Successful long-term kidney-pancreas transplants regardless of C-peptide status or race.

BACKGROUND: We have previously shown that our patient population of 60% minority races has end-stage renal disease primarily as a result of diabetes mellitus and hypertension. It therefore was logical to explore the restoration of normal insulin production and renal function by simultaneous pancreas-kidney (SPK) transplantation, without regard to race. This study represents new analyses integrating race with C-peptide status and reports the outcome of 136 SPK transplantations performed over the last 10 years. RESULTS: Of the 49 African-Americans with diabetes mellitus and end-stage renal disease, 60% were type I and 40% were type II, based on C-peptide levels. In comparison, only 16% of Caucasians were type II. The average age at onset of diabetes mellitus was 15.7 years for type I compared with 20.7 years for type II (P>0.05). The actuarial 10-year survival rates for the 136 SPKs were 91.79% (patient), 85.07% (pancreas), and 83.58% (kidney). The type I and type II survival rates were similar in the two diabetic groups. CONCLUSIONS: The data strongly suggest that pretransplant C-peptide status does not influence the outcome of SPK transplantation in patients with renal failure from diabetes mellitus. SPK transplants should be offered to all suitable diabetic patients with renal failure regardless of C-peptide status or race.

Development and implementation of a semester program in Mexico for senior nursing students.

The College of Nursing (CON), Michigan State University (MSU), in collaboration with the School of Nursing and Obstetrics, University of Guanajuato, Celaya, Mexico, developed a semester-long study-abroad program for senior MSU nursing students offered for the first time in the fall of 1998. The program provides intensive Spanish language classes and allows students to take required nursing courses in Mexico with a substantial amount of course content provided by Mexican faculty without an MSU CON faculty member on site at all times. Students receive a broad perspective of nursing and health care in Mexico, and develop an appreciation for its language and culture as well. This program represents an innovative approach to the development and implementation of a study-abroad program in nursing.

A comparison of daclizumab to ATGAM induction in simultaneous pancreas-kidney transplant recipients on triple maintenance immunosuppression.

Daclizumab (DAC) is a molecularly engineered humanized IgGa monoclonal Ab directed against the alpha chain of the interleukin-2 receptor (IL2R). Inhibiting the amplification of the immune response by blocking IL2R can reduce the frequency of acute rejection without the attendant risk of infection. The purpose of this retrospective study was to compare DAC to antithymocyte (ATGAM) induction in 24 simultaneous pancreas-kidney (SPK) transplants performed between September 1995 and September 1998. The primary endpoints were the incidence within 6 months posttransplant of: 1) biopsy-proven acute rejection; and 2) infection. The two groups (DAC, n = 12; ATGAM, n = 12) were matched on age, race, ESRD, number of HLA mismatches, PRA level, and cold ischemia time. DAC (1 mg/kg) was given on the day of transplant, then every other week (a total of five doses); ATGAM (15 mg/kg) was given on post-transplant day 1, then daily for 7-10 d. Immunosuppressive therapy consisted of cyclosporine (Neoral 8-10 mg/kg/d) or Prograf (0.16-0.2 mg/kg/d), mycophenolate mofetil (Cell- 2-3 g/d) and steroids. Of the 12 DAC patients, 3 patients (25%) had biopsy-proven acute rejection versus 8/12 (67%) of the ATGAM patients. The time to acute rejection was significantly different by group (DAC = 110 d; AT-GAM = 26 d). There was a reduction in the number of patients receiving antilymphocyte drugs for moderate to severe rejection (DAC = 2/12; ATGAM = 4/12), with 2 of the 4 ATGAM patients experiencing more than two episodes of biopsy-proven rejection. There was an increase in infection by group (DAC = 4/12; ATGAM = 7/12): total of three septic infections occurred in the ATGAM group opposed to none in the DAC group. Patient, pancreas, kidney 6-month survival rates were 100% for both groups. We conclude that DAC induction coupled with triple immunosuppressive therapy reduces the incidence of rejection in SPK transplant patients. The time to acute rejection was prolonged in the DAC group compared with the ATGAM group without the attendant risks of rejection.

Tacrolimus vs Neoral in renal and renal/pancreas transplantation.

In a retrospective analysis we compared the outcome of a group of 63 kidney or kidney/pancreas transplant recipients who were transplanted between June 1994 and February 1997 and received either tacrolimus (FK, n = 22) or Neoral (NEO, n = 41) as part of a triple immunosuppressive protocol. Ten patients in the NEO group has recurrent rejection episodes between 1 and 8 months post-transplant and were converted to FK. CellCept was the secondary immunosuppressive agent in about half the FK, three-quarters of the NEO, and in all but one in the conversion (CON) groups. Patients in all groups were on prednisone in equal amounts. Mean duration of follow-up for FK, NEO and CON groups was 32, 19 and 13 months, respectively. One-yr patient and graft survival was 100% in all groups. At 2 yr, graft survival was 95, 96 and 100% in FK, NEO and CON groups, respectively. Acute rejection at 1 yr was twice as high in the NEO group as the FK group. There were no rejection episodes among the FK patients who also received CellCept. The mean current serum creatinines (mg%) were: FK = 1.6, NEO = 1.8, CON = 1.9. Recurrent infection was more common with FK (8/22) than NEO (1/31) (p = 0.023). Our experience suggests there is less rejection but more infection in recipients treated with FK compared to NEO. In patients with recurrent rejection, conversion from NEO to FK stabilizes renal function and minimizes subsequent rejection episodes.

Successful long-term kidney-pancreas transplants in diabetic patients with high C-peptide levels.

BACKGROUND: Pancreas transplants are rarely done in type 2 (noninsulin dependent) diabetic patients. Most researchers believe that in type 2 diabetic patients, peripheral insulin resistance plays a central role and also is associated with relative insulin deficiency or an insulin secretory defect. This suggests that in patients receiving transplants, the new beta cells will be overstimulated, leading to beta cell "exhaustion" and graft failure. METHODS: Early in our experience, simultaneous pancreas-kidney transplant candidates were selected using only clinical criteria for type 1 diabetes, i.e., early onset of diabetes and rapid onset of insulin use. Pretransplant sera were available for C-peptide analysis in 70 of 94 of those patients. Forty-four percent (31/70) were African American (AA). RESULTS: Thirteen patients (12 AA) with a nonfasting C-peptide level >1.37 ng/ml were identified. In these patients with high C-peptide levels, pancreas and kidney survival rates were 10O%. The results did not differ statistically from the low C-peptide group (< or =1.37 ng/ ml). There were no differences between patient and pancreas-kidney survival rates when the patients were separated into AA and non-AA groups. The follow-up was 1-89 months, with a mean of 45.5 months. CONCLUSIONS: Long-term pancreas graft function is attainable and beta cell "exhaustion" does not occur in patients with high preoperative C-peptide (>1.37 ng/ ml) levels. AA and non-AA patients have equivalent long-term patient, kidney, and pancreas-kidney graft survival rates.

Donor hepatitis C virus status does not adversely affect short-term outcomes in HCV+ recipients in renal transplantation.

BACKGROUND: Recipient hepatitis C virus (HCV) seropositivity has been associated with inferior outcomes in renal transplantation (RTx). We sought to determine whether donor HCV+ status influenced the incidence of rejection, liver dysfunction, and graft survival in HCV+ recipients. METHODS: We reviewed 44 HCV+ recipients (R+) receiving RTx from HCV+ (D+) and HCV- (D-) donors between February 1991 and September 1996. All patients were followed to the end of the study period (mean=36 months, range=12-60 months). We compared the R+ group with a demographically matched cohort of 44 HCV- recipients (R-). RESULTS: Of the 44 R+, 25 (57%) had a total of 48 rejection episodes. Among the 44 R-, 32 (73%) had 58 rejection episodes (P>0.1). Within the R+ group, 28 were D+/R+; of these 14 (50%) had 27 rejection episodes, whereas among the 16 D-/R+, 11 (68%) had 21 rejection episodes (P>0.3). Graft and patient survival was similar in both the groups (86.4% and 91%, respectively). Liver dysfunction was slightly increased in the R+ group (4/44 vs. 0/44, P>0.1), with one death due to liver failure in this group. CONCLUSION: Donor HCV+ status had no influence on outcomes in HCV+ recipients after kidney transplantation in the short term. The incidence of rejection, graft loss, and mortality was comparable between the D+/R+ and D-/R+ groups. Furthermore, rejection, graft loss, and death were identical in R+ and R-groups throughout the 5-year study period. We therefore conclude that HCV+ recipients can safely receive kidney transplants without concern about donor HCV status or fear of adverse events from their own HCV+ status.

The significance of the IgG anti-B-cell crossmatch on renal transplant outcome.

Transplantation in the presence of anti-class I antibodies usually results in allograft hyperacute rejection. Because of the perception of its uncertain clinical significance, B-cell crossmatch which identifies presence of anti-class II antibodies is not universally performed. In a retrospective study, the clinical course of renal transplant recipients with IgG anti-B-cell antibodies was analyzed and compared with case control patients transplanted contemporaneously, matched demographically and immunologically. The incidence of hyperacute, acute, and chronic rejection as well as graft loss were significantly higher in the group with anti-IgG B-cell antibodies compared to the control. We conclude that anti-B-cell IgG antibodies are harmful to allografts with a spectrum of events that include hyperacute, acute, vascular and chronic rejection. While allografts were successful in some patients, our experience suggests caution whenever anti-donor B-cell IgG is present. If transplants are performed, then more potent immunosuppression should be used.

Use of Wallstents for hemodialysis access-related venous stenoses and occlusions untreatable with balloon angioplasty.

PURPOSE: To determine whether the Wallstent endoluminal prosthesis can be used to maintain patency of venous stenoses and occlusions related to hemodialysis access. MATERIALS AND METHODS: Wallstents were placed in 52 patients with 56 lesions. Thirty-two lesions were in central veins and 24 were in peripheral veins. Stents were placed immediately after failed angioplasty in 39 patients, because of early restenosis after angioplasty in four, and for treatment of a lesion unsuitable for angioplasty in eight. The remaining five lesions were treated at the operator's discretion after predilation. RESULTS: The procedural success rate was 96%. The cumulative primary patency rate was 46% at 6 months and 20% at 12 months; however, with repeat treatment, the cumulative assisted patency rate was 76% at 6 months and 33% at 12 months. Known causes of recurrence included intimal hyperplasia in or near the stent, stent slippage, and remote stenoses. Complications included two stent migrations due to central line placement and one stent-related pseudoaneurysm. CONCLUSION: Wallstents are safe to deploy for dialysis access. Wallstents are useful for treating lesions that fail angioplasty and catheter-related central venous occlusions.

Phase I results of pullback atherectomy for hemodialysis access.

PURPOSE: Balloon angioplasty and directional atherectomy frequently have short-lived results for stenoses associated with hemodialysis. Results are reported for a phase I trial of the pullback atherectomy catheter (PAC) for treatment of hemodialysis access-related stenoses. PATIENTS AND METHODS: Six intragraft and six venous stenoses in nine patients were treated with the PAC. Two lesions were treated with adjunctive balloon angioplasty, and two were treated with adjunctive directional atherectomy. Clinical and angiographic follow-up were obtained for all patients. All specimens were examined histologically. RESULTS: Initial procedural success was achieved in 83% of stenoses (10 of 12). For intragraft stenoses, the 6-month primary patency was 60% (three of five) and the 6-month secondary patency was 80% (four of five). All six venous stenoses restenosed or thrombosed within 3 months. All specimens contained fibrous plaque or intimal hyperplasia. In addition, all six venous stenosis specimens contained media and two contained adventitia. Significant complications during treatment of venous stenoses included severe venous spasm in three and venous pseudoaneurysms in two. One PAC tip fracture occurred during treatment of an intragraft stenosis. CONCLUSION: Pullback atherectomy is potentially safe and effective for intragraft stenoses; however, it is not safe or effective for venous stenoses.

Clinical and hemodynamic sequelae of lower-extremity, deep-vein thrombosis after total joint arthroplasty.

To determine the long-term sequelae of lower-extremity deep-vein thrombosis (DVT) after total hip or knee arthroplasty, 25 patients with venographically proven lower-extremity DVT were studied. A study group of 16 patients was available 14 months postoperatively. The results of clinical and hemodynamic evaluation were compared with those of a randomly selected group of patients who had negative venographic findings after total joint arthroplasty. There were no statistically significant differences in calf pain or swelling between the two groups. The presence of venous varicosities and pigmentation were unreliable indicators of the post-thrombotic syndrome. There were no statistically significant differences in vein patency, valve competency, and venous recovery times. There was a high incidence of hemodynamic abnormalities in the historically uninvolved extremities of patients with postoperative DVT.

The risk of perioperative stroke in patients with asymptomatic carotid bruits undergoing peripheral vascular surgery.

Three hundred patients without neurologic symptoms had 374 elective peripheral vascular procedures and they were screened preoperatively for incidental asymptomatic carotid bruits prior to surgery. The bruits were hemodynamically evaluated with the GEE-OPG. A bruit was considered hemodynamically significant if the OPG test was positive. Seventy-four patients (24.7%, 74/300) were found to have 118 carotid bruits. Twenty-five (22.3%, 25/112) of the 112 bruits with OPG studies were hemodynamically significant. There were three perioperative strokes that occurred for an incidence of 0.8 per cent (3/374). There was no stroke in patients without bruits and with nonhemodynamically significant bruits. The incidence of perioperative stroke in patients with hemodynamically significant bruits was 16 per cent (3/19). There is a subgroup of patients with hemodynamically significant carotid bruits who are at high risk for perioperative stroke.

Surgical management of subclavian and axillary vein thrombosis in patients with a functioning arteriovenous fistula.

Until recently, secondary thrombosis of the deep veins of the upper extremity was rarely encountered. The expanding use of the subclavian vein as a route to the central circulation has increased its occurrence, but symptoms are uncommon. Patients on hemodialysis with a functioning arteriovenous fistula become symptomatic with venous hypertension and swelling. Treatment becomes necessary, and fistula ligation is usually recommended; however, this renders the extremity unsuitable for a future life-sustaining access. Patency of grafts in the venous system has been accomplished with a temporary arteriovenous fistula. In six patients with chronic renal failure and a functioning arteriovenous fistula, a polytetrafluoroethylene graft was used to replace or bypass the obstructed vein. Symptoms resolved, and the fistula was preserved in three of the six patients for 1 to 3 years.

Iatrogenic entrapment of the femoropopliteal bypass.

Three cases of infragenicular femoropopliteal bypass grafts are presented in which iatrogenic entrapment of the distal portion of the graft occurred between the medial head of the gastrocnemius muscle and the posterior surface of the tibia. The condition should be suspected if ischemia of the leg develops postoperatively when the knee is hyperextended and is improved when the knee joint is flexed. Measurements of the ankle pressure index or Pulse Volume Recorder tracings at the ankle in both flexed and extended positions will confirm the diagnosis. The entrapment of the bypasses in these three patients was easily corrected by transection of the medial head of the gastrocnemius muscle. Relief of the occlusion of the bypass can be easily demonstrated by noninvasive studies.

Importance of cytotoxic lymphocytes during cytomegalovirus infection in renal transplant recipients.

Thirty renal transplant recipients were studied prospectively to evaluate the relationship of cytomegalovirus-specific cytotoxic lymphocyte responses to clinical outcome during cytomegalovirus infection. Cytomegalovirus infection developed in 20 patients; of these 20, 14 had cytomegalovirus-specific cytotoxic lymphocyte responses whereas six did not. Clinical findings (fever, leukopenia, thrombocytopenia, or elevations in serum transaminase levels) were significantly more frequent among patients without responses than among patients with responses (p less than 0.001), and prolonged viremia and complications of infection including superinfection, interstitial pneumonitis, pancreatitis, and death occurred exclusively among patients without responses. Acute allograft dysfunction during infection was experienced by four patients without responses but by only one patient with response (p = 0.02), indicating that the virus-specific cytotoxic response did not result in a renal immunopathologic condition, and may have protected against virus-induced injury to the graft. In seven of nine patients with responses who shed virus, cytotoxic responses occurred within one week of detection of activation of virus shedding. Absence of cytotoxic responses correlated with prior high-dose, intravenous methylprednisolone treatment, and apparently resulted from inhibition of cytotoxic T cell precursors. Immunosuppressive treatment to inhibit graft rejection should be minimized, and methods should be developed that do not inhibit cytomegalovirus-specific cytotoxic T cell responses.

Histopathology of argon laser photocoagulation in juvenile diabetic retinopathy.

A 24-year-old woman had insulin-dependent juvenile diabetes for 15 years. She developed Sheehan's syndrome (postpartum pituitary necrosis) and diabetic nephropathy at 20 years of age. She had multiple sessions of argon laser photocoagulation for proliferative diabetic retinopathy. Histologically, loss of outer retina and pigmented epithelium occurred at the laser sites. Trypsin retinal digest preparations revealed microaneurysms and markedly decreased numbers of pericytes. The kidneys displayed nodular glomerulosclerosis (Kimmelstiel-Wilson syndrome). The anterior pituitary showed cystic degeneration and old hemorrhage.