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- Pancreas-Kidney Transplantation: Analysis of 150 patients from one Centre in PortugalPublication . Martins, La Salete; Fonseca, Isabel; Aguiar, P.; Rocha, A.; Costa, R.; Santos, C.; Malheiro, J.; Pedroso, S.; Almeida, M.; Dias, L.; Castro-Henriques, A.; Cabrita, A.; Davide, J.Introduction: Simultaneous pancreas-kidney transplantation (SPKT) outcomes are conditioned in the short-term mostly by post-operative complications. In the long-term, cardiovascular (CV) disease and immunological loss are the main limitations to transplant survival. Aims: To analyse retrospectively the results from 150 SPKT performed at our centre. Patients and Methods: The 81 females and 69 males had a mean age of 35±6 years; they were diabetic for 24±6 years and had been on dialysis for 30±21months (except 5 preemptive). Anti-lymphocyte globulin, tacrolimus, mycophenolate and steroids were used as immunosuppressive therapy. Deceased-donor mean age was 28±11 years. In 28.7% the transplant was performed with 6 HLA-mismatches. Results: Acute rejection’s incidence was 16%. Ten SPKT patients died; infection was the leading cause of death (five cases), followed by Cardiovascular/cerebrovascular disease (three cases). In 21 patients the pancreas failed, mainly due to thrombosis or bleeding (11 cases), and infection (five cases); in two it was due to late acute rejection. In four patients only the kidney failed, due to chronic rejection. Five patients lost both grafts, from late acute rejection in four and thrombosis in one. We analyzed the 110 SPKT patients (73.3%) with both grafts functioning. Their mean serum creatinine was 1.2±0.4mg/dl; creatinineclearance was 76±24 ml/min; fasting glycaemia was 81±10mg/dl; and HbA1c was 5.3±0.4%. Hypertension has been treated in 47.2% of patients, in the majority (28.2%) with only one drug. Hyperlipidaemia was observed in 19.1% and excessive weight (>25kg/m2) in 17.3%. Conclusions: From our cohort of SPKT, 93.3% of patients are alive, 73.3% have both grafts functioning. Rejection was the main cause of late pancreas loss. Early mortality was due to infection (3.3%). CV/cerebrovascular disease was the main cause of late mortality (2%). The prevalence of hyperlipidaemia and overweight was inferior to 20%. Hypertension was the most frequently found CV risk factor.
- Neutrophil gelatinase-associated lipocalin in kidney transplantation is an early marker of graft dysfunction and is associated with one-year renal functionPublication . Fonseca, Isabel; Carlos Oliveira, José; Almeida, M.; Cruz, M.; Malho, A.; Martins, La Salete; Dias, L.; Pedroso, S.; Santos, J.; Lobato, L.; Castro-Henriques, A.; Mendonça, D.Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF (n = 18). Shortly after KTx (3-6 h), uNGAL values were higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function.
- Steroid Withdrawal in Simultaneous Pancreas-Kidney Transplantation:Publication . Malheiro, J.; Martins, La Salete; Fonseca, Isabel; Gomes, A.M.; Santos, J.; Dias, L.; Dores, J.; Oliveira, F.; Seca, R.; Almeida, R.; Henriques, A.; Cabrita, A.; Teixeira, M.ABSTRACT Simultaneous pancreas-kidney transplantation (SPK) is the treatment of choice for selected diabetic patients with end-stage renal disease. Maintenance steroid therapy is associated with significant morbidity and mortality among SPK transplant recipients. Steroid withdrawal regimens are becoming more common, albeit with reservations regarding its safety and efficacy. We performed retrospective review of 77 SPK transplant recipients from May 2000 to December 2007. The subjects received induction therapy with thymoglobulin followed by maintenance immunosuppression with tacrolimus and myco- phenolate mofetil. late steroid withdrawal protocol was adopted. The rates of acute rejection, graft and patient survival, and side effects were analyzed. One-year patient, kidney, and pancreas survivals were 93%91%and 86%respectively. Eleven patients experienced acute rejection. Mean follow-up time was 1155.5 776.1 days. Prednisolone withdrawal was carried out between and 12 months posttransplantation in 42 patients (77.8%with at least year follow-up; no case of acute rejection occurred. At present, 72 patients have functioning kidney graft, and 65 patients also have functioning pancreas graft. The mean serum creatinine is 1.12 0.49 mg/dL and the mean HbA1c concentration is 4.5% 0.4%The patients have low prevalence of hypertension, hyperlipidemia, and obesity. Steroid withdrawal was successful and safe in the majority of in-study patients and safe without an increase of immune events. Our patient and graft outcomes are within other international SPK transplant units standards.
- Posttransplant allosensitization in low immunological risk kidney and kidney-pancreas graft recipients.Publication . Malheiro, J.; Tafulo, S.; Dias, L.; Martins, La Salete; Fonseca, Isabel; Almeida, M.; Pedroso, S.; Freitas, F.; Beirão, I.; Castro-Henriques, A.; Cabrita, A.INTRODUCTION: Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled. METHODS: Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes. RESULTS: Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%, P = 0.03). In multivariable Cox analysis, delayed graft function (HR = 6.1, P < 0.01), HLA mismatches >3 (HR = 10.2, P = 0.03), and antibody positivity for anti-HLA class II (HR = 5.1, P = 0.04) or class I/II (HR = 13.8, P < 0.01) were independent predictors of graft loss. CONCLUSIONS: Allosensitization against HLA class II ± I after transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients.
- Impact Assessment in Living Kidney Donation: Psychosocial AspectsPublication . Frade, I.C.; Fonseca, Isabel; Dias, L.; Henriques, A.C.; Martins, La Salete; Santos, J.; Sarmento, M.; Lopes, A.ABSTRACT Background. Living donor kidney transplantation has positive influence on graft survival and recipient quality of life (QoL)We assessed the psychosocial impact of donation to the donor. Methods. Before and after the procedure 32 living kidney donors (mean age 41 years) completed the Zung Self-Rating Anxiety and Depression Scales; Sociodemographic, Short-Form 36 Health Survey (SF-36)and Donation Perceptions Questionnaire. Results. Living kidney donors were siblings (62.5%)parents (34.4%)or daughter (3.1%)Transplantation was not successful in two cases: one recipient death and one graft failure. No significant changes were observed in donor QoL except for the SF-36 social functioning subscale that showed significant improvement after donation (.038) reduction in depression symptom frequency was verified after donation (from 65.6% to 46.9%)There was an almost significant decrease in depression scores (.077)which was in fact was significant when one considered only successful transplants (.021)There was no significant variation in anxiety scores among donors. Time since transplantation was inversely correlated with overall anxiety (.443, .011)and with somatic anxiety subscales (.357, .045)For most donors, the decision to donate was easy and spontaneous. Nearly all donors would donate again and strongly encourage others to donate. Conclusions. Except for the social functioning scale that improved, no significant changes were observed in QoL of living kidney donors after the procedure. Depression scores significantly decreased after donation, but anxiety scores remained stable. Donors, who were mostly siblings, showed positive perceptions about donation, did not regret their decision, and strongly recommend it to others.
- Impact of hepatitis C virus on renal transplantation: association with poor survival.Publication . Pedroso, S.; Martins, La Salete; Fonseca, Isabel; Dias, L.; Henriques, A.C.; Sarmento, A.M.; Cabrita, A.Transplant Proc. 2006 Jul-Aug;38(6):1890-4. Impact of hepatitis C virus on renal transplantation: association with poor survival. Pedroso S, Martins L, Fonseca I, Dias L, Henriques AC, Sarmento AM, Cabrita A. Nephrology and Transplant Departments, Hospital Geral de Santo António, Largo Professor Abel Salazar, 4050-011 Porto, Portugal. sofiapedroso@sapo.pt Abstract Data concerning the effect of hepatitis C virus (HCV) infection on the long-term outcome of patient and allograft survival are conflicting. We performed a retrospective study including all renal transplant recipients who underwent the procedure at our center between July 1983 and December 2004. We compared HCV-positive (n = 155) versus HCV-negative (n = 1044) recipients for the prevalence of anti-HCV, patient/donor characteristics, and graft/patient survival. The prevalence of HCV-positive patients was 12%. The anti-HCV positive recipients displayed a longer time on dialysis (P < .001), more blood transfusions prior to transplant (P < .001), and a higher number of previous transplants (P < .001). There were no differences in the incidence of acute rejection between the two groups. Patient (P = .006) and graft survival (P = .012) were significantly lower in the HCV-positive than the HCV-negative group. Graft survival censored for patient death with a functioning kidney did not differ significantly between HCV-positive and HCV-negative recipients (P = .083). Death from infectious causes was significantly higher among the HCV-positive group (P = .014). We concluded that HCV infection had a significant detrimental impact on patient and renal allograft prognosis. Death from infectious causes was significantly more frequent among HCV-positive than the non-HCV population. PMID: 16908314 [PubMed - indexed for MEDLINE
- Impact of Homocysteinemia on Long-Term Renal Transplant SurvivalPublication . Fonseca, Isabel; Martins, La Salete; Queirós, J.; Mendonça, D.; Dias, L.; Sarmento, A.M.; Henriques, A.C.; Cabrita, A.Impact of Homocysteinemia on Long-Term Renal Transplant Survival I. Fonseca, L. Martins, J. Queirós, D. Mendonça, L. Dias, A.M. Sarmento, A.C. Henriques, and A. Cabrita ABSTRACT Aim. We prospectively followed cohort of 202 renal transplant recipients for years to examine the impact of fasting homocysteinemia on long-term patient and renal allograft survival. Methods. Cox proportional hazards regression analysis was used to identify independent predictors of all-cause mortality and graft loss. Results. Hyperhomocysteinemia (tHcy 15 mol/L) was present in 48.7% of the 202 patients, predominantly among men (55.8%as opposed to women (37.1%)At the end of the follow-up period, 13 (6.4%patients had died including 10 from cardiovascular disease, and 23 had (11.4%had lost their grafts. Patient death with functioning allograft was the most prevalent cause of graft loss (13 recipients)Levels of tHcy were higher among patients who died than among survivors (median 23.9 vs 14.3 mol/L; .005)Median tHcy concentration was also higher among the patients who had lost their allografts than those who did not (median 19.0 vs 14.1 mol/L; .001)In Cox regression model including gender, serum creatinine concentration, transplant duration, traditional cardio- vascular risk factors, and associated conditions, such as past cardiovascular disease, only tHcy concentration (ln) (HR 5.50; 95% CI, 1.56 to 19.36; .008) and age at transplantation (HR 1.07; 95% CI, 1.02 to 1.13; .01) were independent predictors of patient survival. After censoring data for patient death, tHcy concentration was not risk factor for graft loss. Conclusions. This prospective study shows that tHcy concentration is significant predictor of mortality, but not of graft loss, after censoring data for patient death.