The contribution of donor quality to differential graft survival in African American and Caucasian renal transplant recipients.

Although a number of factors contributing to the disparity in graft survival between African American (AA) and Caucasian kidney transplant recipients have been described, the role of donor quality is less well understood. This study was undertaken to determine the impact of donor quality differences on this disparity, based on review of UNOS (United Network for Organ Sharing) data on deceased donor renal transplantation from 2000 to 2010. Donor quality was determined by the kidney donor risk index (DRI), and was compared between AA and Caucasian recipients. There were 33,405 Caucasians and 22,577 African Americans in the study, with mean DRI of 1.17 versus 1.27 (p < 0.001), respectively. In analysis 2,446 recipients of each race matched by propensity scoring (based on medical, socioeconomic and immunologic covariates), mean DRI was 1.25 for Caucasians and 1.28 (p = 0.02) for AA. The hazard ratio (HR) for graft failure associated with AA race was 1.8 (p < 0.001) on unadjusted analysis, and decreased to 1.6 (p < 0.001) after matching for DRI. These results indicate a significant disparity in quality of kidneys received by African Americans, which propensity analysis indicates is partially explained by differences in medical, immunologic and socioeconomic factors. Furthermore, this difference in donor quality partially accounts for poorer graft survival in African Americans.

Cytomegalovirus disease in African-American kidney transplant patients.

BACKGROUND: Cytomegalovirus (CMV) disease is a serious infection after kidney transplantation. The risk factors and the impact of CMV disease in African-American (AA) kidney transplant patients have not been well characterized. METHODS: We performed a retrospective analysis on 448 AA patients transplanted between 1996 and 2005. A 3-month universal chemoprophylaxis with ganciclovir or valganciclovir was administered to CMV donor-positive/recipient-negative (D+/R-) patients and to those treated with anti-thymocyte globulin for rejection, but not routinely to those with other D/R serostatus. RESULTS: A total of 31 AA patients (7%) developed clinical CMV disease. Compared with other D/R serostatus groups, the D+/R- group had the highest 3-year cumulative incidence of CMV disease (16.9% vs. 6.3% in D+/R+, 4.9% in D-/R+, and 2.4% in D-/R-). The D+/R- group also had the worst 3-year death-censored allograft survival (75% vs. 92% in D+/R+, 94% in D-/R+, and 96% in D-/R-, log-rank P = 0.01). Multivariate analysis found that D+/R- serostatus (odds ratio [OR] 5.4, 95% confidence interval [CI] 0.6-48.2, P = 0.003) and donor age > 60 years (OR 9.1, 95% CI 1.3-65, P = 0.03) were independent risk factors for CMV disease. CONCLUSION: The D+/R- group has the highest incidence of CMV disease and the worst 3-year renal allograft survival despite 3-month universal prophylaxis. Prolonged chemoprophylaxis may be needed to prevent the late development of CMV disease and to improve allograft survival in the high-risk group of AA kidney transplant recipients.

Making enhanced recovery the norm not the exception.

BACKGROUND: Enhanced Recovery After Surgery ("STAAR" in our system) is multimodal care focused on the reduction of physiological and psychological stress. While enhanced recovery is well established in colorectal surgery, and there is evidence for effectiveness in other surgical disciplines, to date widespread use is limited. METHOD: We implemented a Lean process that, within 12 months, expanded STAAR to 13 surgical services lines involving >130 surgeons, and impacting the care of >6000 surgical patients/year. RESULTS: Implementation involved educational and administrative meetings (279 in the first 6 months) and rounding. Use of STAAR was defined as >60% compliance. LOS was reduced up to 40%, mortality index and transfusion decreased 67% and 23% respectively. Case mix index increased 17%. Readmission rates, infections, ER visits were not increased. CONCLUSION: Using a Lean process focused on value, STAAR protocols became the standard rather than the exception. Time investment by senior surgical leadership was extensive.

Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: a pilot study in de novo kidney allograft recipients.

This randomized, pilot study compared the Janus kinase inhibitor CP-690,550 (15 mg BID [CP15] and 30 mg BID [CP30], n = 20 each) with tacrolimus (n = 21) in de novo kidney allograft recipients. Patients received an IL-2 receptor antagonist, concomitant mycophenolate mofetil (MMF) and corticosteroids. CP-690,550 doses were reduced after 6 months. Due to a high incidence of BK virus nephropathy (BKN) in CP30, MMF was discontinued in this group. The 6-month biopsy-proven acute rejection rates were 1 of 20, 4 of 20 and 1 of 21 for CP15, CP30 and tacrolimus groups, respectively. BKN developed in 4 of 20 patients in CP30 group. The 6-month rates of cytomegalovirus disease were 2 of 20, 4 of 20 and none of 21 for CP15, CP30 and tacrolimus groups, respectively. Estimated glomerular filtration rate was >70 mL/min at 6 and 12 months (all groups). NK cells were reduced by

Long-term outcome of single pediatric donor kidney transplants between African-American and non-African-American adults.

BACKGROUND: African-American (AA) ethnicity has been considered a risk factor for graft loss after kidney transplant. The long-term graft survival of single pediatric donor kidney transplants in AA adults has not been reported. METHODS: We retrospectively compared the outcome of 43 AA and 32 non-African-American (NAA) adults transplanted with single pediatric kidneys from donors aged 10 years or less in our center. A combination of tacrolimus, mycophenolic acid and steroid was utilized as the maintenance therapy. RESULTS: Similar immunosuppressive dose and targeted level were achieved between the AA and the NAA groups. Median body weight (BW) of donors was 20 kg (8 - 36) in the AA group and 19 kg (8.5 - 35) in NAA group. There was no statistically significant difference in the incidence of rejection between the AA and NAA groups (26 vs. 16%, p = 0.45). The surgical complications, delayed graft function, and development of proteinuria and focal and segmental glomerulosclerosis (FSGS) were similar in both groups. The patient and graft survivals in the AA group were slightly higher compared to the NAA group. The death-censored analysis demonstrated no difference in graft survival between the AA and NAA groups (p = 0.90): 86 vs. 82% at 1 year, 70 vs. 71% at 3 years, and 62 vs. 64% at 5 years. CONCLUSIONS: Single pediatric donor kidney transplant in AA adults can be achieved with acceptable complications and equivalent long-term outcomes as in NAA adults in the era of potent immunosuppressive regimen.

Diffuse glomerular basement membrane lamellation in renal allografts from pediatric donors to adult recipients.

The transplantation of kidneys from pediatric cadaveric donors into adult recipients is performed in many centers. However, some studies indicate that the outcome of such renal transplants may be inferior compared with that of adult donors, particularly if the donor is an infant. Morphologic studies of failed pediatric donor kidneys in adult recipients describe various degrees of segmental or global glomerular sclerosis. The authors have performed ultrastructural examinations on such transplants and have identified six cases with diffuse irregular lamellation of the glomerular basement membrane (GBM), a change that may develop as early as 10 weeks after transplantation. The age of all donors was < or =6 years; three were infants. The incidence of the lesion was 9% at our institution in renal transplant patients who received a graft from donors <10 years old. Diffuse GBM lamellation has not been found in renal transplants from adult donors. Light microscopy showed various degrees of diffuse mesangial expansion, usually with segmental glomerular sclerosis. The patients had severe proteinuria. While recurrent focal segmental glomerular sclerosis (FSGS) has to be excluded, such diffuse GBM lamellation is generally not seen in recurrent FSGS cases. The pathogenesis of the lesion is most likely related to hyperperfusion injury of small pediatric donor kidneys grafted into adult recipients.

Baseline glomerular size as a predictor of function in human renal transplantation.

BACKGROUND: Nonimmune mechanisms have been implicated in chronic renal allograft injury. In experimental studies, a strong correlation exists between glomerular size and the degree of glomerular sclerosis that develops after subtotal nephrectomy. Therefore, we assessed the impact of glomerular maximal planar area (MPA) in baseline biopsy specimens of human renal allografts on later graft function. METHODS: The MPA was measured, by point counting and by computer planimetry, in postperfusion biopsy specimens from 96 allograft kidneys from nonhypertensive donors that had functioned for at least 2 years. Clinical data were analyzed throughout a follow-up period averaging 7.46+/-2.46 years. RESULTS: Both methods produced equivalent estimates of MPA. MPA proved to be a strong predictor of late renal allograft function, with a significant correlation (P = 0.02 to P < 0.01) between MPA at baseline and later serum creatinine level and creatinine clearance, beginning at 6 months after transplantation and persisting through follow-up. Creatinine level at discharge and occurrence of rejection were also independent predictors, whereas donor age, gender and race, cold ischemia time, cadaveric versus living donor, delay in initial function, and HLA mismatch did not predict clinical outcome. CONCLUSION: Larger glomeruli at baseline, measured by a simple point-counting technique, provide an early predictor of risk for late allograft dysfunction and may identify a subpopulation of patients in whom treatment to prevent/ameliorate glomerular enlargement and/or hypertension may be efficacious.

Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant therapy.

The effectors of cell death in allograft rejection are poorly understood. Oxygen derived free radicals (ODFR) may participate in graft destruction. We examined the impact of the antioxidants ascorbic acid (AA) and alpha-tocopherol (AT) with low dose CsA on rat cardiac allograft survival. Lewis rats that had undergone heterotopic abdominal cardiac transplantation with Wistar-Furth allografts (day 0) were divided into 6 groups. Group 1 was the control group; groups 2 and 3 received AA (1200 mg/kg), and groups 4 and 5 received AT (800 IU/kg) by gavage daily until rejection. Groups 3, 5, and 6 were given CsA (2.5 mg/kg i.m.) days 1-15. Allograft rejection times (in days) were 7.7 +/- 1, 10.3 +/- 1.5 (P < 0.01 vs. group 1), 37.1 +/- 6.4 (P < 0.01 vs. group 1, P = 0.0004 vs. group 6), 9.0 +/- 1.4, 26.5 +/- 3.6 (P < 0.01 vs. group 1, P < 0.03 vs. group 6), and 20 +/- 4.9 (P < 0.01 vs. group 1) for groups 1, 2, 3, 4, 5, and 6. To assess the impact of AA on ODFR production, chemiluminescence was performed on zymosan-activated Lewis whole blood from control rats and rats administered AA. AA significantly decreased peak chemiluminescence (P < 0.05) as compared with nontreated rats indicating effective ODFR scavenging. To determine whether AA and AT inhibit lymphocyte stimulation, mixed lymphocyte response testing was performed with irradiated Wistar-Furth lymphocytes as stimulator cells for Lew responder cells from rats treated as groups 3, 5, and 6. CsA significantly suppressed (P < .05) proliferation as compared with untreated controls. Neither AA nor AT enhance CsA's immunosuppressive effect by mixed lymphocyte response testing. In summary, prolongation of allograft survival with antioxidants AA and AT does not result from abrogation of lymphocyte responsiveness or alteration in CsA bioavailability. Rather, these data suggest that ODFR are involved in allograft destruction and support a role for effective antioxidant therapy in the treatment of allograft rejection.

Extrapancreatic pseudoaneurysm after pancreas transplantation.

Pseudoaneurysms after pancreatic transplantation are an infrequent event. Repair usually involves removal of the transplant. We describe a patient with a pseudoaneurysm associated with pancreatic transplantation. The pseudoaneurysm originated from the external iliac artery distal to the donor Y-graft anastomosis. Diagnosis was made by duplex ultrasound. Surgical repair was effected through a retroperitoneal incision enabling vascular control. The patient has done well postoperatively, and with 1-year follow-up, continues to have normal renal and pancreatic allograft function.

Laparoscopic living donor nephrectomy: advantages of the hand-assisted method.

INTRODUCTION: The laparoscopic technique for living donor nephrectomy is a technically difficult procedure that has not yet gained widespread acceptance in the transplant community. The procedure may be more acceptable if alterations to the technique made it easier to perform and decreased operative times. METHODS: In August 1998, we altered the laparoscopic procedure to include the use of a device allowing hand assistance. Subsequently, all living donor nephrectomies have been done using the hand-assisted method. In this article, the results of 10 cases performed using the original laparoscopic technique are compared with the results of 12 cases using the hand-assisted technique, and a brief description of modifications to the original technique is given. RESULTS: No patients where turned down as living donors, and no contraindications to the pure or hand-assisted laparoscopic techniques where found. The hand-assisted technique significantly reduced the operative time (2.02+/-0.44 vs. 3.12+/-0.36 hr, P<0.05) and the warm ischemic time (1.23+/-0.54 vs. 3.91+/-0.53 min, P<0.05). The length of stay and recovery time to normal activities were not different between the pure laparoscopic and hand-assisted groups. CONCLUSION: The advantages of the hand-assisted technique include the ability to use tactile sense to facilitate dissection, retraction, and exposure. In addition, the final stages of vascular stapling and kidney removal are more sure and rapid. The modifications of the laparoscopic technique presented here provide measurable and subjective improvements to laparoscopic living donor nephrectomy. The hand-assisted method of laparoscopic nephrectomy may make the operation available to more transplant centers.

A prospective randomized comparison of quadruple versus triple therapy for first cadaver transplants with immediate function.

In January 1988, we initiated a prospective, randomized comparison of prophylactic antilymphoblast globulin (ALG; quadruple therapy) versus no prophylactic ALG (triple therapy) in the setting of immediate graft function (defined by a brisk diuresis and a 20% decline in serum creatinine within 24 hr). Recipients were stratified according to presence of diabetes and age greater or less than 50 years. Recipients on quadruple therapy (n = 61) received 7 days of prophylactic Minnesota ALG (5 mg/kg on day 1, 10 mg/kg on day 2, 20 mg/kg on days 3-7). CsA, 10 mg/kg/day, began on day 6. AZA began at 2.5 mg/kg/day and was adjusted according to white blood cell count. Recipients on triple therapy (n = 60) began immediate CsA, 10 mg/kg/day orally and AZA, 5 mg/kg/day, tapering to 2.5 mg/kg/day by day 8. Both groups received identical prednisone tapers beginning at 1 mg/kg/day, decreasing to 0.5 mg/kg/day by 2 weeks and to 0.15 mg/kg/day by 6 months. Demographic characteristics between groups were not different with respect to diabetes, age, sex, race, per cent panel-reactive antibodies (PRA), or HLA matching. Follow-up ranged from 2 to 4.5 years. Patient survival was 93% for the quadruple therapy group and 90% for triple therapy. Actuarial graft survival was 79% in the quadruple group and 72% in the triple group (P = 0.18). Graft loss due to rejection occurred in 6/61 receiving ALG versus 7/60 in the immediate CsA group. Three of 4 high PRA recipients in the immediate CsA group lost their grafts within 30 days compared with none in the ALG group. The mean time to graft loss was significantly longer for the quadruple therapy group (17 +/- 8 months) compared with the triple therapy group (4 +/- 5 months), P = 0.006. The total number of rejection episodes was similar for both groups (29/61 vs. 31/60), as was the number who were rejection free (51% vs. 47%). The use of OKT3 was also similar between groups (28% vs. 30%). The quadruple therapy group had a higher incidence of CMV infection: 20% vs. 7% (P < 0.05), but no grafts or patients were lost as a result. Serum Cr was not different at 1 and 12 months (1.5 and 1.6 vs. 1.6 and 1.7, respectively), nor were Cr clearances (63 and 68 vs. 60 and 63). Conclusion. Early initiation of oral CsA in the setting of immediate graft function is not associated with significant nephrotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Heterogeneity of glomerular size in normal donor kidneys: impact of race.

Glomerular size has been the subject of many studies and, in a number of settings, has a direct association with the development of glomerular sclerosis. However, the normal distribution of glomerular size has not been thoroughly evaluated in the general population in the United States. To address this issue, we analyzed the baseline biopsy specimens of 103 human donor kidneys to determine the maximal planar area (MPA) of the glomerular tuft in a heterogeneous human population. The MPA of each glomerulus was determined by measurement of sections through the vascular pole and/or origin of the proximal tubule, and was determined on each section by two methods: point counting and computer planimetry. There was very high agreement between these two methods. Multivariate analysis was used to identify significant correlates with MPA. Overall, younger donors had smaller glomeruli (P < 0.0001). Black donors had a larger MPA (23.4+/-8.6 mm2 x 10(-3)) than white donors (17.9+/-6.7 mm2 x 10(-3); P < 0.001), independent of donor age. MPA was not significantly different between genders. This heterogeneity in glomerular size may confound clinical studies if not recognized and may help explain differences in glomerular structure and function in response to injurious processes.

Microstimulation of the primate cerebellar vermis during saccadic eye movements.

The cerebellar vermal cortex in monkey was electrically stimulated through a microelectrode with brief pulse strains synchronized to the onset of selected saccadic eye movements. The delivery of these intrasaccadic microstimuli were randomly interposed in groups of saccadic eye movements made by trained monkeys to known target locations. The trajectory of the saccades with intrasaccadic stimuli were then compared to those made to the same target without stimulation. Contralaterally directed saccades were consistently slowed from their normal trajectory (normally at 12 ms after stimulus onset) and were made hypometric. Ipsilaterally directed saccades were not affected. Vertical eye movement components were also affected at some stimulating sites. Changing the stimulus train duration from 10 to 80 ms had no effect on the change in velocity or amount of dysmetria produced in contralateral saccades. Taken together these results suggest that a different set of cerebellar elements were being stimulated by the intrasaccadic mode as contrasted to stimulation at the same site at random times. Furthermore, the short period of time during an ongoing saccade presents a unique instant in which to test the relationship of various central structures to the saccadic system. Based on current concepts of the organization of the brainstem saccadic pulse generators, these data are interpreted to suggest that: (1) the cerebellar vermis has a rather direct influence on the contralateral saccade generator, (2) this influence can act to recode (diminish) the generator's representation of the size of motor error, (3) the effect occurs at a point in the generator where motor error is spatially coded.

Making hand-assisted laparoscopy easier: preventing CO2 leak.

Hand assistance has been a significant advance in making laparoscopy an easier and safer method for certain procedures such as nephrectomy. The value of this technique is realized when comparing patient outcomes (e.g., less postoperative pain, shorter hospital stay, quicker recovery time) with those of the standard open approaches. One reported disadvantage of the Pneumo Sleeve device for hand-assisted laparoscopy is leakage of CO2 gas from around the ring base. We describe in detail our technique to secure the Pneumo Sleeve to the abdomen in such a way as to prevent leakage of intraperitoneal gas and fluid.

Giant biliary cystadenoma: case report and literature review.

Biliary cystadenoma is a very rare cystic neoplasm of the liver. This tumor is insidiously progressive and usually presents in white females in their fifth decade. It has a characteristic appearance on ultrasound, computed tomography, and angiography. The exact etiology of these tumors is unknown, but several theories have been proposed. Historically these cystic tumors have been treated by a variety of techniques including aspiration, fenestration, internal drainage, and resection. Previously reported series have confirmed a >90 percent recurrence rate with anything less than complete excision. In addition biliary cystadenoma is a premalignant lesion and only surgical excision can differentiate it from its malignant counterpart, biliary cystadenocarcinoma.

Deceased donor management and demographic factors related to kidney allograft rejection and graft survival.

BACKGROUND: There is agreement that the number of organ donors and the number of organs recovered per donor are not maximized despite promotion of awareness and new guidelines for transplant teams. A single standard for donor management does not exist, in part because there is no consensus with respect to donor factors and management effect on transplant outcomes. METHODS: This retrospective study analyzed the long-term outcomes of 402 deceased donor kidney transplant recipients with respect to donor factors. This study differed from previous studies in that all recipients were treated with the same selection and immunosuppressive protocols. RESULTS: Factors associated with improved graft survival included cause of death, more organs donated, and lower peak sodium (P < .01). Delayed graft function (DGF) decreased if more organs were donated, but increased when the donor was given dopamine. Recipients of donor kidneys with higher final creatinine values were more likely to show DGF (P < .01). A decrease in acute rejection episodes was observed among patients whose donors had received dopamine, donated more organs, and had a shorter time between incision and cross clamp (P < .05). Kidneys from donors with a higher final creatinine displayed fewer rejection episodes; those with a higher peak creatinine experienced more rejection episodes (P < .05). CONCLUSION: The effect of donor variables on kidney transplant outcomes is important and may not be consistent with traditional expectations. Additional data collection and assessment of both short- and long-term transplant outcomes are critical to improve our understanding of the impact of deceased donor factors and management.