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.

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.

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.

Unusual vascular findings in transplanted kidneys.

Of 189 unsuccessful renal transplant cases, eight were selected for retrospective analysis because they had been classified histologically as "chronic rejection with marked vascular changes" even though they had been removed less than 60 days after transplantation. Review of these cases revealed that only one of the eight transplants had postoperative function and that this transplant had only marginal functions. All eight kidneys had intimal damage that was unlike the usual lesions of rejection. Five kidneys showed evidence of thrombosis with recanalization, and five had what appeared to be a double layer of the intima. The findings in eight cases suggest that severe intimal damage occurred within 60 days of implantation and may not represent the usual rejection processes; it may reflect, in part, damage to the intima prior to or during implantation.

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.

Surgical management of infected Thomas shunts.

Infected Thomas shunts pose a problem for the surgeon treating end-stage renal failure patients. Complete removal of the prosthesis with ligation of the femoral vessels may jeopardize the limb. Removal of the shunt without the Dacron patch usually will not eradicate the infection. The present article describes a two-stage approach in six patients with arterial bypass of the infected area and complete removal of the prosthesis. There were no postoperative complications. Arterial circulation was maintained, and all operative sites healed completely.

Acute renal failure as a complication of hypertonic saline abortion in a kidney allograft recipient.

Acute renal failure following abortion by intra-amniotic hypertonic saline administration has been described only occasionally. This report concerns a patient with end-stage renal failure who was successfully treated with a kidney allograft and developed reversible acute renal failure following the termination of her pregnancy by intra-amniotic infusion of saline. We suspect that the combination of hemoglobinuria and low grade intravascular coagulation might have been a contributing factor in the development of renal insufficiency in this patient. To our knowledge this modality of abortion has not been used previously in pregnant women with transplanted kidneys. From our experience with one patient it seems wise to express a word of caution on the use of this technique in patients with a functioning kidney allograft.

PIP: A case of acute renal failure subsequent to hypertonic saline abortion is reported. A 26-year-old woman who had received a kidney allograft 7 months earlier was admitted to hospital for midtrimester abortion. Shortly after saline installation she developed a fever. Fetus and placenta were passed the following day but her temperature continued to rise. Urine output rose sharply; urinalysis showed a specific gravity of 1.005, 1+ proteinuria, moderate hemoglobinuria, 5-10 leukocytes, and a few granular casts. Her medications were 125 mg/day azathioprine, 25 mg/day prednisone, aluminum hydroxide gel, calcium carbonate, dihydrotachysterol and multivitamins. Her condition improved to the point of discharge 1 week postabortion. It is hypothesized that a combination of hemoglobinuria and mild intravascular coagulation contributed to the condition. Caution is advised when considering saline abortion for patients with transplanted kidneys.

Captopril-induced acute renal failure in a kidney transplant recipient.

A living related kidney transplant recipient with normal renal function and severe hypertension secondary to renal artery stenosis, was treated with captopril and developed reversible renal failure requiring temporary hemodialysis. This complication of captopril, an angiotensin converting enzyme inhibitor, has been reported previously in hypertensive patients with renal artery stenosis with and without a kidney transplant. It is recommended that this drug be used with caution in this setting.

Successful renal transplantation in polyarteritis nodosa.

Hemodialysis and renal transplantation were performed in a patient with end stage renal disease caused by polyarteritis nodosa. Severe peripheral neuropathy developed during hemodialysis. Five years after transplantation, marked improvement of the neuropathy associated with adequate function of the allograft has been noted. There has been no detectable clinical or pathologic signs of recurrent disease. These observations favor the consideration of renal transplantation in patients with polyarteritis nodosa and renal failure, particularly in the absence of extensive organ involvement.

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.

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.

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.

Restrospective correlation of clinical and histologic findings of 189 exchanged kidneys.

Tissues samples from 189 unsuccessful renal allografts, 47 recovered at autopsy and the others removed surgically, were examined histologically by light microscopy. Tissues samples were obtained from cadaver kidneys that had been exchanged regionally for transplantation. Each allograft tissue sample was rated as to extent of pathologic changes denoting rejection and was classified accordingly. Surgical and autopsy reports, as well as clinical data, were then obtained and these were compared with the retrospective pathologic findings of this study. Our pathologic findings agreed with the original pathologic diagnosis as to presence or absence of rejection changes in 180 cases, but disagreed with the clinical diagnosis of rejection in 28 of the 63 cases with minimal or no histologic evidence of rejection. There was less disagreement with the clinical diagnosis for the 87 cases with histologic evidence of rejection which had been judged as sufficient to cause allograft loss, 70 having been clinically diagnosed as rejected. Disagreement occurred most often where the allograft had never functioned or had been lost within 3 months. Retrospective analysis did not disclose any association between rejection histology and preformed antibodies or length of kidney perfusion time. Sufficient allografts appeared to have been lost for reasons other than rejection to cast doubt on the validity of interpreting renal allograft data only by graft survival statistics.