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Papers by Laurence chan

Clinical Science, 1987

1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the na... more 1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the natriuretic effects of atriopeptin III (AP-III) and to compare these effects with those of frusemide. AP-III (1 μg) or frusemide (1 mg) were added to the perfusate (100 ml) after two 15 min control collection periods. 2. Compared with the control group, AP-III and frusemide increased urinary sodium excretion (UNaV, 5.6 ± 1.1 and 4.6 ± 0.6 vs control 1.8 ± 0.3 μmol min−1 g−1, mean ± sem, P < 0.01 and P < 0.05, respectively), fractional sodium excretion (FENa, 4.8 ± 1.1 and 6.7 ± 0.8 vs control 2.0 ± 0.2%, P < 0.05 and P < 0.001, respectively) and potassium excretion (UKV, 3.2 ± 0.3 and 3.0 ± 0.3 vs control 1.5 ± 0.3 μmol min−1 g−1, both P < 0.01). However, AP-III, but not frusemide, increased glomerular filtration rate (820 ± 55 vs 590 ± 24 μl min−1 g−1, P < 0.01) and urine flow rate (V 97.5 ± 8.0 vs 44.1 ± 5.2 μl min−1 g−1, P < 0.001). Calculated distal delivery of sod...

American Journal of Kidney Diseases, 1988

American Journal of Kidney Diseases, 1994

The most common cause of renal allograft failure, after the first year posttransplant, is chronic... more The most common cause of renal allograft failure, after the first year posttransplant, is chronic rejection (CR). The impact on allograft loss of CR has remained constant despite the improvements in immunosuppression that have occurred. This process is characterized by a gradual decline in graft function over months to years. Proliferation of vascular smooth muscle cells and fibrosis of the large arteries are the main pathologic characteristics of CR. The clinical course varies widely among patients, from stable function for years to graft failure within several months. The precipitating factors of CR may be many and are unknown. Chronic rejection is likely to be, at least in part, immune mediated. A history of acute rejection episodes correlates strongly with the development of CR. No method has been clearly shown to prevent or treat CR.

Clinical transplantation, 2014

MORE was a four-yr, prospective, observational study at 40 transplant centers in the US. Data wer... more 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...

Annals of transplantation : quarterly of the Polish Transplantation Society, Jan 17, 2014

Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical conce... more Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; <12, nonadherence). A logistic regression model was used to identify factors associated with nonadherence. In total, 808/946 recipients (85.4%) provided ≥1 ITAS score. Nonadherence was reported by 24.8%, 31.5%, 33.0%, 39.8%, 35.4% and 26.4% at months 3, 6, 12, 24, 36 and 48, respectively. Mean ITAS score was higher w...

Journal of Transplantation, 2012

Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodi... more Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodium with tacrolimus (EC-MPS+Tac) in renal transplant recipients (RTxR). In this 6-month, prospective, open-label, multicenter study,de novoRTxR were randomized (1 : 1) to low-dose (LD) or standard-dose (SD) Tac with basiliximab, EC-MPS 720 mg bid, and steroids. Primary objective was to compare renal function at 6-month posttransplantation. Secondary objectives were to compare the incidences of biopsy-proven acute rejection (BPAR), graft loss and death, and new-onset diabetes mellitus (NODM). 292 patients (LDn=151, SDn=141) were included. Mean Tac levels were at the low end of the target range in standard-exposure patients (SD,n=141) and exceeded target range in low-exposure patients (LD = 151) throughout the study. There was no significant difference in mean glomerular filtration rate (GFR) between treatments (ITT-population: 63.6 versus 61.0 mL/min). Incidence of BPAR was similar (10.6% ...

Transplantation Journal, 2010

Principles of Molecular Medicine

Transplant Rejection and Its Treatment R ejection is the major cause of graft failure, and if the... more Transplant Rejection and Its Treatment R ejection is the major cause of graft failure, and if the injury to the tubules and glomeruli is severe, the kidney may not recover. It is therefore important to diagnose acute rejection as soon as possible to institute prompt antirejection therapy. Generally, the success with which rejection can be reversed by immunosuppressive agents determines the chance of long-term success of the transplant [1,2].

Seldin and Giebisch's The Kidney, 2013

Transplantation, 2007

Background. The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophen... more Background. The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the potential impact of concomitant calcineurin inhibitor. Methods. In this 3-month, prospective, multicenter, longitudinal, open-label trial, MMF-treated renal transplant patients with gastrointestinal symptoms receiving cyclosporine or tacrolimus were converted to equimolar doses of EC-MPS. Change in gastrointestinal symptom burden was evaluated using a validated Gastrointestinal Symptom Rating Scale (GSRS). Results. A significant improvement in GSRS score was observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81-1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74-188; both PϽ0.0001 versus baseline). The mean change in overall GSRS score from baseline to month 1 was Ϫ0.74 overall (cyclosporine: Ϫ0.73 and tacrolimus: Ϫ0.74; all PϽ0.0001 versus baseline), with a slight further improvement (Ϫ0.79) at month 3 (cyclosporine: Ϫ0.82 and tacrolimus: Ϫ0.78; all PϽ0.0001 versus baseline). A significant improvement in GSRS subscale scores was also observed in the total population regardless of calcineurin inhibitor at month 1, sustained to month 3 (all PϽ0.0001 versus baseline). The improvement in GSRS score postconversion was similar in African-American and non-African-American patients, and in diabetic and nondiabetic patients. Conclusions. This exploratory study in 728 patients demonstrates that following conversion from MMF to EC-MPS, regardless of concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.

Clinical transplants, 2010

Clinical transplants, 2011

We have previously shown poor outcomes in a cohort of kidney recipients with de novo donor specif... more We have previously shown poor outcomes in a cohort of kidney recipients with de novo donor specific anti-HLA antibodies (DSA) detected via post-transplant screening, were due to prior acute rejection (AR) episodes. In this report, we sought to identify DSA characteristics associated with poor outcomes in the absence of AR. All living and cadaveric donor kidney/ kidney-pancreas recipients from 9/07 to 10/09 were screened for class I and II DSA at 1, 6, 12, and 24 months post-transplant, in addition to whenever clinically indicated, using single antigen beads and Luminex technology. Mean florescence intensity (MFI) > 500 was defined as positive. Compared to DSA(-) patients, those who developed both class I and II DSA experienced worse graft survival (p < .001). Graft survival in those with class I or II alone was unchanged. Patients with DSA MFI > 6000 experienced worse 1-year modification of diet in renal disease glomerular filtration rate (MDRD GFR) (p = 0.022) and 2-year g...

Transplantation, 1999

Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Transplantation. ... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Transplantation. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining ...

Transplantation, 2011

Background. Two open-label studies demonstrated that conversion from mycophenolate mofetil (MMF) ... more Background. Two open-label studies demonstrated that conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) significantly reduces gastrointestinal (GI) symptom burden and improves GI-specific health-related quality of life. Using a randomized design, this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment. Methods. In this 4-week, multicenter, randomized, prospective, double-blind, parallel-group trial, renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitorϮcorticosteroids were randomized to an equimolar dose of EC-MPSϩMMF placebo or continue on their MMF-based regimenϩEC-MPS placebo. The primary efficacy outcome was a change from baseline in total Gastrointestinal Symptom Rating Scale score of a minimally important difference of more than or equal to 0.3. Results. Three hundred ninety-six patients (EC-MPS group: nϭ199; MMF group: nϭ197) were included. A greater proportion of EC-MPS patients (62%) reached the primary efficacy outcome compared with MMF patients (55%); however, the difference was not statistically significant (Pϭ0.15). EC-MPS patients had a significantly greater decrease in the Gastrointestinal Symptom Rating Scale indigestion syndrome dimension versus MMF patients. Within the subgroups of patients with diabetes, patients transplanted 6 to 12 months of study enrollment, and patients on steroids, a statistically significant greater proportion of EC-MPS versus MMF patients reached the primary efficacy outcome. Conclusions. Conversion from MMF to EC-MPS may be associated with improvements in presence and severity of GI symptoms, particularly in patients with indigestion, diabetes, on steroids, and in patients converted between 6 and 12 months posttransplantation.

Transplantation, 2013

Background. Prospective data regarding immunosuppression and rejection in African American patien... more Background. Prospective data regarding immunosuppression and rejection in African American patients receiving modern immunosuppressive regimens are sparse. Methods. One-year data were analyzed from 901 tacrolimus-treated de novo kidney transplant patients in the prospective Mycophenolic Acid Observational Renal Transplant registry. Results. Mean tacrolimus dose was significantly higher in African Americans (n=217) versus nonYAfrican Americans (n=684), but mean tacrolimus trough concentrations were similar. The proportion of patients receiving mycophenolic acid dose equal to or more than 2000 mg per day (mycophenolate mofetil equivalents) was significantly higher with enteric-coated mycophenolate sodium versus mycophenolate mofetil at month 6 among African Americans and at month 3 in nonYAfrican Americans, but rates of acute rejection and adverse events (including gastrointestinal events) were similar. The 1-year incidence of biopsy-proven acute rejection (BPAR) was 14.1% in African Americans versus 7.5% in nonYAfrican Americans. On multivariate analysis, African American ethnicity was associated with a higher risk of BPAR (hazard ratio, 1.93; 95% confidence interval, 1.19Y3.09; P=0.007). Mean (standard deviation) glomerular filtration rate at month 12 estimated by the Chronic Kidney Disease Epidemiology Collaboration formula was 59.2 (22.2) mL/min/1.73 m 2 in African Americans versus 58.8 (19.9) mL/min/1.73 m 2 in nonYAfrican Americans (confidence interval of the difference, j3.4 to 4.3; P=0.83). Conclusion. This observational study confirms that African Americans require higher doses of tacrolimus to achieve target trough concentrations and are more likely to experience BPAR during the first year after kidney transplantation despite modern immunosuppression regimens. In our 1-year study, this was not associated with significantly inferior graft survival.

Transplantation, 2011

Background. Donor-specific antibodies (DSAs) after kidney transplantation have been associated wi... more Background. Donor-specific antibodies (DSAs) after kidney transplantation have been associated with poor graft outcomes in multiple studies. However, these studies have generally used stored sera or a single cross sectional screening test to identify patients with DSA. We evaluated the effectiveness of a prospective DSA screening protocol in identifying kidney and kidney/pancreas recipients at risk for poor graft outcomes. Methods. From September 2007 through September 2009, 244 consecutively transplanted kidney and kidney/pancreas recipients without pretransplant DSA were screened for de novo DSA at 1, 6, 12, and 24 months and when clinically indicated. Results. DSA was detected in 27% of all patients by protocol or indication screening. Patients with DSA (DSAϩ) were significantly more likely to have experienced acute rejection (AR) compared with no DSA (DSAϪ) (29% vs. 9.5%, PϽ0.001), and lower estimated 2-year graft survival (83% vs. 98%, PϽ0.001). Only 3 of 19 DSA (ϩ) patients with AR had DSA detected before the AR episode. When excluding patients with AR, 2-year graft survival was similar between DSA (ϩ) and DSA (Ϫ) patients (100% vs. 99%) as was estimated glomerular filtration rate. Patients with DSA detected by protocol screening had similar outcomes compared with DSA (Ϫ), whereas those with DSA detected by indication experienced significantly worse outcomes. Conclusions. Patients with de novo DSA experience worse graft outcomes due to previous/concurrent episodes of AR. A prospective DSA screening protocol failed to identify patients at risk for AR or poor short-term graft outcomes.

Transplantation, 2006

Background. The benefit of converting renal transplant recipients with gastrointestinal (GI) comp... more Background. The benefit of converting renal transplant recipients with gastrointestinal (GI) complaints from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) has not been evaluated using patientreported outcomes. Methods. A multicenter, open-label, prospective study was undertaken in MMF-treated renal transplant patients. Patients experiencing GI complaints were converted to equimolar EC-MPS (Cohort A). Patients without GI complaints remained on MMF (Cohort B). At baseline and Visit 2 (4-6 weeks postbaseline), patients completed the Gastrointestinal Symptom Rating Scale (GSRS), Gastrointestinal Quality of Life Index (GIQLI) and Psychological General Wellbeing Index (PGWBI). At Visit 2, patients and physicians completed the Overall Treatment Effect (OTE) scale for GI symptoms. Additionally, patients completed the OTE for health-related quality of life (HRQoL). Minimal important difference (MID) was calculated for GSRS and GIQLI based on patients' and physicians' OTE evaluation. Results. Of 328 patients enrolled (i.e. the intent-to-treat and safety populations), 278 formed the per-protocol population (Cohort A, nϭ177; Cohort B, nϭ101). At baseline, Cohort A had significantly worse scores on all GSRS, GIQLI and PGWBI subscales compared to Cohort B (all PϽ0.0001). All GSRS, GIQLI and PGWBI subscale scores improved significantly in Cohort A between baseline and Visit 2 (all PϽ0.0001). Mean improvements in all GSRS subscales and most GIQLI subscores exceeded the calculated MID. GSRS, GIQLI and PGWBI subscales remained stable in Cohort B. Conclusion. This first exploratory study indicates that converting patients with mild, moderate or severe GI complaints from MMF to EC-MPS significantly reduces GI-related symptom burden and improves patient functioning and well-being.

Nephron Experimental Nephrology, 2009

Background: Cyclosporine and/or sirolimus impair recovery of renal transplants. This study examin... more Background: Cyclosporine and/or sirolimus impair recovery of renal transplants. This study examines the changes in urine metabolite profiles as surrogate markers of renal cell metabolism and function after cyclosporine and/or sirolimus treatment employing a rat kidney transplantation model. Methods: Using inbred Lewis rats, kidneys were transplanted into bilaterally nephrectomized recipients followed by treatment with either CsA (cyclosporine) 10, Rapa (sirolimus) 1, CsA10/Rapa1 or CsA25/Rapa1 mg/kg/day for 7 days. On day 7, urine was analyzed by 1H-NMR spectroscopy. Blood and kidney tissue drug concentrations, tissue high-energy compounds (including ATP, ADP) and oxidative stress markers (15-F2t-isoprostanes) in urine were measured by HPLC mass spectrometry. Results: Changes in urine metabolites followed the order Rapa1 < CsA10 < CsA10/Rapa1 < CsA25/Rapa1. Compared with controls, CsA25/Rapa1 showed the greatest changes (creatinine –36%, succinate –57%, citrate –89%, α-keto...

Renal Failure, 1990

Thirteen patients found to be hypertensive following renal transplantation were treated with eith... more Thirteen patients found to be hypertensive following renal transplantation were treated with either a calcium channel blocker or other antihypertensive therapy for control of blood pressure. Immunosuppression was either with cyclosporine and prednisone alone or with ...

Clinical Science, 1987

1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the na... more 1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the natriuretic effects of atriopeptin III (AP-III) and to compare these effects with those of frusemide. AP-III (1 μg) or frusemide (1 mg) were added to the perfusate (100 ml) after two 15 min control collection periods. 2. Compared with the control group, AP-III and frusemide increased urinary sodium excretion (UNaV, 5.6 ± 1.1 and 4.6 ± 0.6 vs control 1.8 ± 0.3 μmol min−1 g−1, mean ± sem, P < 0.01 and P < 0.05, respectively), fractional sodium excretion (FENa, 4.8 ± 1.1 and 6.7 ± 0.8 vs control 2.0 ± 0.2%, P < 0.05 and P < 0.001, respectively) and potassium excretion (UKV, 3.2 ± 0.3 and 3.0 ± 0.3 vs control 1.5 ± 0.3 μmol min−1 g−1, both P < 0.01). However, AP-III, but not frusemide, increased glomerular filtration rate (820 ± 55 vs 590 ± 24 μl min−1 g−1, P < 0.01) and urine flow rate (V 97.5 ± 8.0 vs 44.1 ± 5.2 μl min−1 g−1, P < 0.001). Calculated distal delivery of sod...

American Journal of Kidney Diseases, 1988

American Journal of Kidney Diseases, 1994

The most common cause of renal allograft failure, after the first year posttransplant, is chronic... more The most common cause of renal allograft failure, after the first year posttransplant, is chronic rejection (CR). The impact on allograft loss of CR has remained constant despite the improvements in immunosuppression that have occurred. This process is characterized by a gradual decline in graft function over months to years. Proliferation of vascular smooth muscle cells and fibrosis of the large arteries are the main pathologic characteristics of CR. The clinical course varies widely among patients, from stable function for years to graft failure within several months. The precipitating factors of CR may be many and are unknown. Chronic rejection is likely to be, at least in part, immune mediated. A history of acute rejection episodes correlates strongly with the development of CR. No method has been clearly shown to prevent or treat CR.

Clinical transplantation, 2014

MORE was a four-yr, prospective, observational study at 40 transplant centers in the US. Data wer... more 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...

Annals of transplantation : quarterly of the Polish Transplantation Society, Jan 17, 2014

Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical conce... more Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; <12, nonadherence). A logistic regression model was used to identify factors associated with nonadherence. In total, 808/946 recipients (85.4%) provided ≥1 ITAS score. Nonadherence was reported by 24.8%, 31.5%, 33.0%, 39.8%, 35.4% and 26.4% at months 3, 6, 12, 24, 36 and 48, respectively. Mean ITAS score was higher w...

Journal of Transplantation, 2012

Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodi... more Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodium with tacrolimus (EC-MPS+Tac) in renal transplant recipients (RTxR). In this 6-month, prospective, open-label, multicenter study,de novoRTxR were randomized (1 : 1) to low-dose (LD) or standard-dose (SD) Tac with basiliximab, EC-MPS 720 mg bid, and steroids. Primary objective was to compare renal function at 6-month posttransplantation. Secondary objectives were to compare the incidences of biopsy-proven acute rejection (BPAR), graft loss and death, and new-onset diabetes mellitus (NODM). 292 patients (LDn=151, SDn=141) were included. Mean Tac levels were at the low end of the target range in standard-exposure patients (SD,n=141) and exceeded target range in low-exposure patients (LD = 151) throughout the study. There was no significant difference in mean glomerular filtration rate (GFR) between treatments (ITT-population: 63.6 versus 61.0 mL/min). Incidence of BPAR was similar (10.6% ...

Transplantation Journal, 2010

Principles of Molecular Medicine

Transplant Rejection and Its Treatment R ejection is the major cause of graft failure, and if the... more Transplant Rejection and Its Treatment R ejection is the major cause of graft failure, and if the injury to the tubules and glomeruli is severe, the kidney may not recover. It is therefore important to diagnose acute rejection as soon as possible to institute prompt antirejection therapy. Generally, the success with which rejection can be reversed by immunosuppressive agents determines the chance of long-term success of the transplant [1,2].

Seldin and Giebisch's The Kidney, 2013

Transplantation, 2007

Background. The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophen... more Background. The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the potential impact of concomitant calcineurin inhibitor. Methods. In this 3-month, prospective, multicenter, longitudinal, open-label trial, MMF-treated renal transplant patients with gastrointestinal symptoms receiving cyclosporine or tacrolimus were converted to equimolar doses of EC-MPS. Change in gastrointestinal symptom burden was evaluated using a validated Gastrointestinal Symptom Rating Scale (GSRS). Results. A significant improvement in GSRS score was observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81-1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74-188; both PϽ0.0001 versus baseline). The mean change in overall GSRS score from baseline to month 1 was Ϫ0.74 overall (cyclosporine: Ϫ0.73 and tacrolimus: Ϫ0.74; all PϽ0.0001 versus baseline), with a slight further improvement (Ϫ0.79) at month 3 (cyclosporine: Ϫ0.82 and tacrolimus: Ϫ0.78; all PϽ0.0001 versus baseline). A significant improvement in GSRS subscale scores was also observed in the total population regardless of calcineurin inhibitor at month 1, sustained to month 3 (all PϽ0.0001 versus baseline). The improvement in GSRS score postconversion was similar in African-American and non-African-American patients, and in diabetic and nondiabetic patients. Conclusions. This exploratory study in 728 patients demonstrates that following conversion from MMF to EC-MPS, regardless of concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.

Clinical transplants, 2010

Clinical transplants, 2011

We have previously shown poor outcomes in a cohort of kidney recipients with de novo donor specif... more We have previously shown poor outcomes in a cohort of kidney recipients with de novo donor specific anti-HLA antibodies (DSA) detected via post-transplant screening, were due to prior acute rejection (AR) episodes. In this report, we sought to identify DSA characteristics associated with poor outcomes in the absence of AR. All living and cadaveric donor kidney/ kidney-pancreas recipients from 9/07 to 10/09 were screened for class I and II DSA at 1, 6, 12, and 24 months post-transplant, in addition to whenever clinically indicated, using single antigen beads and Luminex technology. Mean florescence intensity (MFI) > 500 was defined as positive. Compared to DSA(-) patients, those who developed both class I and II DSA experienced worse graft survival (p < .001). Graft survival in those with class I or II alone was unchanged. Patients with DSA MFI > 6000 experienced worse 1-year modification of diet in renal disease glomerular filtration rate (MDRD GFR) (p = 0.022) and 2-year g...

Transplantation, 1999

Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Transplantation. ... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Transplantation. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining ...

Transplantation, 2011

Background. Two open-label studies demonstrated that conversion from mycophenolate mofetil (MMF) ... more Background. Two open-label studies demonstrated that conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) significantly reduces gastrointestinal (GI) symptom burden and improves GI-specific health-related quality of life. Using a randomized design, this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment. Methods. In this 4-week, multicenter, randomized, prospective, double-blind, parallel-group trial, renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitorϮcorticosteroids were randomized to an equimolar dose of EC-MPSϩMMF placebo or continue on their MMF-based regimenϩEC-MPS placebo. The primary efficacy outcome was a change from baseline in total Gastrointestinal Symptom Rating Scale score of a minimally important difference of more than or equal to 0.3. Results. Three hundred ninety-six patients (EC-MPS group: nϭ199; MMF group: nϭ197) were included. A greater proportion of EC-MPS patients (62%) reached the primary efficacy outcome compared with MMF patients (55%); however, the difference was not statistically significant (Pϭ0.15). EC-MPS patients had a significantly greater decrease in the Gastrointestinal Symptom Rating Scale indigestion syndrome dimension versus MMF patients. Within the subgroups of patients with diabetes, patients transplanted 6 to 12 months of study enrollment, and patients on steroids, a statistically significant greater proportion of EC-MPS versus MMF patients reached the primary efficacy outcome. Conclusions. Conversion from MMF to EC-MPS may be associated with improvements in presence and severity of GI symptoms, particularly in patients with indigestion, diabetes, on steroids, and in patients converted between 6 and 12 months posttransplantation.

Transplantation, 2013

Background. Prospective data regarding immunosuppression and rejection in African American patien... more Background. Prospective data regarding immunosuppression and rejection in African American patients receiving modern immunosuppressive regimens are sparse. Methods. One-year data were analyzed from 901 tacrolimus-treated de novo kidney transplant patients in the prospective Mycophenolic Acid Observational Renal Transplant registry. Results. Mean tacrolimus dose was significantly higher in African Americans (n=217) versus nonYAfrican Americans (n=684), but mean tacrolimus trough concentrations were similar. The proportion of patients receiving mycophenolic acid dose equal to or more than 2000 mg per day (mycophenolate mofetil equivalents) was significantly higher with enteric-coated mycophenolate sodium versus mycophenolate mofetil at month 6 among African Americans and at month 3 in nonYAfrican Americans, but rates of acute rejection and adverse events (including gastrointestinal events) were similar. The 1-year incidence of biopsy-proven acute rejection (BPAR) was 14.1% in African Americans versus 7.5% in nonYAfrican Americans. On multivariate analysis, African American ethnicity was associated with a higher risk of BPAR (hazard ratio, 1.93; 95% confidence interval, 1.19Y3.09; P=0.007). Mean (standard deviation) glomerular filtration rate at month 12 estimated by the Chronic Kidney Disease Epidemiology Collaboration formula was 59.2 (22.2) mL/min/1.73 m 2 in African Americans versus 58.8 (19.9) mL/min/1.73 m 2 in nonYAfrican Americans (confidence interval of the difference, j3.4 to 4.3; P=0.83). Conclusion. This observational study confirms that African Americans require higher doses of tacrolimus to achieve target trough concentrations and are more likely to experience BPAR during the first year after kidney transplantation despite modern immunosuppression regimens. In our 1-year study, this was not associated with significantly inferior graft survival.

Transplantation, 2011

Background. Donor-specific antibodies (DSAs) after kidney transplantation have been associated wi... more Background. Donor-specific antibodies (DSAs) after kidney transplantation have been associated with poor graft outcomes in multiple studies. However, these studies have generally used stored sera or a single cross sectional screening test to identify patients with DSA. We evaluated the effectiveness of a prospective DSA screening protocol in identifying kidney and kidney/pancreas recipients at risk for poor graft outcomes. Methods. From September 2007 through September 2009, 244 consecutively transplanted kidney and kidney/pancreas recipients without pretransplant DSA were screened for de novo DSA at 1, 6, 12, and 24 months and when clinically indicated. Results. DSA was detected in 27% of all patients by protocol or indication screening. Patients with DSA (DSAϩ) were significantly more likely to have experienced acute rejection (AR) compared with no DSA (DSAϪ) (29% vs. 9.5%, PϽ0.001), and lower estimated 2-year graft survival (83% vs. 98%, PϽ0.001). Only 3 of 19 DSA (ϩ) patients with AR had DSA detected before the AR episode. When excluding patients with AR, 2-year graft survival was similar between DSA (ϩ) and DSA (Ϫ) patients (100% vs. 99%) as was estimated glomerular filtration rate. Patients with DSA detected by protocol screening had similar outcomes compared with DSA (Ϫ), whereas those with DSA detected by indication experienced significantly worse outcomes. Conclusions. Patients with de novo DSA experience worse graft outcomes due to previous/concurrent episodes of AR. A prospective DSA screening protocol failed to identify patients at risk for AR or poor short-term graft outcomes.

Transplantation, 2006

Background. The benefit of converting renal transplant recipients with gastrointestinal (GI) comp... more Background. The benefit of converting renal transplant recipients with gastrointestinal (GI) complaints from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) has not been evaluated using patientreported outcomes. Methods. A multicenter, open-label, prospective study was undertaken in MMF-treated renal transplant patients. Patients experiencing GI complaints were converted to equimolar EC-MPS (Cohort A). Patients without GI complaints remained on MMF (Cohort B). At baseline and Visit 2 (4-6 weeks postbaseline), patients completed the Gastrointestinal Symptom Rating Scale (GSRS), Gastrointestinal Quality of Life Index (GIQLI) and Psychological General Wellbeing Index (PGWBI). At Visit 2, patients and physicians completed the Overall Treatment Effect (OTE) scale for GI symptoms. Additionally, patients completed the OTE for health-related quality of life (HRQoL). Minimal important difference (MID) was calculated for GSRS and GIQLI based on patients' and physicians' OTE evaluation. Results. Of 328 patients enrolled (i.e. the intent-to-treat and safety populations), 278 formed the per-protocol population (Cohort A, nϭ177; Cohort B, nϭ101). At baseline, Cohort A had significantly worse scores on all GSRS, GIQLI and PGWBI subscales compared to Cohort B (all PϽ0.0001). All GSRS, GIQLI and PGWBI subscale scores improved significantly in Cohort A between baseline and Visit 2 (all PϽ0.0001). Mean improvements in all GSRS subscales and most GIQLI subscores exceeded the calculated MID. GSRS, GIQLI and PGWBI subscales remained stable in Cohort B. Conclusion. This first exploratory study indicates that converting patients with mild, moderate or severe GI complaints from MMF to EC-MPS significantly reduces GI-related symptom burden and improves patient functioning and well-being.

Nephron Experimental Nephrology, 2009

Background: Cyclosporine and/or sirolimus impair recovery of renal transplants. This study examin... more Background: Cyclosporine and/or sirolimus impair recovery of renal transplants. This study examines the changes in urine metabolite profiles as surrogate markers of renal cell metabolism and function after cyclosporine and/or sirolimus treatment employing a rat kidney transplantation model. Methods: Using inbred Lewis rats, kidneys were transplanted into bilaterally nephrectomized recipients followed by treatment with either CsA (cyclosporine) 10, Rapa (sirolimus) 1, CsA10/Rapa1 or CsA25/Rapa1 mg/kg/day for 7 days. On day 7, urine was analyzed by 1H-NMR spectroscopy. Blood and kidney tissue drug concentrations, tissue high-energy compounds (including ATP, ADP) and oxidative stress markers (15-F2t-isoprostanes) in urine were measured by HPLC mass spectrometry. Results: Changes in urine metabolites followed the order Rapa1 < CsA10 < CsA10/Rapa1 < CsA25/Rapa1. Compared with controls, CsA25/Rapa1 showed the greatest changes (creatinine –36%, succinate –57%, citrate –89%, α-keto...

Renal Failure, 1990

Thirteen patients found to be hypertensive following renal transplantation were treated with eith... more Thirteen patients found to be hypertensive following renal transplantation were treated with either a calcium channel blocker or other antihypertensive therapy for control of blood pressure. Immunosuppression was either with cyclosporine and prednisone alone or with ...