Tammy Ojo

Comparison of the long-term outcomes of kidney transplantation: USA versus Spain

BACKGROUND The long-term outcomes of kidney transplantation are suboptimal because many patients lose their allografts or experience premature death. Cross-country comparisons of long-term outcomes of kidney transplantation may provide insight into factors contributing to premature graft failure and death. We evaluated the rates of late graft failure and death among US and Spanish kidney recipients. METHODS This is a cohort study of US (n = 9609) and Spanish (n = 3808) patients who received a deceased donor kidney transplant in 1990, 1994, 1998 or 2002 and had a functioning allograft 1 year after transplantation with follow-up through September 2006. Ten-year overall and death-censored graft survival and 10-year overall recipient survival and death with graft function (DWGF) were estimated with multivariate Cox models. RESULTS Among recipients alive with graft function 1 year after transplant, the 10-year graft survival was 71.3% for Spanish and 53.4% for US recipients (P < 0.001). The 10-year, death-censored graft survival was 75.6 and 76.0% for Spanish and US recipients, respectively (P = 0.73). The 10-year recipient survival was 86.2% for Spanish and 67.4% for US recipients (P < 0.001). In recipients with diabetes as the cause of ESRD, the adjusted DWGF rates at 10 years were 23.9 and 53.8 per 1000 person-years for Spanish and US recipients, respectively (P < 0.001). Among recipients whose cause of ESRD was not diabetes mellitus, the adjusted 10-year DWGF rates were 11.0 and 25.4 per 1000 person-years for Spanish and US recipients, respectively. CONCLUSIONS US kidney transplant recipients had more than twice the long-term hazard of DWGF compared with Spanish kidney transplant recipients and similar levels of death-censored graft function. Pre-transplant medical care, comorbidities, such as cardiovascular disease, and their management in each countrys health system are possible explanations for the differences between the two countries.

Etanercept-associated Pulmonary Granulomatous Inflammation in Patients with Rheumatoid Arthritis

To the Editor: We describe 4 patients with rheumatoid arthritis (RA) who developed noninfectious pulmonary granulomatous disease while treated with etanercept (Table 1).All patients improved with withdrawal of etanercept and addition of prednisone, without use of antibiotic, antifungal, or antimycobacterial medications. They were subsequently treated with adalimumab with no recurrence of pulmonary toxicity. Patient 1. After an inadequate response to leflunomide, a 60-year-old man with 1 year of seropositive RA started etanercept, with subsequent improvement. He then experienced progressive malaise and a 40-lb weight loss. Chest radiograph and computed tomography (CT) scan revealed multiple pulmonary nodules bilaterally. Open-lung biopsy demonstrated ...

Longitudinal forced vital capacity monitoring as a prognostic adjunct after lung transplantation

RATIONALE After lung transplantation, spirometric values are routinely followed to assess graft function. FEV1 is used to characterize chronic allograft dysfunction, whereas the course of FVC change has been less acknowledged and rarely used. OBJECTIVES To better understand the temporal relationship and prognostic ability of FEV1 and FVC decline after lung transplantation. METHODS Serial FEV1 and FVC values were studied among 205 bilateral lung transplant recipients. Different decline patterns were characterized and evaluated for prognostic value via restricted mean modeling of mortality and times to other pertinent events. MEASUREMENTS AND MAIN RESULTS Baseline FEV1 was achieved earlier than baseline FVC (median, 296 vs. 378 d; P < 0.0001). Decline in FEV1 or FVC from their respective post-transplant baselines occurred in 85 patients (41%). Fifty-nine of 85 (69%) had an isolated FEV1 decline, with 80% later meeting the FVC decline criterion. This subsequent FVC decline was associated with worsening FEV1 and lower median survival. Twenty-five of 85 patients (29%) demonstrated concurrent FEV1 and FVC decline. Patients with concurrent decline had higher 1- and 5-year mortality rates (1-yr, 53% vs. 18%, P < 0.0001; 5-yr, 61% vs. 48%, P = 0.001). These patients were more likely to have rapid-onset of spirometry decline (P = 0.05) and lower FEV1% predicted (P = 0.04) at presentation. CONCLUSIONS FVC decline from its post-transplant baseline provides valuable prognostic information. Concurrent FEV1 and FVC decline identifies patients with fulminant, rapid deterioration and is the strongest clinical predictor of poor survival. Subsequent FVC decline in patients with an initial isolated FEV1 decline identifies disease progression and portends poor prognosis.

Mycophenolic acid pharmacokinetics in lung transplant recipients with cystic fibrosis.

Background: Lung transplantation is an established treatment for cystic fibrosis (CF) patients with end-stage lung disease. Current immunosuppression includes the prodrug mycophenolate mofetil (MMF), which has led to improved transplant outcomes. Given the pancreatic insufficiency and malabsorption in CF patients, some transplant centers give higher doses of MMF to these patients based on lower predose levels (C0), even though C0 values correlate poorly with mycophenolic acid (MPA) exposure. The focus of this pilot study was to determine the pharmacokinetics (PK) of MPA in CF when compared with noncystic fibrosis (NCF) lung transplant recipients. Methods: Five CF and 5 NCF patients had 3 separate PK analyses performed through our clinical research center. In addition to MMF, all patients were on tacrolimus and prednisone and were diabetic on insulin. Twelve-hour total serum concentration–time profiles of MPA and MPA glucuronide (MPAG) were obtained after oral administration of MMF. Concentrations of total MPA and MPAG were determined by a validated liquid chromatography–tandem mass spectrometry method. PK parameters of MPA were calculated by the noncompartmental method. Student t test or Mann–Whitney test was used to assess the differences in the PK parameters between the 2 cohorts. Results: CF patients were significantly younger (30.6 versus 59.4 years; P < 0.001) and had significantly lower serum albumin (3.8 versus 4.1 g/dL; P = 0.0018) than NCF patients. CF patients had significantly lower MPA area under the curve (47.7 versus 83.1 mg·h·L−1; P = 0.016) and MPAG area under the curve (569 versus 911 mg·h·L−1; P = 0.047) when compared with NCF patients. In addition, C0 (2.6 versus 4.6 mg/L; P = 0.026) and maximum serum concentration (9.2 versus 20.3 mg/L; P = 0.016) were significantly lower, and apparent oral clearance (0.26 versus 0.13 L·h−1·kg−1; P = 0.009) was significantly higher in CF patients. Tmax was delayed in CF patients but not significantly. No difference between CF and NCF patients was observed for intra- and interindividual variability. Conclusions: Given these results, the lower MPA exposure in CF patients may impact transplant outcome in this lung transplant population.