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C Vivas

Publications and source records attributed to C Vivas.

At least 19 recordsLinked to original sources

An analysis of early renal transplant protocol biopsies--the high incidence of subclinical tubulitis.

To investigate the possibility that we have been underestimating the true incidence of acute rejection, we began to perform protocol biopsies after kidney transplantation. This analysis looks at the one-week biopsies. Between March 1 and October 1, 1999, 100 adult patients undergoing cadaveric kidney or kidney/pancreas transplantation, or living donor kidney transplantation, underwent 277 biopsies. We focused on the subset of biopsies in patients without delayed graft function (DGF) and with stable or improving renal function, who underwent a biopsy 8.2+/-2.6 d (range 3-18 d) after transplantation (n = 28). Six (21%) patients with no DGF and with stable or improving renal function had borderline histopathology, and 7 (25%) had acute tubulitis on the one-week biopsy. Of the 277 kidney biopsies, there was one (0.4%) serious hemorrhagic complication, in a patient receiving low molecular weight heparin; she ultimately recovered and has normal renal function. Her biopsy showed Banff 1B tubulitis. In patients with stable or improving renal allograft function early after transplantation, subclinical tubulitis may be present in a substantial number of patients. This suggests that the true incidence of rejection may be higher than is clinically appreciated.

Adult↗

Outcome after steroid withdrawal in pediatric renal transplant patients receiving tacrolimus-based immunosuppression.

BACKGROUND: Corticosteroids have always been an integral part of immunosuppressive regimens in renal transplantation. The primary goal of this analysis was to assess the safety of steroid withdrawal in our pediatric renal transplant recipients receiving tacrolimus-based immunosuppression. METHODS: Between December 1989 and December 1996, 82 renal transplantations were performed in pediatric patients receiving tacrolimus-based immunosuppression. Two of these patients lost their grafts within 3 weeks of transplantation (and were still on steroids at the time of graft loss), and were excluded from further analysis. Seventy-four patients (92.5%) were taken off prednisone a median of 5.7 months after transplantation. Of these 74, 56 (70%) remained off prednisone (OFF), and 18 (22.5%) were restarted on prednisone a median of 14.8 months after discontinuing steroids (OFF --> ON). 6(7.5%) were never taken off prednisone (ON). The mean follow-up was 59 +/- 23 months. RESULTS: The 1-, 3-, and 5-year actuarial patient survival rates in the OFF group were 100%, 98%, and 96%, respectively; in the OFF --> ON group, they were 100%, 100%, and 100%, and in the ON group, they were 100%, 83%, and 83%. The 1-, 3-, and 5- year actuarial graft survival rates in the OFF group were 100%, 95%, and 82%, respectively; in the OFF --> ON group, they were 100%, 89%, and 83%; and in the ON group, they were 100%, 50%, and 33%. Two of the six graft losses in the OFF group, three out of four in the OFF --> ON Group, and two out of five in the ON group, were to chronic rejection. A time-dependent Cox regression analysis showed that the hazard for graft failure for those who came and stayed off prednisone was 0.178 relative to those who were never withdrawn from prednisone (P=0.005). Patients who were 10 years of age or younger were withdrawn from prednisone earlier (median: 5 months) than those older than 10 years (median: 7.3 months, P=0.02). In addition, patients who never had acute rejection were withdrawn from steroids earlier (median: 5 months) than those who had one or more episodes of acute rejection (median: 7.6 months, P=0.001). There was no effect of donor age, race, sex, recipient race, sex, cadaveric versus living donor, 48-hr graft function, panel reactive antibody, and total HLA mismatches or matches on the likelihood of being weaned off steroids. Serum creatinine at most recent follow-up in the OFF group was 1.2 +/- 0.5 mg/dl; in the OFF --> ON group, it was 1.8 +/- 0.9 mg/dl, and in the ON group it was 2.0 mg/dl (P<0.003). The incidence of rejection in the OFF, OFF --> ON, and ON groups was 39%, 77%, and 100%, respectively (P<0.05). CONCLUSION: These data suggest that steroid withdrawal in pediatric renal transplant patients receiving tacrolimus-based immunosuppression is associated with reasonable short- and medium-term patient and graft survival, and acceptable renal function. Patients who discontinue and then resume steroids had patient and graft survival rates comparable with those in patients who discontinue and stay off steroids, but had a higher serum creatinine and a higher incidence of rejection.

Adolescent↗

Biopsy of marginal donor kidneys: correlation of histologic findings with graft dysfunction.

BACKGROUND: Kidney biopsies are being used to evaluate marginal donors, but rigorous statistical validation of this practice with multivariate analysis has not been performed. METHODS: To analyze histologic parameters in 78 donor biopsies for their ability to predict graft dysfunction, we used a proportional odds model that included both donor and recipient factors. Glomerulosclerosis was categorized into grades 0, 1, 2, and 3, corresponding to 0, 1-10%, 11-20%, and 21-30% global sclerosis, respectively. The degrees of interstitial fibrosis, tubular atrophy, arteriosclerosis, and arteriolar hyalinosis were graded from 0 to 3+, using definitions suggested by the Banff Schema of allograft pathology. RESULTS: Increasing donor age was associated with higher glomerulosclerosis, tubular atrophy, and arteriosclerosis. Kidneys with any degree of interstitial fibrosis were 2.6 times [odds ratio (OR)] more likely to experience a worse outcome at 6 months (P = 0.02). This association held up after correction for acute rejection (OR 2.5, P = 0.03) and high panel-reactive antibody (OR 3.4, P = 0.006), However, the OR was reduced to 1.9 (P = 0.15) after controlling for recipient age. With each increment in the grade of glomerulosclerosis, the odds for a worse outcome at 12 months increased to 2.3 (P = 0.005). The value for OR became 2.0 (P = 0.03) when controlling for recipient age (P = 0.01), 2.4 (P = 0.005), when controlling for acute rejection, and 2.3 (P = 0.006) when controlling for high panel-reactive antibody. CONCLUSIONS: Histopathological parameters present in donor biopsies can independently predict post-transplant graft function. Implications for the pool of donor organs available for transplantation are discussed.

Adolescent↗

Initial pleural pressure measurement in spontaneous pneumothorax.

To assess whether pleural pressure (PP) measurement is helpful in evaluating the evolution of spontaneous pneumothorax (SP). To measure the inspiratory and expiratory PP at tidal volume in the SP in 85 cases. Ninety-one percent were cured with medical treatment, whereas the remaining 9% required surgery. In the cases medically resolved, the inspiratory pleural pressure (IPP) was -9 +/- 5 mbar, and the expiratory pleural pressure (EPP) was -3 +/- 6 mbar, whereas in the surgical cases, IPP was -7 +/- 2 mbar (p = not significant), and EPP was 1 +/- 3 mbar (p < 0.01). In the SP cases, which resolved in less than 7 days of drainage, IPP was -10 +/- 5 mbar, and EPP was -3 +/- 5 mbar, whereas IPP was -8 +/- 3 mbar (p < 0.01), and EPP was 0 +/- 4 mbar (p < 0.001) in those cases in which SP resolution required more than 7 days. The sensitivity to predict the need for surgery with an EPP > or = 2 mbar was 100%, with a specificity of 49%. The cutoff of the curve was > or = 1 mbar, with a sensitivity of 65% and specificity of 70%. The values of PP at the end of an expiration to tidal volume were negative in the SP cases, which were resolved by medical treatment, whereas they were atmospheric in those cases that required surgery. The static inspiratory and expiratory PP in the SP cases requiring thoracic drainage during < 7 days showed more negative PP than those that resolved in a period longer than 7 days.

Adolescent↗

Acute renal allograft rejection with severe tubulitis (Banff 1997 grade IB).

Recent studies have correlated renal allograft function with individual histologic lesions defined in the Banff schema of kidney transplantation pathology. The clinical significance of severe tubulitis (Banff 97 grade t3) has not been specifically examined. We compared the clinical course and response to antirejection therapy in 36 patients with t3 tubulitis, and 137 patients with milder grades of tubulitis and varying grades of intimal arteritis. Rejection associated with severe tubulitis (grade t3) was associated with graft outcome that was worse than mild to moderate tubulitis (grades t1 or t2) and approached that seen in grade v1 intimal arteritis. Rejection characterized by grade v2 or v3 intimal arteritis had worse prognosis than v1 intimal arteritis and all grades of tubulitis without coexisting intimal arteritis. These observations validate the Banff 97 recommendation that the severity of both tubulitis and intimal arteritis needs to be graded in renal allograft biopsies. In addition, grade t3 tubulitis is identified as a lesion which should be a cause for clinical concern.

Acute Disease↗

Posttransplant lymphoproliferative disorders in adult and pediatric renal transplant patients receiving tacrolimus-based immunosuppression.

Between March 27, 1989 and December 31, 1997, 1316 kidney transplantations alone were performed under tacrolimus-based immunosuppression at our center. Posttransplant lymphoproliferative disorders (PTLD) developed in 25 (1.9%) cases; the incidence in adults was 1.2% (15/1217), whereas in pediatric patients it was 10.1% (10/99; P<.0001). PTLD was diagnosed 21.0+/-22.5 months after transplantation, 25.0+/-24.7 months in adults and 14.4+/-18.2 months in pediatric patients. Of the 4 adult cases in whom both the donor and recipient Epstein Barr virus (EBV) serologies were known, 2 (50%) were seropositive donor --> seronegative recipient. Of 7 pediatric cases in whom both the donor and recipient EBV serologies were known, 6 (86%) were EBV seropositive donor --> seronegative recipient. Acute rejection was observed before the diagnosis of PTLD in 8 (53%) of 15 adults and 3 (30%) of 10 pediatric patients. Initial treatment of PTLD included a marked decrease or cessation of immunosuppression with concomitant ganciclovir therapy; two adults and two pediatric patients required chemotherapy. With a mean follow-up of 24.9+/-30.1 months after transplantation, the 1- and 5-year actuarial patient and graft survival rates in adults were 93% and 86%, and 80% and 60%, respectively. Two adults died, 3.7 and 46.2 months after transplantation, of complications related to PTLD, and 10 (including the 2 deaths) lost their allograft 3.7-84.7 months after transplantation. In children, the 1- and 5-year actuarial patient and graft survival rates were 100% and 100%, and 100% and 89%, respectively. No child died; one child lost his allograft 41.3 months after transplantation. One child had presumed recurrent PTLD that responded to discontinuation of tacrolimus and reinitiation of antiviral therapy. The mean serum creatinine level in adults was 2.5+/-1.2 mg/dl, and in children, it was 1.3+/-0.6 mg/ dl. Under tacrolimus-based immunosuppression, PTLD is less common after renal transplantation in adults than in children, but PTLD in children is associated with more favorable outcomes than in adults.

Adolescent↗

Epstein-Barr virus-related disorders in children undergoing renal transplantation with tacrolimus-based immunosuppression.

In children undergoing renal transplantation, Epstein-Barr virus- (EBV) related disorders, including posttransplant lymphoproliferative disorder, constitute a major complication associated with tacrolimus-based immunosuppression. In this study, we reviewed the EBV complications in 81 children, all of whom had EBV serological studies before renal transplantation. We also highlight the data in a subgroup of 30 children transplanted more recently who were monitored sequentially for EBV symptoms and signs and with immunological studies, and in whom the donor EBV serology was also determined. During a mean follow-up time of 3.9+/-2.3 years, 19 children developed symptomatic Epstein-Barr virus (EBV*) infection. This consisted of the clinical syndrome of infectious mononucleosis in 7 children; in addition, 10 children developed posttransplant lymphoproliferative disorder (PTLD), which was histologically confirmed in 8, and 2 others developed malignant lymphoma. Recipient seronegativity (EBV-) and donor EBV seropositivity (EBV+) predicted a high probability for seroconversion (P=0.0072) and for developing PTLD or malignancy (P<0.01). In the subgroup of 30 children studied prospectively, seroconversion occurred in 15 of 19 seronegative recipients of EBV seropositive grafts at 6.6+/-2.6 months (mean+/-SD) after transplantation. Seven children developed symptomatic EBV infection (including three with PTLD) in association with seroconversion and a rise in EBV viral load in the peripheral blood, demonstrated by an EBV-specific polymerase chain reaction (EBV-PCR). Of 15 seroconverters, 7 who developed symptomatic infection had received EBV+ grafts; 8 others with EBV+ grafts seroconverted but did not become symptomatic. These two subgroups did not differ in age, rejection rate, antiviral prophylaxis, or level of immunosuppression. In the overall group of 81 children, only the two with malignant lymphoma who were managed with chemotherapy had substantial morbidity. The 10 individuals with PTLD received a regimen combining i.v. ganciclovir and CytoGam, and stopping or reducing the tacrolimus. Four children with associated marked tonsilar growth underwent tonsillectomy. All 19 individuals with EBV disorders resolved their symptoms and signs, and all have maintained good allograft function during a follow-up time of 3.0+/-2.5 years (mean+/-SD) after the development of symptomatic EBV infection, PTLD, or malignancy. We conclude that seronegative recipients of EBV+ grafts are at high risk for developing EBV-related disorders after renal transplantation under tacrolimus-based immunosuppression, although the ultimate clinical outcomes have been remarkably good. These data form the basis for formulating strategies for early identification of children at risk for EBV complications, and for instituting preventive and treatment strategies that permit these children to realize the substantial benefits offered by tacrolimus-based immunosuppression.

Adolescent↗

Renal transplantation in recipients over the age of 60: the impact of donor age.

BACKGROUND: Kidneys from older donors exhibit a series of changes characterized by glomerular, vascular, and tubular senescence. These changes may be aggravated by atherosclerosis, hypertension, or diabetes, which are highly prevalent in older individuals. METHODS: We analyzed the outcome after transplantation in 230 recipients over the age of 60, who received transplants between February 1990 and December 1996. We assessed the 1- and 5-year patient and graft survival, the quality of renal function, tacrolimus levels, the incidence of rejection, and the incidence of delayed graft function, and compared the outcomes in recipients of kidneys from donors over the age of 60 (group 1, n = 40) with those in recipients of kidneys from donors under the age of 60 (group 2, n = 190). There were no differences between the two groups in terms of recipient sex, race, age, and cold ischemia time. Immunosuppression was with tacrolimus and steroids in 61% of cases; in the remainder of the patients, a third agent, either azathioprine, cyclophosphamide (for 1 week), or mycophenolate mofetil was administered as well. The median follow-up was 31.5 months (range: 1-86). RESULTS: In recipients over the age of 60 receiving tacrolimus-based immunosuppression, overall patient survival at 1 and 5 years was 90% and 76%, and was not significantly compromised in recipients receiving a kidney from a donor over the age of 60. The overall 1-and 5-year actuarial graft survival was 84% and 64%; in recipients from donors over the age of 60, it was 73% and 52%, whereas in recipients of kidneys from donors under the age of 60, it was 87% and 66% (P<0.05). Most of the effect on graft survival was seen by 1 year. The mean serum creatinine was 2.6+/-2.7 mg/dl, without any difference between the two groups. Although the incidence of delayed graft function was higher in recipients of kidneys from donors over the age of 60, this difference did not reach statistical significance. CONCLUSIONS: Although the overall outcomes of transplantation in older recipients remain reasonable, the inferior outcomes with older donor kidneys call into question proposals to utilize older donor kidneys preferentially in older recipients.

Adult↗

A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/prednisone/mycophenolate mofetil in renal transplant recipients.

BACKGROUND: Between September 20, 1995 and September 20, 1997, 208 adult patients undergoing renal transplantation were randomized to receive tacrolimus/prednisone (n=106) or tacrolimus/prednisone/mycophenolate mofetil (n=102), with the goal of reducing the incidence of rejection. METHODS: The mean recipient age was 50.7+/-13.7 years. Sixty-three (30.3%) patients were 60 years of age or older at the time of transplantation. The mean donor age was 34.5+/-21.7 years. The mean cold ischemia time was 30.5+/-9.2 hr. The mean follow-up is 15+/-7 months. RESULTS: The overall 1-year actuarial patient survival was 94%; the overall 1-year actuarial graft survival was 87%. When the patient and graft survival data were stratified to recipients under the age of 60 who did not have delayed graft function, the overall 1-year actuarial patient survival was 97%, and the corresponding 1-year actuarial graft survival was 93%. There were no differences between the two groups. The overall incidence of rejection was 36%; in the double-therapy group, it was 44%, whereas in the triple therapy group, it was 27% (P=0.014). The mean serum creatinine was 1.6+/-0.8 mg/dl. A total of 36% of the successfully transplanted patients were taken off prednisone; 32% of the patients were taken off antihypertensive medications. The incidence of delayed graft function was 21%, the incidence of cytomegalovirus was 12.5%, and the initial and final incidences of posttransplant insulin-dependent diabetes mellitus were 7.0% and 2.9%; again, there was no difference between the two groups. CONCLUSIONS: This trial suggests that the combination of tacrolimus, steroids, and mycophenolate mofetil is associated with excellent patient and graft survival and a lower incidence of rejection than the combination of tacrolimus and steroids.

Adolescent↗

Pediatric renal transplantation under tacrolimus-based immunosuppression.

BACKGROUND: Tacrolimus has been used as a primary immunosuppressive agent in adult and pediatric renal transplant recipients, with reasonable outcomes. Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction anti-lymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipient age was 10.6+/-5.2 years (range: 0.7-17.9). Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with living donors, and 48 (59%) were with cadaveric donors. The mean donor age was 27.3+/-14.6 years (range: 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5+/-8.8 hr. The mean number of HLA matches and mismatches was 2.8+/-1.2 and 2.9+/-1.3; there were five (6%) O-Ag mismatches. The mean follow-up was 4.0+/-0.2 years. RESULTS: The 1- and 4-year actuarial patient survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1+/-0.5 mg/dl, and the corresponding calculated creatinine clearance was 88+/-25 ml/min/1.73 m2. A total of 66% of successfully transplanted patients were withdrawn from prednisone. In children who were withdrawn from steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were -2.3+/-2.0, -1.7+/-1.0, and +0.36+/-1.5. Eighty-six percent of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between December 1989 and December 1993, it was 63%, and between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within 1 week of transplantation. The incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 12%. The incidence of early Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppression and institution of antiviral therapy, without patient or graft loss. CONCLUSIONS: These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti-hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD.

Actuarial Analysis↗

Clinical significance of renal biopsies showing concurrent acute rejection and tacrolimus-associated tubular vacuolization.

BACKGROUND: The clinical significance of biopsies showing both rejection and isometric tubular vacuolization has not been well defined in the literature. METHODS: The clinical picture, sequential histopathologic findings, and response to therapy were compared between 24 renal allograft biopsies showing both tubular vacuolization and rejection and 14 biopsies showing vacuolization alone. RESULTS: The rejection was categorized as grade 1 in 4/24 (16.6%), grade 2A in 10/24 (41.6%), and grade 2B in 10/24 (41.6%) cases (Banff schema, 1993-1995). Treatment with additional steroids and tacrolimus led to a decrease in the interstitial inflammation score (2.6+/-0.1 to 1.3+/-0.1, P<0.001), tubulitis score (2.6+/-0.1 to 1.1+/-0.1, P<0.001), and serum creatinine (4.4+/-2.2 mg/dl to 3.3+/-2.6 mg/dl, P=0.001). Complete response, partial response and no response to antirejection therapy were observed in 16/24 (66.7%), 3/24 (12.5%), and 5/24 (20.8%) patients, respectively. Although there was a rise in the plasma (1.4+/-0.2 ng/ml to 2.8+/-0.3 ng/ml, P<0.001) and whole blood (16.5+/-2.8 ng/ml to 31.2+/-5.7 ng/ml, P<0.001) tacrolimus levels, repeat biopsy showed no change in the size or extent of tubular vacuolization (mean score 2.88+/-0.19 vs. 2.83+/-0.21). The morphologic characteristics of the tubular vacuoles in these cases did not differ from those observed in 14 cases of tacrolimus nephrotoxicity not complicated by rejection. CONCLUSION: Patients with concurrent acute rejection and tubular vacuolization usually benefit from increased immunosuppression. The pathogenesis of the vacuolization in this clinical setting is not clear, but may reflect immune-mediated tubular injury.

Acute Disease↗

Human polyoma virus-associated interstitial nephritis in the allograft kidney.

BACKGROUND: Asymptomatic polyoma virus infection documented by urine cytology or serology is well known, but the clinical course of biopsy-proven interstitial nephritis is not well defined. METHODS: Twenty-two cases were identified by histology, immunostaining, in situ hybridization, electron microscopy, or polymerase chain reaction. RESULTS: The clinical features mimicked acute rejection (n=19), chronic rejection with incidental diagnosis at nephrectomy (n=2), or drug toxicity (n=1). Histology showed homogenous intranuclear inclusions. In situ hybridization showed BK virus (BKV) to be the predominant species, but polymerase chain reaction documented JC virus co-infection in one of five cases so tested. Electron microscopy in seven cases showed 20-51-nm virions. The two cases diagnosed at nephrectomy received no therapy. Initial antirejection therapy in 12 cases led to clearance of the virus in 1/12 (8%), partial therapeutic response in 3/12 (25%), and graft loss in 8/12 (67%) cases. The last recorded creatinine in patients with functional grafts ranged from 1.9 to 7.0 (median: 4.5) mg/dl, 0.4-45 (median: 4.0) months after initial diagnosis. The remaining eight cases treated by reduction of immunosuppression at the outset have been free of graft loss for 0.2-10.0 (median: 4.8) months since diagnosis, and clearance of virus has been documented in three of six (50%) cases. The serum creatinine in these patients is 1.7-6.0 (median: 2.4) mg/dl, 0.2-10 (median: 4.8) months after diagnosis. Follow-up biopsies performed 1-23.5 months after diagnosis show chronic allograft nephropathy. CONCLUSIONS: Polyoma virus tubulo-interstitial nephritis-associated graft dysfunction usually calls for judicious decrease in immunosuppression and monitoring for acute rejection. Development of methods to serially quantify the viral load in individual patients could potentially improve clinical outcome.

Adolescent↗

Cytomegalovirus infection of the native ureter after liver-kidney transplantation.

We report a case of invasive cytomegalovirus (CMV) infection in the native ureter of a patient 7 years after liver-kidney transplantation. Previous reports of CMV ureteritis in transplant patients have involved only the allograft ureter, usually within 3 months of transplantation. The common characteristics of these patients, the possible risk factors, and the diagnostic findings of CMV ureteritis are discussed. Combined surgical and medical intervention are required for successful treatment.

Adult↗