ABSTRACT
BACKGROUND AND HYPOTHESIS: Early steroid withdrawal (ESW) is often preferred over conventional steroid maintenance (CSM) therapy for kidney transplant recipients with low immunological risks because it may minimize immunosuppression-related adverse events while achieving similar transplant outcomes. However, the risk-benefit balance of ESW could be less favorable in retransplant recipients given their unique immunological risk profile. We hypothesized that the association of ESW with transplant outcomes would differ between first-transplant and retransplant recipients. METHODS: To assess whether the impact of ESW differs between first and retransplant recipients, we studied 210 086 adult deceased-donor kidney transplant recipients using the Scientific Registry of Transplant Recipients. Recipients who discontinued maintenance steroids before discharge from transplant admission were classified with ESW; all others were classified with CSM. We quantified the association of ESW (vs. CSM) with acute rejection, death-censored graft failure, and death, addressing retransplant as an effect modifier, using logistic/Cox regression with inverse probability weights to control for confounders. RESULTS: In our cohort, 26 248 (12%) were retransplant recipients. ESW was used in 30% of first-transplant and 20% of retransplant recipients. Among first-transplant recipients, ESW was associated with no significant difference in acute rejection (aOR = 1.04 [95% CI = 1.00-1.09]), slightly higher hazard of graft failure (HR = 1.09 [95% CI = 1.05-1.12]), and slightly lower mortality (HR = 0.93 [95% CI = 0.91-0.95]) compared to CSM. Nonetheless, among retransplant recipients, ESW was associated with notably higher risk of acute rejection (OR = 1.42 [95% CI = 1.29-1.57]; interaction p < 0.001) and graft failure (HR = 1.24 [95% CI = 1.14-1.34]; interaction p = 0.003), and similar mortality (HR = 1.01 [95% CI = 0.94-1.08]; interaction p = 0.04). CONCLUSIONS: In retransplant recipients, the negative impacts of ESW on transplant outcomes appear to be non-negligible. A more conservatively tailored approach to ESW might be necessary for retransplant recipients.
ABSTRACT
Topical steroid withdrawal syndrome (TSW) is a debated condition marked by burning erythema, severe itching, and dry skin following the discontinuation of topical corticosteroids (TCS). This study reviewed reported pediatric TSW cases. With a total of 21 cases reported (inconsistent data provided), 60% (6/10) used TCS on the face; 69% (9/13) were associated with an escalation in potency of TCS and 75% (3/4) were the erythematoedematous variant. Overall, data on TSW in children is lacking and standardized diagnostic criteria are needed.
ABSTRACT
BACKGROUND: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids. METHODS: The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards. RESULTS: Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P = .041).The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period. CONCLUSIONS: With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients. Trial registration: Clinical trial registration number: Investigator Initiated Trial (NCT00724022, FU study DRKS00005786).
Subject(s)
Kidney Transplantation , Aged , Humans , Antibodies, Monoclonal , Basiliximab , Follow-Up Studies , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/prevention & control , Graft Survival , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/therapeutic use , Steroids , Tacrolimus/adverse effectsABSTRACT
BACKGROUND: Early steroid withdrawal (ESW) improves growth following kidney transplant (KT). It is not known whether these children achieve target height within mid-parental height range post-KT. METHODS: Retrospective analysis of growth patterns of KT recipients following ESW in our center between 2009 and 2020 had minimum follow-up period of 12 months. RESULTS: Forty-eight (female 29.2%) KT recipients, median age 5.3 years at first KT, were included. At KT, 29 (60.4%) recipients had normal height (SDS≥-1.88) and in 23 (47.9%), the height was within their target height (parental-adjusted height SDS within ±1.55). The proportion of children achieving normal height at 1-, 2-, 3-, and 5-years post-KT (median 5.5 years) were 75%, 83.3%, 86.5%, and 88% respectively. The proportion of children achieving target height measured at the same intervals was 68.8%, 73.8%, 73%, and 80%, respectively. Children <6 years were most growth impaired at KT but were most likely to achieve target height within first-year post-KT (72%; p = .023). All 19 children with short stature at KT received dialysis. Three children received growth hormone post-KT. Children who did not achieve target height post-KT (n = 14), five had eGFR <60 mL/min/1.73 m2 , and eight were on corticosteroid therapy at latest follow-up. CONCLUSIONS: Although vast majority of children achieved normal height post-KT following ESW during the first 5 years post-KT, 20% of these children had not achieved their target height post-KT.
Subject(s)
Kidney Transplantation , Child , Humans , Female , Child, Preschool , Retrospective Studies , Renal DialysisABSTRACT
Topical corticosteroids (TCS) are the most commonly prescribed treatment for children with atopic dermatitis and are supported by the American Academy of Dermatology (AAD) atopic dermatitis treatment guidelines with level I strength A evidence; however, fear regarding their use, coined "steroid phobia," is widespread. In this study, we analyzed steroid phobia-related content on popular social media platforms. We found much of this content consists of patients describing negative personal experiences with TCS and subsequently discouraging viewer use. We conclude that social media may contribute to steroid phobia, and we hope that our study motivates dermatologists with social media platforms to combat common misconceptions surrounding TCS use.
Subject(s)
Dermatitis, Atopic , Dermatologic Agents , Phobic Disorders , Social Media , Child , Humans , Dermatitis, Atopic/drug therapy , Surveys and Questionnaires , Glucocorticoids , Steroids , Adrenal Cortex HormonesABSTRACT
BACKGROUND: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. METHOD/OBJECTIVE: This comprehensive review aims to discuss steroid-related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. RESULTS: Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. CONCLUSION: SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid-inclusive maintenance immunosuppression in pediatric kidney transplant recipients.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Child , Humans , Withholding TreatmentABSTRACT
PURPOSE: Literature regarding endogenous Cushing syndrome (CS) largely focuses on the challenges of diagnosis, subtyping, and treatment. The enigmatic phenomenon of glucocorticoid withdrawal syndrome (GWS), due to rapid reduction in cortisol exposure following treatment of CS, is less commonly discussed but also difficult to manage. We highlight the clinical approach to navigating patients from GWS and adrenal insufficiency to full hypothalamic-pituitary-adrenal (HPA) axis recovery. METHODS: We review the literature on the pathogenesis of GWS and its clinical presentation. We provide strategies for glucocorticoid dosing and tapering, HPA axis testing, as well as pharmacotherapy and ancillary treatments for GWS symptom management. RESULTS: GWS can be difficult to differentiate from adrenal insufficiency and CS recurrence, which complicates glucocorticoid dosing and tapering regimens. Monitoring for HPA axis recovery requires both clinical and biochemical assessments. The most important intervention is reassurance to patients that GWS symptoms portend a favorable prognosis of sustained remission from CS, and GWS typically resolves as the HPA axis recovers. GWS also occurs during medical management of CS, and gradual dose titration based primarily on symptoms is essential to maintain adherence and to eventually achieve disease control. Myopathy and neurocognitive dysfunction can be chronic complications of CS that do not completely recover. CONCLUSIONS: Due to limited data, no guidelines have been developed for management of GWS. Nevertheless, this article provides overarching themes derived from published literature plus expert opinion and experience. Future studies are needed to better understand the pathophysiology of GWS to guide more targeted and optimal treatments.
Subject(s)
Adrenal Insufficiency , Cushing Syndrome , Adrenal Insufficiency/diagnosis , Cushing Syndrome/diagnosis , Glucocorticoids/therapeutic use , Humans , Hydrocortisone , Hypothalamo-Hypophyseal System , Pituitary-Adrenal SystemABSTRACT
Growth failure persists after pediatric liver transplantation and impairs pediatric development and quality of life. Steroid dose minimization attempts to prevent growth impairment, yet long-term assessment in pediatric liver recipients is lacking. We identified risk factors for impaired linear growth after pediatric liver transplantation, with a special focus on low-dose steroid therapy. This is a single-center retrospective analysis of height development in pediatric liver recipients up to 5 years after transplantation. Risk factors for impaired linear growth (height Z-scores≤-2) at transplantation, after two (n = 347) and five years (n = 210) were identified by univariate and multivariate logistic regression. At transplantation, growth retardation was found in 52.2%, predominantly younger children. Height Z-scores improved from -2.23 to -1.40 (SE 0.11; 95%CI 0.74-1.16; p < .001) two years and -1.19 (SE 0.07;0.08-0.34; p = .017) five years post-transplant. Multivariate analysis showed previous growth impairment (OR=1.484; 95%-CI=1.107-1.988; p = .004), graft loss (49.006;2.232-1076; p = .006), and prolonged cold ischemic time (1.034;1.007-1.061; p = .011) as main long-term risk factors; steroid use was a significant predictor of 2-year but not 5-year growth impairment. In univariate analysis, impaired growth after 2 and 5 years was associated with continuous low-dose (2.5 mg/m2 BSA) steroid therapy (OR=3.323;1.578-6.996; p < .001/OR=8.352;1.089-64.07; p = .006)and graft loss (OR=2.513;1.395-4.525; p = .003/OR=3.378;1.815-7.576; p < .001). Furthermore, indication and era of transplantation affected growth. Our results show significant catch-up growth after pediatric liver transplantation, yet growth failure strongly affects particularly young liver recipients. The main influenceable long-term risk factor is pre-existing growth failure, emphasizing the importance of early aggressive nutritional therapy. Moreover, low-dose steroid therapy might impair growth and should therefore be critically questioned in long-term immunosuppression.
Subject(s)
Body Height/drug effects , Growth Disorders/prevention & control , Immunosuppressive Agents/administration & dosage , Liver Transplantation , Postoperative Complications/prevention & control , Prednisolone/administration & dosage , Adolescent , Child , Child, Preschool , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Growth Disorders/etiology , Humans , Immunosuppressive Agents/adverse effects , Infant , Infant, Newborn , Logistic Models , Male , Postoperative Complications/etiology , Prednisolone/adverse effects , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: Little data exist on re-hospitalization rates in pediatric kidney recipients (KTx) particularly with the evolution of transplant immunosuppression. METHODS: In a single-center, retrospective study of pediatric KTx between 2006 and 2016, we assessed re-hospitalization after KTx admission, stratified by whether the re-admit was early (<30 days post-KTx discharge) or late (>30 days), and compared two different immunosuppression eras (one with and one without steroids). RESULTS: Of 197 KTx, 156 (79%) patients were re-hospitalized in 1st year, 85 (56%) within 30 days of discharge (total 490 1st year re-hospitalizations). Younger age was associated with early and late re-hospitalizations. African American race was associated with early re-hospitalizations. Of the 123 and 74 discharged on steroid-avoidance (maintenance immunosuppression included MMF in 95%; FK in 50%; CSA in 50%) and steroid-inclusive (AZA in 66%; MMF in 34%; FK in 30%; CSA in 70%), re-hospitalization rates, timing post-transplant, length, and number were not significantly different (P .38; .1; .56; .11). Admission diagnoses analysis demonstrated that steroid-avoidance recipients had anemia/leucopenia/thrombocytopenia, significantly more often, as one of their admission diagnoses (16% vs 4%; P < .001) and had a rejection diagnosis significantly less often (6% vs 18%; P < .001). Infection diagnoses were not statistically different between groups. Re-hospitalization, early or late, did not predict worse graft/ patient survival but predicted further hospitalizations. CONCLUSIONS: Re-hospitalization is common after pediatric transplant discharge and predicts further hospitalization regardless of discharge on or off steroids.
Subject(s)
Graft Rejection/epidemiology , Kidney Transplantation , Patient Readmission/statistics & numerical data , Postoperative Complications/epidemiology , Adolescent , Black or African American , Age Factors , Child , Child, Preschool , Female , Graft Rejection/diagnosis , Graft Rejection/prevention & control , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Infant , Male , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/therapy , Prognosis , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
Recurrent glomerulonephritis (GN) is a common cause of graft loss after kidney transplantation. Steroids are critical to GN management before transplantation, but it is unclear if early steroid withdrawal after transplantation increases the risk of graft loss in patients with GN. Here USRDS data were used to examine the association of early steroid withdrawal with death censored graft loss and all cause graft loss in GN and non-GN adult, non-diabetic, non-sensitized first kidney-only transplant recipients from 1998-2012. A 2-stage propensity score-based matching algorithm was used to match early steroid withdrawal to steroid-maintained patients in the GN and non-GN groups. Multivariate Cox models using a robust variance estimator to account for matched pairs were used to examine the association of early steroid withdrawal with death censored or all cause graft loss in patients with (6388 patients each in early steroid withdrawal and steroid groups) or without GN (6590 each in early steroid withdrawal and steroid groups). Early steroid withdrawal was not associated with an increased risk of death censored or all cause graft loss in patients with or without GN. These findings were consistent across GN types and after accounting for transplant center. Thus, our findings support consideration of early steroid withdrawal in patients with GN at high risk of the adverse consequences of prolonged steroid exposure.
Subject(s)
Glomerulonephritis/drug therapy , Glucocorticoids/administration & dosage , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Postoperative Complications/prevention & control , Adult , Drug Administration Schedule , Female , Follow-Up Studies , Glomerulonephritis/etiology , Glomerulonephritis/mortality , Glucocorticoids/adverse effects , Graft Rejection/etiology , Graft Rejection/mortality , Graft Survival , Humans , Immunosuppressive Agents/adverse effects , Kaplan-Meier Estimate , Kidney Failure, Chronic/mortality , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/mortality , Propensity Score , Recurrence , Secondary Prevention/methods , Time FactorsABSTRACT
BACKGROUND: 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. METHODS: 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 ± 3.8 years, for whom ambulatory blood pressure monitoring (ABPM) data were available. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Glucocorticoids/adverse effects , Hypertension/prevention & control , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Withholding Treatment , Adolescent , Allografts/immunology , Allografts/physiopathology , Blood Pressure/drug effects , Blood Pressure Monitoring, Ambulatory , Child , Circadian Rhythm/physiology , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Female , Glomerular Filtration Rate/physiology , Glucocorticoids/administration & dosage , Graft Rejection/immunology , Graft Rejection/physiopathology , Graft Rejection/prevention & control , Humans , Hypertension/chemically induced , Hypertension/diagnosis , Immunosuppressive Agents/administration & dosage , Kidney/immunology , Kidney/physiopathology , Male , Methylprednisolone , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Prospective Studies , Transplantation, Homologous/adverse effectsABSTRACT
Concerns about topical steroid withdrawal are causing some patients to cease long-term topical corticosteroid therapy, however, little is known about the ensuing clinical outcomes. This qualitative case series studied 10 children whose parents stopped their chronic topical corticosteroid use and subsequently developed features typically reported in adults experiencing topical steroid withdrawal. Patients were seen in an Australian general practice between April 2014 and October 2018, with follow-up periods ranging from 18 months to 4 years. Symptoms were difficult initially for the children and their families, however, all ultimately improved. At the final review, 4 of the children had clear skin and another 4 had symptoms consistent with their original, pre-treatment atopic dermatitis. More research is required into long-term topical corticosteroid use and its discontinuation, including topical steroid withdrawal, particularly in the pediatric population.
Subject(s)
Adrenal Cortex Hormones/adverse effects , Dermatitis, Exfoliative/chemically induced , Erythema/chemically induced , Pain/chemically induced , Pruritus/chemically induced , Substance Withdrawal Syndrome/etiology , Administration, Cutaneous , Adolescent , Child, Preschool , Female , Humans , Infant , Male , Qualitative Research , Skin Diseases/drug therapy , Withholding TreatmentABSTRACT
Black kidney transplant recipients have more acute rejection (AR) and inferior graft survival. We sought to determine whether early steroid withdrawal (ESW) had an impact on AR and death-censored graft loss (DCGL) in blacks. From 2006 to 2012, AR and graft survival were analyzed in 483 kidney recipients (208 black and 275 non-black). Rates of ESW were similar between blacks (65%) and non-blacks (67%). AR was defined as early (≤3 months) or late (>3 months). The impact of black race, early AR, and late AR on death-censored graft failure was analyzed using univariate and multivariate Cox models. Blacks had greater dialysis vintage, more deceased donor transplants, and less HLA matching, yet rates of early AR were comparable between blacks and non-blacks. However, black race was a risk factor for late AR (HR: 3.48 (95% CI: 1.87-6.47)) Blacks had a greater rate of DCGL, partially driven by late AR (HR with late AR: 5.6; 95% CI: 3.3-9.3). ESW had no significant interaction with black race for risk of early AR, late AR, or DCGL. Independent of ESW, black kidney recipients had a higher rate of late AR after kidney transplantation. Late AR was highly predictive of DCGL and contributed to inferior graft survival in blacks.
Subject(s)
Graft Rejection/etiology , Graft Survival/drug effects , Healthcare Disparities , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Steroids/administration & dosage , Withholding Treatment/statistics & numerical data , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/diagnosis , Humans , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Postoperative Complications , Prognosis , Retrospective Studies , Risk Factors , Survival RateABSTRACT
Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long-term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5-year prospective, randomized, single-center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil (MMF) with that of tacrolimus (TAC) plus MMF, when steroids were withdrawn 6 months after kidney transplantation in low-risk patients. We now report the 10-year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study (TAC group n = 62; CsA group n = 55). The 10-year patient survival, death-censored graft survival, and acute rejection-free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low-risk patients, there was no difference in long-term patient and graft survival between TAC- and CsA-based late steroid withdrawal regimens that included MMF treatment. More long-term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation.
Subject(s)
Cyclosporine/therapeutic use , Graft Rejection/drug therapy , Graft Survival/drug effects , Kidney Transplantation/adverse effects , Living Donors/supply & distribution , Tacrolimus/therapeutic use , Withholding Treatment/statistics & numerical data , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Rejection/mortality , Humans , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Postoperative Complications , Prognosis , Prospective Studies , Retrospective Studies , Risk Factors , Survival RateABSTRACT
Steroid withdrawal following renal transplantation is challenging and widely debated. This retrospective study aimed at investigating the frequency and determinants of successful steroid withdrawal guided by surveillance biopsies. We analyzed 156 pretransplant DSA-negative renal transplants receiving basiliximab induction and maintenance immunosuppression with tacrolimus-mycophenolate-steroids. The absence of rejection in surveillance biopsies at 3 or 6 months post-transplant initiated steroid withdrawal, which was monitored by subsequent indication and/or surveillance biopsies. The primary outcome was the frequency of successful (i.e., rejection-free) steroid withdrawal at 1 year post-transplant. In the whole study population, successful steroid withdrawal was achieved in 73 of 156 patients (47%). Steroid withdrawal was initiated in 98 of 156 patients (63%) and successful in 73 of 98 patients (74%). Subsequent clinical rejection occurred in only one of 98 patients (1%), whereas 24 of 98 patients (24%) experienced subclinical rejection. Steroid withdrawal was not initiated in 58 of 156 patients (37%) mainly due to current or prior severe (Banff TCMR ≥IA) subclinical rejection. Prediction of successful steroid withdrawal by pretransplant or early post-transplant parameters was poor. In conclusion, (sub)clinical rejection-free steroid withdrawal can be expected in about half of pretransplant DSA-negative patients. As successful steroid withdrawal cannot be well predicted by pre- and early post-transplant parameters, guidance by surveillance biopsies is an attractive strategy.
Subject(s)
Graft Rejection/prevention & control , Graft Survival/drug effects , Kidney Transplantation/adverse effects , Postoperative Complications/prevention & control , Steroids/administration & dosage , Withholding Treatment , Aged , Biopsy , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Humans , Immunosuppressive Agents/therapeutic use , Kidney Function Tests , Male , Middle Aged , Population Surveillance , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Risk FactorsSubject(s)
Phobic Disorders , Social Media , Humans , Phobic Disorders/drug therapy , Surveys and Questionnaires , SteroidsABSTRACT
BACKGROUND: Immunosuppressive regimens in renal transplantation frequently contain corticosteroids, but many centers withdraw steroids as a consequence of unwanted side effects of steroids. The optimal timing to withdraw steroids after transplantation, however, remains unclear. The aim of this study was to determine an optimal time point following kidney transplantation that is associated with reduced mortality without jeopardizing the allograft to allow safe discontinuation of steroids. METHODS: We conducted a retrospective cohort study and computed a concatenated landmark-stratified Cox supermodel to estimate hazard ratios and 95% confidence intervals for mortality and graft loss using dynamic propensity score matching to adjust for confounding by indication. RESULTS: A total of 6070 first kidney transplant recipients in the Austrian Dialysis and Transplant Registry who were transplanted between 1990 and 2012 were evaluated and classified according to steroid treatment status throughout follow-up after kidney transplantation; 2142 patients were withdrawn from steroids during the study period. Overall, 1131 patients lost their graft and 821 patients in the study cohort died. Steroid withdrawal within 18 months after transplantation was associated with an increased rate of graft loss compared to steroid maintenance during that time (6 months after transplantation: HR = 1.8; 95% CI, 1.3 to 2.6; 18 months after transplantation: HR = 1.3; 95% CI, 1.1 to 1.6; 24 months after transplantation: HR = 1.2; 95% CI, 0.9 to 1.5), while mortality was not different between groups. CONCLUSIONS: Our findings suggest that steroid withdrawal after anti-IL-2 induction in the first 18 months after transplantation is associated with an increased risk of allograft loss.
Subject(s)
Graft Rejection/prevention & control , Immunosuppressive Agents/adverse effects , Kidney Transplantation/statistics & numerical data , Steroids/administration & dosage , Substance Withdrawal Syndrome/epidemiology , Adult , Austria , Cohort Studies , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Steroids/adverse effects , Transplantation, HomologousABSTRACT
Long-term use of steroids results in predictable secondary effects that can lead to increased morbidity and mortality. In this study, we present 10 years worth of data of early steroid withdrawal (ESW) immunosuppression consisting of mycophenolate, sirolimus, and tacrolimus. From 2003 to 2013, 563 kidney transplant recipients were weaned off steroids prior to discharge. We compared outcomes with that of our 65 historical controls maintained on steroids. We analyzed graft and patient survival and determined the incidence of steroid-related comorbidities such as hypertension, hypercholesterolemia, diabetes, coronary artery disease, and weight gain. Patients on ESW maintenance immunosuppression had improved patient and graft survival compared to controls. (HR: 0.23; P≤.011, 0.57; P=.026). Rates of biopsy-proven acute rejection were not different among both groups (HR: 1.24; P=.610). Incidence of post-transplant diabetes were reduced but not statistically significant (OR: 0.67; P=.138). Additionally, the development of hypertension (OR: 0.86, P≤.01), hypercholesterolemia (RR: 0.82; P=.027), CAD (RR: 0.43; P=.002), and >20 lbs. weight gain (RR: 0.29; P≤.01) was significantly improved over 10 years following initiation of ESW protocols. Early steroid withdrawal in renal transplant recipients results in improved patient and graft survival as well as better rates of post-transplant comorbid conditions.
Subject(s)
Cardiovascular Diseases/mortality , Graft Rejection/mortality , Graft Survival , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Steroids/administration & dosage , Withholding Treatment , Adult , Cardiovascular Diseases/etiology , Cardiovascular Diseases/pathology , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Rejection/pathology , Humans , Immunosuppressive Agents/therapeutic use , Kidney Function Tests , Kidney Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/mortality , Prognosis , Risk FactorsABSTRACT
The mechanism(s) underlying photorefractoriness in temperate zone seasonally breeding birds remains undetermined. Our recent findings reveal a link between the upregulation of GABAA receptors (GABAARs) in the premammillary nucleus (PMM) and the state of photorefractoriness. Gonadal steroid levels fluctuate during the breeding season; increasing after gonadal recrudescence and declining sharply once gonadal regression begins. Here, we examined the effect of gonadal steroid withdrawal on the expression of GABAARs in the turkey PMM. Exogenous ovarian steroids were administered and then withdrawn from turkey hens to mimic the decline of ovarian steroids levels at the end of a breeding season. The upregulation of GABAAR α3, α4, δ, π, and γ2-subunits was observed in the PMM of the steroid withdrawal group when compared to the non-steroid treatment group. The level of tyrosine hydroxylase, photopigment melanopsin, and circadian clock genes in the PMM of the steroid withdrawal group resembled the levels observed in the natural photorefractory hens and were significantly lower than those of the short-day light stimulated group. A reduction in gonadotropin-releasing hormone-I mRNA expressed within the nucleus commissurae pallii was also observed in hens undergoing steroid withdrawal. These results suggest that the natural decline in circulating ovarian steroid levels may modulate the GABAergic system in the PMM through the upregulation of GABAA receptors. This, in turn, could diminish the reproductive neuroendocrine responses to light and favor a condition resembling the state of photorefractoriness.
Subject(s)
Neurosecretory Systems/metabolism , Ovary/metabolism , Receptors, GABA-A/genetics , Steroids/chemistry , Turkeys , Animals , Female , Photoperiod , Up-RegulationABSTRACT
A steroid-free protocol for ABO-compatible renal transplantation has been used at our center since 1983. To minimize the adverse effects of steroids, we also developed a steroid sparing protocol for ABO-incompatible renal transplantation in 2008. The present study is a report of our results. A retrospective review of the first 50 ABO-incompatible renal transplantations performed at a single university center. If no immunological events occurred in the post-transplant period, prednisolone tapering was initiated approximately 3 months after transplantation. Forty-three patients completed prednisolone tapering after 289 ± 58 days. Three patients died during follow-up, and four patients lost graft function. None of these adverse events were rejection related. Eleven patients experienced rejections; seven were on prednisolone and four were after weaning from prednisolone. All patients responded well to antirejection treatment. Overall, 1-year rejection rate was 19%. One- and 3-year graft survival was 94% and 91%, respectively. One-year post-transplant median serum creatinine was 123 µmol/L. We found acceptable rejection rates, graft survival, and creatinine levels in patients undergoing ABO-incompatible renal transplantations with a steroid sparing protocol. However, a longer follow-up of a lager cohort is needed before firm conclusions can be made.