Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

Lower airway flow influences peak nasal inspiratory flow in school-aged children.

BACKGROUND: Rhinitis and asthma frequently coexist. Peak nasal inspiratory flow (PNIF) objectively evaluates nasal obstruction. Lower airway flow's impact on PNIF has seldom been analysed in children. We aimed to study the associations between PNIF and: 1)forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) in children with allergic rhinitis and asthma and healthy controls; 2)allergic rhinitis and asthma control subjective evaluation. METHODS: Sequential assessments of PNIF before and after nasal decongestion and spirometry with bronchodilation test were performed in 65 children (6-12 years) with allergic rhinitis and asthma, and 24 gender, age-matched healthy controls. The Control of Allergic Rhinitis and Asthma Test in children (CARATkids) was used for control assessment. Associations were investigated by multiple linear regression models. RESULTS: Baseline and decongested PNIF correlated with baseline and post-bronchodilation FEV1 and PEF, observed independently of rhinitis and asthma diagnosis. The best model for PNIF included PEF, age and gender. No association was found between PNIF and CARATkids scores, except for nasal obstruction self-report. CONCLUSION: In school-aged children, besides age and gender, PEF values should ideally be known to interpret PNIF values. PNIF can be complementary to subjective control assessment in children with allergic rhinitis and asthma.

Participation of osteoclastogenic factors in immunopathogenesis of human chronic periapical lesions.

BACKGROUND: Chronic periapical lesions (CPLs) are common lesions of the oral cavity and are the result of caries, tooth fracture, iatrogenic causes, or factors causing contamination and pulp necrosis. Inflammatory cells participate in the expansion of CPLs by releasing factors that stimulate or inhibit osteolytic activity. The objective of this study was to investigate the participation of RANKL, TNF-α, cathepsin K, IL-33, and OPG in the development of radicular cysts (RCs) and periapical granulomas (PGs). METHODS: Paraffin-embedded sections of 30 RCs and 22 PGs were submitted to immunohistochemistry. RESULTS: Immunoexpression of the proteins studied was observed in the epithelium and capsule of RCs, as well as in connective tissue of PGs. The expression of the osteoclastogenic factors studied differed significantly in RCs and PGs (P < .001), with lower expression of OPG in RCs. In PGs, the lowest expression was observed for cathepsin K. Comparison of the 2 lesions showed a similar participation of RANKL and IL33, while a significant difference was observed for OPG (P < .001), TNF-α (P = .002), and cathepsin K (P = .016). No association of the expression of the proteins with lesions size was observed. CONCLUSIONS: This study demonstrated the participation of RANKL, TNF-α, IL-33, cathepsin K, and OPG in the development of RCs and PGs, with emphasis on the highest immunoreactivity of cathepsin in RCs and TNF-α and OPG in PGs. OPG possibly determines the slower growth of PGs compared to RCs.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families.

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.

Keratocystic odontogenic tumour arising as a periapical lesion.

AIM: To document a case of a keratocystic odontogenic tumour (KOT) involving the apical region in the maxilla mimicking a periapical lesion of endodontic origin. SUMMARY: Benign and malignant tumours, including odontogenic lesions, can be erroneously diagnosed as periapical radiolucencies. KOTs mimicking periapical lesions of endodontic origin are uncommon, especially when the lesions involve the maxilla. This article describes a 55-year-old man with a well-delimited, oval-shaped, radiolucent lesion, occupying the middle and apical third of teeth 22 and 23. After 30 days, the clinical and radiographic findings remained unchanged and the patient was referred for surgical removal of the lesion. Clinical, radiographic and histopathological features are also discussed and compared with current literature.

Analysis of the frequency and nature of hyaline ring granulomas in inflammatory odontogenic cysts.

AIM: To determine the prevalence of hyaline ring granulomas (HRGs) in a large case series of inflammatory odontogenic cysts, and to investigate the nature of these structures. METHODOLOGY: All records from the patients diagnosed with inflammatory odontogenic cysts between January 1970 and April 2009 were reviewed. Histologic sections were evaluated by light microscopy and cases with HRGs for which sufficient biological material was available were submitted to histochemical analysis (Masson's trichrome) and immunohistochemistry (CD34, CD68 and collagen IV). RESULTS: Twenty-two (3.3%) of the 661 cases of inflammatory odontogenic cysts diagnosed during the study period presented HRGs. The relative frequency of HRGs was higher amongst residual radicular cysts (6.1%), followed by paradental cysts (5.6%) and radicular cysts (3.0%). HRGs appeared as roughly circular homogeneous/fibrillar masses in 14 (63.6%) cases and as round structures enclosing amorphous material in 3 (13.6%) cases. Most (77.8%) roughly circular homogeneous/fibrillar masses were positive for collagen, whereas all (100.0%) round structures enclosing amorphous material were negative for this protein. Immunohistochemistry showed that most mononucleated cells and all multinucleated giant cells were positive for CD68, but negative for CD34, in all cases. In addition, collagen IV immunostaining was negative in amorphous structures and weakly positive in homogeneous/fibrillar masses. CONCLUSIONS: The present results suggest a very low frequency of HRGs in inflammatory odontogenic cysts and support the hypothesis that these structures arise from the implantation of foreign material, most likely food particles of plant or vegetable origin. The diverse microscopic features of HRG possibly represent different developmental stages of this structure.

Diagnosis and treatment of acute humoral kidney allograft rejection.

Acute humoral rejection (AHR) is a severe form of rejection associated with poor graft survival. Prompt diagnosis and rapid institution of therapy are crucial to improve the prognosis. A therapeutic approach based on plasmapheresis, intravenous imunoglobulin, and rituximab seems to be effective in refractory cases. Herein we have described our experience with 11 patients with biopsy-proven AHR who were treated between January 2005 and June 2008. Seven of these patients had panel reactive antibodies titers more than 50%. The diagnosis was based on Banff 2001 criteria; treatment consisted of a combination of plasmapheresis and intravenous immunoglobulin. Four refractory cases were also treated with a single dose of rituximab. One graft was lost due to thrombosis. All other patients recovered graft function with an average creatinine level of 1.6 mg/dL at 8.6 +/- 2.7 months of follow-up.

Pancreas-kidney transplantation and the evolution of pancreatic autoantibodies.

The recurrence or persistence of pancreatic autoantibodies after pancreas-kidney transplantation (PKT) is an intriguing finding. We prospectively analyzed 77 PKTs, searching for risk factors for the expression of these autoimmune markers and their impact on pancreas graft function. Among the 77 PKTs, 24.7% had 0 HLA matches, 20.8% displayed delayed graft function, and 14.3% had acute rejection episodes. Immunosuppression included antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and steroids. Sixty-five patients had both grafts functioning as a follow-up of more than 6 months. In 11 patients anti-glutamic acid decarboxylase (GAD) positivity persists (n = 8) or has recurred (n = 3), 4 of whom show increasing titers. Two patients maintain positive islet cell antibodies (ICA) and anti-GAD antibodies. The 9 patients positive for ICA included 2 who were negative before PKT and 7 who remain positive. The "positive" group (22 patients with positive ICA and/or anti-GAD) did not differ from the global group of 65 functioning PKT in terms of acute rejection episodes, HLA match, and steroid withdrawal. Among the positive patients, there were 2 with borderline glucose levels; however, among the entire "positive" group, the mean fasting glucose, HbA1c, and C-peptide measurements were not significantly different, when compared with the other 65 PKTs. In conclusion, pancreatic autoantibodies may be persistently positive or recur after PKT, despite appropriate immunosuppression. Its impact on long-term pancreas graft survival is unknown. We could not identify risk factors for their expression. An extended follow-up with monitoring and search for other risk factors may be necessary to increase our knowledge in this field.

A Survival Analysis of Living Donor Kidney Transplant.

BACKGROUND: Superior patient and graft survival rates have been attributed to living donor kidney transplant (LDKT) when compared to deceased donor transplantation. The aim of this study was to assess graft survival in a population of LDKT in the last 14 years and the potential impact of some clinical features. METHODS: A retrospective observational study was conducted, reviewing the records of all patients undergoing LDKT in one center from January 1, 2004, to December 31, 2017. Survival data were evaluated by Kaplan-Meier, log rank test, and Cox regression. RESULTS: Two hundred seventy-seven LDKT were performed. The median follow-up time was 4 (0-13) years. Graft loss was observed in 9% of patients; 4 patients died. The overall survival was 97% at year 1, 94% at year 5, and 83% at years 10 and 13. We found a significantly worse graft survival in patients with early vascular complications that required surgical intervention (P = .00) ≥3 HLA MM (P = .01), ≥1 HLA-DR MM (P = .04) and female recipients (P = .01). The negative impact of ≥1 HLA-B MM on survival was borderline (P = .05). After excluding early graft losses secondary to vascular events, ≥1 HLA-A MM and rejection have also implicated a negative impact on survival (P = .04 and .01, respectively). In the multivariate analysis, these variables were still related to inferior survival. CONCLUSIONS: We observed a good overall graft survival (>80% after 13 years). Possible factors related to poor outcomes suggested by this study were early vascular complications; HLA mismatches; rejection; and, with less certainty, female recipients.

Chylous ascites in a renal transplant recipient under sirolimus (rapamycin) treatment.

Ascites is a rare complication of renal transplantation. Ascites has been reported after kidney transplantation due to rejection, decapsulation of the graft, urinary or vascular leak, lymphocele, transudation, or infection. While technical complications of the procedure are the most frequent cause, portal hypertension and graft rejection are other causes. Ascites can occur after renal transplantation independent of kidney function. Usually, a time relation can be made between the surgical procedure and ascites development. Chylous ascites is still more uncommon; it is usually related to traumatic lymphatic injury. Drugs are rarely associated with the genesis of ascites. Sirolimus has been associated with a high rate of lymphoceles, lymphedema, and pulmonary alveolar proteinosis. The exact mechanisms remain unknown. The risk for lymphocele formation with sirolimus is 12% to 15%. Ascites is an adverse effect with an incidence between 3% and 20%, but no relation between sirolimus and chylous ascites was previously established. We present a clinical report of chylous ascites in a renal transplant patient under sirolimus therapy; our investigation pointed to sirolimus as the cause.

Impact assessment in living kidney donation: psychosocial aspects in the donor.

BACKGROUND: Living donor kidney transplantation has a 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; a Sociodemographic, Short-Form 36 Health Survey (SF-36), and a Donation Perceptions Questionnaire. RESULTS: Living kidney donors were siblings (62.5%), parents (34.4%), or a 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 (P = .038). A reduction in depression symptom frequency was verified after donation (from 65.6% to 46.9%). There was an almost significant decrease in depression scores (P = .077), which was in fact was significant when one considered only successful transplants (P = .021). There was no significant variation in anxiety scores among donors. Time since transplantation was inversely correlated with overall anxiety (r = .443, P = .011), and with somatic anxiety subscales (r = .357, P = .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.

The influence of HLA mismatches and immunosuppression on kidney graft survival: an analysis of more than 1300 patients.

New immunosuppressive drugs used in kidney transplantation decreased the incidence of acute rejection. It was hypothesized that, with their power, the importance of HLA matching was decreased. To evaluate the influence of HLA matching, immunosuppression, and other possible risk factors, we analyzed data of 1314 consecutive deceased donor kidney transplantation. We divided the patient population into 4 cohorts, according to the era of transplantation: era 1, before 1990, azathioprine (Aza) and cyclosporine (Csa) no microemulsion; era 2, between 1990 and 1995, Csa microemulsion; era 3, between 1996 and 2000, wide use of mycophenolate mofetil (MMF) and anti-thymocyte globulin (ATG); and era 4, after 2000, marked by sirolimus and tacrolimus (TAC) use. Multivariate analysis compared death-censored graft survival. Using as reference the results obtained with 0 HLA mismatches, we verified, during era 1 and era 2, an increased risk of graft loss for all of the subgroups with HLA mismatch >0. However, during era 3 and era 4, the number of HLA mismatches did not influence graft survival. Although acute rejection and delayed graft function, which decreased in the later periods, remained as prognostic factors for graft loss. Considering the immunosuppressive protocol with Csa+Aza+Pred as reference, protocols used after 1995 with Pred+Csa+ATG, with Pred+Csa+MMF, and with Pred+Tac+MMF presented better survival results. Results showed that the significance of HLA matching decreased while the results improved with the new immunosuppressant drugs. These observations support the hypothesis that the weakened importance of HLA matching may be a consequence of the increasing efficacy of the immunosuppression.

Renal transplantation in patients over 60 years of age: a single-center experience.

The prevalence of end-stage renal disease (ESRD) increases with advancing age. In most countries renal transplant recipients are getting older, too. Transplantation must be considered for ESRD patients older than 60 years; however, there are few data regarding outcomes in this population. We retrospectively reviewed the clinical course of recipients aged > or =60 years (n = 43) who underwent primary or repeated grafts from August 1988 to December 2004. We then compared recipient and donor characteristics as well as graft and patient survivals with recipients aged 18 to 59 years (n = 1058) who were transplanted during the same time. Donor age tended to be higher among the oldest recipient group (P < .001). Mean follow-up was significantly shorter in the group aged > or =60 years (P < .001), as our institution only recently has frequently accepted patients > or =60 years. Older recipients showed more frequent delayed graft function (P = .007), longer initial hospitalization (P = .005), and a significantly lower incidence of posttransplant acute rejection episodes (P = .015). Patient (P = .057), graft (P = .407), and death-censored graft (P = .649) survivals were not different between the two groups. Seven recipients aged > or =60 years died; the main cause of which was cardiovascular in origin. The loss of organs (n = 11) in the older patients was mainly due to death with a functioning kidney (54.5%). Our results confirm that renal transplant must be considered in selected patients older than 60 years as patient and graft survivals are similar to those of younger patients.

Impact of hepatitis C virus on renal transplantation: association with poor survival.

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.

Simultaneous pancreas-kidney transplantation: five-year results from a single center.

We report the 5-year results of our simultaneous pancreas-kidney transplantation (SPKT) program, started on May 2, 2000. Forty-two SPKT were performed on 42 type I diabetic patients with chronic renal failure. The procedure was performed with enteric diversion and vascular anastomosis to the iliac vessels. Immunosuppressive protocol included antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. The 24 women and 18 men had a mean age of 33.5 +/- 6.3 years and mean 22.8 +/- 14.2 years time of diabetes evolution. Forty patients had been on dialysis for 34.3 +/- 24.1 months, and two were preemptive transplantations. Acute rejection episodes were treated in eight patients (19.1%): in three cases they affected both organs; in two only the kidney was affected; and the other three were pancreas graft rejections. The incidence of postoperative complications requiring re-operation was 42.9%, mostly pancreas graft related. Two patients died, one due to cardiovascular disease; the other was transplant related. Three kidney grafts were lost, and the causes were immunologic, thrombosis, and patient death. Pancreas graft loss occurred in seven patients: thrombosis (n = 3); infection (n = 3); immunologic (n = 1). The patients with surviving grafts were doing well, with normal kidney and pancreas function: serum creatinine = 0.89 +/- 0.15 mg/dL; fasting blood glucose = 79 +/- 16 mg/dL; HbA1c = 4.7 +/- 1.1%. The 1-year patient, kidney, and pancreas survival rates were 97.3%, 94.6%, and 83.8% and 5-year values, 91.7%, 89.2%, and 78.7%, respectively. In conclusion, these results are similar to the most recent UNOS/IPTR reports, leading us to consider our experience with SPKT very positive.

Conversion From Twice-Daily to Once-Daily Tacrolimus in Stable Kidney Graft Recipients.

INTRODUCTION: Immunosuppression has a pivotal role in kidney transplantation. The new prolonged-release formulation of tacrolimus was developed to provide a more convenient once-daily dosing to improve patient adherence. METHODS: We selected 60 stable kidney transplant recipients who underwent tacrolimus conversion in our unit. Conversion was made on a 1 mg:1 mg basis in 66.7% of patients (n = 40) and on a 1 mg:1.1 mg basis in the remaining 33.3% (n = 20). Clinical and analytical data at conversion and postconversion was analyzed retrospectively to evaluate the efficacy and safety of conversion from tacrolimus twice-daily to once-daily formulation. RESULTS: A significant reduction in tacrolimus blood levels requiring an increase in tacrolimus daily dose was observed postconversion. Postconversion tacrolimus blood level reduction >25% was significantly higher in the conversion group 1 mg:1 mg basis (P = .004). In patients converted 1 mg:1 mg, female sex and higher tacrolimus level at conversion were significant risk factors for a reduction >25% in tacrolimus blood levels after conversion. No significant change was detected between mean glomerular filtration rate at conversion (57 mL/min) and at 3, 6, and 9 months postconversion. CONCLUSIONS: Once-daily tacrolimus at similar doses to the twice-daily formulation is an efficient and safe treatment option. Conversion made on 1 mg:1.1 mg basis seems advantageous at least in some patients.

Immunosuppression with antithymocyte globulin in renal transplantation: better long-term graft survival.

We analyzed the impact of antithymocyte globulin (ATG) in renal transplantation. We retrospectively studied 1217 recipients performed from July 83 to December 03. ATG-Fresenius-S (ATG-F) was used for induction therapy in 492 patients (40.4%; group I) and compared with group II, 725 patients (59.6%), without antilymphocyte induction. Groups were comparable in terms of recipient gender and race distribution; time on dialysis; cause of renal disease; number of human leukocyte antigen (HLA) mismatches; donor age, gender, and creatinine; and cold ischemia time. Patients with ATG-F were younger (35.8 +/- 13.8 vs 38.9 +/- 12.5 years, P < .001), more frequently hypersensitized (10% vs 3%, P < .001), and had more second transplants (15.7% vs 5.8%, P < .001). The incidence of acute rejection episodes was lower among ATG-F patients (23.6% vs 32.1%, P = .004). Admission time and incidence of delayed graft function (DGF) were similar in the two groups. Graft survival at 1, 5, 10, and 15 years was 88.9%, 80.7%, 71.3%, and 64.9% in group I and 86.4%, 77.4%, 60.7%, and 48.4% in group II (P = .003). The difference in patient survival over the same follow-up did not reach statistical significance. Multivariate analysis showed that the risk of graft failure was higher for those who did not receive ATG-F (HR = 1.51; 95% CI, 1.14 to 2.00; P = .004). Donor age and DGF were also independent predictors of graft failure. Our results showed a better long-term graft survival among patients who received ATG-F, despite their higher immunological risk. The absence of induction with ATG-F, donor age, and DGF were independent risk factors for graft failure.

Conversion to sirolimus in a population of kidney and kidney-pancreas transplant recipients.

INTRODUCTION: Calcineurin inhibitors (CI) are associated with nephrotoxicity that might reduce long-term graft survival. We report our experience with sirolimus (SRL) conversion among a population of kidney and kidney pancreas transplant recipients. METHODS: Thirty transplant recipients (6 women, 24 men; age 41 +/- 10.5 years old) were converted to SRL therapy at 25.97 +/- 32.5 months after transplantation. Indications for conversion were: intolerance to mycophenolate mofetil (n = 13), diabetes mellitus (n = 3), CI nephrotoxicity (n = 11), CI nephrotoxicity with chronic allograft rejection (n = 2), and side effects of azathioprine (n = 1). Follow-up after conversion is 3 to 45 months. RESULTS: No significant changes were observed in the 3 months postconversion in renal function, hematological profile, and mean arterial blood pressure. In contrast there was a significant increase in cholesterol values (pre: 198.7 +/- 49.4, versus post 221.2 +/- 60.8, P = .018). At a follow-up of 15.2 +/- 9.9 months after conversion two patients (6.7%) died with functioning allograft (one because of infection and one to myocardial infarct) three kidney allografts (10.7%) have been lost: two chronic rejection; one infection. In two patients SRL therapy was discontinued (one infection, one refractory edema). Neither significant change in renal function nor episodes of acute rejection were observed. CONCLUSIONS: Conversion to SRL was safe. There was no deterioration in renal function nor episodes of acute rejection. There was a significant increase in cholesterol values after conversion. The size of the sample and the time of follow-up may have determined our results.

Impact of homocysteinemia on long-term renal transplant survival.

AIM: We prospectively followed a cohort of 202 renal transplant recipients for 5 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 micromol/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 a 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 micromol/L; P = .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 micromol/L; P = .001). In a Cox regression model including gender, serum creatinine concentration, transplant duration, traditional cardiovascular risk factors, and associated conditions, such as past cardiovascular disease, only tHcy concentration (ln) (HR = 5.50; 95% CI, 1.56 to 19.36; P = .008) and age at transplantation (HR = 1.07; 95% CI, 1.02 to 1.13; P = .01) were independent predictors of patient survival. After censoring data for patient death, tHcy concentration was not a risk factor for graft loss. CONCLUSIONS: This prospective study shows that tHcy concentration is a significant predictor of mortality, but not of graft loss, after censoring data for patient death.