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E Pohanka

Publications and source records attributed to E Pohanka.

At least 19 recordsLinked to original sources
PubMed2006

Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.

BACKGROUND: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST. RESULTS: Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. CONCLUSIONS: Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Aged↗
PubMed2006

Long-term safety and efficacy after conversion of maintenance renal transplant recipients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPA, myfortic).

AIM: A 12-month multicenter, double-blind trial in which maintenance renal transplant patients were randomized to remain on mycophenolate mofetil (MMF) or convert to enteric-coated mycophenolate sodium (EC-MPS, myfortic) has demonstrated that conversion from MMF to EC-MPS is safe. Patients completing the study were invited to enter an open-label extension. Upon entry to the extension, patients who had received MMF during the randomized phase were converted to EC-MPS ("newly-exposed EC-MPS" group) and were monitored separately from those who had been randomized to EC-MPS ("long-term EC-MPS" group). The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS, and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population. METHODS: All patients received EC-MPS 720 mg b.i.d. with cyclosporine microemulsion and corticosteroids per local practice. Data derived from the analysis of the first 24 months of the extension phase are presented. RESULTS: Of the 297 patients who completed the core study, 260 (88%) entered the extension; 195 (75%) completed the 24-month extension visit. For on-treatment patients > 95% of the planned daily dose of EC-MPS was administered, and < 13% of patients in both groups had discontinued EC-MPS due to adverse events by 24 months. The overall incidence of adverse events during the extension phase, including infections and hematological abnormalities, was comparable to that seen in the core study, with a similar safety profile in the newly-exposed and long-term EC-MPS groups. There were 3 deaths during the first 24 months of the extension, and 2 graft failures in both the "newly-exposed" and "long-term" EC-MPS groups. CONCLUSIONS: These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients, and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option.

Adult↗
PubMed2005

Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium: results of a 1-year extension study.

Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in <12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.

Adult↗
PubMed2005

Improved attainment of NKF classified lipid target levels after conversion from cyclosporine to tacrolimus in renal graft recipients.

In an open, prospective, multicenter study, stable renal graft recipients were converted to tacrolimus because of cyclosporine-related side effects. Seventy-five patients were switched primarily because of hyperlipidemia. After the switch to tacrolimus, mean total cholesterol was reduced by 15% at month 6. One hundred seventy-seven additional patients were switched primarily for other indications: hypertrichosis, gingival hyperplasia, and arterial hypertension, and these symptoms also improved after the switch. In this analysis, serum lipid levels were categorized according to a modified standard classification of lipid parameters for renal transplant patients (published by the NKF Work Group). The aim was to estimate the proportion of patients reaching normal lipid levels after the conversion to tacrolimus therapy. In patients with primary indication hyperlipidemia, the proportion with normal cholesterol levels increased significantly from 5.6% at baseline to 37.5% at month 6 (P < .05). For LDL cholesterol, the increase was from 54.1% at baseline to 64.9% at month 6, and for triglycerides the improvement was from 25.4% to 33.8%. HDL cholesterol levels remained stable. Similar changes of lipid parameters were also observed in the subgroups of patients converted to tacrolimus primarily because of other indications. After conversion from cyclosporine to tacrolimus, a significantly higher proportion of stable renal graft recipients reached normal total cholesterol levels. For LDL cholesterol and triglycerides, a trend for normalization was observed. Thus, the improvement of serum lipid levels resulted for many patients in a change to a better level class and improved or normalized their cardiovascular risk parameters.

Cholesterol, LDL↗
PubMed2003

One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study.

BACKGROUND: Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

Creatinine↗
PubMed2001

New immunosuppressive drugs: an update.

An increasing number of immunosuppressive drugs became available for clinical use over the past few decades. These include substances with recently recognized immunosuppressive properties, which needed careful evaluation in various trials before they could be approved for use in different diseases. The effectiveness of other agents was already established, but knowledge about their modes of action or the mechanisms that lead to side effects was acquired much later. This understanding also contributed to the development of new drugs that display synergistic effects or lack certain adverse effects. The greater choice afforded by such research endeavours allows us to select the best therapeutic strategy for an individual patient; however, this requires a comprehensive knowledge of the available options. The present review provides an update of current knowledge of the most important substances (including calcineurin and target of rapamycin inhibitors, regulators of gene expression, and inhibitors of purine and pyrimidine synthesis) and surveys some of the novel agents that are expected to play an important role in the future.

Adrenal Cortex Hormones↗
PubMed2000

Recombinant human granulocyte colony-stimulating factor after kidney transplantation: a retrospective analysis to evaluate the benefit or risk of immunostimulation.

BACKGROUND: Leukopenia due to immunosuppressive drugs represents a well-known complication in graft recipients, which might put patients at an increased risk for infections. In this study, recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that selectively stimulates neutrophil colony formation and neutrophil cell differentiation, was tested for safety and efficacy. METHODS: We evaluated 30 episodes of leukopenia (<2000/mm3) in 19 kidney graft recipients treated with rhG-CSF. This cohort was compared with an age- and sex-matched historical control group without therapy. Peripheral and differential blood cell counts were analyzed, and the duration of leukopenia was estimated. Furthermore, the occurrence of infections associated with leukopenia was investigated. RESULTS: All patients responded to rhG-CSF therapy. Peripheral leukocyte counts increased from 1756+/-582 to a peak of 8723+/-3038/mm3 (P<0.0001). On the average, the peak was reached after 2.7 days (range 1 to 8). Furthermore, the effect was fairly persistent, because in 22 of 30 episodes leukocyte counts were within the normal range after 7 days. The elevation of total leukocytes was mainly due to a specific increase in neutrophil granulocytes from 1143+/-514 to 6895+/-1950/mm3 on the peak day (P<0.0001). Patients in the G-CSF group were leukopenic for a mean of 1.29+/-0.59 days, whereas in the control group leukopenia persisted for at least 7 days. Consequently, the rate of infections was significantly higher (P<0.045) in nontreated patients. CONCLUSION: rhG-CSF was safe and effective in leukopenic kidney graft recipients. Leukopenic episodes in treated patients were significantly shorter, and infections occurred at a significantly lower rate. No evidence was found that rhG-CSF therapy might trigger rejection episodes, and no side effects were observed.

Antilymphocyte Serum↗
PubMed1999

Effects of sodium nitroprusside on hemodialysis-induced platelet activation.

BACKGROUND: Hemodialysis (HD) is associated with increased platelet activation as reflected by enhanced P-selectin expression on platelets and by increased formation of heterotypic platelet-leukocyte aggregates. Both may play a pathophysiologic role in HD-associated platelet dysfunction or the propagation of atherosclerosis. As nitric oxide (NO) is a potent inhibitor of platelet activation, we were interested in whether HD-induced platelet activation could be blunted by a NO donor. METHODS: After a pilot study in 12 patients to gain an estimate for the sample size, the main trial was conducted as a randomized, double-blind, placebo-controlled, two-way, cross-over study. Twelve patients received an infusion of sodium nitroprusside (1 microgram/kg/min for over 15 min) or placebo into the inlet port of the HD device. RESULTS: Platelet activation increased within five minutes after start of HD (P < 0.05). Infusion of sodium nitroprusside neither decreased platelet activation (P-selectin + platelets) nor affected the number of platelet-leukocyte aggregates (CD41+ neutrophils) as measured by flow cytometry. CONCLUSION: Although NO may have inhibitory effects on platelet activation in vivo, our results confirm recent findings showing that NO donors were ineffective in preventing platelet activation by extracorporeal circulation during cardiopulmonary bypass or plateletpheresis. Thus, NO donors do not appear to be ideal candidate drugs to inhibit HD-associated platelet activation.

Adult↗
PubMed1998

Posttransplant hemolytic uremic syndrome in adult retransplanted kidney graft recipients: advantage of FK506 therapy?

BACKGROUND: Posttransplant hemolytic uremic syndrome (pHUS) is a rare but severe disorder that confers a poor prognosis on an allograft due to thrombotic microangiopathy. Immunosuppression with cyclosporine (CsA) is implicated as a significant risk factor for the development of pHUS. In early reports, it was hypothesized that immunosuppression with FK506 (tacrolimus) would avoid the development of pHUS. However, this initially supposed beneficial effect remains controversial, because pHUS associated with tacrolimus therapy has been published in some later case reports. This article aims to further evaluate FK506 with respect to the development and resolution of pHUS. METHODS: We describe the course of seven adult kidney graft recipients with pHUS, treated with FK506 either as initial immunosuppression for retransplantation or after discontinuation of CsA for resolution of pHUS. Work-up for pHUS was initiated when certain clinical features, such as hemolytic anemia, thrombocytopenia, and deterioration of graft function, were found. The diagnosis was confirmed by histologic examination of a renal allograft biopsy specimen (thrombotic microangiopathy). With the onset of pHUS, additional plasma exchange was performed in all patients. RESULTS: Two patients suffered from end-stage renal disease due to primary HUS and had a history of recurrent pHUS in previous renal transplants. In both patients, the attempt to regraft was only made because of the early optimistic reports using FK506. Despite initial FK506 therapy, both recipients developed pHUS again, leading to loss of graft function. Two additional kidney graft recipients with primary renal failure other than HUS also received FK506 as initial immunosuppression. One of them (loss of the first kidney graft due to CsA-induced pHUS) was successfully treated with FK506 for his second renal transplant. The other recipient, a patient in whom de novo pHUS had occurred in the first graft despite initial therapy with FK506, was treated with CsA for his second graft and again developed pHUS. The latter process, however, could be reversed by a switch to steroids and azathioprine. In all three patients regrafted for reasons other than pHUS, development of de novo pHUS was treated by CsA withdrawal and a switch to FK506; this approach was effective in two patients. CONCLUSION: Our results demonstrate that three of seven renal allograft recipients benefited from FK506 therapy for prevention or resolution of pHUS. Treatment or prophylaxis with FK506 can be considered advantageous in some patients with de novo pHUS, but FK506 fails to prevent recurrent pHUS in patients with primary HUS.

Adult↗
PubMed1998

GBV-C/HGV in hemodialysis patients: anti-E2 antibodies and GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells.

Hepatitis G virus (GBV-C/HGV), a recently identified RNA virus adds to the risk of parenteral transmitted viral infections in hemodialysis patients. We studied the prevalence of GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells (PMNC) by reverse transcription-polymerase chain reaction (RT-PCR) and determined antibodies against the envelope protein E2 of GBV-C/HGV by ELISA. A total of 119 dialysis patients were studied. GBV-C/HGV-RNA was found in 16 of 119 patients (13%) as compared with 2% of healthy controls (P = 0.014). Two of the 16 GBV-C/HGV-RNA+ patients were co-infected with HCV, and none was positive for HBV-DNA. In 38% of serum GBV-C/HGV-RNA+ patients GBV-C/HGV-RNA was also detected in PMNC. In addition, GBV-C/ HGV-RNA was identified in PMNC of 2 patients negative for GBV-C/ HGV-RNA in serum. Twenty-four patients had anti-E2 antibodies in serum (20%), but were GBV-C/HGV-RNA-. In addition, two of the 16 GBV-C/HGV-RNA+ patients were concomitantly positive for anti-E2 antibodies. Only one of the 16 GBV-C/HGV infected patients had elevated aminotransferases; this patient was co-infected with hepatitis C virus. GBV-C/HGV-RNA positivity was independent on duration of hemodialysis, but GBV-C/HGV-RNA+ patients had received more units of blood in the past. Combined data of past contact, as assessed by anti-E2 antibodies, and present infection, documented by GBV-C/HGV-RNA, indicate a high overall exposure to GBV-C/HGV in dialysis patients.

Adult↗
PubMed1998

Broadband ultrasound attenuation of the calcaneus. A tool for assessing bone status in patients with chronic renal failure.

PURPOSE: To evaluate broadband ultrasound attenuation (BUA) for the assessment of bone status and to correlate this to dual-energy X-ray absorptiometry (DXA) in haemodialysis patients. MATERIAL AND METHODS: In 60 patients, BUA (dB/MHz) was determined for the calcaneus. The results were expressed as Z-scores and T-scores, i.e. units of standard deviations respectively from age- and sex-matched normal values and from sex-matched normal mean values in healthy young adults. Ultrasound data were correlated to relevant clinical, biochemical and DXA data (g/cm2), which were examined at the femoral neck and at the lumbar spine in 50 patients. RESULTS: The BUA Z-score was < -1 in 53% of the patients and < -2 in 22%. The BUA T-score was < -1 in 88% and < -2 in 62%. Moderate correlation was found for calcaneal BUA to DXA in men (r = 0.47-0.48, p < 0.01) and to DXA of the lumbar spine in women (r = 0.51, p < 0.05). The best correlation was observed for BUA to DXA of the femoral neck in women (r = 0.61, p < 0.01). CONCLUSION: Calcaneal BUA is an additional tool for the surveillance of bone density in haemodialysed patients.

Absorptiometry, Photon↗
PubMed1997

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Adolescent↗
PubMed1997

n-butyrate downregulates the stimulatory function of peripheral blood-derived antigen-presenting cells: a potential mechanism for modulating T-cell responses by short-chain fatty acids.

Modulation of proliferative T-cell responses by n-butyrate has been suggested to result from direct interference with cell cycle progression. Considering the important role of antigen-presenting cells (APC) in T-cell activation, we were particularly interested in studying the impact of n-butyrate on these cells. We demonstrated that pretreatment of human peripheral blood mononuclear cells (PBMC) or monocytes with this agent resulted in a dose- and time-dependent downregulation of their capability to stimulate T-cell responses with a similar pattern of inhibition when this agent was present throughout the culture period. Pretreatment with n-butyrate was effective in preventing both alloresponses and T-cell proliferation to immobilized anti-CD3 monoclonal antibody (mAb) suggesting alteration of costimulatory function. Flow cytometric analysis revealed that interferon-gamma (IFN-gamma)-induced upregulation of B7-1 expression on monocytes was profoundly inhibited by n-butyrate. Furthermore, this agent significantly suppressed the expression of intercellular adhesion molecule-1 (ICAM-1) or lymphocyte function-associated antigen-3 (LFA-3). In contrast, constitutive as well as cytokine-induced expression of B7-2 was enhanced by n-butyrate. Additionally, in monocytes, but not in T cells, treatment with n-butyrate led to significant alteration of membrane integrity owing to apoptotic cell death. Our findings indicate that modulation of T-cell responses by n-butyrate could also result from altered APC function, possibly as a consequence of downregulating distinct adhesion and/or costimulatory receptors as well as of inducing apoptosis. A potential clinical relevance of short-chain fatty acids for reducing T-cell-mediated immune reactions via modulating APC function is speculated.

Antigen-Presenting Cells↗
PubMed1997

Orellanine poisoning: rapid detection of the fungal toxin in renal biopsy material.

BACKGROUND: Mushroom poisoning by some species of the Cortinarius (Agaricales) often lead to irreversible renal failure caused by the nephrotoxin orellanine. In 1994 and 1995, six poisoning outbreaks involving ten individuals in Northern Italy and in Austria were investigated. METHODS: A total of 87 clinical samples (urine and blood samples including renal biopsy material of three patients) were examined for the presence of orellanine by thin layer chromatography. RESULTS: Orellanine can be detected after a relatively long period following poisoning by performing a simple thin layer chromatography technique using small quantities of renal biopsy material. No toxin was found in urine or blood samples. CONCLUSIONS: Orellanine is rapidly concentrated in the kidneys in a relatively soluble form and cannot be detected in urine, blood and dialysis fluids at the time when first symptoms appear.

2,2'-Dipyridyl↗
PubMed1997

Living on chronic hemodialysis between dryness and fluid overload.

The hydration state of a hemodialysis patient reflects the balance between fluid overload, normovolemia and underhydration. Since chronic volume overload enhances the cardiac mortality, and chronic underhydration carries the risk for dialysis-associated hypotension, treatment for the deranged water homeostasis of hemodialysis patients needs to focus on an accurate assessment of dry body weight. Non-invasive methods such as echocardiography of the inferior caval vein diameter (ICVD) or conductivity measurements are considered as reliable techniques to estimate the hydration state of hemodialysis patients. The value of biochemical parameters for an adequate assessment of dry body weight remains controversial. In our study we have determined cyclic guanosine 3'5'-monophosphate (cGMP) serum levels in 125 patients undergoing regular hemodialysis. Predialytic cGMP significantly decreased from 46.1 +/- 26.0 to 17.0 +/- 9.3 pmol/liter post-dialysis (P < 0.001). In 35 patients cGMP level after hemodialysis remained > 20 pmol/liter, but non of these patients displayed any clinical signs of fluid overload. In a group of patients with normal heart function (N = 29) additional sonography of the ICVD revealed normovolemia in 16 patients, underhydration in 5 patients and fluid overload in 4 patients. The respective post-dialytic mean cGMP level was significantly higher in the overhydrated group compared to normovolemic and underhydrated patients (25.3 +/- 10.8 vs. 14.7 +/- 6.4 and 11.4 +/- 5.3 pmol/liter, P < 0.02). However, there was no significant correlation between cGMP level and ICVD (r = 0.5, NS). We conclude that there is no single parameter to define the adequate dry body weight of a hemodialysis patient. Our own data demonstrate the limitations using cGMP, particularly in estimating underhydration. ICVD and bioimpedance offer non-invasive methods for both volume overload and underhydration, and seem to be reliable in the routine assessment of dry body weight.

Atrial Natriuretic Factor↗