G. Alves-Filho

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full‐dose cyclosporine (CsA) (Neoral®). Two multicenter randomized controlled studies were performed to compare 12‐month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced‐dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral® dose guided by C2 (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced‐dose Neoral®, demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral®.

Posttransplant Diabetes Mellitus: Incidence and Risk Factors

UNLABELLED Posttransplant diabetes mellitus (PTDM) is common post transplantation and is associated with tacrolimus (TAC) and steroid therapy. The aim of the present study was to analyze the incidences of PTDM and associated risk factors. METHODS We selected renal transplant recipients treated with TAC, mycophenolate mofetil (MM), and steroids. Exclusion criteria were recipients <18 years old, history of diabetes, recipients of kidney/pancreas, and/or those receiving cyclosporine or sirolimus. PTDM was defined as glucose >126 mg/dL, with or without drug therapy. RESULTS Among 67 patients who fulfilled the inclusion criteria, 18 (26.8%) developed PTDM within 2 months of transplantation. Compared with normal glucose patients, the PTDM group was older, male, received a kidney from deceased donors, and showed higher pretransplant glucose levels. No differences were noticed in renal function or daily dose of TAC or steroids. However, TAC trough levels in the first month were higher among the PTDM group, despite the lower dose per kilogram. After 1 year of follow-up, weight gain as well as daily TAC per kilogram dose was less among PTDM patients. Analysis of potential risk factors showed a higher incidence of hepatitis C virus infection in the PTDM group, as well as a higher frequency of HLA DR13. CONCLUSION The incidence of PTDM diagnosed in the early posttransplant period in the present series was 26.8%. Risk factors included older age, male gender, recipients of kidneys from deceased donors, hepatitis C virus infection, higher pretransplant glucose levels, and higher TAC trough levels during the first month posttransplant.

Delayed Graft Function in Renal Transplant Recipients : Risk Factors and Impact on 1 -Year Graft Function: A Single Center Analysis

UNLABELLED Delayed graft function (DGF), a frequent complication after kidney transplantation, occurs among about 60% of recipients of kidneys from deceased donors. DGF has a multifactorial etiology. It is characterized by acute tubular necrosis (ATN) upon biopsy. In this study we sought to identify among a group of recipients of kidneys from deceased donors, the incidence, risk factors, and impacts on patient and graft survivals of DGF. MATERIALS AND METHODS We retrospectively analyzed medical records from renal transplant recipients aged >18 years who received a deceased donor kidney graft between January 2003 and December 2006. Kidneys lost during the first week posttransplantation were excluded from this series. RESULTS Among 165 transplants, 111 (67%) displayed DGF, defined as the need for dialysis during the first week posttransplantation. The incidence of DGF was higher among patients with a cold ischemia time (CIT) > 24 hours: 85% vs 60%, DGF vs no DGF (P < .05), as well as for grafts from older donors. After 1-year follow-up, the DGF group showed worse graft function (serum creatinine 1.6 +/- 0.7 vs 1.3 +/- 0.4 mg/dL; P < .05) as well as a greater incidence of graft loss. CONCLUSION Prolonged cold ischemia and older donor age were associated with a greater incidence of DGF in this series, leading to prolonged hospitalization, increased risk for an acute rejection episode, and reduced graft function and survival after 1 year.

Acute tubulointerstitial nephritis and uveitis with antineutrophil cytoplasmic antibody

We report a case of acute tubulointerstitial nephritis and uveitis (TINU syndrome) in a 47-year-old woman who also was found to have antineutrophil cytoplasmic antibody. The patient developed severe acute renal failure that improved after a high dose (1 mg/kg/d) of corticosteroid therapy. The diagnosis of the disorder is discussed, as well as the finding of antineutrophil cytoplasmic antibody.

Tuberculosis in Renal Transplant Recipients: A Brazilian Center Registry

UNLABELLED Renal transplant recipients receiving immunosuppression show an increased risk for developing opportunistic infections, such as tuberculosis (TB). TB represents the major cause of morbidity and mortality in the world, mainly in underdeveloped countries. The aim of this study was to analyze the incidence of TB and its presentation among renal transplant recipients over 20 years. PATIENTS AND METHODS This retrospective analysis included medical records of renal transplant recipients from January 1984 to April 2007. RESULTS Among 1342 renal transplant recipients, 31 received treatment for TB due to clinical disease (n = 23) or prophylaxis (n = 8). The overall incidence of TB was 1.71%, which was diagnosed at 53 +/- 49 months posttransplantation. The indications for TB prophylaxis were a previous history of TB (n = 6) or direct contact with a TB carrier (n = 1). The most common clinical presentation was extrapulmonary (n = 13). The classical treatment was effective in 16 cases. However, 7 cases of resistant TB required ethambutol added to therapy. Adverse events of treatment included liver toxicity (n = 1) and peripheral neuropathy (n = 1). Three patients died due to TB-related complications. Graft loss was observed in 3 patients after cessation of TB treatment. None of the patients on prophylaxis developed clinical disease. CONCLUSIONS TB incidence was significantly greater among renal transplant recipients compared with the local population, with a higher incidence of extrapulmonary disease. TB prophylaxis in selected cases was effective, avoiding new infections.

Chronic liver disease in kidney recipients with hepatitis C virus infection

Abstract: Background:  The prevalence of anti‐hepatitis C virus (HCV) positive test is higher among patients in dialysis and in kidney recipients than in general population. Hepatitis C virus infection is the main cause of chronic liver disease in renal transplant patients. Liver biopsy and virological analysis were performed to clarify the grade of liver damage in kidney recipients.

Systemic Lupus Erythematosus After Renal Transplantation: Is Complement a Good Marker for Graft Survival?

BACKGROUND Renal transplantation is considered a safe procedure for patients with systemic lupus erythematosus (SLE). However, the recurrence of disease and its impact on graft survival remains controversial. METHODS To analyze the presence of lupus serology activity during dialysis and its impact on lupus recurrence after transplantation, we performed a retrospective analysis of 23 lupus patients who received 26 kidney transplantations. RESULTS Twenty-three patients received 26 renal transplantations from 1984 to 2003. Twelve patients presented pretransplant lupus activity (low complement and ANA > 1/40), without correlation with length of dialysis, but associated with proliferative glomerulonephritis (class IV) pretransplant. Among 26 grafts, 6 were lost in the first 6 months posttransplant. Among the remaining 20 functioning grafts, low complement activity occurred in 8, being associated with recurrence of immune deposits in 3 cases. Analysis of lupus activity showed that only one patient with a normal complement level posttransplant presented SLEDAI > 4, associated with persistent proteinuria and a graft biopsy without immune deposits. Graft survival was reduced in the presence of low complement posttransplantation. CONCLUSION Low complement levels after renal transplantation, in association with proteinuria may be considered to be a risk factor for recurrence of immune deposits, with a negative impact on graft survival.

Skin Malignancies in Renal Transplant Recipients: A Brazilian Center Registry

UNLABELLED Renal transplant recipients have an increased risk of malignancies, especially nonmelanoma skin cancers, compared with the normal population. The aim of the present study was to analyze the incidence of skin malignancies in a setting of renal transplant recipients over 20 years follow-up. PATIENTS AND METHODS This retrospective analysis of medical records included posttransplant patients with biopsy-proven skin cancer. Recipients of pancreas kidney transplants or with suspected but not biopsy-proven skin malignancy were excluded from this series. RESULTS Among 1300 renal transplant recipients from January 1984 to December 2006, 33 (2.5%) were diagnosed with skin malignancies during follow-up. The majority of patients were men (70.2%), of white race (97%), and with a mean posttransplant follow-up of 65 months. The most frequent skin cancer was squamous cell carcinoma (46.2%), in single or multiple lesions (50% each group). Basal cell carcinoma was diagnosed in seven patients; most presented as a single lesion (71.3%). Eight patients presented with more than one histologic type of skin cancer; most frequently squamous and basal cell carcinomas. Kaposi sarcoma was diagnosed in four patients, one of whom also had a basal cell carcinoma. CONCLUSION The incidence of skin malignancies in this series was 2.5%. The most frequent tumor was squamous cell carcinoma, isolated or in association with basal cell carcinoma. An higher frequency was observed in white male patients, at a mean follow-up of 5 years posttransplantation.

Changes in Serological Markers of Hepatitis B Virus After Renal Transplantation

An estimated 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Immunosuppression after renal transplantation seems to enhance viral replication and increase the risk of developing cirrhosis and hepatocellular carcinoma. This retrospective study was performed to assess the prevalence among and serological status of HBV infection after renal transplantation at a single university Brazilian center. Thirty six (4.2%) patients among 850 kidney recipients showed positive HBsAg for more than 6 months; 31 were hepatitis B surface antigen (HBsAg) positive at transplantation. Of the 15 hepatitis B e antigen (HbeAg) positive patients, six had spontaneous HBeAg seroconversion and three also had HBsAg clearance. An additional two showed HBeAg clearance with Lamivudine without seroconversion. Among 15 HBeAg-negative patients, three developed HBeAg reversion with no elevation of alanine transferase (ALT) levels and one had HBsAg clearance. Only one patient had acute exacerbation of hepatitis B (ALT > 20 times normal range) but remained HbeAg negative. During follow-up, five patients became HBsAg positive; two reactivations of resolved hepatitis B, two with previous anti-HBS induced by vaccination, and one with no serological marker for HBV. Lamivudine was prescribed for 16 patients, two of whom had HbeAg clearance without seroconversion and five who developed viral resistance to Lamivudine after a mean of 29.2 months. No hepatocellular carcinoma or deaths related to hepatitis B were seen in this group. In summary, prevalence of HBV in kidney transplant patients was 4.2%. Immunosuppression after renal transplantation in HBV infection led to an increased risk of liver complications and changes in HBV serological status.