7 research outputs found
Mycophenolate mofetil in kidney transplantation
Mycophenolate mofetil is a new immunosupressive drug, exhibiting its effect through
inhibition of proliferation ofT- and B-Iymphocytes. Superior efficacy of mycophenolate
mofetil compared to azathioprine, in combination with cyclosporine and prednisone, in the
prevention of acute rejection in organ transplantation has made mycophenolate mofetil one of
the standard immunosupressive drugs after transplantation. Mycophenolate mofetil also is an
interesting candidate drug for many other, mainly auto-immune mediated diseases. The use of
mycophenolate mofetil in several of these diseases is discussed. The defmitive place of
mycophenolate mofetil will depend on the results of randomised trials currently under way
Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study
Uncertainty exists regarding the necessity of continuing triple therapy
consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and
prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx,
212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or
continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice
daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10
mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute
rejection occurred in 14 (22%) of 63 patients after CsA withdrawal
compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1
(1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic
rejection was present in one patient in the control group, in nine
patients after CsA withdrawal (P = 0.006 versus control group); and in
four patients after discontinuation of Pred (NS). Graft loss occurred in
two versus one patient after CsA or Pred withdrawal, respectively, and in
two patients in the control group (NS). Patients who successfully withdrew
CsA had a significantly lower serum creatinine during follow-up. Pred
withdrawal resulted in a reduction in mean arterial pressure, and the
total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal
at 6 mo after RTx results in a significantly increased incidence of
biopsy-proven acute and chronic rejection. Pred withdrawal was safe and
resulted in a reduction in mean arterial pressure. However, patient and
graft survival and renal function 2 yr after RTx were not different among
groups
Development of the Rotterdam Renal Replacement Knowledge-Test (R3K-T)
Introduction: There is currently a lack of validated or standardized measures to test the level of knowledge among renal patients regarding kidney disease and available treatment options. We conducted a pilot study to develop a questionnaire measuring knowledge of kidney disease, dialysis and transplantation options. The main aim of this study was to develop such an instrument for further use in research and practice.
Method: An initial 61 item pool was generating by searching the literature and consulting experts in this area for additional items. This questionnaire was completed by 182 renal disease patients from 4 dialysis centers in the Rotterdam municipality. A factor analysis was conducted using the maximum likelihood factor method followed by direct oblimin rotation to obtain variance explained by each factor. Questions that loaded ≥ .30 on a factor were included.
Results: Twenty-seven patients (24%) were in the pre-RRT phase, 60 (54%) were undergoing haemodialysis, 16 (14%) were undergoing peritoneal dialysis, and 9 (8%) had a graft failure. Forty (36%) were female and 72 (64%) were male. Age range 19-87 (median = 59). A factor analys
Cytomegalovirus colitis in a CMV-seropositive renal transplant recipient on triple drug therapy (including mycophenolate)
Mycophenolic acid plasma concentrations in kidney allograft recipients with or without cyclosporin: a cross-sectional study
BACKGROUND: Combining cyclosporin (CsA) and prednisone with mycophenolate
mofetil (MMF) results in a significant reduction in the rate of
biopsy-proven acute rejection after kidney transplantation. This is
achieved with a standard daily MMF dosage of 2 or 3 g. Whether monitoring
of the pharmacologically active metabolite mycophenolic acid (MPA) will
lead to improved safety and efficacy is unclear. METHODS: We monitored MPA
trough levels in 18 kidney transplant recipients treated with CsA,
prednisone, and MMF (63 samples) and in 11 patients (31 samples) treated
with prednisone and MMF only, in a cross-sectional study. All patients
were at least 3 months after transplantation with stable graft function.
All patients were treated with 2 g MMF for at least 3 months and 10 mg
prednisone. RESULTS: The MPA trough levels in the CsA-treated patients
were significantly lower (P<0.0001; Mann-Whitney) than those in patients
on MMF and prednisone only (mean MPA levels 1.98+/-0.12 vs 4.38+/-0.40
mg/l respectively). CONCLUSIONS: Although all patients were treated with
an identical MMF dose, a significant difference was found in the MPA
trough levels between CsA- vs non-CsA-treated patients. This suggests that
CsA influences the MPA trough level. The level at which CsA affects the
MPA trough levels is unclear
Effect of mycophenolate mofetil on erythropoiesis in stable renal transplant patients is correlated with mycophenolic acid trough levels
BACKGROUND: Both mycophenolate mofetil (MMF) and azathioprine (AZA) are
immunosuppressive drugs that inhibit purine synthesis. In theory, MMF
selectively inhibits lymphocyte proliferation, while AZA has well-known
effects on red blood cells and thrombocytes as well. In renal transplant
recipients we replaced CsA therapy by MMF in an attempt to reduce the
immunosuppressive load 1 year after kidney transplantation. During this
study we observed the effect of MMF on haematological parameters such as
haemoglobin (Hb), leukocytes, and thrombocytes. METHODS: One year after
kidney transplantation 26 stable patients were converted from cyclosporin
A (CsA) to MMF (2 g/day). Thereafter, these patients were tapered twice in
their MMF dose from 2 g to 1.5 g (4 months after conversion) and from 1.5
to 1 g (8 months after conversion) per day. The Hb levels, leukocyte and
thrombocyte counts, and mycophenolic acid (MPA) trough levels were
routinely measured. RESULTS: After conversion from CsA to MMF not only
creatinine levels and the number of leukocytes, but also the haemoglobin
(Hb) level significantly decreased in 21/26 patients (P=0.0004). In eight
patients the Hb level dropped more than 1 mmol/l (=1.61 g/dl). Only in two
of eight patients was an explanation for blood loss found. The effect on
Hb level did not ameliorate after the first MMF dose reduction to 1.5
g/day. After tapering the MMF dose to 1 g/day, the Hb approached the
pre-conversion level. Not only the MMF dose but also the mycophenolic acid
(MPA) trough level correlated with the Hb level. CONCLUSIONS: After
conversion from CsA to MMF 1 year after kidney transplantation, a decrease
in Hb level and leukocyte count was observed. The MPA trough level
correlated also with the Hb level. The effect on the Hb level was
reversible after dose reduction. This finding suggests that MMF exerts a
negative effect on erythropoietic cells
Tapering immunosuppression in recipients of living donor kidney transplants.
We have previously suggested that the in vitro donor-specific cytotoxic
T-lymphocyte precursor (CTLp) assay can guide us to identify patients in
which the immunosuppressive load can be tapered. In a clinical trial we
had observed that a low (<10/10(6) PBMC) frequency of these CTLp was
predictive for an uneventful rejection-free clinical course in patients
that were converted from calcineurin inhibitors to mycophenolate mofetil
or azathiopine. In the present prospective study in 81 stable kidney
transplant recipients, already converted from calcineurin inhibitors, we
measured CTLp frequencies and reduced the immunosuppressive load on a
routine basis when CTLp were <10/10(6) PBMC. Donor-specific cytotoxicity
could not be measured in 50/81 patients, while their reactivity against
third-party lymphocytes was not impaired. These 50 patients were tapered
in their immunosuppression. Only in one patient, who had stopped all his
medication, was a rejection episode diagnosed. We conclude that in
patients with a low donor-specific CTLp frequency it is safe to reduce the
immunosuppression