Effect Of Steroid Withdrawal Research Articles

Steroid withdrawal improves blood pressure control and nocturnal dipping in pediatric renal transplant recipients: analysis of a prospective, randomized, controlled trial.

Variable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far. In a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n = 42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.2 ± 3.8years, for whom ambulatory blood pressure monitoring (ABPM) data were available. In the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM > 1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p = 0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p < 0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p = 0.014) and to 14.3% of control (p = 0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p = 0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change. Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping.

Effect of Steroid Withdrawal on the Appearance of De Novo Donor-Specific HLA Antibodies in Kidney Transplant Recipients

Effect of Steroid Withdrawal on the Appearance of De Novo Donor-Specific HLA Antibodies in Kidney Transplant Recipients

Steroid avoidance or withdrawal for kidney transplant recipients.

Steroid-sparing strategies have been attempted in recent decades to avoid morbidity from long-term steroid intake among kidney transplant recipients. Previous systematic reviews of steroid withdrawal after kidney transplantation have shown a significant increase in acute rejection. There are various protocols to withdraw steroids after kidney transplantation and their possible benefits or harms are subject to systematic review. This is an update of a review first published in 2009. To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients. We searched the Cochrane Kidney and Transplant Specialised Register to 15 February 2016 through contact with the Information Specialist using search terms relevant to this review. All randomised and quasi-randomised controlled trials (RCTs) in which steroids were avoided or withdrawn at any time point after kidney transplantation were included. Assessment of risk of bias and data extraction was performed by two authors independently and disagreement resolved by discussion. Statistical analyses were performed using the random-effects model and dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals. We included 48 studies (224 reports) that involved 7803 randomised participants. Of these, three studies were conducted in children (346 participants). The 2009 review included 30 studies (94 reports, 5949 participants). Risk of bias was assessed as low for sequence generation in 19 studies and allocation concealment in 14 studies. Incomplete outcome data were adequately addressed in 22 studies and 37 were free of selective reporting.The 48 included studies evaluated three different comparisons: steroid avoidance or withdrawal compared with steroid maintenance, and steroid avoidance compared with steroid withdrawal. For the adult studies there was no significant difference in patient mortality either in studies comparing steroid withdrawal versus steroid maintenance (10 studies, 1913 participants, death at one year post transplantation: RR 0.68, 95% CI 0.36 to 1.30) or in studies comparing steroid avoidance versus steroid maintenance (10 studies, 1462 participants, death at one year after transplantation: RR 0.96, 95% CI 0.52 to 1.80). Similarly no significant difference in graft loss was found comparing steroid withdrawal versus steroid maintenance (8 studies, 1817 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.17, 95% CI 0.72 to 1.92) and comparing steroid avoidance versus steroid maintenance (7 studies, 1211 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.09, 95% CI 0.64 to 1.86). The risk of acute rejection significantly increased in patients treated with steroids for less than 14 days after transplantation (7 studies, 835 participants: RR 1.58, 95% CI 1.08 to 2.30) and in patients who were withdrawn from steroids at a later time point after transplantation (10 studies, 1913 participants, RR 1.77, 95% CI 1.20 to 2.61). There was no evidence to suggest a difference in harmful events, such as infection and malignancy, in adult kidney transplant recipients. The effect of steroid withdrawal in children is unclear. This updated review increases the evidence that steroid avoidance and withdrawal after kidney transplantation significantly increase the risk of acute rejection. There was no evidence to suggest a difference in patient mortality or graft loss up to five year after transplantation, but long-term consequences of steroid avoidance and withdrawal remain unclear until today, because prospective long-term studies have not been conducted.

Long-term follow-up of bone mass after orthotopic liver transplantation: effect of steroid withdrawal from the immunosuppressive regimen.

Glucocorticoids have been suggested to play a major role in transplantation-related osteopenia. In this study we assess the long-term changes and the effect of steroid withdrawal from the standard immunosuppressive regimen on bone mineral density (BMD) after orthotopic liver transplantation (OLT). Sixty-nine non-osteoporotic patients (20 women, 49 men), aged 48 +/- 9.5 years (mean +/- SD), and with a follow-up of 58.3 +/- 23.2 months (range 24-121 months) were studied. Immunosuppressive treatment consisted of prednisone, cyclosporin A and azathioprine. In 41 patients (group A), prednisone was tapered and withdrawn after 36.2 +/- 19.3 months (range 13-79 months), whereas in 28 patients (group B) prednisone was maintained. BMD in the spine (L1-L4) was serially measured by dual-energy X-ray absorptiometry (Hologic QDR 1,000w) at baseline, before steroid withdrawal and at the end of study. Age- and sex-matched Z-scores of BMD were calculated. No differences were found in age, body mass index, time since OLT, or baseline BMD between the two groups. BMD had significantly increased in both groups at the end of follow-up period (group A, +8.1 +/- 8.7%; group B, +3.2 +/- 8.0%, p < 0.05). However, the Z-score was significantly higher in group A than in group B at the end of study (-0.44 +/- 1.05 vs -0.99 +/- 0.77; p<0.05). BMD recovery was lower in pre-OLT biliary cirrhosis patients. Bone mass improvement was independent of the time since OLT in both groups, and of the time of steroid withdrawal in group A. Our data confirm that steroid withdrawal accelerates the recovery of bone mass in patients who have undergone a successful liver transplantation.

Treatment of hyperlipidemia in renal transplant recipients.

Treatment of hyperlipidemia in renal transplant recipients.

Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to benzodiazepine modulation in rat CA1 hippocampus.

1. The withdrawal properties of the endogenous steroid progesterone (P) were tested in female rats as a function of benzodiazepine modulation of gamma-aminobutyric acid-A (GABAA)-gated current with the use of the whole cell patch-clamp technique on acutely dissociated CA1 hippocampal neurons. In a previous study, this steroid was shown to exhibit withdrawal properties, behaviorally. 2. One day withdrawal from in vivo administration of physiological doses of P (5 mg ip, 5 days/wk for 3 withdrawal cycles) or its metabolite, the GABAA modulator 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP or allopregnanolone, 20 mg/kg ip) prevented the normally potentiating effect of lorazepam (LZM; 10(-7)-10(-4) M) on GABAA-gated current. Withdrawal from 500 micrograms P administered concomitantly with 2 micrograms 17 beta-estradiol also markedly diminished LZM potentiation of GABAA current. This effect was seen only after three withdrawal cycles. 3. P withdrawal produced no inhibitory effect on either basal levels of GABAA-evoked current, the GABAA EC50, or barbiturate (+/-Pentobarbital, 10(-7)-10(-4) M) modulation of this parameter. 4. The effect of steroid withdrawal on LZM modulation of GABAA-evoked current was blocked by picrotoxin as well as by indomethacin, a drug that prevents conversion of P to its metabolite, the GABAA modulator 3 alpha,5 alpha-THP. These results suggest that the withdrawal properties of P may be due to changes in GABAA receptor function produced by 3 alpha,5 alpha-THP.

The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine-treated kidney and kidney-pancreas transplant recipients.

Lipoprotein profiles were measured before and two months after complete withdrawal of prednisone in 34 kidney and 9 kidney-pancreas transplant recipients subsequently maintained on cyclosporine and azathioprine. Withdrawal of steroid therapy was accompanied by a 17% reduction in total serum cholesterol levels. However, there was a parallel reduction in all other measured lipoprotein concentrations, including an 18% reduction in high-density lipoprotein cholesterol levels. In diabetic recipients of a kidney or kidney-pancreas transplant, the ratio of total to high-density lipoprotein cholesterol was unchanged after steroid withdrawal. In nondiabetic kidney transplant recipients, this ratio actually increased significantly following withdrawal of prednisone. These observations suggest that it is premature to presume that withdrawal of steroid therapy will reduce the cardiovascular risk related to hyperlipidemia in cyclosporine-treated kidney or kidney-pancreas transplant recipients.

The Adrenocortical System Responds Slowly to Removal of Corticosterone in the Absence of Concurrent Stress*

After removal of corticosteroid feedback by surgical or pharmacological adrenalectomy, plasma ACTH increases more rapidly than can be explained by changes in receptor-mediated gene expression. In aminoglutethimide-treated rats, plasma ACTH increased only at doses much higher than those inhibiting plasma corticosterone, suggesting that adrenal enzyme blockers may themselves be stressful. To determine the adrenocortical system response to stressless corticosterone removal, adrenalectomized rats maintained for 5 days on corticosterone in the drinking water were switched to steroid-free fluid (-B) or again given steroid (+B); additional rats were adrenalectomized (ADX). Plasma ACTH did not differ between -B and +B rats until 18-24 h after steroid removal, regardless of whether steroid was withdrawn at the circadian maximum or minimum. Plasma ACTH was similar between -B and ADX rats 0.5-14 days after corticosterone removal, although morning plasma ACTH was more stable in -B rats at 4-7 days. Evening plasma ACTH increased significantly after day 3 in ADX and -B rats. Unlike ADX rats, -B rats did not exhibit pituitary ACTH depletion at 12 and 24 h, but both -B and ADX groups had significantly elevated pituitary ACTH by 6.5 days. We conclude that 1) rapid increases in ACTH secretion after surgical or pharmacological adrenalectomy result from interaction between stress and loss of corticosteroid feedback; 2) no immediate interaction occurs between loss of feedback and circadian stimuli; and 3) the effects of steroid withdrawal may require at least 3 days to be stably expressed.