Measurement of hemodynamic and anatomic parameters in a swine arteriovenous fistula model.

PURPOSE: Although arteriovenous fistulae (AVFs) are currently the preferred mode of permanent hemodialysis access they do have significant problems due to initial non-maturation and a later venous stenosis. These problems appear to have been exacerbated following a push to increase AVF prevalence in the US. The reasons for both AVF non-maturation and the later venous stenoses are unclear but are thought to be related to abnormal hemodynamic wall shear stress (WSS) profiles. This technical note aims to describe the successful development of measurement techniques that can be used to establish a complete hemodynamic profile in a pig model with two different configurations of AVF. METHODS AND RESULTS: The curved and straight AVF configurations were created in an in vivo pig model. Flow and pressure in the AVFs were measured using the perivascular flow probes and Doppler flow wires while the pressure was recorded using a pressure transducer. The anatomical configuration was obtained using two different approaches: a) combination of intravascular ultrasound (IVUS) and angiograms, (b) 64 slice CT angiography. 3D models were reconstructed using image processing and computer modeling techniques. Numerical calculations were then performed by applying the measured flow and pressure data into the configurations to obtain the hemodynamic WSS profiles. CONCLUSION: The described methodologies will allow the calculation and optimization of WSS profiles in animal models. This information could then be translated to the clinical setting where it would have a positive impact on improving the early maturation rates of AVFs as well as reducing the late venous stenoses.

A prospective, pilot study of early corticosteroid cessation in high-immunologic-risk patients: the Cincinnati experience.

BACKGROUND: The first prospective trial of steroid withdrawal dedicated to high-immunologic-risk patients is reported herein. METHODS: Twenty-five patients were enrolled prospectively in an IRB-approved HIPAA-compliant protocol. Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12 ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The protocol for the next 15 patients was modified because of high acute rejection rates to include received T-cell-depleting antibody induction therapy with thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes were diagnosed by biopsy and graded using Banff '97 criteria. RESULTS: Twenty-five patients were enrolled and median follow-up was 402 days. Forty percent of recipients were black, 68% of patients were repeat transplant recipients, 68% received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute rejection, graft survival, and patient survival rates of 40%, 88%, and 96%, respectively, were observed for the duration of the study. Acute rejection occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute rejection rates fell to 27% when thymoglobulin was introduced (P = .1). CONCLUSIONS: This study supports our previous observations in a multivariate analysis of early CSWD patients, wherein polyclonal antibody induction therapy reduced acute rejection. High-immunologic-risk patients may be able to undergo early CSWD with acceptable rates of acute rejection.

African American renal transplant recipients benefit from early corticosteroid withdrawal under modern immunosuppression.

African Americans have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. Modern immunosuppression has reduced rejections and improved graft survival in African Americans and may allow successful corticosteroid withdrawal. Outcomes in 56 African Americans were compared to 56 non-African Americans enrolled in early withdrawal protocols. Results are reported as African American versus non-African American. Acute rejection at 1 year was 23% and 18% (P = NS), while patient and graft survival was 96% versus 98% and 91% versus 91% (P = NS), respectively. In conclusion, early withdrawal in African Americans is associated with acceptable rejection rates and excellent patient and graft survival, indicating that the risks and benefits of early withdrawal are similar between African Americans and non-African Americans. Additional followup is needed to determine long-term renal function, graft survival, and cardiovascular risk in African Americans with early steroid withdrawal.

Early steroid withdrawal does not increase risk for recurrent focal segmental glomerulosclerosis.

UNLABELLED: Experience with early corticosteroid withdrawal (CSWD) in renal transplant recipients with focal segmental glomerulosclerosis (FSGS) has not been previously reported. Since corticosteroids are used to treat primary FSGS, concern exists as to whether early CSWD regimens will be associated with an increased risk of FSGS recurrence posttransplant. The purpose of the present study was to evaluate the results of early CSWD in FSGS recipients and compare these results to a historic control group of FSGS patients who underwent renal transplantation under corticosteroid-based immunosuppression. METHODS: Forty-three patients with FSGS underwent renal transplantation with early CSWD. Results in these patients were compared to FSGS patients that underwent renal transplantation with chronic corticosteroid therapy. All rejection episodes were biopsy proven with grading by Banff criteria. Statistical analyses included Student's t test and chi square tests. RESULTS: Results in 43 patients with a median follow-up of 569 days were analyzed and compared to control patients. There was no significant difference in recurrent FSGS, time to recurrence, or graft loss. CONCLUSION: CSWD does not increase risk for recurrence of FSGS. These observations indicate that ECSW can be achieved in FSGS patients, thereby affording them the benefits of steroid elimination.

Pilot study of early corticosteroid elimination after pancreas transplantation.

UNLABELLED: Early corticosteroid withdrawal has recently been shown to be possible in recipients of simultaneous pancreas kidney transplants; however, its feasibility in solitary pancreas recipients has not been documented. In the present study, we provide evidence that early withdrawal can be achieved in pancreas as well as pancreas-kidney recipients. METHODS: Twenty type I diabetics underwent 13 pancreas-kidney transplants and 7 pancreas-only transplants with early withdrawal (methylprednisone 6-day taper). Additional immunosuppression consisted of tacrolimus, mycophenolate mofetil, and thymoglobulin induction (five doses). RESULTS: Transplants included 13 pancreas-kidney, 6 pancreas after kidney transplant, and 1 pancreas after islet transplant. Overall mean follow-up was 7.3 months. One episode of pancreas transplant rejection after pancreas-only transplant was detected on protocol biopsy without biochemical abnormalities. One renal allograft rejection occurred 65 days posttransplant in a pancreas-kidney recipient and was graded as a Banff IA rejection. A single pancreas graft loss occurred due to thrombosis 6 days after pancreas-kidney transplantation. CONCLUSIONS: These results indicate that relatively short thymoglobulin induction (five doses) with tacrolimus and mycophenolate mofetil can allow early withdrawal in both pancreas-kidney and pancreas-only transplant recipients.

Donor kidneys with small renal cell cancers: can they be transplanted?

INTRODUCTION: The purpose of this study was to determine whether incidentally discovered, small renal cell cancers (RCC) in donor kidneys can be excised and safely transplanted. METHODS: The Israel Penn International Transplant Tumor Registry database was searched and all small RCC that were identified and resected prior to transplantation of deceased and living donor kidneys were reviewed. Patient demographics, tumor characteristics, recurrence, and survival were examined. RESULTS: Fourteen kidneys were identified in which small RCC were noted at the time of procurement and where the tumors were excised ex vivo and then transplanted. Eleven kidneys were obtained from living related donors and three were from deceased donors. Median tumor size was 2 cm (range 0.5 to 4 cm). All 14 tumors were of histological Furhman grade II/VI (n = 8) or Furhman grade I/VI (n = 6). All kidneys had pathologically confirmed negative margins. The mean age of the recipients was 40.8 +/- 9.2 years, with the majority being men (11 men; 3 women). Median follow-up for this group was 69 months (range 14 to 200 months). There have been no recurrences of tumor in these recipients and the 1-, 3-, and 5-year patient and graft survivals are 100%, 100%, and 93%. CONCLUSIONS: These data represent the only data available (to our knowledge) on this issue. This experience indicates that donor kidneys with small, incidental RCC and low histological grade (Furhman grade I and II/IV) can be managed with excision and transplantation, with a low risk of tumor recurrence in the recipient.

Pancreas transplantation in Ohio: a 15-year outcomes analysis.

BACKGROUND: Beginning in 1984, all pancreas transplantations performed in the state of Ohio have been tracked by the Ohio Solid Organ Transplantation Consortium (OSOTC). In this study the outcomes of these transplantations were compared across 3 eras to determine whether increasing experience has been beneficial. METHODS: Between July 1984 and December 1999, 765 kidney-pancreas (KPTx) and 76 pancreas only (Ptx) transplantations were performed. Outcomes measures for these 841 pancreas transplantations were compared over 3 eras, 1984 to 1989, 1990 to 1994, and 1995 to 1999. RESULTS: One-year patient survivals for KPTx patients were 87%, 92%, and 94% in the 3 eras, respectively. Graft survival at 1 year was also markedly improved between era 1 and era 3, increasing for PTx patients from 21% to 85% and for KPTx patients from 68% to 85%. Average waiting time increased from 132 to 318 days between era 1 and era 3. Conversely, average length of stay in hospital was significantly decreased from 34 to 18 days. The cost of the procedure, as measured by hospital charges, also decreased when compared in 1985 dollars as a technique to control for inflation. CONCLUSIONS: These data suggest that pancreas transplantation in Ohio has become a very successful and cost-effective therapeutic intervention for patients with type I diabetes with or without concomitant end-stage renal failure.

Immediate allograft dysfunction due to atheroembolic disease.

Atheroembolic disease is a known cause of renal failure following invasive vascular procedures in patients with atherosclerosis. It is, however, not generally associated with renal transplant dysfunction. We report on a case of donor-transmitted atheroembolic renal disease, which led to an immediate loss of the transplant kidney in the operating room. Risk factors associated with this condition and methods to prevent this complication are discussed.

Use of tacrolimus eliminates acute rejection as a major complication following simultaneous kidney and pancreas transplantation.

This retrospective study illustrates the efficacy of tracrolimus-based immunosuppression following simultaneous kidney and pancreas transplantation. Between March 1995 and December 1996, 24 simultaneous kidney and pancreas transplant recipients received tacrolimus-based maintenance immunosuppression. All patients received sequential therapy with an antilymphocyte agent, azathioprine, prednisone and tacrolimus. The dose of tacrolimus was adjusted to achieve a whole blood trough level of 8-15 ng/mL (IMx). The mean follow-up was 25 months with a median of 26 months (range 12-33 months). A rise in serum creatinine of > 20% over baseline was investigated with a renal biopsy, after mechanical causes for renal dysfunction had been excluded. Mean serum creatinine concentrations at 3, 6, 12, 18 and 24 months post-transplantation were 1.1, 1.2, 1.3, 1.3 and 1.3 mg/dL respectively. The blood glucose concentrations at the corresponding time period were 115, 94, 95, 93 and 95 mg/dL. Four pancreas allografts were lost (three in the immediate post-transplant period due to thrombosis, and one following iliac artery repair for aneurysm). Transient hyperglycemia requiring treatment was seen in 3 patients. There were four (17%) acute rejection episodes--one of the pancreas allograft alone and three involving the kidney. At a mean follow-up of 25 months, the patient survival and renal allograft survival were 100%, with pancreas allograft survival rate of 78.4% (Kaplan-Meier analysis). Nine (37.5%) patients had evidence of tacrolimus toxicity on renal histology. In conclusion, tacrolimus-based maintenance immunosuppression is associated with stable renal and pancreas allograft function, with freedom from acute rejection in 83% of patients.

Early operative intervention for urologic complications of kidney-pancreas transplantation.

Bladder drainage of exocrine secretions during pancreas transplantation can be associated with significant complications. We present a proactive approach to these complications consisting of early cystoenteric conversion (CEC). Although 81 patients underwent pancreas transplant between March 1985 and May 1995; 26 (32%) required CEC. Complications presented as urine leaks, other complications, and refractory metabolic acidosis. There were 13 patients who presented with a urine leak: 12 with acute abdominal pain, and 1 asymptomatic. Serum amylase and creatinine rose a mean of 823 IU and 0.61 mg/dl, respectively. The interval to CEC ranged from 2 to 45 months. One patient died of fungal sepsis. Postoperative complications included duodenojejunal anastomotic bleed (n = 1), negative relaparotomy (n = 1), myocardial infarction (n = 1), graft pancreatitis (n = 1), and wound infection (n = 1). Twelve patients presented with other complications: three women with cystitis (n = 2) or hematuria (n = 1), and nine men with urethritis (n = 6), scrotal edema (n = 2), or dysuria (n = 1), The interval to conversion ranged from 1 to 108 months. There were no deaths. One patient required relaparotomy for anastomotic bleed. One patient was converted because of refractory metabolic acidosis. Admissions and inpatient days were significantly reduced. Overall mortality was 3.8%, morbidity 23.1%, and graft salvage rate 96.1%. Leak-associated mortality was 7.7%, morbidity 38.5%, and graft salvage rate 92.3%. For other complications the mortality was 0, morbidity 7.7%, and graft salvage rate 100%. CEC is a safe, effective treatment for urologic complications of pancreas transplantation. Morbidity and mortality were acceptable; admissions and hospital days were decreased. Early CEC results in superior outcomes and improved quality of life. It is preferable to nondefinitive measures for management of urologic complications of pancreatic transplantation.

Combined kidney-pancreas and parathyroid transplantation: a case report.

We report the first successful multiorgan kidney-pancreas and parathyroid tissue transplant in a patient with autoimmune polyglandular syndrome and medullary cystic disease. Successful transplantation included quadruple drug induction therapy consisting of antithymocyte globulin, azathioprine, cyclosporine and prednisone. All three grafts are functioning 2 yr after transplantation.

Rescue therapy with tacrolimus after combined kidney/pancreas and isolated pancreas transplantation in patients with severe cyclosporine nephrotoxicity.

This study details 11 pancreas transplant recipients (10 combined kidney and pancreas and 1 pancreas after kidney) who were converted to tacrolimus (FK506) due to acute severe cyclosporine nephrotoxicity in 8 cases and persistent rejection with cyclosporine toxicity in three cases. Arteriolopathy was documented by renal histology in all cases. Cyclosporine was discontinued for 24 hr immediately prior to initiation of tacrolimus. Tacrolimus was started orally at 0.1 mg/kg twice daily with dose adjustments to maintain whole blood trough levels of 8-15 ng/mL by IMx. Tacrolimus was initiated a mean of 14.5 months (range 1-81) after pancreas transplantation. The mean serum creatinine level had increased to 2.9 mg/dl from 1.0 mg/dl at the diagnosis of cyclosporine arteriolopathy (P=0.003). The mean serum creatinine and blood glucose levels at the time of initiation of tacrolimus were 2.1 mg/dl and 104 mg/dl, respectively. Serum creatinine was 1.7 mg/dl, 1.9 mg/dl, 1.8 mg/dl, and 1.7 mg/dl after 1, 2, 3, and 6 months of tacrolimus therapy, respectively; ANOVA (P = 0.02). The corresponding blood glucose levels were 117 mg/dl, 112 mg/dl, 109 mg/dl, and 116 mg/dl, respectively (P=NS). Normal C-peptide levels were present before (5.9 ng/ml) and after (6.2 ng/ml), the initiation of tacrolimus therapy (P=NS), and mean HbA1C was 6.1% before and 6.3% after tacrolimus therapy, (P=NS). There were 4 episodes of acute rejection, 3 responded to intravenous methylprednisolone, and 1 required OKT3 during tacrolimus therapy. Reversible tacrolimus nephrotoxicity was noted in three patients without any evidence of progressive vasculopathy. All 11 patients are alive, and 10/11 kidney and pancreas grafts are functioning with a mean follow-up of 7.7 months (range 5-10). In this study, conversion from cyclosporine to tacrolimus in kidney and pancreas recipients resulted in improvement and stabilization of renal function while maintaining stable blood glucose, C peptide, and HbA1C levels.