High incidence of mild hyponatraemia in females using ecstasy at a rave party.

BACKGROUND: Globally, millions of subjects regularly use ecstasy, a drug popular due to its empathogenic and entactogenic effects. Dilutional hyponatraemia, mainly caused by direct stimulation of antidiuretic hormone (ADH) secretion by ecstasy, is among the many side effects of the drug (active substance 3, 4-methylenedioxymethamphetamine, MDMA). Severe, symptomatic hyponatraemia related to the use of MDMA has been reported in more than 30 cases. The mortality of this complication is high and mainly females are involved. Dramatic cases that reach the literature probably represent the tip of the iceberg. We decided to study the incidence of hyponatraemia in subjects using MDMA at an indoor rave party. METHODS: The study was performed at the indoor event 'Awakenings', held in Amsterdam in the fall of 2010. The plasma sodium concentration was measured at the party using a point of care method in 63 subjects using MDMA and 44 controls. The use of MDMA was confirmed by a urine test. RESULTS: The plasma sodium concentration in subjects using MDMA was significantly lower than in those not using the drug (138 ± 2 mmol/L versus 140 ± 2 mmol/L, respectively, P < 0.001). The overall incidence of hyponatraemia, defined as a plasma sodium concentration <136 mmol/L, was 14.3% in MDMA users (9/63 subjects). Most cases of hyponatraemia occurred in females, in whom the incidence was 26.7% (8 of 30 females), with lowest values of 133 mmol/L. The number of ecstasy pills ingested by the females developing hyponatraemia was not different from that ingested by those who did not develop this complication. Fluid intake in ecstasy users exceeded that of non-users, suggesting a dipsogenic effect of the drug. CONCLUSIONS: Only 3% of males, but no less than ∼25% of females attending a rave party and using MDMA developed mild hyponatraemia during the event. Especially females are therefore probably also at risk of developing severe symptomatic hyponatraemia. Not using MDMA is obviously the best option to prevent MDMA-induced hyponatraemia. However, accepting the fact that millions use the drug every weekend, strategies should also be developed to prevent hyponatraemia in subjects choosing to take MDMA. This would include matching the electrolyte content of the fluids and food ingested to that of the fluids that are lost during the use of MDMA, mainly by perspiration. Users of MDMA and emergency health care workers should become more aware of the relatively high incidence of MDMA-induced hyponatraemia and of potential strategies to prevent this complication.

Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation.

There is increasing interest in tacrolimus-minimization regimens. ASSET was an open-label, randomized, 12-month study of everolimus plus tacrolimus in de-novo renal-transplant recipients. Everolimus trough targets were 3-8 ng/ml throughout the study. Tacrolimus trough targets were 4-7 ng/ml during the first 3 months and 1.5-3 ng/ml (n = 107) or 4-7 ng/ml (n = 117) from Month 4. All patients received basiliximab induction and corticosteroids. The primary objective was to demonstrate superior estimated glomerular filtration rate (eGFR; MDRD-4) at Month 12 in the tacrolimus 1.5-3 ng/ml versus the 4-7 ng/ml group. Secondary endpoints included incidence of biopsy-proven acute rejection (BPAR; Months 4-12) and serious adverse events (SAEs; Months 0-12). Statistical significance was not achieved for the primary endpoint (mean eGFR: 57.1 vs. 51.7 ml/min/1.73 m(2)), potentially due to overlapping of achieved tacrolimus exposure levels (Month 12 mean ± SD, tacrolimus 1.5-3 ng/ml: 3.4 ± 1.4; tacrolimus 4-7 ng/ml: 5.5 ± 2.0 ng/ml). BPAR (months 4-12) and SAE rates were comparable between groups (2.7% vs. 1.1% and 58.7% vs. 51.3%; respectively). Everolimus-facilitated tacrolimus minimization, to levels lower than previously investigated, achieved good renal function, low BPAR and graft-loss rates, and an acceptable safety profile in renal transplantation over 12 months although statistically superior renal function of the 1.5-3 ng/ml tacrolimus group was not achieved.

Orbital mass as manifestation of Wegener's granulomatosis: an ophthalmologic diagnostic approach.

OBJECTIVES: Orbital manifestation of Wegener's granulomatosis is diverse and diagnosis is often difficult. This study aims to improve the diagnostic strategy in orbital Wegener. METHODS: A review of the diagnostic process in patients in whom a diagnosis of orbital WG was considered. RESULTS: Thirty-three patients were analysed, consisting of 15 patients with orbital WG, 11 with idiopathic orbital inflammation, 6 with orbital sarcoidosis and one with aspergillosis. Diagnostic findings indicating orbital WG were ear/nose/throat involvement, multiple organ system involvement, a positive ANCA, and on histology vasculitis, whereas granulomatous inflammation without signs of vasculitis was more indicative of another orbital disease. CONCLUSIONS: The diagnostic process of orbital WG should include CT scanning of the orbit and sinuses, ANCA blood testing, consultation of a rheumatologist, an ophthalmologist, and an ear-nose-throat specialist, and biopsy of an easily accessible, active inflammatory lesion.

Kidneys from donors after cardiac death provide survival benefit.

The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait for a conventional kidney from a brain-dead donor (DBD). This observational cohort study included all 2575 patients who were registered on the Dutch waiting list for a first kidney transplant between January 1, 1999, and December 31, 2004. From listing until the earliest of death, living-donor kidney transplantation, or December 31, 2005, 459 patients received a DCD transplant and 680 patients received a DBD transplant. Graft failure during the first 3 months after transplantation was twice as likely for DCD kidneys than DBD kidneys (12 versus 6.3%; P=0.001). Standard-criteria DCD transplantation associated with a 56% reduced risk for mortality (hazard ratio 0.44; 95% confidence interval 0.24 to 0.80) compared with continuing on dialysis and awaiting a standard-criteria DBD kidney. This reduction in mortality translates into 2.4-month additional expected lifetime during the first 4 years after transplantation for recipients of DCD kidneys compared with patients who await a DBD kidney. In summary, standard-criteria DCD kidney transplantation associates with increased survival of patients who have ESRD and are on the transplant waiting list.

Effects of probiotics on acquisition and spread of multiresistant enterococci.

Ampicillin-resistant Enterococcus faecium (ARE) and vancomycin-resistant E. faecium (VRE) are important nosocomial pathogens. We quantified effects of probiotics and antibiotics on intestinal acquisition of ARE colonization in patients hospitalized in two non-intensive care unit (non-ICU) wards with high ARE prevalence. In a prospective cohort study with crossover design, all patients with a length of stay of >48 h were offered a multispecies probiotic product twice daily until discharge (4.5 months, intervention period) or not (4.5 months, control period). Perianal ARE carriage was determined <48 h after admission, twice weekly, and <48 h before discharge. The first isolates were genotyped by multiple-locus variable-number tandem repeat analysis (MLVA). Risk factors for acquisition were determined by Cox proportional hazards modeling, with special emphasis on ecological postantibiotic effects and delays between actual acquisition and culture positivity. Of 530 patients included, 94 (18%) were ARE colonized on admission. Of the remaining 436 noncolonized patients, 92 acquired ARE colonization: 28 (25%) of 110 probiotic users and 64 (20%) of 326 control patients (chi(2) test, P = 0.325). In all, 661 ARE strains were isolated from 186 patients, of which 186 were genotyped. In both wards, two MLVA types (MTs; MT1 and MT159) were responsible for >80% of acquisitions. Both MTs were genetically different from the probiotic E. faecium strain. Antibiotics to which ARE is resistant (hazard ratio [HR], 7.73 [95% confidence interval (CI), 4.52 to 13.22]), an ecological postantibiotic effect (HR, 7.11 [95% CI, 3.10 to 16.30]), and age (HR, 1.01 [95% CI, 0.99 to 1.02]) were associated with ARE acquisition. The HR of probiotics was 1.43 (95% CI, 0.88 to 2.34). In a setting with high selective antibiotic pressure, probiotics failed to prevent acquisition of multiresistant enterococci.

Pre-kidney-transplant blood transfusions do not improve transplantation outcome: a Dutch national study.

BACKGROUND: Female renal transplant candidates are prone to be sensitized by prior pregnancies, and undetected historical sensitization might decrease transplantation outcome. Hypothesis of our study was that pre-transplant blood transfusions (PTFs) can elucidate historical sensitization and that the avoidance of the associated antigens can improve transplantation outcome. METHODS: Data from all female non-immunized renal transplant candidates who received a random PTF (rPTF) (n = 620), matched PTF (mPTF) (one HLA-A and B and one HLA-DR match) (n = 86) or donor-specific blood transfusion (DST) (n = 100) between 1996 and 2006 were collected. Complement-dependent cytoxicity was used to detect anti-HLA antibodies. Sensitization and transplantation outcomes after a PTF were analyzed. Non-immunized female renal transplant recipients who did not receive a PTF were used as the control group. RESULTS: In 165 patients, anti-HLA antibodies (IgG) were detected after the PTF. Both historical and primary sensitizations were found. A DST induced donor-specific anti-HLA antibodies in 25% of the DST recipients. Our policy did not improve transplantation outcome in recipients of a kidney from a deceased donor (n = 368) or in recipients of a living donor [DST (n = 49) and mPTF (n = 66)]. CONCLUSIONS: A PTF did elucidate historical sensitization but induce primary sensitization as well. No beneficial effect of PTFs on transplantation outcome was found, and PTFs with the intention to detect historical sensitization are therefore not suggested.

High acquisition and environmental contamination rates of CC17 ampicillin-resistant Enterococcus faecium in a Dutch hospital.

BACKGROUND: Enterococcus faecium has rapidly emerged as a nosocomial pathogen worldwide, and the majority of these isolates belong to clonal complex-17 (CC17). In Europe, CC17 isolates are usually ampicillin-resistant, but most are still vancomycin-sensitive. We aimed to study ampicillin-resistant E. faecium (ARE) epidemiology in our hospital. METHODS: In a 3 month study, 210 of 358 admissions (59%) to haematology and gastroenterology/nephrology were screened for rectal ARE colonization on admission (<48 h) and 148 of 210 (70%) also at discharge (<72 h). In a second (3 month) study, environmental swabs from eight predetermined sites were obtained from ARE-colonized haematology patients once weekly. All ARE isolates were genotyped by multiple-locus variable-number tandem repeat analysis (MLVA). RESULTS: ARE admission prevalence was 10% and 16% and acquisition rates were 39% and 15% in haematology and gastroenterology/nephrology, respectively. Carriage on admission was associated with previous admission <1 year (OR 5.0, 95% CI 1.8-14.0) and acquisition with beta-lactam (OR 2.7, 95% CI 1.1-6.7) and quinolone use (OR 3.1, 95% CI 1.1-8.2). Five of the 57 (9%) colonized patients developed invasive ARE infections. Genotyping revealed 12 genotypes (all CC17) with two MLVA types responsible for 94% of acquisitions. In 18 of the 19 colonized patients, the environment was contaminated with ARE. Sites most often contaminated were the toilet seat (43%), over-bed table (34%) and television remote control (28%). CONCLUSIONS: CC17 ARE epidemiology is characterized by high admission (10% to 16%), acquisition (15% to 39%) and environmental contamination (22%) rates, resulting from cross-transmission, readmission and antibiotic pressure. A multifaceted infection control approach will be needed to curtail further spread.

Oral ulcers in kidney transplant recipients treated with sirolimus and mycophenolate mofetil.

BACKGROUND: In an attempt to reduce calcineurin inhibitor toxicity, transplant patients treated with tacrolimus can be switched to maintenance treatment with sirolimus. METHODS: In a prospective, randomized, multicenter trial, 33 kidney transplant recipients on steroid-free maintenance treatment with tacrolimus and mycophenolate mofetil continued tacrolimus and mycophenolate mofetil (control group, n=18) or were converted from tacrolimus to sirolimus (study group, n=15) at 1 year after transplantation. RESULTS: The study was prematurely stopped as a result of a cluster of nine patients suffering from painful oral ulcerations in the study group. Oral ulcerations did not occur in the control group. The authors here report on the individual cases suffering from this side effect of the instituted immunosuppressive regimen. CONCLUSIONS: The authors review the literature with respect to the occurrence of oral ulcers associated with the use of sirolimus or mycophenolate mofetil and speculate on the causes of the high incidence of oral ulcers in their study group. Possible explanations are overimmunosuppression during the period of the conversion from tacrolimus to sirolimus without antiviral prophylaxis, the use of the oral emulsion instead of tablets, or the lack of corticosteroid co-administration.

Different effects of tacrolimus and cyclosporine on renal hemodynamics and blood pressure in healthy subjects.

BACKGROUND: The side effects of cyclosporine, nephrotoxicity and hypertension, contribute to long-term renal graft failure and cardiovascular morbidity in graft recipients. It is not clear whether tacrolimus is as nephrotoxic and hypertensive as cyclosporine. Data on this subject are not consistent because of differences in dosage and duration of treatment and the presence of comorbidity in the studied patients. A comparison of both drugs with respect to renal hemodynamics and blood pressure has not been performed yet in healthy subjects. METHODS: We studied blood pressure, glomerular filtration rate, and effective renal plasma flow in eight healthy subjects at baseline and after 2 weeks administration of cyclosporine and tacrolimus, in randomized order. Trough levels of either drug were within the currently recommended therapeutical range of 100-200 ng/ml for cyclosporine and 5-15 ng/ml for tacrolimus. RESULTS: Tacrolimus did not influence renal hemodynamic parameters, in contrast to cyclosporine. During cyclosporine, glomerular filtration rate decreased from 98+/-9 ml/min/1.732 to 85+/-10 ml/min/1.732 (P<0.05), and ERPF decreased from 597+/-108 ml/min/1.732 to 438+/-84 ml/min/1.732 (P<0.01). Mean arterial blood pressure increased from 93+/-8 mmHg to 108+/-10 mmHg (P<0.05) during cyclosporine and remained unchanged during tacrolimus. CONCLUSIONS: We conclude that tacrolimus given during 2 weeks in the currently advised dosage has no unfavorable effects on renal hemodynamics and blood pressure in healthy individuals. The use of tacrolimus in organ transplant recipients may in the long-term lead to better renal function and less cardiovascular morbidity than the use of cyclosporine.

No important influence of limited steroid exposure on bone mass during the first year after renal transplantation: a prospective, randomized, multicenter study.

BACKGROUND: Steroid-related bone loss is a recognized complication after renal transplantation. In a prospective, randomized, multicenter study we compared the influence of a steroid-free immunosuppressive regimen with a regimen with limited steroid exposure on the changes in bone mass after renal transplantation. METHODS: A total of 364 recipients of a renal transplant were randomized to receive either daclizumab (1 mg/kg on days 0 and 10 after transplantation; steroid-free group n=186) or prednisone (0.3 mg/kg per day tapered to 0 mg at week 16 after transplantation; steroids group n=178). All patients received tacrolimus, mycophenolate mofetil, and, during the first 3 days, 100 mg prednisolone intravenously. Changes in bone mineral density (BMD) were evaluated in 135 and 126 patients in the steroid-free and steroids group, respectively. RESULTS: The mean (+/- SD) BMD of the lumbar spine decreased slightly in both groups during the first 3 months after transplantation (steroid-free -1.3 +/- 4.0% [P<0.01]; steroids -2.3 +/-4.2% [P<0.01]). In the following months, lumbar BMD recovered in both groups (P<0.01), resulting in a lumbar BMD at 12 months after transplantation comparable with the baseline value. No difference between the groups was found at 3 months (steroid-free versus steroids +1.0%; 95% confidence interval -0.0%-+2.0%, P=0.060) and at 12 months after transplantation (steroid-free versus steroids +0.9%; 95% confidence interval -0.8%-+2.6%, NS). CONCLUSION: The use of a moderate dose of steroids during 4 months after transplantation has no important influence on bone mass during the first year after renal transplantation. On average, both regimens prevented accelerated bone loss.

15-year follow-up of a multicenter, randomized, calcineurin inhibitor withdrawal study in kidney transplantation.

BACKGROUND: Calcineurin inhibitors (CNIs) are essential immunosuppressive drugs after renal transplantation. Because of nephrotoxicity, withdrawal has been a challenge since their introduction. METHODS: A randomized multicenter trial included 212 kidney patients transplanted between 1997 and 1999. All patients were initially treated with mycophenolate mofetil (MMF), cyclosporine A (CsA), and prednisone (pred). At 6 months after transplantation, 63 patients were randomized for MMF/pred, 76 for MMF/CsA, and 73 for MMF/CsA/pred. Within 18 months after randomization 23 patients experienced a rejection episode: MMF/pred (27.0%), MMF/CsA (6.8%) and MMF/CsA/pred (1.4%) (P<0.001). RESULTS: During 15 years of follow-up, 73 patients died with a functioning graft, and 43 patients lost their graft. Ninety-six were alive with a functioning graft. Intention-to-treat analysis did not show a significant difference in patient and graft survival. In multivariate analysis, death-censored graft survival was significantly associated with serum creatinine at 6 months after transplantation and maximum PRA but not with the randomization group. CNI withdrawal did not result in a reduced incidence of or death by malignancy or cardiovascular disease. Death-censored graft survival was significantly worse in those patients randomized for CNI withdrawal that had to be reverted to CNI. Independent of randomization group, compared with no rejection, death-censored graft survival was significantly worse in 23 patients with acute rejection after randomization. CONCLUSION: Fifteen years after conversion to a CNI free regimen, there was no benefit regarding graft and patient survival or regarding prevalence of or death by comorbidities. However, rejection shortly after CNI withdrawal was associated with decreased graft survival.

A randomized trial comparing renal function in older kidney transplant patients following delayed versus immediate tacrolimus administration.

BACKGROUND: This large, randomized, multicenter trial evaluated if basiliximab induction and delayed tacrolimus can preserve renal function in older kidney transplant patients. METHODS: Patients aged 60 years and older received delayed tacrolimus with basiliximab and mycophenolate mofetil with early steroid discontinuation (Tac-d, n=132) or standard tacrolimus with mycophenolate mofetil and steroids until day 91 (Tac-s, n=122). Tacrolimus trough levels were 5 to 10 ng/mL after day 43 in both groups. Renal function at month 6 was measured by calculated creatinine clearance (Cockcroft-Gault formula). RESULTS: In both groups, mean recipient age was 66 years, mean donor age was 63 years with 73% of donors aged 60 years and older. Steroid discontinuation was slower than protocol specified. In the Tac-d group, 56.1% were steroid free at day 14 and 81.8% at month 6. In the Tac-s group, 37.7% were steroid free at month 4 and 63.9% at month 6. Mean (+/-SD) calculated creatinine clearance was 45.7+/-16.1 mL/min (Tac-d) and 45.0+/-18.2 mL/min (Tac-s) (P=ns), mean glomerular filtration rate (modified diet in renal disease formula) was 44.9+/-16.2 mL/min and 41.6+/-16.8 mL/min, respectively. Incidences of biopsy-proven acute rejection were 18.9% (Tac-d) and 18.0% (Tac-s). Delayed graft function was 30.3% (Tac-d) and 23.8% (Tac-s). Estimated patient survival rates (Kaplan-Meier) in the Tac-d and Tac-s groups were 96.1% vs. 99.2% and estimated graft survival rates were 90% vs. 87.6%, respectively. Safety results were similar with both regimens. CONCLUSION: Delayed tacrolimus with basiliximab induction did not provide an advantage in preserving renal function or reducing delayed graft function in older kidney transplant patients.

Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation.

Because survival of recipients of allogeneic hematopoietic stem cell transplantation (HSCT) has improved, long-term complications become more important. We studied the incidence and risk factors of chronic kidney disease in these patients and evaluated associated posttransplant complications and mortality. We performed a retrospective cohort study of 266 adults who received myeloablative allogeneic HSCT and who survived for >6 months in an 11-year period at a Dutch university medical center. Primary outcome was the incidence of chronic kidney disease defined as a glomerular filtration rate (GFR) of <60 mL/min/1.73 m(2). Chronic kidney disease developed in 61 (23%) of 266 patients, with a cumulative incidence rate of 27% at 10 years. Severe kidney disease (GFR of <30 mL/min/1.73 m(2)) developed in 3% of patients. Only 6 patients developed the thrombotic microangiopathic syndrome SCT nephropathy, and 2 of them needed dialysis. Pretransplant risk factors for chronic kidney disease were lower GFR at day 0 (P < .0001, odds ratio [OR] 0.95 95% confidence interval [CI] 0.93-0.97), female gender, and higher age (P = .001 and P < .0001, respectively). The occurrence of hypertension after transplantation was associated with chronic kidney disease (P < .0001, OR 0.34 95% CI 0.18-0.62). Mortality was 39% after a mean follow-up of 5.1 years. There was no significant difference in survival between patients with and without chronic kidney disease. Chronic kidney disease is a common late complication of myeloablative allogeneic HSCT. Because of the natural decline in renal function with time there is a risk of developing end-stage renal disease in the future. SCT nephropathy seems to be a specific cause of chronic kidney disease that is typically associated with severe kidney disease.

The influence of obesity on short- and long-term graft and patient survival after renal transplantation.

To determine short- and long-term patient and graft survival in obese [body mass index (BMI) >or= 30 kg/m(2)] and nonobese (BMI < 30 kg/m(2)) renal transplant patients we retrospectively analyzed our national-database. Patients 18 years or older receiving a primary transplant after 1993 were included. A total of 1,871 patients were included in the nonobese group and 196 in the obese group. In the obese group there were significantly more females (52% vs. 38.6%, P < 0.01) and patients were significantly older [52 years (43-59) vs. 48 years (37-58); P < 0.05]. Patient survival and graft survival were significantly decreased in obese renal transplant recipients (1 and 5 year patient survival were respectively 94% vs. 97% and 81% vs. 89%, P < 0.01; 1 and 5 year graft survival were respectively 86% vs. 92% and 71% vs. 80%, P < 0.01). Initial BMI was an independent predictor for patient death and graft failure. This large retrospective study shows that both graft and patient survival are significantly lower in obese renal transplant recipients.

Cardiovascular risk factors in renal transplant patients: cyclosporin A versus tacrolimus.

The hypertensive and hyperlipidemic effects of cyclosporin A (CsA) may contribute to the high cardiovascular morbidity in renal transplant patients and to the development of chronic transplant nephropathy. Tacrolimus is reported to have less effect on BP and lipids, but steroids, other drugs, and renal function may confound this. This study assessed 24-h BP and lipid profile in stable renal transplant recipients (n = 17) while they were receiving CsA, after 4 wk of receiving tacrolimus, and again after 4 wk of receiving CsA. Antihypertensives were stopped at least 3 wk before. A few patients used low-dose steroids and lipid-lowering drugs, which were not changed during the study. Mean daytime BP decreased from 149 +/- 12 and 95 +/- 8 mmHg to 138 +/- 13 and 87 +/- 9 mmHg (P: < 0.001) after patients were switched to tacrolimus. Mean nighttime BP also decreased, from 140 +/- 12/86 +/- 7 mmHg to 132 +/- 17/79 +/- 10 mmHg (P: < 0.05). Total and low-density lipoprotein cholesterol decreased from 6.1 +/- 0.7 and 3.84 +/- 0.79 mmol/L to 5.1 +/- 0.8 and 2.98 +/- 0.75 mmol/L (P: < 0.001). Return to CsA caused an increase in BP and cholesterol to values similar as during the first CsA period. The conclusion is that tacrolimus has fewer unfavorable effects on BP and lipids than does CsA. Elective conversion from CsA to tacrolimus in stable renal transplant recipients may lead to attenuation of cardiovascular morbidity and chronic transplant nephropathy in the long term.

Endothelial cell activation in thrombotic thrombocytopenic purpura (TTP): a prospective analysis.

It is generally assumed that endothelial cell injury is the primary event in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In this study, we have determined the extent of vascular perturbation during acute episodes of the disease. We performed a prospective, serial study of nine patients with relapsing TTP during hospitalization and treatment, and assessed the degree of endothelial cell involvement at admission, exacerbation and remission by measurement of von Willebrand factor (VWF) and VWF-propeptide levels. Measurement of both VWF and its propeptide enabled discrimination between acute and chronic perturbation of the endothelium. Elevated levels of both VWF and propeptide were found at admission. These levels decreased immediately upon plasma exchange therapy. However, plasma VWF and propeptide concentrations did not change, even at the time of acute exacerbation. These observations suggest that endothelial cell activation is not the primary event leading to TTP. Vascular perturbation seems to be a consequence, rather than a cause, of the disease.

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.

Steroid-withdrawal at 3 days after renal transplantation with anti-IL-2 receptor alpha therapy: a prospective, randomized, multicenter study.

Steroids have been included in most immunosuppressive regimens after renal transplantation, but are feared for their side-effects. We conducted a prospective multicenter study to investigate whether it is feasible to withdraw steroids early after transplantation with the use of anti-IL-2Ralpha induction, tacrolimus and mycophenolate mofetil (MMF). A total of 364 patients were randomized to receive either two doses of daclizumab (1 mg/kg) and, for the first 3 days, 100 mg of prednisolone (daclizumab group n = 186), or steroids (tapered to 0 mg at week 16; controls n = 178). All patients received tacrolimus and MMF. The incidence of biopsy-confirmed acute rejection at 12 months was not different between the daclizumab group (15%) and the controls (14%) (95% confidence interval of difference: -6 to + 8%, NS). Graft survival at 12 months was comparable in the two groups (daclizumab group: 91%; controls: 90%). Mean arterial blood pressure, serum lipids, and incidence of patients with hyperglycemia were temporary lower in the daclizumab group compared with controls. The immunosuppressive regimen of the daclizumab group was associated with increased costs. In conclusion, with the use of anti-IL-2Ra induction and daily therapy with tacrolimus and MMF it is feasible to withdraw steroids at 3 days after renal transplantation.

MR urography for the preoperative evaluation of living renal donors.

The purpose of this study was to assess the image quality and diagnostic value of MR urography in detecting abnormalities of the urinary collecting system relevant for the preoperative evaluation of living renal donors. Study subjects were selected from the existing intravenous urography (IVU) reports: 18 consecutive patients with a duplication or another abnormality of the collecting system and 20 consecutive patients with normal anatomy. They underwent a respiratory-triggered 3D T2-weighted fast spin-echo acquisition after oral administration of furosemide, without and with abdominal compression. The MR images were evaluated by two independent blinded observers. The IVU was used as the standard of reference. Image quality of the MR urograms with compression was overall better than those without compression, and the former were regarded as adequate for the evaluation of small filling defects and deformities of the pelvis and calyces in 76-81% of the kidneys and 74-79% of the patients. Both observers correctly diagnosed all 13 kidneys with a partial or complete duplication. The image quality of MR urography was inadequate to evaluate the calyces and pelvis for small filling defects or deformities in approximately 25% of the patients; however, the technique was accurate in the detection of abnormalities of the urinary collecting system relevant for the preoperative evaluation of living renal donors.