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M Klinger

Publications and source records attributed to M Klinger.

At least 19 recordsLinked to original sources
PubMed2006

Enzymuria and low molecular weight protein excretion as the differentiating marker of complications in the early post kidney transplantation period.

Renal function in the early post-transplantation period depends largely on factors affecting the kidney prior to implantation. Function of the graft may be also disturbed by the most common complications of the early post-operative period such as acute graft rejection (AGR), acute tubular necrosis (ATN) and may be modified by nephrotoxic action of cyclosporine A (CsA). Evaluation of excretion of enzymes and low molecular weight proteins (LMWP) may help in the differentiation of these complications. Aim Comparison of the urinary excretion of markers of tubular injury in patients with AGR, ATN, or patients with stable graft function (SGF) was made and differences between groups and correlations between markers and cold ischemia time (CIT), warm ischemia time (WIT) and blood trough level of cyclosporine A (CsA0) were determined. Material and methods In 60 cadaveric renal allograft recipients in the early post-transplantation period urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and B isoenzyme (NAG-B), alanylaminopeptidase (AAP), gamma-glutamyltransferase (GGT), alpha and pi isoenzymes of glutathione S-transferase (alpha-GST, pi-GST), retinol binding protein (RBP) and beta2- microglobulin (beta2M), were analyzed. Results NAG and NAB-B activities were higher in ATN (P<0.05, P<0.01) and in AGR (P<0.005, P<0.02) than in SGF. Excretion of pi-GST was higher in AGR than in SGF (P<0.0002) or ATN (P<0.007). CIT and WIT in patients with ATN were higher (P<0.05) than in SGF group. In ATN patients, correlations of CIT with RBP (P<0.05) and pi-GST (P<0.05), and WIT with RBP (P<0.05), and pi-GST (P<0.001) were found. Conclusions High urinary NAG and NAG B excretion characterizes ATN and AGR patients. Evaluating urinary excretion of pi-GST may be helpful in differentiating AGR from ATN. However, taking into account ischemia time is necessary in interpreting the pi-GST value in early post transplant period.

Adult↗
PubMed2006

Efficacy and safety of enteric-coated mycophenolate sodium (myfortic) in de novo renal transplant recipients: results of a 12-month multicenter, open-label, prospective study.

Enteric-coated mycophenolate sodium (EC-MPS) has been developed as an alternative formulation of mycophenolate acid aiming for improved gastrointestinal (GI) tolerability. This 12-month, open-label, multicenter, prospective study investigated the efficacy and tolerability of EC-MPS (720 mg twice a day) given in combination with cyclosporine microemulsion (CsA-ME) in de novo renal transplant recipients (n=140). The efficacy evaluation was the incidence of treatment failure (defined as biopsy-proven acute rejection [BPAR], graft loss, or death) after 6 and 12 months of treatment. The incidences of treatment failure, BPAR, and graft loss were comparable at 6 and 12 months (18.6% vs 22.1%, 15.7% vs 19.3%, and 1.4% vs 2.1%, respectively). Renal function at 6 and 12 months (creatinine clearance) was 60.6+/-19.8 mL/min and 63.2+/-27.1 mL/min, respectively. EC-MPS was generally well tolerated; 95.9% of the reported GI adverse events (AEs) were rated as mild or moderate. The rate of EC-MPS dose reduction was 26.4%; 4.3% were due to GI AEs. The rate of EC-MPS dose interruption was 10%; 2.1% were due to GI AEs. In summary, EC-MPS given in combination with CsA-ME demonstrates good efficacy and tolerability in de novo renal transplant recipients.

Adult↗
PubMed2006

Continuous Erythropoietin Receptor Activator (C.E.R.A.) administered at extended administration intervals corrects anaemia in patients with chronic kidney disease on dialysis: a randomised, multicentre, multiple-dose, phase II study.

This dose-finding, open-label study examined the potential of subcutaneous Continuous Erythropoietin Receptor Activator (C.E.R.A.) to correct anaemia at extended administration intervals in 61 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease (CKD) on dialysis. After a 4-week run-in, patients were randomised to C.E.R.A. 0.15, 0.30 and 0.45 microg/kg/week. Within these dose groups, patients were further randomised to once weekly, once every 2 weeks or once every 3 weeks treatment. Mean changes in haemoglobin (Hb) increased with increasing C.E.R.A. dose during a period of 6 weeks where no dose adjustments were permitted. The effect was independent of administration schedule. Erythropoietic responses were sustained until the end of the study (12 weeks) in all groups. In total, 90% of patients in the 0.30 microg/kg/week group and 79% in the 0.45 microg/kg/week group responded to treatment (Hb increase > or =1.0 g/dl), compared with 72% in the 0.15 microg/kg/week group. Faster median response time was associated with increasing dose (51, 38 and 31 days, respectively) and response was unrelated to administration frequency. C.E.R.A. was generally well tolerated. Our results suggest that 0.60 microg/kg twice monthly would be a suitable starting dose of C.E.R.A. for the initiation of anaemia correction in patients with CKD on dialysis. Phase III studies will confirm the feasibility of using C.E.R.A. at extended administration intervals in patients with CKD and anaemia.

Adult↗
PubMed2006

Autonomously contracting human cardiomyocytes generated from adult pancreatic stem cells and enhanced in co-cultures with myocardial biopsies.

Myocardial regeneration with artificially applied cardiomyocytes is emerging as a promising issue of significant scientific and clinical impact. Nevertheless the source of cells for human cardiomyocyte differentiation especially from adult tissue is still unclear. We hypothesized that human pancreatic stem cells may differentiate into cardiomyocyte-like cells and may increase in number when co-cultured with myocardial tissue. Adult stem cells were harvested from pancreatic tissue of patients undergoing operative procedures including the pancreas. The cells were selected, cultured and passaged. To promote self-differentiation into cardiomyocytes, human pancreatic stem cells were co-cultered with biopsies of human myocardium. After co-culture and breeding, cells were phenotyped as well with respect to RNA, protein and cardiomyocyte specificity at the electron-microscopic level.Pancreatic stem cells have already differentiated spontaneously into cardiomyocyte-like cells performing netlike cell clusters with rare but distinct multilocular cellular autonomous contractions with a frequency of about 20 beats per minute. The number of contracting areas however could be enhanced by co-culture with human myocardial biopsies. On RNA and protein levels as well as in electron-microscopy, evidence for cardiomyocyte specificity is shown. To the best of our knowledge this is the first report demonstrating the feasibility of generating autonomously contracting cardiomyocyte-like cells from adult human pancreatic stem cells and their enhancement by myocardial co-culture. This procedure might prove to be an alternative source and method for myocardial regenerative medicine.

Adult↗
PubMed2005

Outcome of autogenous fistula construction in hemodialyzed patients over 75 years of age.

BACKGROUND: There are controversies regarding the feasibility of autogenous vascular access creation in elderly hemodialysis (HD) patients. The aim of this retrospective study was to evaluate the results of creating different types of autogenous arteriovenous fistulas (AVFs) in a consecutive series of HD patients over 75 years of age. METHODS: The analysis was performed in 131 patients (65 females, 66 males, average age 79.1 +/- 3.6 years) in whom the creation of an autogenous AVF was considered within a 6-year period (February 1998 to February 2004). Among them, 26.7%were diabetics, 66.3% had hypertension, 30.7% were smokers, and 35.6% were obese. Patient survival and primary and secondary AVF patency were assessed. RESULTS: The survival rates for patients were 94, 88, 66, and 45% at 6 months and at 1, 3, and 5 years, respectively. Successful autogenous AVF formation was finally achieved in 107 patients (81.6%): in 99 patients in the forearm and in 8in the upper arm. A Kaplan-Meier analysis showed primary AVF patency rates of: 74 +/- 4.3% (+/- SE) at 1 month; 70 +/- 4.7% at 6 months; 59 +/- 4.9% at 1 year; 59 +/- 4.9% at 2 years; 59+/- 4.9% at 3 years; 59 +/- 4.9% at 4 years, and 58 +/- 4.9% at 5 years. The secondary patency rates were: 95 +/- 2.0; 92 +/- 2.2; 84 +/- 3.3; 79 +/- 4.0; 72 +/- 4.3; 71 +/- 4.4, and 69 +/- 4.5% in the corresponding periods, respectively. All postoperative complications in 10 patients were treated surgically, if applicable, without endovascular techniques. CONCLUSIONS: By exploiting all suitable types of autogenous AVF it is possible to establish the best form of vascular access even in the majority of elderly patients.

Aged↗
PubMed2005

Innate antiviral immunity is not impaired in patients with chronic renal failure on hemodialysis.

UNLABELLED: Although it is well documented that chronic renal failure patients are susceptible to infectious diseases, the reason for this has not been clarified. The aim of the study was to assess the antiviral natural (innate) immunity of peripheral leukocytes in 37 hemodialysis patients and compare it with that of a of control group (70 blood donors). We investigated 16 patients with anti-hepatitis C virus (HCV) antibodies, anti-HCV(+) and 21 patients without anti-HCV antibodies, anti-HCV(-). METHODS: Innate immunity was measured using the method of direct infection of peripheral blood leukocytes with indicatory VS virus. The VS virus did not replicate in leukocytes with strong innate immunity, whereas by impaired immunity the virus multiplied to high titer. RESULTS: Patients on hemodialysis expressed the same levels of nonspecific antiviral immunity as the control group. We found complete, partial or deficient of innate immunity respectively in 33, 52.5, 14.5% of anti-HCV(-) patients, 43, 43 and 14% of anti-HCV(+) patients, and 44, 40 and 16% of controls. CONCLUSIONS: Innate antiviral immunity was not impaired (disturbed) in chronic HD patients. The categories of innate immunity disposition in dialysis patients and the healthy population did not differ.

Adult↗
PubMed2005

Sirolimus delays recovery from posttransplant renal failure in kidney graft recipients.

The aim of this study was to evaluate the impact of sirolimus and cyclosporine (CsA) combined therapy on the incidence and duration of delayed graft function (DGF), and the impact of the latter on 1-year graft function. The study entailed 23 cadaveric renal recipients treated with sirolimus-CsA-prednisone regimen (sirolimus group). The reference group entailed 23 patients treated with CsA-azathioprine-prednisone. In the sirolimus group the frequency of DGF was 39% and was essentially the same as in reference group (34.8%). The duration of DGF was significantly longer in SRL group and lasted 21.2 +/- 12.2 days versus 6.8 +/- 2.5 in reference group (P = .004). Serum creatinine level decreased below 3.0 mg/dL after 36 +/- 22 days in sirolimus group versus 16.8 +/- 6 days in reference group (P < .04). Cold ischemia was slightly longer and donors were older in DGF patients in both groups. Sirolimus dose during first month was higher in DGF patients (3.5 versus 2.6 mg), whereas level of CsA was lower (230 versus 310 ng/mL). Biopsy-proven acute rejection (AR) occurred in most of DGF patients and during the DGF period. Serum creatinine level at the 12th month posttransplant was higher in DGF versus non-DGF patients (2.0 +/- 0.5 versus 1.5 +/- 0.4 mg/dL). One-year patient and graft survival was 100% in sirolimus group and 100% and 95% in reference group. In conclusion, sirolimus significantly retards the recovery from posttransplant renal failure; however, it does not increase the incidence of DGF. Patients who suffered from posttransplant acute renal failure had worse renal function at 1 year after transplantation, independent of the treatment protocol.

Adult↗
PubMed2005

Prospective, multicenter, randomized trial to compare incidence of new-onset diabetes mellitus and glucose metabolism in patients receiving cyclosporine microemulsion versus tacrolimus after de novo kidney transplantation.

New-onset diabetes mellitus (NODM) is associated with increased risk of graft failure and death in renal transplant recipients. Some clinical studies have indicated that NODM risk is higher with tacrolimus than cyclosporine, but no comparative trial has used American Diabetic Association (ADA)/World Health Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes Incidence After Renal Transplantation, Neoral C2 Monitoring Versus Tacrolimus (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700 de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are randomized to tacrolimus (C0 monitoring) or Neoral (C2 monitoring), stratified by baseline diabetic status and ethnicity. All patients receive basiliximab, corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid (myfortic). Pooled interim 3-month results from a subset of 115 patients receiving either tacrolimus or Neoral showed that the primary efficacy end-point (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11 patients (10%). There were four graft losses and only one death, which occurred after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired fasting glucose or impaired glucose tolerance, and another 5 patients received hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit, resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 micromol/L. Full complete results are expected in December 2005.

Adrenal Cortex Hormones↗
PubMed2005

Mycophenolate mofetil but not the type of calcineurin inhibitor (cyclosporine vs tacrolimus) influences the intragraft mRNA expression of cytokines in human kidney allograft biopsies by in situ RT-PCR analysis.

The aim of the study was to assess the molecular background of the alloimmune response by the detection of low-abundance mRNA of cytokines in 34 core needle biopsies from kidney allografts with histopathological findings of acute rejection (AR). Recipients were immunosuppressed with a calcineurin inhibitor (CNI), cyclosporine or tacrolimus, and prednisone and azathioprine or mycophenolate mofetil (MMF). Tubular and glomerular expression of IL-2, IL-6, IL-10, IFN-gamma, TGF-beta1, and PDGF-B mRNA were assessed using semiquantitative evaluations of RT-PCR in situ on paraffin tissue sections. This procedure resulted in light microscopy visualization of granular precipitates at the sites of the corresponding mRNA chains. The tubular expression of mRNA for IL-6 and TGF-beta1 was significantly lower in biopsies with AR (n = 34) obtained from patients treated with MMF (n = 12) than in biopsies obtained from patients treated with azathioprine (n = 22) (P < .02). Responsiveness to corticosteroids tended to be more frequent among the MMF group (11 of 12 recipients vs 15 of 22 recipients, P = ns). Moreover, 8 of 12 recipients in the MMF-treated group displayed serum creatinine levels equal or less than 167 mmol/L 1 year after biopsy compared to 7 of 22 recipients in the azathioprine-treated group. There was no significant difference between the groups that had or had not received corticosteroids or between those treated with each type of CNI. These results suggest stronger inhibition of humoral responses and down-regulation of fibrosis by MMF among recipients with AR.

Biopsy↗
PubMed2005

Regression of Kaposi's sarcoma in renal graft recipients after conversion to sirolimus treatment.

Kaposi's sarcoma (KS) is a rare complication of renal transplantation in Poland (in our center 2 of 1000 patients). Neovascularization (typical for KS) is promoted by KS-related vascular endothelial growth factor (t-r-VEGF). Sirolimus may reduce t-r-VEGF synthesis and inhibit PI3K-p70S6 kinase of endothelial cells. Two men, 58 and 51 years old, were transplanted in 2002. Initial immunosuppression consisted of cyclosporine, azathioprine, and prednisone. In the second patient, at the week 8 the immunosuppression was switched to tacrolimus and mycophenolate mophetil. KS symptoms appeared on hard palate and skin in month 7 in both patients. In the first patient, the X-ray showed enlargement of mediastinal lymph nodes and diffuse interstitial infiltrates with nodular changes in both lungs. Serum creatinine of the first patient was increased from 1.6 to 1.9 mg/dL, while in the second it remained stable (approximately 2.0 mg/dL). Since confirmation of KS immunosuppression has been minimized in both patients; all drugs except prednisone were withdrawn, and sirolimus was introduced (1-2 mg/24 hours blood level 5-8 ng/mL). Within a month the progression of lung and skin disease ceased, and patients' conditions began to improve with lung opacities regressing, the biggest skin lesions diminishing and smaller ones disappearing. Within 1 year renal function improved. Our observation suggests that sirolimus-based immunosuppression proffers the possibility of KS regression with concomitant renal function preservation among renal graft recipients. It is difficult to ascertain whether KS regression may be attributed to sirolimus treatment or to the reduced overall immunosuppression.

Antibiotics, Antineoplastic↗
PubMed2005

Influence of vitamin D receptor gene polymorphisms on secondary hyperparathyroidism and bone density after kidney transplantation.

Secondary hyperparathyroidism and immunosuppressive treatments are the most important pathogenetic factors for bone disease after kidney transplantation. The aim of study was to compare the influence of vitamin D receptor (VDR) genotype on the PTH level and bone mineral density (BMD) in 67 patients, including 45 immunosuppressed with cyclosporine (CsA) and 22 with tacrolimus (Tac) versus 147 healthy volunteers. Two VDR polymorphisms: BsmI and FokI were assayed with RFLP-PCR. Scantibodies were utilized to evaluate 1-84 PTH. BMD was measured by DEXA. Hormone levels were measured on the third day and sixth month after transplantation. BMD was examined at the third and ninth month. The distribution of FokI genotype differed, but the BsmI genotypes did not differ between the transplant patients and the control group. All transplanted patients showed an elevated tPTH at the first examination. The highest PTH values, which were observed in bb genotype, significantly decreased after the transplant procedure. Patients with the FF genotype who were treated with CsA showed higher levels of tPTH than those with the Ff genotype. At 6 months, a decrease in tPTH occurred in both the CsA and the Tac patients. A low BMD at the third month was more frequent among patients of the BB genotype treated with CsA. The Z-score remained low at the third month and at the ninth month. In conclusion, kidney graft recipients show overrepresentation of the Ff genotype. Our preliminary data suggest that the bb genotype exhibits a protective effect on bone loss after renal transplantation.

Adult↗
PubMed2005

Intragraft mRNA expression of cytokines and growth factors in human kidney allograft biopsies by in situ RT-PCR analysis.

The aim of our study was to correlate intragraft mRNA expression of cytokines and growth factors with histopathologic features in renal allograft biopsies. Fifty-six core biopsies performed in 51 kidney transplant recipients were assessed by the Banff '97 classification. Tubular and glomerular expressions of IFN-gamma, TGF-beta1, and PDGF-B as well as IL-2, IL-6, and IL-10 mRNA were assessed using semiquantitative RT-PCR in situ. No significant differences were noted between acute cellular and vascular rejection with regard to the glomerular and tubular mRNA expression of cytokines examined. We observed a positive correlation between tubular and glomerular IL-10 and IFN-gamma mRNAs during acute rejection. In chronic rejection the mRNA expression levels of IFN-gamma and IL-2, IL-6, and IL-10 did not differ from those of acute rejection; moreover, the glomerular expression of mRNA for TGF-beta1 (P < .05) and PDGF-B (P < .1) was even lower than during acute rejection episodes. Both tubular and glomerular IL-2, TGF-beta1, and PDGF-B mRNA expression levels in biopsies with acute rejection were significantly higher than in acute tubular necrosis (ATN). Biopsy samples with borderline changes exhibited the lowest levels of cytokine gene expression and were close to the intensity of control specimens obtained from living donor kidney biopsies taken during organ harvest. Our data failed to show a dichotomy between Th1 and Th2 cytokine activation in biopsy specimens from kidney allograft recipients; both Th1- and Th2-derived cytokines were involved to similar extents in rejection processes.

Biopsy↗
PubMed2004

Vascular abnormalities in patients with autosomal dominant polycystic kidney disease--the influence on arteriovenous fistula creation.

AIM: Patients with autosomal dominant polycystic kidney (ADPKD) present a number of vascular abnormalities, including cerebral aneurysms, heart valve lesions, coarctations of aorta and abdominal aortic aneurysms. The aim of our study was to investigate whether vascular abnormalities that occur in wrist vessels, make native arteriovenous fistula creation difficult in this group of patients. PATIENTS AND METHODS: The problem was analyzed retrospectively in 783 patients with chronic kidney failure who had had arteriovenous fistula created in our centre in the period between 1991 and 2001. ADPKD was the cause of terminal renal failure in 57 patients (7.3%). These were 31 men and 26 women aged 28 - 69 years (52 +/- 16 years on average). RESULTS: A difference between left and right radial artery diameters and a narrow radial artery (below 2 mm), unsuitable for fistula creation, occurred in 12% of patients with ADPKD and in 0.38% of other patients. Instead of a cephalic vein in the typical place, a few small vessels were present in 14% of patients with ADPKD and in 2.17% of patients with other causes of renal failure. CONCLUSION: Our experience shows a higher incidence of wrist vascular abnormalities in patients with ADPKD. This decreases the possibility of wrist native arteriovenous fistula creation in this group of patients.

Arteriovenous Shunt, Surgical↗
PubMed2003

[The influence of a new surface treatment of silicone intracoular lenses with fluoralkylsitan on the adherence of endophthalmitic bacteria in vitro]].

INTRODUCTION: Dynasilan is a fluoroalkylsilan which is able to bind to surface active molecules of intraocular lenses (IOLs), thereby offering a new option for surface modification of silicone lenses. The purpose of this in vitro study was to investigate the influence of this new surface treatment on the adherence of two typical endophthalmitis-inducing bacteria ( Staphylococcus epidermidis, Propionibacterium acnes). MATERIALS AND METHODS: A total of 14 Dynasilan-treated and 14 untreated silicone lenses were incubated at 37 degrees C for 24 h in brain heart infusion broth (10(8) CFU/ml) either with Staphylococcus epidermidis or with Propionibacterium acnes for 1 h. Subsequently, the adherent bacteria were resuspended using ultrasonification at 35 kHz for 3 x 45 s. After a dilution series and incubation at 37 degrees C for 24 h or 3 days the colonies were counted. RESULTS: On untreated IOLs incubated with Staphylococcus epidermidis the average number of bacteria was 3.6 x 10(7)/ml, and on treated IOLs the number of counted colonies was reduced to 1.09 x 10(7)/ml. Incubated with Propionibacterium acnes the average number of adherent bacteria on untreated IOLs was 4.75 x 10(4)/ml and on modified IOLs the number was reduced to 2.94 x 10(4)/ml. CONCLUSION: Dynasilan surface treatment may reduce the adherence of Staphylococcus epidermidis and Propionibacterium acnes on silicone intraocular lenses. Further studies regarding the stability of this treatment, its biocompatibility and influence on lens epithelial cell adhesion are in progress.

Bacterial Adhesion↗
PubMed2003

Cytokine gene expression in kidney allograft donor biopsies after cold ischemia and reperfusion using in situ RT-PCR analysis.

It was previously reported that ischemia-reperfusion injury initiates an inflammatory response and may significantly affect the transplanted organ function. The aim of this study was to assess changes of intragraft cytokine mRNA expression in kidneys after cold ischemia (CI) and following reperfusion. We examined mRNA of a product of activated T lymphocytes (IFN-gamma) and a monocyte product (IL-6). Eleven kidneys were transplanted after CI time ranging from 16 to 39 hours. Renal needle core biopsies were obtained from donors after cold ischemia and approximately after 20 minutes of reperfusion. Tubular and glomerular expression of IFN-gamma and IL-6 mRNA were assessed using semiquantitative evaluation of the RT-PCR in situ. After reperfusion an intense increase of IL-6 mRNA expression was observed in four specimens, a slight increase was noticed in five specimens, and a very slight decrease in two specimens. Changes in IL-6 mRNA expression were limited only to tubules. In contrast, the glomerular and tubular mRNA expression of IFN-gamma and glomerular of IL-6 remained stable. Mean CI time for patients with an intense increase was higher than for patients with a slight increase and with the decrease of IL-6 mRNA expression (32.0 +/- 6.8 vs 25.2 +/- 7.3 and 26.0 +/- 5.7 hours). Our results suggest that early inflammatory changes at the time of implantation of renal allografts depends mainly on monocyte/macrophage-associated products. The observed intensity of their expression in tubules was connected to longer CI time.

Adolescent↗
PubMed2003

The influence of calcineurin inhibitors on mycophenolic acid pharmacokinetics.

Despite the fact that concentrations of mycophenolic acid (MPA) are not routinely measured, accumulating data suggest the usefulness of this monitoring to optimize therapy. The aim of this study was to assess the influence of CsA and tacrolimus on MPA pharmacokinetics. Concentrations of MPA were measured using HPLC. An assay was performed before dose (the C(0)), as well as at 40 minutes and 1, 2, 4, 6, 8, 10, 12 hours after administration of mycophenolate mofetil (MMF). MPA profiles were assessed in 51 patients receiving tacrolimus at a dose of 1.0 g/d and prednisone as well as in 97 patients receiving CsA (2.0 g/d) and prednisone. Significant correlations of MPA levels with serum albumin and GFR were observed in both groups. Women presented with higher levels of MPA than men. C(0) MPA level among the tacrolimus group were significantly higher than those in CsA group: 3.18 +/- 2.21 microg/mL versus 1.68 +/- 1.03 microg/mL (P </=.001). The level of MPA AUC((0-12)) in the tacrolimus group was nonsignificantly higher than that in the CsA group. There was no second peak of MPA level in a group of patients receiving CsA. We developed a limited sampling strategy to estimate MPA AUC((0-12)) in both tacrolimus and CsA groups. We observed a correlation between C(0) MPA and C(0) CsA (r =.35; P </=.001) as well as, between tacrolimus dose and MPA C(40) and MPA C(max) (r =.24; P </=.05; r =.27; P </= 0.05, respectively). No relationship between MPA pharmacokinetics and tacrolimus blood concentrations was noticed. Tacrolimus and CsA both affect the pharmacokinetics of MPA; high MPA concentrations in patients treated with tacrolimus justify MMF dose reduction in this group. Alterations of CsA concentrations must be used to guide MMF dose adjustments.

Adult↗