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1.
Pharmacokinetic Analysis of Mycophenolate Mofetil and Enteric-Coated Mycophenolate Sodium in Calcineurin Inhibitor-Free Renal Transplant Recipients.
Graff, J, Scheuermann, EH, Brandhorst, G, Oellerich, M, Gossmann, J
Therapeutic drug monitoring. 2016;(3):388-92
Abstract
BACKGROUND Considerable interest exists in identifying calcineurin inhibitor (CNI)-free and thus, less-toxic immunosuppressive regimens, with mycophenolic acid (MPA)-based treatments being a suitable approach. Because pharmacokinetic analyses of MPA treatments in stable CNI-free renal transplant recipients are lacking, the authors aimed at comparing the steady-state pharmacokinetic characteristics of MPA in patients on stable treatment with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) plus prednisone (≤5 mg/d). METHODS In the prospective, nonrandomized, open-label study, patients with stable transplant function since ≥6 months received their routine single dose of either MMF (n = 12) or EC-MPS (n = 11). The MPA plasma concentration was recorded over 12 hours. Parameters assessed were predose MPA concentration (C0), postdose minimum and maximum concentration (Cmin and Cmax), time to maximum concentration (Tmax), and area under the concentration-time curve (AUC) for the 12-hours of exposure (AUC0-12). RESULTS Baseline characteristics were comparable between both the groups. Consistent with enteric coating, the mean Tmax was significantly longer after the intake of EC-MPS compared with MMF (2.2 versus 0.8 hours; P = 0.0002). The exposure measures Cmin, Cmax, and AUC0-12 were not significantly different despite the higher mean MPA equivalent dose in patients receiving MMF compared with those receiving EC-MPS (85% versus 64% of the recommended single dose, respectively). Exposures as reflected by the median AUC0-12 values were 50.7 and 58.7 mg·h·L with MMF and EC-MPS, respectively (P = 0.340). All patients achieved a target AUC of >30 mg·h·L, and 61% had an AUC of >50 mg·h·L. CONCLUSIONS The study provides first results on the steady-state pharmacokinetics of the 2 MPA drugs in CNI-free immunosuppressant regimens. Pharmacokinetic parameters measured in this study under real-life conditions were comparable in patients receiving MMF or EC-MPS.
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2.
Everolimus versus azathioprine in a cyclosporine and ketoconazole-based immunosuppressive therapy in kidney transplant: 3-year follow-up of an open-label, prospective, cohort, comparative clinical trial.
Gonzalez, F, Espinoza, M, Herrera, P, Rocca, X, Reynolds, E, Lorca, E, Roessler, E, Hidalgo, J, Espinoza, O
Transplantation proceedings. 2010;(1):270-2
Abstract
In cyclosporine-based protocols, everolimus is more effective than azathioprine to reduce acute rejection. Ketoconazole may reduce cyclosporine and everolimus requirements. We compared kidney transplant patients treated with everolimus or azathioprine in a ketoconazole- and cyclosporine-based immunosuppressive regimen. This open-label, prospective trial of low immunologic risk patients. Included one group (n = 11) who received everolimus (target blood level, 3-8 ng/mL) and the other (n = 11) azathioprine (2.0-2.5 mg/kg/d). Both received steroids, ketoconazole, and cyclosporine with C(0) targets (ng/mL) in the everolimus group of 200-250, 100-125, and 50-65 for months 1 and 2 and thereafter and in the azathioprine group of 250-300 in month 1, 200-250 in month 2, 180-200 until month 6, and 100-125 thereafter. Their baseline characteristics were similar. Two biopsy-proven acute rejections occurred in each group. Three-year graft and patient survival in both groups was 100%. Creatinine clearances at months 6, 12, 24, and 36 were 63.7 +/- 25.4, 58.9 +/- 24.9, 56.0 +/- 22.9, and 57.0 +/- 27.6 in the everolimus group versus 72.6 +/- 20, 68.6 +/- 21.3, 71.4 +/- 23.2, and 68.4 +/- 19.2 in the azathioprine group (NS for every comparison). Major complications were rare and similar in both groups. Five patients in the everolimus group received simvastatin versus 4 in the azathioprine cohort (P = .53). The average cyclosporine doses to achieve targets were 0.8-1.2 mg/kg in the everolimus group and 1.6-2.2 mg/kg in the azathioprine group. The average everolimus dose after month 2 was 0.75-0.9 mg/d. We concluded that with cyclosporine, ketoconazole, and steroids, everolimus was as effective and safe as azathioprine. Cyclosporine reduction with everolimus did not influence graft survival or function at 3 years.
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3.
Does calcium channel blocker improvement of perfusion impact the functioning of kidney graft in early period after transplantation?
Nowacki, M, Droździk, M, Safranow, K, Kaminski, M, Sulikowski, T, Zietek, Z, Romanowski, M, Sienko, J, Mizerski, A, Ignaczak, E, et al
Transplantation proceedings. 2008;(4):1056-8
Abstract
The aim of the study was to evaluate the influence of reduced vascular resistance following calcium channel blocker verapamil administration on kidney function at 3 months after transplantation. A group of 48 kidneys received 100 microg verapamil by injection directly into renal artery before starting perfusion. The control group included 48 paired kidneys without verapamil addition. Calcium channel blocker therapy with verapamil greatly decreased renal vascular resistance but it did not affect graft function. Administration of calcium channel blockers improved kidney function in the early period after transplantation. A better-functioning graft seems to be based more on metabolic than hemodynamic effects.
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4.
Does repeated Ramadan fasting adversely affect kidney function in renal transplant patients?
Ghalib, M, Qureshi, J, Tamim, H, Ghamdi, G, Flaiw, A, Hejaili, F, Taher, S, Katheri, A, Shaheen, F, Al-Khader, AA
Transplantation. 2008;(1):141-4
Abstract
This is a prospective cohort study in renal transplant patients who fasted or who did not fast for three consecutive Ramadans. The baseline estimated glomerular filtration rate (GFR), mean arterial pressure (MAP), and urinary protein excretion before the first Ramadan were compared to those after the third Ramadan in 35 fasters and 33 nonfasters. The effect of age, time after transplantation, presence of diabetes mellitus (DM), and proteinuria on changes in the GFR were studied. The two groups were comparable in gender, age, donor source, time posttransplantation, presence of DM, hypertension, proteinuria, serum creatinine, and MAP. Among the fasters, there was no change in estimated GFR after fasting for three Ramadans (56.4 mL/min versus 55.4 mL/min, P=0.8) even after adjusting for age, DM, baseline GFR, proteinuria, or time after transplantation. There were no significant differences between the fasters and the nonfasters in the changes in GFR, MAP, and urinary protein excretion between baseline and the third Ramadan.
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5.
Early steroid withdrawal in pediatric renal transplant on newer immunosuppressive drugs.
Delucchi, A, Valenzuela, M, Ferrario, M, Lillo, AM, Guerrero, JL, Rodriguez, E, Cano, F, Cavada, G, Godoy, J, Rodriguez, J, et al
Pediatric transplantation. 2007;(7):743-8
Abstract
Steroids have been a cornerstone in renal transplant immunosuppression. New immunosuppressive drugs have led to protocols using early steroid withdrawal or complete avoidance. A prospective protocol in 23 pediatric renal transplant (ages 2-14 yr) who received decreasing steroid doses stopping at day 7 post-Tx, FK, and MMF were compared with a CsA, AZT, historically matched steroid-based control group. Basiliximab was used in two doses. Anthropometric, biochemical variables, AR rates, and CMV infection were evaluated and compared using Student's t-test and regression analysis. A better growth pattern was seen in steroid withdrawal group. GFR rate and serum glucose were similar in both groups. Total serum cholesterol levels were significantly lower in steroid withdrawal group. The incidence of AR at 12 months was 4.3% in steroid withdrawal group vs. 8.6% in steroid-based group (p = ns). No difference in CMV infection was observed. Hemoglobin levels were low during the first months in both groups; reached normal values after six months. SBP became higher at 12 months in steroid-based group. Patient and graft survival was 98% in both groups at one-yr post-transplant. Early steroid withdrawal was efficacious, safe, and did not increase risk of rejection, preserving optimal growth, renal function, and reducing cardiovascular risk factors.
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6.
Role of dietary intervention on metabolic abnormalities and nutritional status after renal transplantation.
Guida, B, Trio, R, Laccetti, R, Nastasi, A, Salvi, E, Perrino, NR, Caputo, C, Rotaia, E, Federico, S, Sabbatini, M
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2007;(11):3304-10
Abstract
BACKGROUND In these last years, several traditional risk factors for cardiovascular disease, like obesity, dyslipidaemia, hypertension and post-transplant diabetes mellitus have been also identified as important non-immunological risk factors leading to the development of chronic allograft nephropathy, the first cause of graft loss in transplanted patients. The aim of the present study was to determine the effects of a 12-month dietary regimen on the nutritional status and metabolic outcome of renal transplant recipients in the first post-transplant year. METHODS Forty-six cadaver-donor renal transplant recipients (mean age 40.8 +/- 10.1-years), enrolled during the first post-transplant year (4.8 +/- 3.3 months) and followed prospectively for a 12 month period. Biochemical and nutritional markers, anthropometric measurements, body composition (by conventional bioelectrical impedance analysis) and dietary records (using a detailed food-frequency questionnaire) at baseline and after 12 months. RESULTS Compliance to the diet was related to sex (male better than female) and was associated with weight loss primarily due to a decrease in fat mass, with decrease in total cholesterol and glucose plasma levels and with a concomitant rise in serum albumin. CONCLUSION After renal transplantation, health benefits of proper metabolic balance that include reduced body fat, weight loss, lower cholesterol and triglycerides levels and an improvement, fasting glucose levels can be obtained when dietary intervention occurred.
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7.
16-MDCT angiography in living kidney donors at various tube potentials: impact on image quality and radiation dose.
Sahani, DV, Kalva, SP, Hahn, PF, Saini, S
AJR. American journal of roentgenology. 2007;(1):115-20
Abstract
OBJECTIVE The objective of our study was to compare the performance of 16-MDCT angiography at various peak kilovoltage (kVp) settings and the impact of the different settings on image quality and on radiation dose in adult kidney donors. MATERIALS AND METHODS Sixty-two renal donors (32 men, 30 women) who underwent 16-MDCT were divided into three groups: 18 subjects were studied at 140 kVp (group A); 20, at 120 kVp (group B); and 24, at 100 kVp (group C). Other constant scanning parameters were as follows: detector collimation, 0.625 mm; table feed, 9.375 mm/rotation; gantry rotation time, 500 milliseconds; and automatic current tube modulation (ATCM) using a noise index of 15. A total of 135-140 mL of iodinated contrast material (300 mg I/mL) was administered at 5 mL/s via an 18-gauge cannula, and arterial phase scanning was initiated using a bolus-tracking technique. Two observers evaluated image quality of the axial and 3D images and the visibility of branch order in the superior mesenteric artery (SMA) and renal arteries. Attenuation (in Hounsfield units [H]) in the aorta, SMA, and main renal artery was also measured by placing a region of interest. Radiation dose measurements were based on the scanner-generated CT dose index volume (CTDI(vol)). Each parameter tested was compared among the three groups using a nonparametric analysis of variance test, and a p value of 0.05 was considered significant. RESULTS Differences in the quality of the axial images existed between groups A and C (p < 0.001) and between groups B and C (p < 0.01); the image quality of the 3D images and the visibility of branch order in the SMA and renal arteries were comparable for all groups. The difference in mean attenuation of the aorta, SMA, and renal arteries was significant between groups A and C (p < 0.001) and between groups B and C (p < 0.01). All groups had 100% diagnostic accuracy in identifying the number of renal arteries on the side of nephrectomy. The mean radiation dose in CTDI(vol) was 25 +/- 3 mGy at 140 kVp, 17 +/- 4 mGy at 120 kVp, and 12 +/- 3 mGy at 100 kVp (p < 0.001). CONCLUSION Our initial observations suggest that the image quality of 16-MDCT angiography performed at 120 kVp is similar to that of CT angiography (CTA) performed at 140 kVp in adult kidney donors but with a significant radiation dose reduction. CTA at 100 kVp results in higher image noise but provides diagnostically acceptable images with significant radiation dose reduction compared with CTA at 120 or 140 kVp.
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8.
Effect of orange and tangerine juice on cyclosporine levels in renal transplant recipients.
Sorkhi, H, Oliaei, F, Moghadamnia, AA, Pouramin, M, Firoozjahi, AR
Transplantation proceedings. 2007;(4):1228-30
Abstract
INTRODUCTION Cyclosporine Neoral is a major immunosuppressive agent widely used in organ transplant populations. Its pharmacokinetics are influenced by various factors. The aim of this study was to investigate the effects of orange or tangerine juice on the pharmacokinetic pattern of cyclosporine Neoral among renal transplanted patients. MATERIALS AND METHODS Ten renal transplant recipients on cyclosporine Neoral-based immunosuppressive therapy were included in this crossover controlled study. Patients were given their individualized morning dose of cyclosporine with either 250 mL water or 250 mL orange or tangerine juice; 12-hour cyclosporine pharmacokinetic investigations were performed. The three investigation days were separated by at least 7 days. RESULTS The intake of orange juice did not have any significant influence on the area under the curve in the interval from 0 to 12 hours (AUC 0-12; 95% confidence interval [CI]: -769 to 734, P=.77), or the maximum whole blood concentration (Cmax; 95% CI: 264 to 74; P=.32). Similarly, after coadministration of cyclosporine Neoral with tangerine juice, no significant changes were observed in AUC 0-12 (95% CI: -453 to 1166; P=.28) or Cmax (95% CI: -239 to 179; P=.37). CONCLUSION Coadministration of orange (var Tampson) or tangerine (var Unshiu) juice with cyclosporine compared with water did not influence exposure to cyclosporine in renal transplant recipients.
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9.
Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in living renal allograft transplantation.
Minz, M, Sharma, A, Heer, M
Transplantation proceedings. 2006;(7):2041-3
Abstract
OBJECTIVE Enteric-coated mycophenolate sodium (MPS) has been developed to decrease the GI side effects of mycophenolate mofetil (MMF). We did a retrospective analysis of 112 patients to compare the safety and efficacy of enteric coated MPS vs MMF in living renal transplantation. METHODS Patients were divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland] [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients received cyclosporine and prednisolone in addition to mycophenolate. Mean follow-up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively. RESULTS There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%) rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and 10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B, respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P = NS]. CONCLUSION Mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with a similar efficacy and safety profile.
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10.
Impact of Ramadan fasting on renal allograft function.
Einollahi, B, Lessan-Pezeshki, M, Simforoosh, N, Nafar, M, Pour-Reza-Gholi, F, Firouzan, A, Khatami, MR, Nourbala, MH, Pourfarzini, V
Transplantation proceedings. 2005;(7):3004-5
Abstract
Fasting during the holy month of Ramadan is a religious duty for all healthy adult Muslims. They are only allowed to eat and drink between sunset and dawn. This study was designed to find the effect of Ramadan fasting on allograft function. We prospectively studied 19 kidney transplant recipients who voluntarily chose to fast during Ramadan versus 20 matched recipients, who had not fasted for 3 consecutive years. Data were recorded before, during, and after the fasting month. The mean posttransplant periods in the fasting and control groups were 52.6 +/- 30.3 and 56.6 +/- 30.0 months, respectively. A statistical analysis showed no significant changes in serum creatinine concentrations before and after Ramadan 1.07 +/- 0.24 versus 1.08 +/- 0.22 mg/dL (P > .05) and 1.00 +/- 0.24 versus 1.03 +/- 0.28 mg/dL (P > .05) in fasting and control groups, respectively. The results did not show any adverse effects of fasting in recipients with stable renal function. In conclusion, our study suggests that fasting during the month of Ramadan is safe and has no significant harmful effects on kidney transplant recipients with normal renal function.