Twelve-month kidney and liver outcomes of kidney transplantation from Hepatitis C Viremic deceased donors to aviremic recipients.

INTRODUCTION: Utilization of hepatitis C viremic (HCV+) deceased donor kidneys (DDKT) for aviremic recipients increases opportunities for transplantation with excellent short-term outcomes. Our primary aim was to understand longer-term outcomes, specifically assessing kidney and liver function in the first year posttransplant. METHODS: This was a retrospective single-center study of adult DDKT recipients of HCV+ kidneys (cases) matched 1:1 to recipients of HCV- kidneys (comparators). Between-group outcomes were analyzed using comparisons of means and proportions, survival analysis methods, and multivariable mixed effects models. RESULTS: Sixty-five cases and 65 comparators had statistically comparable demographic and clinical characteristics. There were no between-group differences in serum creatinine or estimated glomerular filtration rate at month 12 (p = .662) or in their trajectories over months 1-12 (p > .292). Within the first 60 days, rates of liver function values >3 times upper limit of normal among cases were comparable to comparators for aspartate aminotransferase (AST) (14% vs. 6%, p = .242) and higher for alanine transaminase (ALT) (23% vs. 6%, p = .011). AST declined during the first 8 weeks (p = .005) and stabilized for both groups (p = .406) during the following 10 months. ALT declined during the first 8 weeks (p < .001), continued to decline over months 3-12 (p = .016), and the trajectory was unrelated to antiviral therapy initiation among cases. CONCLUSIONS: Aviremic recipients of HCV+ kidneys had comparable kidney outcomes to matched recipients of HCV- kidneys. Despite more HCV+ recipients having an elevation in ALT within the first 60 days, ALT values normalized with no identified liver complications attributed to HCV.

Integrating pharmacists into a kidney transplant clinic: Developing and implementing a collaborative pharmacy practice agreement.

BACKGROUND: Collaborative pharmacy practice agreements (CPPAs) grant patient care authorities to pharmacists (PharmDs) under a scope of practice without direct physician supervision. OBJECTIVES: The aim of this study was to discuss steps for developing and implementing a CPPA in an outpatient renal transplant clinic and assess changes in physician and nurse burden, integrated pharmacy growth, and patient safety. PRACTICE DESCRIPTION: A CPPA was developed between physicians and pharmacists and implemented into a renal transplant clinic and the integrated pharmacy over the course of several years. PRACTICE INNOVATION: CPPA execution in a post-transplant clinic has not been previously described and is needed to help advance patient care delivery models. EVALUATION METHODS: This single center, retrospective study compared immunosuppressant prescriptions generated by each authorizer type (nurse, physician, pharmacist) across 3 time periods: before pharmacist integration, during CPPA development, and after CPPA implementation. Pharmacy manpower and patient safety concerns post-CPPA implementation were also reviewed. RESULTS: Results show that prescription authorization migrated from either a nurse or physician (57% and 43% respectively) in pre-PharmD period, to mostly by physicians (72%) in PharmD pre-CPPA period, and largely by pharmacists (85%) in PharmD post-CPPA period. Quarterly prescription volume increased (6019 in quarter 3 of 2015 vs. 14,806 in quarter 4 of 2018) and integrated pharmacy staff grew from 8 employees (Pre-PharmD period) to 20 in PharmD post-CPPA period. No safety concerns were reported in any time period. CONCLUSION: CPPAs have the advantage of reducing physician and nurse workload related to prescribing and advancing the role of the pharmacist by utilizing their expertise to take over certain tasks. Lessons learned during the CPPA implementation process include identifying needs, promoting maximal utility of pharmacists, and maintaining optimal communication between the health care team.

Monoclonal antibody treatment for COVID-19 in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at high risk for severe coronavirus disease 2019 (COVID-19). Studies suggest that early intervention with monoclonal antibody (MAB) treatment directed against the SARS-CoV-2 spike protein may reduce the risk of emergency department visits or hospitalization for COVID-19, especially in high-risk patients. Herein, we describe our single-center experience of 93 SOT (50 kidney, 17 liver, 11 lung, nine heart, and six dual-organ) recipients with mild to moderate COVID-19 who were treated with bamlanivimab or casirivimab-imdevimab per emergency use authorization guidelines. Median age of recipients was 55 [(Interquartile range) 44-63] years, and 41% were diabetic. Median time from transplant to MAB was 64 (IQR 24-122) months and median time from the onset of COVID-19 symptoms to the infusion was 6 (IQR 4-7) days. All patients had a minimum 30 days of study follow-up. The 30-day hospitalization rate for COVID-19-directed therapy was 8.7%. Infusion-related adverse events were rare and generally mild. Biopsy-proven organ rejection occurred in two patients, and there were no graft losses or deaths. A comparator group of 72 SOT recipients diagnosed with COVID-19 who were eligible but did not receive MAB treatment had a higher 30-day hospitalization rate for COVID-19-directed therapy (15.3%), although this difference was not statistically significant, after adjustment for age (Odds Ratio 0.49 [95% Confidence Interval 0.18-1.32], p = 0.16). Our experience suggests that MAB treatment, with respect to the available MAB formulations and circulating viral variants present during our study period, may provide favorable outcomes for mild to moderate COVID-19 in SOT recipients.

Kidney Transplantation From Hepatitis C Viremic Deceased Donors to Aviremic Recipients in a Real-world Setting.

Transplantation of hepatitis C viremic (HCV+) deceased donor kidney transplants (DDKT) into aviremic (HCV-) recipients is a strategy to increase organ utilization. However, there are concerns around inferior recipient outcomes due to delayed initiation of direct-acting antiviral (DAA) therapy and sustained HCV replication when implemented outside of a research setting. METHODS: This was a retrospective single-center matched cohort study of DDKT recipients of HCV+ donors (cases) who were matched 1:1 to recipients of HCV- donors (comparators) by age, gender, race, presence of diabetes, kidney donor profile index, and calculated panel-reactive antibody. Data were analyzed using summary statistics, t-tests, and chi-square tests for between-group comparisons, and linear mixed-effects models for longitudinal data. RESULTS: Each group consisted of 50 recipients with no significant differences in baseline characteristics. The 6-mo longitudinal trajectory of serum creatinine and estimated glomerular filtration rate did not differ between groups. All recipients had similar rates of acute rejection and readmissions (all P > 0.05). One case lost the allograft 151 d posttransplant because of acute rejection, and 1 comparator died on postoperative day 7 from cardiac arrest. HCV+ recipients initiated DAA on average 29 ± 11 d posttransplant. Ninety-eight percent achieved sustained virologic response at 4 and 12 wks with the first course of therapy; 1 patient had persistent HCV infection and was cured with a second course of DAA. CONCLUSIONS: Aviremic recipients of HCV+ DDKT with delayed DAA initiation posttransplant had similar short-term outcomes compared with matched recipient comparators of HCV- donors.

Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation.

Background: Despite advances in immune suppression, kidney allograft rejection and other injuries remain a significant clinical concern, particularly with regards to long-term allograft survival. Evaluation of immune activity can provide information about rejection status and help guide interventions to extend allograft life. Here, we describe the validation of a blood gene expression classifier developed to differentiate immune quiescence from both T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). Methods: A five-gene classifier (DCAF12, MARCH8, FLT3, IL1R2, and PDCD1) was developed on 56 peripheral blood samples and validated on two sample sets independent of the training cohort. The primary validation set comprised 98 quiescence samples and 18 rejection samples: seven TCMR, ten ABMR, and one mixed rejection. The second validation set included eight quiescence and 11 rejection samples: seven TCMR, two ABMR, and two mixed rejection. AlloSure donor-derived cell-free DNA (dd-cfDNA) was also evaluated. Results: AlloMap Kidney classifier scores in the primary validation set differed significantly between quiescence (median, 9.49; IQR, 7.68-11.53) and rejection (median, 13.09; IQR, 11.25-15.28), with P<0.001. In the second validation set, the cohorts were statistically different (P=0.03) and the medians were similar to the primary validation set. The AUC for discriminating rejection from quiescence was 0.786 for the primary validation and 0.800 for the second validation. AlloMap Kidney results were not significantly correlated with AlloSure, although both were elevated in rejection. The ability to discriminate rejection from quiescence was improved when AlloSure and AlloMap Kidney were used together (AUC, 0.894). Conclusion: Validation of AlloMap Kidney demonstrated the ability to differentiate between rejection and immune quiescence using a range of scores. The diagnostic performance suggests that assessment of the mechanisms of immunologic activity is complementary to allograft injury information derived from AlloSure dd-cfDNA. Together, these biomarkers offer a more comprehensive assessment of allograft health and immune quiescence.

The effect of pulsatile pump perfusion on hepatitis C transmission in kidney transplantation: A prospective pilot study.

With increasing utilization of hepatitis C (HCV) viremic donor organs, there may be a role for kidney pump perfusion to reduce viral load and prevent HCV transmission. We performed a prospective pilot study of HCV viremic donors; one kidney from each donor pair was pumped with perfusate exchanges and viral load testing at least every 4 hours. Donor, recipient, and transplant characteristics were obtained with clinical outcomes. Linear regression was performed to quantify the association between pump time and perfusate viral load. Six HCV viremic donors for six pairs of aviremic recipients were included. Perfusate of the pumped kidneys showed detectable virus throughout the pump cycles. Although perfusate viral levels decreased with increasing pump times, this was not statistically significant (ß = -.48, P = .36). All recipients had detectable HCV RNA postoperatively. The pumped cohort had an insignificantly reduced mean viral load compared to pumped recipients (1352 ± 2006 vs 26 170 ± 61 211, P = .09). Time to initiation of direct-acting antiviral was 32 ± 12 vs 26 ± 7 days (P = .17) and to undetectable levels was 66 ± 27 vs 55 ± 22 days (P = .82) for the pumped and unpumped cohorts, respectively. Pulsatile perfusion alone does not appear adequate to decrease HCV transmission. Future studies will need to explore additional ex vivo interventions to pumping.

How Should We Manage Renal Transplant Patients with Failed Allografts Who Return to Dialysis?

Patients with failing renal allografts often progress to end-stage renal disease, unlike transplant-naive chronic kidney disease patients, in an accelerated and unpredictable manner. The variability of this population renders decisions regarding placement of permanent dialysis access more difficult. Since patients with failed allografts who return to dialysis experience higher rates of morbidity and mortality, recognition and optimization of factors that will improve survival outcomes and quality of life are tantamount to longer term success. We provide guidelines on several topics such as immunosuppression withdrawal and determination of nephrectomy need versus retaining the allograft based on the current literature and our copious single-center experience.

Unexpected Race and Ethnicity Differences in the US National Veterans Affairs Kidney Transplant Program.

BACKGROUND: Racial/ethnic minorities have lower rates of deceased kidney transplantation (DDKT) and living donor kidney transplantation (LDKT) in the United States. We examined whether social determinants of health (eg, demographics, cultural, psychosocial, knowledge factors) could account for differences in the Veterans Affairs (VA) Kidney Transplantation (KT) Program. METHODS: We conducted a multicenter longitudinal cohort study of 611 Veterans undergoing evaluation for KT at all National VA KT Centers (2010-2012) using an interview after KT evaluation and tracking participants via medical records through 2017. RESULTS: Hispanics were more likely to get any KT (subdistribution hazard ratios [SHR] [95% confidence interval (CI)]: 1.8 [1.2-2.8]) or DDKT (SHR [95% CI]: 2.0 [1.3-3.2]) than non-Hispanic white in univariable analysis. Social determinants of health, including marital status (SHR [95% CI]: 0.6 [0.4-0.9]), religious objection to LDKT (SHR [95% CI]: 0.6 [0.4-1.0]), and donor preference (SHR [95% CI]: 2.5 [1.2-5.1]), accounted for some racial differences, and changes to Kidney Allocation System policy (SHR [95% CI]: 0.3 [0.2-0.5]) mitigated race differences in DDKT in multivariable analysis. For LDKT, non-Hispanic African American Veterans were less likely to receive an LDKT than non-Hispanic white (SHR [95% CI]: 0.2 [0.0-0.7]), but accounting for age (SHR [95% CI]: 1.0 [0.9-1.0]), insurance (SHR [95% CI]: 5.9 [1.1-33.7]), presenting with a living donor (SHR [95% CI]: 4.1 [1.4-12.3]), dialysis duration (SHR [95% CI]: 0.3 [0.2-0.6]), network of potential donors (SHR [95% CI]: 1.0 [1.0-1.1]), self-esteem (SHR [95% CI]: 0.4 [0.2-0.8]), transplant knowledge (SHR [95% CI]: 1.3 [1.0-1.7]), and changes to Kidney Allocation System policy (SHR [95% CI]: 10.3 [2.5-42.1]) in multivariable analysis eliminated those disparities. CONCLUSIONS: The VA KT Program does not exhibit the same pattern of disparities in KT receipt as non-VA centers. Transplant centers can use identified risk factors to target patients who may need more support to ensure they receive a transplant.

Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients.

BACKGROUND: Elevated levels of donor-derived cell-free DNA (dd-cfDNA) in the plasma of renal allograft recipients indicates organ injury and an increased probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens are associated with risk of antibody-mediated rejection (ABMR). This study assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR. METHODS: Donor-derived cell-free DNA was assayed in 90 blood samples with paired DSA and clinically indicated biopsies from 87 kidney transplant patients. Sixteen cases met criteria for active ABMR. Performance characteristics of dd-cfDNA for diagnosis of active ABMR were determined for samples with prior or current positive DSA (DSA+, n = 33). RESULTS: The median level of dd-cfDNA (2.9%) in DSA+ patients with active ABMR was significantly higher than the median level (0.34%) in DSA+ patients without ABMR (P < 0.001). The median level of dd-cfDNA in DSA- patients was 0.29%. The positive predictive value of dd-cfDNA (at 1%) to detect active ABMR in DSA+ patients was 81%, whereas the negative predictive value was 83%. The positive predictive value for DSA+ alone was 48%. CONCLUSIONS: The combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results have a high probability of active ABMR.

Novel pathologic scoring tools predict end-stage kidney disease in light chain (AL) amyloidosis.

BACKGROUND AND OBJECTIVES: Light chain (AL) amyloidosis frequently involves the kidney, causing significant morbidity and mortality. A pathologic scoring system with prognostic utility has not been developed. We hypothesized that the extent of amyloid deposition and degree of scarring injury on kidney biopsy, could provide prognostic value, and aimed to develop pathologic scoring tools based on these features. METHODS: This is a case-control study of 39 patients treated for AL amyloidosis with biopsy-proven kidney involvement at a large academic medical center. Our novel scoring tools, composite scarring injury score (CSIS) and amyloid score (AS) were applied to each kidney biopsy. The primary outcome was progression to dialysis-dependent end-stage kidney disease (ESKD) using a 12-month landmark analysis. RESULTS: At 12 months, nine patients had progressed to ESKD. Patients with an AS ≥7.5 had a significantly higher cumulative incidence of ESKD than those with AS <7.5 (p = .04, 95% CI 0.13-0.64). CONCLUSIONS: Using a 12-month landmark analysis, AS correlated with progression to ESKD. These data suggest that a kidney biopsy, in addition to providing diagnostic information, can be the basis for a pathologic scoring system with prognostic significance.

Outcomes from Autologous Hematopoietic Cell Transplantation versus Chemotherapy Alone for the Management of Light Chain Amyloidosis.

Light chain amyloidosis (AL) results in tissue deposition of misfolded proteins, causing organ dysfunction. In an era of modern therapies, such as bortezomib, reassessment of the benefit of autologous hematopoietic cell transplantation (AHCT) should be considered. In this study, we compared outcomes between patients with AL receiving chemotherapy alone (CT) and those undergoing AHCT. Seventy-four patients with AL were analyzed retrospectively. Two cohorts of patients were studied, those receiving CT (n = 31) and those undergoing AHCT (n = 43). Of the 43 patients in the AHCT cohort, 29 received induction chemotherapy before AHCT, whereas 14 proceeded straight to AHCT without induction therapy. Compared with the CT cohort, patients in the AHCT cohort were younger and had higher ejection fractions, lower brain natriuretic peptide levels, and more severe proteinuria. The majority (87%) of patients in the CT cohort received bortezomib-based treatment. Transplantation-related mortality (TRM) was 7%. Patients receiving AHCT were more likely to achieve complete or very good partial response (P = .048). The median progression-free survival (PFS) and overall survival (OS) were superior in the AHCT cohort (not reached versus 9 months; P < .01 and 74 months versus 8 months; P = .03, respectively). Multivariable analysis demonstrated that improved PFS (hazard ratio, 3.86; 95% confidence interval [CI] 1.3 to 11.5; P = .02) and OS (hazard ratio, 5.6; 95% CI, 1.9 to 16; P < .001) were associated with use of AHCT compared with CT. Patients in the AHCT cohort had deeper and longer durations of response, with superior PFS and OS, compared with those in the CT cohort. Despite the limitations of this study, AHCT should be considered for eligible patients with AL at experienced transplantation centers that can offer this therapy with a low risk of TRM.

Cell-Free DNA and Active Rejection in Kidney Allografts.

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.

Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications.

BACKGROUND: Previous studies have demonstrated that donor-derived cell-free DNA (dd-cfDNA) found in circulating blood of transplant recipients may serve as a noninvasive biomarker of allograft rejection. To better interpret the clinical meaning of dd-cfDNA, it is essential to understand the biological variation of this biomarker in stable healthy recipients. This report establishes the biological variation and clinical reference intervals of dd-cfDNA in renal transplant recipients by using an analytically validated assay that has a CV of 6.8%. METHODS: We sampled venous blood at patient surveillance visits (typically at posttransplant months 1-4, 6, 9, and 12) in a 14-center observational study. Patients with stable renal allograft function spanning ≥3 serial visits were selected. We used AlloSure®, a targeted next-generation sequencing-based approach, to measure dd-cfDNA in the plasma and computed the intraindividual CV (CVI) and interindividual CV (CVG), the index of individuality (II), and reference change value (RCV). RESULTS: Of 93 patients, 61% were men, 56% were Caucasian, mean age was 49 years, and 63% were deceased donor kidney recipients. Of 380 blood samples, the dd-cfDNA median value was 0.21% (interquartile range 0.12%-0.39%) and the 97.5th percentile was 1.20%. In 18 patients with an average of 4.1 tests, the CVI was 21%, CVG was 37%, II was 0.57, and RCV was 61%. CONCLUSIONS: In a renal transplant recipient, a dd-cfDNA level above 1.2% is out of range and potentially abnormal. A serial increase of up to 61% in level of dd-cfDNA in a patient may be attributable to biological variation.Clinicaltrials.gov Identifier: NCT02424227.

Has the Department of Veterans Affairs Found a Way to Avoid Racial Disparities in the Evaluation Process for Kidney Transplantation?

BACKGROUND: Minority groups are affected by significant disparities in kidney transplantation (KT) in Veterans Affairs (VA) and non-VA transplant centers. However, prior VA studies have been limited to retrospective, secondary database analyses that focused on multiple stages of the KT process simultaneously. Our goal was to determine whether disparities during the evaluation period for KT exist in the VA as has been found in non-VA settings. METHODS: We conducted a multicenter longitudinal cohort study of 602 patients undergoing initial evaluation for KT at 4 National VA KT Centers. Participants completed a telephone interview to determine whether, after controlling for medical factors, differences in time to acceptance for transplant were explained by patients' demographic, cultural, psychosocial, or transplant knowledge factors. RESULTS: There were no significant racial disparities in the time to acceptance for KT [Log-Rank χ = 1.04; P = 0.594]. Younger age (hazards ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.99), fewer comorbidities (HR, 0.89; 95% CI, 0.84-0.95), being married (HR, 0.81; 95% CI, 0.66-0.99), having private and public insurance (HR, 1.29; 95% CI, 1.03-1.51), and moderate or greater levels of depression (HR, 1.87; 95% CI, 1.03-3.29) predicted a shorter time to acceptance. The influence of preference for type of KT (deceased or living donor) and transplant center location on days to acceptance varied over time. CONCLUSIONS: Our results indicate that the VA National Transplant System did not exhibit the racial disparities in evaluation for KT as have been found in non-VA transplant centers.

Non-immunoglobulin A mesangial immune complex glomerulonephritis in kidney transplants.

We have observed a predominantly mesangial non-immunoglobulin A immune complex mesangial glomerulopathy (MG) in renal transplants with mesangial deposits by immunofluorescence and electron microscopy. Clinicopathological features of 28 patients with MG were analyzed and compared with 28 transplant controls, matched for age, sex, ethnicity, donor type, estimated glomerular filtration rate, and interval from transplant to biopsy. Indications for biopsy in the MG group were allograft dysfunction in 64%, allograft dysfunction/proteinuria in 29%, and proteinuria in 7%. Biopsy indications in controls were allograft dysfunction (61%), allograft dysfunction/proteinuria (18%), proteinuria (14%), and delayed graft function (7%). Most MG cases had mild mesangial hypercellularity with endocapillary proliferation in 2 and crescents in 2 without fibrinoid necrosis. Immunoglobulin M-dominant deposits were present in 83%, and immunoglobulin G was dominant in 17% with mesangial deposits in 93% of cases by electron microscopy. Compared with controls, MG had higher Banff interstitial inflammation score (i) (P = .036) and was associated with concurrent acute T-cell-mediated rejection (P = .023), but not with acute or chronic antibody-mediated rejection. MG patients and controls had similar prevalence of polyomavirus nephropathy and Epstein-Barr virus infection. At follow-up, most MG patients had stable estimated glomerular filtration rate with no or stable proteinuria. Disease-specific graft survival was not different in MG versus controls. We conclude that, in view of the apparent self-limited nature of this lesion, additional treatment may not be required in these patients. Awareness of this lesion may thus spare patients unwarranted further intervention.

Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study.

Tremor is a common side effect of tacrolimus correlated with peak-dose drug concentration. LCPT, a novel, once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate-release tacrolimus. In this phase 3b study, kidney transplant recipients (KTR) on a stable dose of tacrolimus and with a reported clinically significant tremor were offered a switch to LCPT. Tremor pre- and seven d post-conversion was evaluated by independent, blinded movement disorder neurologists using the Fahn-Tolosa-Marin (FTM) scale and by an accelerometry device; patients completed the QUEST (quality of life in essential tremor) and the Patient Global Impression of Change. There were 38 patients in the mITT population. A statistically and clinically significant improvement in tremor (FTM score, amplitude as measured by the accelerometry device and QOL [p-values < 0.05]) resulted post-conversion. Change in QUEST was significantly (p = 0.006) correlated (R = 0.44) with change in FTM; 78.9% of patients reported an improvement after switching to LCPT (p < 0.0005). To our knowledge this is the first trial in KTR that utilizes a sophisticated and reproducible measurement of tremor. Results suggest LCPT is associated with clinically meaningful improvement of hand tremor and may be an alternative management approach in lieu of further dose reduction of immediate-release tacrolimus for patients experiencing tremor.

Long-term dosing patterns of enteric-coated mycophenolate sodium or mycophenolate mofetil with tacrolimus after renal transplantation.

MORE was a four-yr, prospective, observational study at 40 transplant centers in the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing over time in 904 de novo kidney transplant recipients receiving enteric-coated mycophenolate sodium (EC-MPS, n = 616) or mycophenolate mofetil (MMF, n = 288) with tacrolimus. Induction therapy and steroid treatment were similar in the two subpopulations. The proportion of patients receiving the maximal recommended MPA dose was 80.5%, 43.9%, 39.2%, 34.6%, and 30.1% at baseline and years 1, 2, 3, and 4, respectively. More patients received the maximal recommended MPA dose with EC-MPS vs. MMF at month 1 (79.2% vs. 71.7%, p = 0.016), month 3 (68.5% vs. 56.9%, p = 0.001), and month 6 (52.9% vs. 44.0%, p = 0.028). Multivariate analysis showed the risk of biopsy-proven acute rejection, graft loss or death to be similar for EC-MPS vs. MMF. Estimated glomerular filtration rate (GFR) was similar with EC-MPS vs. MMF at all time points. There were no significant differences in any category of adverse event between the EC-MPS and MMF cohorts during follow-up, including gastrointestinal events. In conclusion, MPA dose was maintained more effectively in the first six months after kidney transplantation using EC-MPS vs. MMF, without an increase in adverse events.