Alan C. Farney

Increased Rates of Donation With Laparoscopic Donor Nephrectomy

ObjectiveTo examine the impact of laparoscopic nephrectomy and recipient education on the proportion of kidney recipients who could identify a potential live donor, and on the live donor (LD) transplantation rate. Summary Background DataLaparoscopic donor nephrectomy (LDN) results in less postoperative surgical pain, a shorter hospital stay, and quicker recovery than the standard open donor nephrectomy (ODN). The authors hypothesized that the availability of this less invasive surgical technique would enhance the willingness of family and friends to donate. MethodsThe study population consisted of 3,298 end-stage renal disease patients referred for kidney transplant evaluation between November 1991 and February 2000, divided into three groups. The first group received no formal LD education and had only ODN available. The second group received formal education about the LD process and had only ODN available. The third group had both formal LD education and LDN available. Records were examined to determine what proportion of each group had any potential donors tissue-typed, and the rate at which they received an LD transplant. ResultsBefore LDN availability and formal LD education, only 35.1% of referrals found a potential donor, and only 12.2% received an LD transplant within 3 years. Institution of a formal education program increased the volunteer rate to 39.0%, and 16.5% received an LD transplant. When LDN became available, 50% of patients were able to find at least one potential donor, and within 3 years 24.7% received an LD transplant. Regression analysis indicated that availability of LDN was independently associated with a 1.9 relative risk of receiving an LD transplant. Kaplan-Meier death-censored 1- and 3-year graft survival rates for ODN transplants were 95.8% and 90.6%, versus 97.5% and 94.8% for LDN. ConclusionsThe availability of LDN and an LD family education program has doubled the live donor transplantation rate, and outcomes remain excellent.

Laparoscopic versus open donor nephrectomy: comparing ureteral complications in the recipients and improving the laparoscopic technique.

BACKGROUND Laparoscopic live donor nephrectomy (LDN) is a recently developed procedure, the performance of which needs to be studied. Given the reported advantages in the donors, this study looks at graft outcome and ureteral complications in recipients of kidneys procured by open donor nephrectomy (ODN) versus LDN. METHODS The LDN recipients consisted of 193 patients since 3/27/96. A total of 168 ODN recipients from 1991 to 1998 served as controls. Immunosuppression protocols were similar for both groups. RESULTS Two-year graft survival for LDN and ODN was 98% and 96%, respectively. Two-year patient survival for LDN and ODN was 98% and 97%, respectively. The incidence of delayed graft function and mean serum creatinine at 3 and 12 months was similar in both groups. However, the number of ureteral complications that required operative repair was significantly higher for LDN recipients compared to ODN recipients, 7.7% (n=15) vs. 0.6% (n=1) respectively (P=0.03). Ureteral stenting was required in an additional 3.1% (n=6) of LDN and 2.4% (n=4) of ODN (P=NS). There was, however, a learning curve with time. For the first 130 LDN patients, a total of 20 ureteral complications were recorded, whereas only one occurred in the more recent 63 patients (P=0.03). CONCLUSIONS The higher ureteral complication rate in LDN recipients has improved over time as technical causes have been identified. We have noted significant improvement in ureteral viability by using the endogastrointestinal anastomosis instrument on the ureter and peri-ureteral tissue. LDN is therefore an excellent alternative to ODN. Identification of hazards unique to this technique is critical before its broader application.

A high panel-reactive antibody rescue protocol for cross-match-positive live donor kidney transplants.

Background. Alloimmunization can present a virtually insurmountable barrier to kidney transplantation. Past protocols to desensitize patients using plasmapheresis and cyclophosphamide have not been broadly applied because of the fear of complications, including high rates of immunologic failure. Methods. Fifteen patients with a positive donor-recipient cross-match were desensitized with plasmapheresis to permit live donor (LD) transplantation under newer maintenance immunosuppressants. Pretransplant the patients received plasmapheresis three times weekly for a planned maximum of six treatments, plus intravenous hyperimmune globulin, tacrolimus, mycophenolate mofetil, and prednisone. Patients who were successfully desensitized and received transplants were given 10 days of OKT3 postoperatively. Results. Eleven of the 15 patients became anti-human globulin cross-match-negative after one to five plasmapheresis treatments and underwent LD transplantation. Relatively low initial titers of donor-specific antibody were predictive of successful attainment of a negative cross-match. Few side effects and rejection episodes were observed. All transplant patients remain dialysis-free after 3–26 months of follow-up. Conclusion. A positive cross-match is not necessarily a contraindication to LD transplantation, especially for patients with low donor-specific alloantibody titers.

Superiority of portal venous drainage over systemic venous drainage in pancreas transplantation: a retrospective study.

ObjectiveTo compare portal and systemic venous drainage of pancreas transplants and demonstrate an immunologic and survival superiority of portal venous drainage. Summary Background DataTraditionally, solitary pancreas transplants have been performed using systemic venous and bladder drainage, but more recently, the advantages of enteric drainage have been well documented. Although physiologic benefits for portal venous drainage have been described, the impact of portal venous drainage, especially with solitary pancreas transplants, has yet to be determined. MethodsSince August 1995, 280 pancreas transplants with enteric duct drainage were analyzed. One hundred and seventeen were simultaneous pancreas and kidney (SPK), 63 with systemic venous drainage (SV) and 54 with portal venous drainage (PV). The remainder were solitary transplants; 97 pancreas after kidney (PAK; 42 SV and 55 PV) and 66 transplants alone (PTA; 26 SV and 40 PV). Immunosuppressive therapy was equivalent for both groups. ResultsThe groups were similar with respect to recipient characteristics and HLA matching. Thirty-six month graft survival for all transplants was 79% for PV and 65% for SV (P = .008). By category, SPK graft survival was 74% for PV and 76% for SV, PAK graft survival was 70% for PV and 56% for SV, and PTA graft survival was 84% for PV and 50% for SV. The rate of at least one rejection episode was also significantly higher in the SV group. At 36 months, for all pancreas transplants, the rejection rate was 21% for PV and 52% for SV (P < .0001). For SPK, rejection rates were 9% for PV and 45% for SV. For PAK, rejection rates were 16% for PV and 65% for SV, and for PTA 36% for PV and 51% for SV. The rejection rates for kidneys following SPK were also lower in the PV group (26% versus 43% for SV). Furthermore, the grades of rejection were milder in PV for all transplants (P = .017). By multivariate analysis, portal venous drainage was the only parameter that significantly affected rejection. ConclusionGraft survival and rejection is superior for PV. These clinical findings are consistent with published reports of experimentally induced portal tolerance and strongly argue that PV drainage should be the procedure of choice for pancreas transplantation.

Pancreas transplantation: the histologic morphology of graft loss and clinical correlations.

Background. Graft losses due to leaks, bleeding, thrombosis, infections, and early pancreatitis are grouped together under the category of technical failure. Among these complications, massive vascular thrombosis continues to be the most important cause of early graft loss due to technical failure. Pathological evaluation of most allografts lost early in the posttransplantation period shows vascular thrombosis with associated proportional parenchymal necrosis. The morphological findings in allografts that are considered to be lost due to technical failure has not been systematically addressed. In particular, the role of acute rejection in early graft loss has not been well studied. Methods. Seventy-four consecutive pancreas graft pancreatectomies were studied histologically to evaluate for thrombosis (recent versus organized), type of vessel involved by thrombosis (arteries, veins, or both), acute rejection grade, chronic rejection grade, endotheliitis, transplant arteritis, coagulation necrosis, acute pancreatitis, presence of infectious organisms, transplant (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta islet cells, and immunoglobulin and complement deposition. The histological findings were correlated with donor and recipient data as well as clinical presentation. Results. In 23 out of 39 grafts lost in the first 4 weeks posttransplantation, the only pathological changes found were vascular thrombosis and bland ischemic parenchymal necrosis. In these cases, no underlying vascular pathology or any other specific histological change was identified. Most of these grafts (78%) were lost in less than 48 hr and all in the first 2 weeks posttransplantation. Massive vascular thrombosis occurring in an otherwise histologically normal pancreas was the most common cause of graft loss in the first 4 weeks posttransplantation (59%). In most of the remaining cases (33%), although the clinical presentation suggested technical failure, there was clear histological evidence that the massive thrombosis resulted from vascular injury due to immune damage (acute and hyperacute rejection). Increased incidence of early graft thrombosis was seen in grafts from older donors and longer cold ischemia times. After the first month posttransplantation, graft pancreatectomies revealed a wider variety of pathological processes that included severe acute rejection, combined acute and chronic rejection, chronic rejection, and infections. Acute and chronic vascular thrombosis in large and small vessels was commonly seen at all times posttransplantation; chronic, organized thrombosis was strongly associated with chronic rejection. Conclusions. (a) Early acute thrombosis occurring in a histologically normal pancreas defines a true technical failure. This study showed that acute rejection leading to massive thrombosis, which clinically simulates technical failure, results in a significant proportion of early graft losses. (b) Systematic histological evaluation of failed grafts is absolutely necessary for the accurate classification of the cause of graft loss. (c) There is morphological evidence that chronically ongoing thrombosis is an important, common, contributing factor for late graft loss.

Simultaneous Cadaver Pancreas Living-Donor Kidney Transplantation: A New Approach for the Type 1 Diabetic Uremic Patient

ObjectiveTo review the authors’ experience with a new approach for type I diabetic uremic patients: simultaneous cadaver-donor pancreas and living-donor kidney transplant (SPLK). Summary Background DataSimultaneous cadaver kidney and pancreas transplantation (SPK) and living-donor kidney transplantation alone followed by a solitary cadaver-donor pancreas transplant (PAK) have been the transplant options for type I diabetic uremic patients. SPK pancreas graft survival has historically exceeded that of solitary pancreas transplantation. Recent improvement in solitary pancreas transplant survival rates has narrowed the advantage seen with SPK. PAK, however, requires sequential transplant operations. In contrast to PAK and SPK, SPLK is a single operation that offers the potential benefits of living kidney donation: shorter waiting time, expansion of the organ donor pool, and improved short-term and long-term renal graft function. MethodsBetween May 1998 and September 1999, the authors performed 30 SPLK procedures, coordinating the cadaver pancreas transplant with simultaneous transplantation of a laparoscopically removed living-donor kidney. Of the 30 SPLKs, 28 (93%) were portally and enterically drained. During the same period, the authors also performed 19 primary SPK and 17 primary PAK transplants. ResultsOne-year pancreas, kidney, and patient survival rates were 88%, 95%, and 95% for SPLK recipients. One-year pancreas graft survival rates in SPK and PAK recipients were 84% and 71%. Of 30 SPLK transplants, 29 (97%) had immediate renal graft function, whereas 79% of SPK kidneys had immediate function. Reoperative rates, early readmission to the hospital, and initial length of stay were similar between SPLK and SPK recipients. SPLK recipients had a shorter wait time for transplantation. ConclusionsEarly pancreas, kidney, and patient survival rates after SPLK are similar to those for SPK. Waiting time was significantly shortened. SPLK recipients had lower rates of delayed renal graft function than SPK recipients. Combining cadaver pancreas transplantation with living-donor kidney transplantation does not harm renal graft outcome. Given the advantages of living-donor kidney transplant, SPLK should be considered for all uremic type I diabetic patients with living donors.

A decade of experience with renal transplantation in African-Americans.

ObjectiveTo evaluate the strategies instituted by the authors’ center to decrease the time to transplantation and increase the rate of transplantation for African-Americans, consisting of a formal education program concerning the benefits of living organ donation that is oriented to minorities; a laparoscopic living donation program; use of hepatitis C-positive donors in documented positive recipients; and encouraging vaccination for hepatitis B, allowing the use of hepatitis B core Ab-positive donors. Summary Background DataThe national shortage of suitable kidney donor organs has disproportional and adverse effects on African-Americans for several reasons. Type II diabetes mellitus and hypertension, major etiologic factors for end-stage renal disease, are more prevalent in African-Americans than in the general population. Once kidney failure has developed, African-Americans are disadvantaged for the following reasons: this patient cohort has longer median waiting times on the renal transplant list; African-Americans have higher rates of acute rejection, which affects long-term allograft survival; and once they are transplanted, the long-term graft survival rates are lower in this population than in other groups. MethodsFrom March 1990 to November 2001 the authors’ center performed 2,167 renal transplants; 944 were in African-Americans (663 primary cadaver renal transplants and 253 primary Living donor renal transplants). The retransplants consisted of 83 cadaver transplants and 17 living donor transplants. Outcome measures of this retrospective analysis included median waiting time, graft and patient survival rates, and the rate of living donation in African-Americans and comparable non-African-Americans. Where applicable, data are compared to United Network for Organ Sharing national statistics. Statistical analysis employed appropriate SPSS applications. ResultsOne- and 5-year patient survival rates for living donor kidneys were 97.1% and 91.3% for non-African-Americans and 96.8% and 90.4% for African-Americans. One- and 5-year graft survival rates were 95.1% and 89.1% for non-African-Americans and 93.1% and 82.9% for African-Americans. One- and 4-year patient survival rates for cadaver donor kidneys were 91.4% and 78.7% for non-African-Americans and 92.4% and 80.2% for African-Americans. One- and 5-year graft survival rates for cadaver kidneys were 84.6% and 73.7% for non-African-Americans and 84.6% and 68.9% for African-Americans. One- and 5-year graft and patient survival rates were identical for recipients of hepatitis C virus-positive and anti-HBc positive donors, with the exception of a trend to late graft loss in the African-American hepatitis C virus group due to higher rates of noncompliance, an effect that disappears with censoring of graft loss from that cause. The cadaveric renal transplant median waiting time for non-African-Americans was 391 days compared to 734 days nationally; the waiting time for African-Americans was 647 days compared to 1,335 days nationally. When looking at all patients, living and cadaver donor, the median waiting times are 220 days for non-African-Americans and 462 days for African-Americans. ConclusionsPrograms specifically oriented to improve volunteerism in African-Americans have led to a marked improvement in overall waiting time and in rates of living donation in this patient group. The median waiting times to cadaveric renal transplantation were also significantly shorter in the authors’ center, especially for African-American patients, by taking advantage of the higher rates of hepatitis C infection and encouraging hepatitis B vaccination. These policies can markedly improve end-stage renal disease care for African-Americans by halving the overall waiting time while still achieving comparable graft and patient survival rates.

Solitary renal allografts from pediatric cadaver donors less than 2 years of age transplanted into adult recipients

Background. Transplantation of solitary pediatric renal allografts from donors 2 years of age or younger into adult recipients is controversial. Methods. Between 1998 and 2001, 15 solitary renal allografts from pediatric donors 2 years of age or younger were transplanted into adult recipients. Thirty-three en bloc renal allografts transplanted between 1994 and 2001 were used for comparison. En bloc kidneys were considered for separation if they measured greater than or equal to 6 cm in length. Renal function (creatinine clearance [CrCl]) was estimated using the Cockroft-Gault formula. Results. Two-year graft survival for the solitary and en bloc groups were 93% and 77%, respectively (P =0.405). Five grafts were lost because of arterial thrombosis (four en bloc and one solitary). Ureteral complications occurred in three grafts in the en bloc group. One-year postoperative CrCl of the surviving solitary (n=14) and en bloc (n=26) grafts were 51.4±26.2 mL/min and 55.1±27.5 mL/min (P >0.05), respectively. Donor weight and kidney length were greater in the solitary group (14.3±3.5 kg and 6.3±0.4 cm, respectively) compared with the en bloc group (10.8±2.6 kg and 5.9±0.3 cm, respectively) (P =0.001 and P <0.001). Conclusions. Separation of en bloc pairs into solitary allografts can be considered when the graft measures greater than or equal to 6 cm in length and donor weight is greater than or equal to 14 kg. The transplantation of solitary pediatric kidneys into adult recipients is successful, and the majority of pediatric en bloc allografts can be separated before transplantation.

Mycophenolate mofetil reduces the risk of acute rejection less in African-American than in Caucasian kidney recipients

BACKGROUND Multicenter clinical trials have shown that mycophenolate mofetil (MMF) reduces the risk of acute rejection, but it is unknown whether African-Americans constitute a subgroup of recipients less likely to benefit from MMF. METHODS This study compared the acute rejection rates within 6 months of kidney transplantation in MMF-treated transplant patients with those on azathioprine (AZA) at a single center. The study population consisted of 353 consecutive recipients of cadaver or living donor kidney transplants. African-Americans constituted 43% of the patients on AZA and 49% of the patients on MMF. Variables used in a Cox regression analysis included MMF immunosuppression, recipient race, type of transplant, delayed graft function, postoperative immune induction, average cyclosporine trough level, and HLA mismatch. RESULTS Significantly fewer patients on MMF experienced a biopsy-proven rejection episode than those treated with AZA (24% vs. 42%, respectively; relative risk [RR]=0.57, P=0.001). This decrease in risk was greater in Caucasian transplant recipients (MMF vs. AZA: 16% vs. 46%, RR=0.35, P < 0.001) than in African-American patients (32% vs. 36%, RR=0.88, P=0.6). Within each race stratum, the mean cyclosporine trough levels averaged over 2-week intervals were nearly identical for AZA- compared with MMF-treated patients. In the regression model, the effect of MMF on the incidence of rejection was again less in African-American than in Caucasian patients. CONCLUSIONS Kidney recipients treated with MMF have a significantly lower risk of acute rejection within 6 months of transplantation than those given AZA. This reduction in risk is significantly less in African-American recipients than Caucasians.

The shrinking renal replacement therapy 'break-even' point

BACKGROUND This study examines the current cost of live donor (LD) transplantation at our institution, and compares it with that of dialysis. METHODS The study population consisted of 184 consecutive adult recipients of laparoscopically procured LD kidney transplants. Cost-containment measures instituted during this series included elimination of routine postoperative antilymphocyte induction and an accelerated discharge clinical pathway with planned discharge of the recipient on postoperative day (POD) 2. Costs of the transplants to Medicare were estimated from hospital charges, readmission rates, and immunosuppressant usage. These were compared with published costs of dialysis to Medicare in terms of a fiscal transplant-dialysis break-even point. RESULTS Kaplan-Meier patient and graft survival rates at 1 year were 97 and 93%, respectively. Among patients followed for at least 90 days and treated with no induction and either cyclosporine-mycophenolate mofetil or tacrolimus-mycophenolate mofetil, acute rejection rates were low (27.6 and 13.9%, respectively). In the last 124 patients, 32.3% were discharged by POD 3 and 71.8% by POD 6, with corresponding mean transplant hospital charges (excluding organ acquisition) of