgr;mol/L; mean CrCl 63.2±22 mL/min vs. 56.7±20 mL/min). Conclusions. This study shows that ABOi live-donor transplantation can be successfully accomplished using a steroid-sparing protocol.

Expanding the Donor Pool: Living Donor Nephrectomy in the Elderly and the Overweight

Background Increasing demand for donor kidneys, in parallel with trends toward more elderly and obese populations, make it important to continuously review donor pool inclusion criteria. Acceptance of elderly and obese living donors remains controversial, with a higher incidence of comorbidity and the greater risk of postoperative complications sighted as reasons for caution. Drawing on our center’s experience, we aim to determine whether older age and obesity are in fact associated with greater perioperative risk, and longer term complications in donors undergoing nephrectomy. Methods Three hundred eighty-three living donor nephrectomies conducted at one of the United Kingdom’s largest transplant units over the last 5 years were stratified into groups according to age and body mass index. Perioperative endpoints and postdonation follow-up data collected at 6-to-12-monthly intervals were analyzed and compared. Results No significant differences in operative parameters, including operative time and estimated blood loss, were reported between groups. Rates of early postoperative complications were not significantly different, although subgroup analysis showed a higher incidence of respiratory complications at the extremes of obesity (body mass index ≥40 kg/m2). On follow-up, renal function parameters showed significant change postnephrectomy, but between-group variation was not significant. Mortality and major complication rates were comparably low in all groups of study. Conclusions In our unit’s experience, nephrectomy in selected donors who may otherwise have been precluded from participation on account of their age or weight, is feasible and associated with perioperative and longer term outcomes comparable with their younger nonobese counterparts. It provides a basis for informed consent of “extended criteria” donors.

The magnitude and time course of changes in mycophenolic acid 12-hour predose levels during antibiotic therapy in mycophenolate mofetil-based renal transplantation.

There is increasing evidence that monitoring predose plasma levels of mycophenolic acid (MPA) is of benefit in renal transplant recipients treated with mycophenolate mofetil (MMF). Concomitant treatment with oral antibiotics leads to a 10% to 30% reduction in MPA area under the curve (AUC)0-12, probably by reducing enterohepatic recirculation (EHR). Because of the timing of EHR (6 to 12 hours postdose), the magnitude of predose MPA level reduction may be disproportionately larger than that of AUC0-12. However, changes in predose MPA levels and the time course over which these changes occur and resolve during antibiotic treatment have not been studied. The purpose of this study was to define the extent and time course of MPA predose level reduction during antibiotic therapy. A total of 64 MMF-treated renal transplant recipients (with tacrolimus cotherapy) were prospectively studied. Clinically indicated cotherapy with either oral ciprofloxacin or amoxicillin with clavulanic acid resulted in a reduction in 12 hour predose MPA level to 46% of baseline within 3 days of antibiotic commencement. No demographic or biochemical variables were associated with the magnitude of MPA level reduction. No further fall in MPA level was seen by day 7, but MPA levels recovered spontaneously to 79% of baseline after 14 days of antibiotics. Levels normalized within 3 days of antibiotic cessation. No changes in daily MMF dose (normalized for body weight) were made during antibiotic treatment. This data should help the clinician to recognize the extent of MPA predose level reduction during antibiotic therapy, and to avoid inappropriate MMF dose escalation and potential risk of toxicity.

Postanastomotic Transplant Renal Artery Stenosis: Association With De Novo Class II Donor‐Specific Antibodies

In this study, we analyze the outcomes of transplant renal artery stenosis (TRAS), determine the different anatomical positions of TRAS, and establish cardiovascular and immunological risk factors associated with its development. One hundred thirty‐seven of 999 (13.7%) patients had TRAS diagnosed by angiography; 119/137 (86.9%) were treated with angioplasty, of which 113/137 (82.5%) were stented. Allograft survival in the TRAS+ intervention, TRAS+ nonintervention and TRAS− groups was 80.4%, 71.3% and 83.1%, respectively. There was no difference in allograft survival between the TRAS+ intervention and TRAS− groups, p = 0.12; there was a difference in allograft survival between the TRAS− and TRAS+ nonintervention groups, p < 0.001, and between the TRAS+ intervention and TRAS+ nonintervention groups, p = 0.037. TRAS developed at the anastomosis, within a bend/kink or distally. Anastomotic TRAS developed in living donor recipients; postanastomotic TRAS (TRAS‐P) developed in diabetic and older patients who received grafts from deceased, older donors. Compared with the TRAS− group, patients with TRAS‐P were more likely to have had rejection with arteritis, odds ratio (OR): 4.83 (1.47–15.87), p = 0.0095, and capillaritis, OR: 3.03 (1.10–8.36), p = 0.033. Patients with TRAS‐P were more likely to have developed de novo class II DSA compared with TRAS− patients hazard ratio: 4.41 (2.0–9.73), p < 0.001. TRAS is a heterogeneous condition with TRAS‐P having both alloimmune and traditional cardiovascular risk factors.