Clinical features and outcomes of kidney transplant recipients with focal segmental glomerulosclerosis recurrence.

AIM: Focal segmental glomerulosclerosis recurs in up to 30% and up to 80% of adult and pediatric kidney transplant recipients, respectively. There is no standard of care treatment. The purpose of this study was to evaluate clinical characteristics, treatments and outcomes of patients with focal segmental glomerulosclerosis recurrence (FSGSr). METHODS: This was a retrospective single-center cohort study including FSGSr patients treated with plasmapheresis (PP) and combinations of high dose steroids, cyclosporine and rituximab. RESULTS: Among 61 patients included in this analysis the median time to diagnosis was 19 days. The incidence of first biopsy-confirmed FSGSr was 18% reaching 52.4% with follow-up biopsies. During PP treatment 54% of the patients developed infectious complications. PP was discontinued in 37% of patients due to treatment failure (no remission or graft loss) and in 26% due to an adverse event. All patients who discontinued PP due to adverse event did not show clinical response or lost the allograft. The incidence of acute rejection was 34.4%. The incidences of partial and complete remissions were 16.4% and 27.8%, respectively. Overall 6-years patient and graft survivals were 90.7% and 64.5%, respectively. CONCLUSION: This analysis confirms the low, variable and unpredictable rate of FSGSr remission, inconsistencies among available therapeutic options and its high rate of adverse events, and the negative impact on graft survival.

Is arterial calcification in children and adolescents with end-stage renal disease a rare finding?

AIM: To investigate if calcification and intimal media thickness (IMT) of arteries are present in children and adolescents with end-stage renal disease and to describe the risk factors associated with these alterations. METHODS: In an observational, cross-sectional prospective study, 68 patients were evaluated at the time of renal transplantation. A fragment of the inferior epigastric artery was removed during surgery for histopathological analysis to verify the presence or not of arterial calcification. Two outcomes were considered: the presence of calcium deposition and the measurement of the IMT of the artery. The potential exposure variables were: age, chronic kidney disease aetiology, diagnosis time, systolic blood pressure (SBP), use of oral active vitamin D, homocysteine and C-reactive protein. RESULTS: No arterial calcification was observed in the studied sample. The median value of the IMT of the inferior epigastric artery was 166 µm (interquartile range = 130-208). SBP standard deviation score and age were the only factors associated with this outcome. There was no statistical interaction between SBP and age with the IMT (P = 0.280). CONCLUSION: Arterial calcification is rare in children and adolescents with end-stage renal disease. The factors associated with IMT were age and SBP.

Clinicopathological characteristics and effect of late acute rejection on renal transplant outcomes.

BACKGROUND: Late acute rejection (LAR) has been associated with inferior kidney allograft outcomes. METHODS: We retrospectively evaluated 355 episodes of biopsy-confirmed LAR in a cohort of 5758 kidney transplants performed between 1998 and 2008. Estimated glomerular filtration rate was obtained before, at, and after each LAR episode as well as histology and treatment. Associations of LAR with subsequent death or graft loss were estimated with Cox proportional regression analysis. RESULTS: A total of 215 patients had 1 episode, 57 had 2 episodes, and 13 had 3 episodes of LAR. Rates of LAR-free survival were 97.4% at 1 year and 93.7% at 5 years. Estimated glomerular filtration rate decreased after each episode of LAR (56±21 vs. 44±18 vs. 36±11 mL/min/1.73 m, P<0.01). The majority of rejections were Banff IA or less, but the chronicity scores as well as plasma cell infiltrates increased after each LAR. All patients requiring dialysis lost their grafts. In a multivariable analysis, the severity of histological score (risk ratio [RR], 3.5; 95% confidence interval [CI], 1.58-7.87; P<0.001), the need for dialysis at LAR (RR, 3.31; 95% CI, 1.44-7.59; P<0.001), and treatment with methylprednisolone (RR, 2.31; 95% CI, 1.07-4.94; P=0.03) were independently associated with graft loss at 5 years, whereas tacrolimus and mycophenolate use was associated with reduced risk (RR, 0.46; 95% CI, 0.25-0.87; P<0.001). CONCLUSIONS: The prevalence and recurrence of LAR are considerable and associated with increased incidence of graft loss. Patients who need dialysis during LAR should be carefully evaluated owing to the high prevalence of graft failure.

Serum free light chains and post-transplant lymphoproliferative disorder in patients with renal transplant.

The aim of the present study was to determine whether there is an association between serum free light chains (sFLC) quantification and the development of post-transplant lymphoproliferative disorder (PTLD), using serum samples from a nested case-control cohort of patients with renal transplant. Ten new cases of PTLD and 46 controls were enrolled. Additional comparison groups consisted of five human immunodeficiency virus (HIV)-infected individuals, five with untreated Hodgkin lymphoma and six normal individuals. Serum κ and λ FLC concentrations were measured by nephelometry and compared with reference ranges (normal and renal ranges). κ and/or λ were above the normal range in 90% of cases and in 65% of matched controls. There was no statistically significant difference between all groups, except for λ FLC concentrations between cases of PTLD and normal individuals (p = 0.016). The κ/λ sFLC ratios of cases and controls were within the renal range and normal range. Our results suggest that sFLC are not useful to predict PTLD development in renal transplant recipients.

Monitoring for HHV-6 infection after renal transplantation: evaluation of risk factors for sustained viral replication.

BACKGROUND: Human herpesvirus-6 (HHV-6) is known to reactivate after renal transplantation and has been associated with several clinical manifestations. Risk factors for sustained viral replication, however, remain unclear. METHODS: Thirty consecutive kidney transplant patients were prospectively followed for HHV-6 replication between February 2007 and February 2008. Plasma samples for DNA detection were collected from the donor and the recipient before transplantation and from the recipient weekly for the first 2 months after transplantation and then every 2 weeks for 2 additional months. HHV-6 active infection was defined as detection of viral DNA in plasma, by polymerase chain reaction, in at least two consecutive samples over an interval of at least 1 week. RESULTS: Active viral infection was detected in 25% of the recipients before transplantation and 27% (8 of 30) of the patients after transplantation. The mean time to onset of viral replication was 28.1 days after transplantation and 7 of 8 (87.5%) were asymptomatic. Risk factors associated with active HHV-6 infection were receiving an organ from a living donor (P=0.028), recipients with IgM antibodies detected before transplantation (P=0.005), and pretransplantation recipient HHV-6 viral load more than 10,000 copies/mL plasma (P=0.034). CONCLUSIONS: Active HHV-6 infection occurs early after renal transplantation and is mostly asymptomatic. Donor or recipient infection may occur at the time of transplantation and are related to higher rates of posttransplantation infections.

Nephrotoxicity and efficacy assessment of polymyxin use in 92 transplant patients.

Polymyxins are old antimicrobials, discontinued for many years because of nephrotoxicity and neurotoxicity reports and reintroduced recently due to the increasing frequency of multiresistant Gram-negative bacterial infections. There are very few data related to toxicity and efficacy from transplanted patients, the major subjects of this study. All solid-organ-transplanted patients from our institution during January 2001 to December 2007 who used polymyxins were retrospectively assessed for nephrotoxicity and treatment efficacy. Microbiological and clinical cure rates were 100% and 77.2%, respectively. Only transplant patients subjected to at least 72 h of intravenous polymyxin were entered in the study. Overall, 92 transplant patients were included, and the nephrotoxicity rate was 32.6%. Multivariate analysis showed a statistically significant association between duration of polymyxin treatment (P = 0.037; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.12) and significant renal dysfunction. Polymyxin use is associated with very high rates of significant decrease in renal function; therefore, polymyxin must be used only when no other option is available and for as briefly as possible in the solid organ transplant setting.

Hemolytic anemia after kidney transplantation: a prospective analysis.

BACKGROUND: Hemolysis may occur in 9% to 40% of patients after solid organ transplantation and be caused by the passenger lymphocyte syndrome (PLS). STUDY DESIGN AND METHODS: We have prospectively examined 217 kidney transplant recipients before (Day -1) and after (up to Days +10, +20, and +30) surgery. ABO-identical transplant was performed in 180 (82.9%) patients, while 37 (17.1%) individuals received ABO-compatible nonidentical grafts. Direct antiglobulin tests (DATs) were performed by tube technique (polyspecific anti-human globulin [IgG + C3d]), positive DAT samples were further tested by gel agglutination (monospecific anti-IgG, -IgM, -IgA, or -C3), and eluates were prepared from DAT-positive red blood cells (RBCs) by the dichloromethane elution test. RESULTS: We observed that 34 of 217 (15.7%) patients developed a positive DAT up to Day +30. The percentage of patients with positive DATs was significantly higher in those having ABO-compatible nonidentical transplants compared to those that received ABO-identical grafts (10/37 = 27.0% vs. 24/180 = 13.3%; p = 0.037). Specific RBC antibodies (anti-A or anti-B) were found in only 5 of 37 (13.5%) patients having ABO-compatible nonidentical transplants who presented with clinical hemolysis. We found only three reactive eluates from 24 patients with positive DATs who received ABO-identical transplants but had no hemolysis. CONCLUSIONS: Our data collected prospectively demonstrated that: 1) positive DATs occurred in 15.7% of all patients up to Day +30 after a kidney transplant; 2) the DAT positivity occurred up to Day +10 in 9.7% of all transplanted patients; 3) the majority of the transplant recipients with a positive DAT had a nonreactive RBC eluate; and 4) PLS was the cause of a positive DAT in 13.5% of patients submitted to ABO-compatible nonidentical kidney transplants.

Contraceptive counseling and use among 197 female kidney transplant recipients.

BACKGROUND: There is growing interest about the quality of life of female transplant recipients, including their sexual and reproductive health. Although menstrual irregularity and infertility are common in women with advanced chronic diseases, most regain their reproductive function shortly after transplantation. Because an unplanned pregnancy soon after transplantation can expose both mother and fetus to considerable risk, it is recommended that these women should receive contraceptive counseling. However, the actual implementation and effectiveness of this recommendation has not been extensively studied. METHODS: A total of 197 reproductive age, female, stable kidney graft recipients attending a large Brazilian transplantation clinic were interviewed. They were asked about menstrual pattern, sexual activity, counseling, and their use of contraceptive methods both before and after the transplant. RESULTS: Before transplantation 70.6% reported menstrual irregularity, 91.9% of them were sexually active, 74.1% were counseled to use contraception and 86.3% used some contraceptive method. After the graft, 50.2% had menstrual irregularity, 79.7% were sexually active, 48.7% were advised to use contraceptives and 72.1% were actually using a method. After transplantation, there were 14 pregnancies in 11 women and 92.9% (13/14) of these were unplanned. CONCLUSIONS: Although most female kidney transplant recipients were sexually active both before and after transplantation, many were not counseled about the need for contraception and did not use any form of birth control. Health professionals involved in the management of these patients need to include contraceptive counseling as part of their routine care.

Clinical outcome of renal transplant patients after coronary stenting.

OBJECTIVE: To assess the clinical outcome of renal transplant patients who developed coronary artery disease and were treated with coronary stenting (TCA-ST). METHODS: A total of 3,334 renal transplants were performed in our service--Hospital do Rim e Hipertensão--HRH (Kidney and Hypertension Hospital) from July, 1998 to November, 2004. During this period, 33 of the renal transplant patients underwent TCA-ST to treat 62 severe stenoses in 54 coronary arteries. A retrospective analysis was performed with renal transplant patients undergoing TCA-ST at HRH. The clinical events were registered using medical charts, medical visits and phone calls. RESULTS: During the 30-month clinical follow-up after TCA-ST, 67% of the patients remained asymptomatic, 18% presented stable angina, 6% presented acute coronary syndrome without ST-segment elevation (ACSWSTE), and 3% presented acute coronary syndrome with ST-segment elevation (ACSSTE). No strokes, CHF or cardiac deaths were observed. Three non-cardiac deaths occurred. A restenosis rate of 9% was observed, which is comparable to those found in studies on drug-eluting stents. CONCLUSION: In conclusion, renal transplant patients who developed CAD and were treated with coronary stenting had a low rate of in-stent restenosis, probably related to the immunosuppressive regimen given to prevent kidney rejection.

Risk factors for hypertension 3 years after renal transplantation in children.

We performed a case-control study in renal transplant patients between 1998 and 2003 to identify risk factors for arterial hypertension over the medium term in pediatric patients undergoing renal transplantation. Three years after transplant, patients were classified into hypertensive or control groups. The following risk factors were analyzed: hypertension before transplant, glomerular filtration rate at sixth posttransplant month, acute rejection episodes, renal artery stenosis, accumulated prednisone and calcineurin inhibitor doses, presence of native kidneys, donor type (living or cadaver), body mass index at 1 year posttransplant, and glomerular disease as renal insufficiency etiology. Of 161 transplants, 124 fulfilled the inclusion criteria; 63 were hypertensive, and 61 were controls. Univariate analysis showed hypertension before transplant (52/63 vs. 27/61, p < 0.001), glomerulopathies (23/63 vs. 12/61, p = 0.001), glomerular filtration rate at 6 months (71 +/- 18 vs, 80 +/- 18 ml/min per 1.73 m(2), p = 0.003) as risk factors. A tendency to statistical significance was observed with regard to body mass index (SDS) in the first year (0.40 +/- 1.10 vs, 0.04 +/- 1.10, p = 0.072). Multivariate analysis showed statistical significance concerning previous hypertension and glomerular filtration rate at 6 months. Hypertension before transplant and early graft function are the major risk factors for hypertension in the medium term following renal transplant.

Evolução clínica pós-stent coronariano em pacientes submetidos a transplante de rim / Clinical outcome of renal transplant patients after coronary stenting

OBJETIVO: Avaliar a evolução clínica de pacientes submetidos a transplante de rim, portadores de doença arterial coronariana, que foram tratados com implante de stent coronariano (ATC-ST). MÉTODOS: Entre julho de 1998 e novembro de 2004, foram realizados, no total, 3.334 transplantes de rim em nossa Instituição (Hospital do Rim e Hipertensão). Desse total, 33 pacientes previamente submetidos a transplante de rim fizeram ATC-ST para o tratamento de 62 estenoses graves em 54 artérias coronárias, nos quais foi realizada análise retrospectiva. O registro dos eventos clínicos foi feito por meio de análise do prontuário médico, consulta médica e ligações telefônicas. RESULTADOS: No seguimento clínico de 30 meses, após a ATC-ST, observou-se que 67 por cento dos pacientes permaneceram assintomáticos, 18 por cento dos pacientes apresentaram quadro de angina estável, 6 por cento apresentaram síndrome coronariana aguda sem supra de ST e 3 por cento apresentaram síndrome coronariana aguda com supra de ST. Não houve pacientes com acidente vascular cerebral, insuficiência cardíaca congestiva ou morte cardíaca. Houve três mortes não-cardíacas. Foi observado índice de reestenose de 9 por cento, que é comparável ao dos estudos de stent farmacológico. CONCLUSÃO: Concluímos que pacientes submetidos a transplante de rim que desenvolveram doença arterial coronariana e que foram tratados com stent coronariano tiveram baixo porcentual de reestenose clínica, provavelmente relacionado ao regime de imunossupressão administrado para evitar rejeição renal.

OBJECTIVE: To assess the clinical outcome of renal transplant patients who developed coronary artery disease and were treated with coronary stenting (TCA-ST). METHODS: A total of 3,334 renal transplants were performed in our service - Hospital do Rim e Hipertensão - HRH (Kidney and Hypertension Hospital) from July, 1998 to November, 2004. During this period, 33 of the renal transplant patients underwent TCA-ST to treat 62 severe stenoses in 54 coronary arteries. A retrospective analysis was performed with renal transplant patients undergoing TCA-ST at HRH. The clinical events were registered using medical charts, medical visits and phone calls. RESULTS: During the 30-month clinical follow-up after TCA-ST, 67 percent of the patients remained asymptomatic, 18 percent presented stable angina, 6 percent presented acute coronary syndrome without ST-segment elevation (ACSWSTE), and 3 percent presented acute coronary syndrome with ST-segment elevation (ACSSTE). No strokes, CHF or cardiac deaths were observed. Three non-cardiac deaths occurred. A restenosis rate of 9 percent was observed, which is comparable to those found in studies on drug-eluting stents. CONCLUSION: In conclusion, renal transplant patients who developed CAD and were treated with coronary stenting had a low rate of in-stent restenosis, probably related to the immunosuppressive regimen given to prevent kidney rejection.

Thrombotic microangiopathy after simultaneous pancreas-kidney transplantation.

Thrombotic microangiopathy (TMA) is rare after transplantation and is associated with a high incidence of kidney graft dysfunction. Between December 2000 and March 2006, 136 simultaneous pancreas-kidney transplantations were performed with an incidence of TMA of 5.1% (71.4% localized to kidney allograft). All cases were diagnosed during the first three months and were attributed to tacrolimus; 74% were women. Systemic TMA presented higher values of lactate dehydrogenase (2658 +/- 659 U/L vs. 1331 +/- 473 U/L, p = 0.04) and a greater decrease in hematocrit (45.8 +/- 17.7% vs. 19.2 +/- 6%, p = 0.02) than in localized TMA. Acute kidney rejection complicated almost 90% of the cases with 43% of kidney graft lost. Tacrolimus was switched to sirolimus and fresh-frozen plasma was administered. Creatinine clearance after a mean follow-up of two yr was 100.7 mL/min/1.73 m(2) and 57.9 mL/min/1.73 m(2) in patients with systemic and localized TMA, respectively. In conclusion, sirolimus is an alternative to TMA associated with tacrolimus.

Evolução clínica pós-stent coronário em pacientes submetidos a transplante de rim / Clinical outcome of renal transplant patients after coronary stenting

Objetivo: Avaliar a evolução clínica de pacientes submetidos a transplante de rim, portadores de doença arterial coronariana, que foram tratados com implante de stent coronariano (ATC-ST). Método: Entre julho de 1998 e novembro de 2004, foram realizados, no total, 3.334 transplantes de rim em nossa instituição (Hospital do Rim e Hipertensão - HRH). Desse total, 33 pacientes previamente submetidos a transplante de rim fizeram ATC-ST para tratamento de 62 estenoses graves em 54 artérias coronárias, nos quais foi realizada análise retrospectiva. O registro dos eventos clínicos foi feito por meio de análise do prontuário médico, consulta médica e ligações telefônicas. Resultados: No seguimento clínico de 30 meses, após a ATC-ST, observouse que 64% dos pacientes permaneceram assintomáticos, 18% dos pacientes apresentaram quadro de angina estável, 6% apresentaram síndrome coronariana aguda sem supra de ST e 3% apresentaram síndrome coronariana aguda com supra de ST. Houve três (9%) mortes não cardíacas. Não houve pacientes com acidente vascular cerebral, insuficiência cardíaca congestiva ou morte cardíaca. Foi observado índice de reestenose de 9%, o qual é comparável aos estudos de stent farmacológico. Conclusão: Concluímos que pacientes submetidos a transplante de rim, que desenvolveram doença arterial coronariana e que foram tratados com stent coronário, tiveram baixo porcentual de reestenose clínica, provavelmente relacionado ao regime de imunossupressão administrado para evitar a rejeição renal.

Objective: To assess the clinical outcome of renal transplant patients who developed coronary artery disease and were treated with coronary stenting (TCA-ST). Method: A total of 3.334 renal transplants were performed in our service-Hospital do Rim e Hipertensão-HRH (Kidney and Hypertension Hospital) from July,1998 to November, 2004. During this period, 33 of the renal transplant patients underwent TCA-ST to treat 62 severe stenoses treated in 54 coronary arteries. A retrospective analysis was performed with renal transplant patients undergoing TCA-ST at HRH. The clinical events were registered using medical charts, medical visits and phone calls. Results: During the 30 months clinical follow-up after TCA-ST, 64% of the patients remained asymptomatic, 18% presented stable angina, 6% presented acute coronary syndrome without ST-segment elevation (ACSWSTE) and 3% presented acute coronary syndrome with ST-segment elevation (ACSSTE). Three (9%) noncardiac deaths occurred. No strokes, CHF or cardiac deaths were observed. A restenosis rate of 9% was observed, which is comparable to those found in studies on drug-eluting stents. Conclusion: In conclusion, renal transplant patients who developed coronary artery disease and were treated withcoronary stenting had a low rate of in-stent restenosis, probably related to the immunosuppressive regimen given to prevent kidney rejection.

Efficacy and tolerance of interferon-alpha in the treatment of chronic hepatitis C in end-stage renal disease patients on hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) show a high prevalence of hepatitis C, with a negative impact on the survival on hemodialysis and after renal transplantation. We evaluated the efficacy and tolerance of interferon-alpha (IFN-alpha) in HCV-infected ESRD patients on dialysis. METHODS: Forty-six HCV-RNA-positive ESRD patients were studied. IFN-alpha regimen consisted of 3 million units three times a week for 12 months, and the patients were followed up for 6 months. End-of-treatment, and sustained biochemical and virological responses were evaluated and tolerance was assessed monthly. RESULTS: A sustained virological response (SVR) was observed in 10/46 patients (22%) and in 10/29 who completed the treatment (34%). Alanine aminotransferase was elevated in 63% of the patients at the beginning of the study and returned to normal levels within the first month in all patients with SVR. Treatment was discontinued because of side effects in 11/46 patients (24%) and six patients (13%) were lost to follow-up. CONCLUSIONS: IFN-alpha monotherapy for hepatitis C in dialysis patients shows a high frequency of adverse effects. However, the SVR is high (34%) in patients who complete treatment, emphasizing the importance of careful selection and close follow-up in order to minimize and control possible side effects.

Effects of Eurocollins solution as aortic flush for the procurement of human pancreas.

BACKGROUND: Belzer solution is considered to be the best preservation media used for pancreas transplantation; however, its high cost accounts for approximately 14.5% of all resources allocated by the Brazilian government toward each pancreatic transplant. The objective of the present study was to test a reduction of Belzer solution during pancreas harvest, thereby lowering procedural cost. METHODS: The patients received pancreas-kidney transplantations during the period from January 2003 to August 2004. Patients were divided into two groups. Patients assigned to Group A (n=30) received only Belzer solution (2 L through the aorta artery), whereas patients in Group B (n=16) were perfused first with 1 L of Eurocollins solution followed by 1 L of Belzer solution. The two groups were assessed for differences in the following clinical parameters: the need for insulin replacement or antifungal and anticytomegalovirus treatment, pancreatitis, acute cellular rejection, graft vascular thrombosis, fistulas, intra-abdominal collection, graft loss, deaths, pancreatic ischemia time, and average hospitalization time. RESULTS: No statistically significant differences were observed in any of the parameters analyzed (P<0.05). The use of Eurocollins solution, followed by Belzer solution during pancreas harvesting, did not result in differences in graft survival or functionality, postsurgical complications, or patient survival and hospitalization time, when compared to the use of Belzer solution alone. CONCLUSIONS: Perfusion with 1 L of Eurocollins solution followed by 1 L of Belzer solution during pancreas harvesting seems to be a simple and efficient alternative for reducing the costs of the harvesting process.

Epstein-Barr viral load, interleukin-6 and interleukin-10 levels in post-transplant lymphoproliferative disease: a nested case-control study in a renal transplant cohort.

The possible correlation among Epstein-Barr virus (EBV) load, interleukin-6 (IL-6) and interleukin-10 (IL-10) levels has become an attractive issue and can provide a useful tool for diagnosis and monitoring of patients at risk for post-transplant lymphoproliferative disease (PTLD) development. At the time of diagnosis of PTLD, 11 patients were prospectively enrolled and 55 nested controls were selected from a 1800 renal transplant cohort. Real-time polymerase chain reaction (PCR) was used to quantify EBV load in peripheral blood mononuclear cells (PBMC). Serum IL-6 and IL-10 levels were determined using an enzyme-linked immunosorbent assay (ELISA). The median EBV load of PTLD cases was 17400 copies/10(6) PBMC, statistically different from controls (P=0.001). The median IL-6 level of PTLD cases was not different from controls (P=0.079). However, median IL-10 levels showed a significant difference in both groups (P < or = 0.001). The receiver-operating characteristic (ROC) curve analysis was applied to estimate the IL-10 cut-off value predictive of PTLD development. We found that 73.5 pg/ml has high sensitivity (1.00) and specificity (0.85). Also, Pearson's analysis showed a strong correlation between EBV load and serum IL-10 concentration (P < or = 0.001). This nested case-control study demonstrates that EBV load at diagnosis of PTLD correlates with IL-10 levels, and that monitoring of IL-10 can provide a less expensive and less time-consuming tool for PTLD diagnosis and close follow-up of patients at risk. Furthermore, we were able to define a cut-off value of IL-10 mostly predictive of PTLD development in this cohort. Our data suggest that serial measurements prior to PTLD development must be carried out to validate our hypothesis.

Efficacy and safety of oral sirolimus to inhibit in-stent intimal hyperplasia.

Sirolimus systemic administration has shown marked inhibition of neointimal hyperplasia (NIH) after balloon angioplasty in porcine models. In this pilot study, we tested the hypothesis that oral sirolimus is safe and effective to inhibit in-stent NIH and therefore to prevent and treat in-stent restenosis (ISR). Twelve patients (18 lesions) with high risk for ISR, including 8 ISR lesions, were admitted. One day before the procedure, patients were given a 15 mg loading dose of oral sirolimus, followed by 5 mg daily for 28 days, with weekly whole blood level measurements. The daily dose was adjusted to keep the concentration at 10-15 ng/ml. Sirolimus was well tolerated by all patients but one, who died at the end of the third week of treatment. The 4- and 8-month follow-up revealed an angiographic late loss of 0.40 +/- 0.24 and 0.67 +/- 0.45 mm (P < 0.01), respectively. At the same time points, the intravascular ultrasound in in-stent relative volumetric obstruction was 14.4% +/- 9.1% and 23.2% +/- 10.1% (P < 0.01), respectively. At 24-month clinical follow-up, adverse events were one (8.3%) death, two (11.1%) target lesion, and four (22.2%) target vessel revascularizations. In conclusion, in this small group of high-risk ISR patients, oral sirolimus inhibited NIH and therefore may be an effective strategy for the prevention and treatment of ISR.

Priority for children in cadaveric kidney sharing: the strategy adopted in Sao Paulo, Brazil.

Early kidney transplantation is crucial in order to accomplish both optimal mental development and the best adult height in children with end-stage renal disease. The aim was to evaluate the efficacy of the child priority policy for cadaveric kidney sharing adopted in the State of Sao Paulo (Brazil). We performed a retrospective study of data collected by the Government Transplant Department in São Paulo, involving all patients included in the waiting list from August 13, 1998 to December 31, 2001. During the study period, the child priority policy had been changed giving: period A--from the outset up to March 14, 2001, where the rule was to direct cadaveric kidneys obtained from children <12 yr, to recipients <12 yr; period B--from March 14, 2001 onwards, where the policy had been broadened to include cadaveric donors <18 yr, destined for recipients <18 yr. We performed the analysis of the data comprising 8940 patients, 8622 being adults (mean age = 48.6 +/- 14.1 yr, 3594 females) and 318 children (mean age = 11.9 +/- 5.1 yr, 156 females). Over the 3.5-yr follow-up there were 1964 deaths [1933 adults and 31 children, odds ratio (OR) 0.37; 95% CI 0.25-0.55], 1032 living donor kidney transplants (963 adults and 69 children, OR 2.20; 95% CI 1.66-2.93), and 556 cadaveric kidney transplants (444 adults and 112 children, OR 10.11; 95% CI 7.75-12.94). Three and a half years after being enrolled on the list, 24% of the children and 75% of the adults, respectively, were still awaiting a cadaveric kidney transplant (log rank test = 539, p < 0.00001). The analysis of period A vs. period B, suggests that the raising of the inclusion age upper limit to 18 yr, resulted in a twofold increase in the percentage of children being grafted within 6 months of enrollment. Overall, our data shows a slow rate of cadaveric kidney transplantation activity in Sao Paulo. Children's chances of receiving a living donor kidney almost doubled. Moreover, 19.5% of pediatric recipients had received their kidney within the first year of being enrolled on the waiting list. The scheme adopted in Sao Paulo is encouraging, but the results remain less favorable than those observed in other countries. The adoption of the priority policy did not result in an unacceptable increase of adult waiting time, given that the number of adults on our waiting list outweighs by far the number of children.

Quantification of Epstein-Barr viral load and determination of a cut-off value to predict the risk of post-transplant lymphoproliferative disease in a renal transplant cohort.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening Epstein-Barr virus (EBV)-driven B-cell malignancy occurring in 1 to 3% of renal transplant patients. Recently, EBV DNA quantification has become a useful tool for identifying patients at risk of developing PTLD. However, studies on EBV load differ in design, methodology and type of patients.