C0 correlates poorly with AUC based on PK0-4. Early AUC based on PK0-4 is more closely associated with AR and CsANT than is C0. Our data suggest that a target AUC0-12 of 9500-11500 or AUC0-4 of 4400-5500 microg x h/L may provide optimal Neoral immunosuppression.

Background and objectives: Cardiovascular disease is an important cause of morbidity and death in kidney transplant recipients. This study examines the Framingham risk score's ability to predict cardiac and stroke events. Because cyclosporine and tacrolimus have different cardiovascular risk profiles, these agents were also examined.Design, setting, participants, & measurements: A prospective cohort evaluation of 540 patients were followed for a median of 4.7 yr in an outpatient kidney transplant clinic. Baseline Framingham risk scores were calculated and all cardiovascular outcomes were collected.Results: Rates per 100 patient-years were 1.79 for cardiac and 0.78 for stroke events. The ratio of observed-to-predicted cardiac events was 1.64-fold higher [95% confidence interval (CI) 1.19 to 2.94] for the cohort, 2.74-fold higher (95% CI 1.70 to 4.24) in patients age 45 to 60 with prior cardiac disease or diabetes mellitus, but not higher in other age subgroups. Stroke was not increased above predicted. Risk scores for cardiac (c ‫؍‬ 0.65, P ‫؍‬ 0.003) and stroke (c ‫؍‬ 0.71, P ‫؍‬ 0.004) events were modest predictors. 10-yr event scores for cardiac (9.3 versus 13.5%, P < 0.001) and stroke (7.1 versus 10.0%, P ‫؍‬ 0.002) were lower for tacrolimus compared with cyclosporine-treated patients. However observed cardiac events were higher in tacrolimus recipients (2.50, 95% CI 1.09 to 5.90) in an adjusted Cox model. Conclusions: Although risk scores are only modest predictors, patients with the highest event rates are easily identified. Treating high-risk patients with cardioprotective medications should remain a priority.

The study examines selection for kidney transplantation and determines who are referred, how many had contraindications and whether comorbidity indices predict transplant status. Of 113 consecutive adult incident end-stage renal disease (ESRD) patients at this single center 47 (41.6%) were referred. Using published guidelines, 48 (42.5%) had a specific contraindication. However 26 (23%) were neither referred nor had contraindications. An ESRD mortality score, acute renal failure status and albumin were independent predictors of referral but only the mortality score was predictive of contraindication status. The Charlson and ESRD comorbidity indices were less predictive of contraindication or referral status. In a comparison of patients who were Candidates (referred and no contraindication, n = 39) compared to those who were Neither (not referred and no contraindications, n = 26), age was the most discriminating factor (c = 0.99, 95% CI 0.97-1.00). Comorbidity and mortality indices were inferior. Neither patients were older (75 ± 7 years) and had comorbidity scores that were higher than Candidates but similar to those with contraindications (ESRD index; Neither 3.3 ± 2.5, Candidate 1.4 ± 1.8, and contraindication 4.1 ± 3.4). Comorbitity indices do not help explain selection practices whereas age is an important discriminator. How many Neither patients would benefit from transplantation is not known.

Polyoma virus nephropathy is an important cause of graft dysfunction in kidney transplant recipients and screening to prevent disease has been advocated. Although screening incurs new costs, our hypothesis is that savings from less immunosuppression in those with positive screening tests could pay for overall costs of screening. In 134 consecutive recipients, polyoma virus (positive decoy cells) was detected in the urine of 34 (25.4%) individuals over a 2-year follow-up. Of these 34, 11 had a plasma BK PCR of >7700 copies/mL. Immunosuppression was reduced stepwise in these patients until viral loads fell <1000/mL. Overall screening costs (including extra plasma PCR testing) were estimated at $33 450. Those with positive PCR had greater reductions in annual immunosuppression costs by year 2 ($6452 vs. $2799, p = 0.0015) compared to those with negative screens. At the end of the 2-year period, 61% of the screening costs were covered by less immunosuppressant costs. At the end of 30 months there were net savings. In summary, reductions in immunosuppression cover the cost of screening for polyoma viral infection. Longer-term follow-up is needed to ensure patient outcomes remain acceptable.

Sensitization has a significant negative impact on the outcome of haploidentical LRD kidney transplants. Sensitized potential recipients and their potential donors should be aware of this in arriving at informed decision-making for transplantation. These patients may benefit from more sensitive cross-match testing, more intense or more novel immunosuppression, or immunomodulation to modify their immune responsiveness.