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• W1543301013 abstract "Corticosteroid use after kidney transplantation results in severe bone loss and high fracture risk. Although corticosteroid withdrawal in the early posttransplant period has been associated with bone mass preservation, there are no published data regarding corticosteroid withdrawal and risk of fracture. We hypothesized lower fracture incidence in patients discharged from the hospital without than with corticosteroids after transplantation. From the United States Renal Data System (USRDS), 77 430 patients were identified who received their first kidney transplant from 2000 to 2006. Fracture incidence leading to hospitalization was determined from 2000 to 2007; discharge immunosuppression was determined from United Networks for Organ Sharing forms. Time-to-event analyses were used to evaluate fracture risk. Median (interquartile range) follow-up was 1448 (808–2061) days. There were 2395 fractures during follow-up; fracture incidence rates were 0.008 and 0.0058 per patient-year for recipients discharged with and without corticosteroid, respectively. Corticosteroid withdrawal was associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59–0.81). Fractures associated with hospitalization are significantly lower with regimens that withdraw corticosteroid. As this study likely underestimates overall fracture incidence, prospective studies are needed to determine differences in overall fracture risk in patients managed with and without corticosteroids after kidney transplantation. Corticosteroid use after kidney transplantation results in severe bone loss and high fracture risk. Although corticosteroid withdrawal in the early posttransplant period has been associated with bone mass preservation, there are no published data regarding corticosteroid withdrawal and risk of fracture. We hypothesized lower fracture incidence in patients discharged from the hospital without than with corticosteroids after transplantation. From the United States Renal Data System (USRDS), 77 430 patients were identified who received their first kidney transplant from 2000 to 2006. Fracture incidence leading to hospitalization was determined from 2000 to 2007; discharge immunosuppression was determined from United Networks for Organ Sharing forms. Time-to-event analyses were used to evaluate fracture risk. Median (interquartile range) follow-up was 1448 (808–2061) days. There were 2395 fractures during follow-up; fracture incidence rates were 0.008 and 0.0058 per patient-year for recipients discharged with and without corticosteroid, respectively. Corticosteroid withdrawal was associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59–0.81). Fractures associated with hospitalization are significantly lower with regimens that withdraw corticosteroid. As this study likely underestimates overall fracture incidence, prospective studies are needed to determine differences in overall fracture risk in patients managed with and without corticosteroids after kidney transplantation. Risk of fracture after kidney transplantation is high. In comparison to the general population, there is an overall 4.5-fold greater risk of fracture (1Abbott KC Oglesby RJ Hypolite IO et al.Hospitalizations for fractures after renal transplantation in the United States.Ann Epidemiol. 2001; 11: 450-457Crossref PubMed Scopus (112) Google Scholar,2Vautour LM Melton 3rd, LJ Clarke BL Achenbach SJ Oberg AL McCarthy JT Long-term fracture risk following renal transplantation: A population-based study.Osteoporos Int. 2004; 15: 160-167Crossref PubMed Scopus (149) Google Scholar). In comparison to patients on hemodialysis, risk of hip fracture is 34% greater (3Ball AM Gillen DL Sherrard D et al.Risk of hip fracture among dialysis and renal transplant recipients.JAMA: J Am Med Assoc. 2002; 288: 3014-3018Crossref PubMed Scopus (355) Google Scholar). Efforts to reduce fracture risk after kidney transplantation have been disappointing; although agents typically used to treat corticosteroid-induced osteoporosis have been demonstrated to increase bone mass after transplantation, no single study of these treatments have been demonstrated to reduce fracture risk (4Palmer SC McGregor DO Strippoli GF Interventions for preventing bone disease in kidney transplant recipients.Cochrane Database Syst Rev. 2007; : CD005015PubMed Google Scholar,5Palmer SC Strippoli GF McGregor DO Interventions for preventing bone disease in kidney transplant recipients: A systematic review of randomized controlled trials.AmJ Kidney Dis. 2005; 45: 638-649Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar). These data are alarming as mortality rates increase more than 60% after hip fracture (1Abbott KC Oglesby RJ Hypolite IO et al.Hospitalizations for fractures after renal transplantation in the United States.Ann Epidemiol. 2001; 11: 450-457Crossref PubMed Scopus (112) Google Scholar). Interventions that lower fracture incidence are urgently needed in the kidney transplant population. Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Immunosuppression regimens combining calcineurin inhibitors with corticosteroids have resulted in 1-year recipient survival exceeding 95% (6OPTN/SRTR Annual report: One year adjusted annual patient survival by organ and year of transplant, 1998 to 2007. Available from: http://optn.transplant.hrsa.gov/ar2009/112a_dh.htm. Accessed May 31, 2011.Google Scholar) while mortality for patients with ESRD on hemodialysis is 225 per 1000 patient-years (7Collins AJ Foley RN Gilbertson DT Chen SC The state of chronic kidney disease, ESRD, and morbidity and mortality in the first year of dialysis.Clin J Am Soc Nephrol. 2009; 4: S5-S11Crossref PubMed Scopus (232) Google Scholar). However, administration of corticosteroids results in multiple untoward clinical consequences. The high corticosteroid doses characteristic of the early posttransplant period are associated with rapid bone loss and high fracture rates (8Mikuls TR Julian BA Bartolucci A Saag KG Bone mineral density changes within six months of renal transplantation.Transplantation. 2003; 75: 49-54Crossref PubMed Scopus (98) Google Scholar, 9Julian BA Laskow DA Dubovsky J Dubovsky EV Curtis JJ Quarles LD Rapid loss of vertebral mineral density after renal transplantation.N Engl J Med. 1991; 325: 544-550Crossref PubMed Scopus (614) Google Scholar, 10Horber FF Casez JP Steiger U Czerniak A Montandon A Jaeger PH Changes in bone mass early after kidney transplantation.J Bone Mineral Res. 1994; 9: 1-9Crossref PubMed Scopus (209) Google Scholar). In the long term, corticosteroid doses are lowered and bone mass may partially recover (11Moreno A Torregrosa JV Pons F Campistol JM Martínez de Osaba MJ Oppenheimer F Bone mineral density after renal transplantation: Long-term follow-up.Transplant Proc. 1999; 31: 2322-2323Crossref PubMed Scopus (46) Google Scholar,12Grotz WH Mundinger FA Gugel B Exner VM Kirste G Schollmeyer PJ Bone mineral density after kidney transplantation. A cross-sectional study in 190 graft recipients up to 20 years after transplantation.Transplantation. 1995; 15: 982-986Crossref Scopus (152) Google Scholar); however, fracture risk remains elevated (2Vautour LM Melton 3rd, LJ Clarke BL Achenbach SJ Oberg AL McCarthy JT Long-term fracture risk following renal transplantation: A population-based study.Osteoporos Int. 2004; 15: 160-167Crossref PubMed Scopus (149) Google Scholar,13Braga Jr., JW Neves RM Pinheiro MM et al.Prevalence of low trauma fractures in long-term kidney transplant patients with preserved renal function.Braz J Med Biol Res. 2006; 39: 137-147Crossref PubMed Google Scholar). To alleviate complications associated with chronic corticosteroid administration, newer immunosuppression regimens with early corticosteroid withdrawal (ECSW) have been developed (14Luan FL Steffick DE Gadegbeku C Norman SP Wolfe R Ojo AO Graft and patient survival in kidney transplant recipients selected for de novo steroid-free maintenance immunosuppression.Am J Transplant. 2009; 9: 160-168Crossref PubMed Scopus (53) Google Scholar, 15Luan FL Steffick DE Ojo AO Steroid-free maintenance immunosuppression in kidney transplantation: Is it time to consider it as a standard therapy?.Kidney Int. 2009; 76: 825-830Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 16Woodle ES First MR Pirsch J Shihab F Gaber AO Van Veldhuisen P A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy.Ann Surg. 2008; 248: 564-577Crossref PubMed Scopus (376) Google Scholar). Currently, more than 30% of kidney transplant recipients in the United States (US) are managed with antibody induction therapy coupled with rapidly tapered high-dose methylprednisolone and are discharged from the hospital without corticosteroids (15Luan FL Steffick DE Ojo AO Steroid-free maintenance immunosuppression in kidney transplantation: Is it time to consider it as a standard therapy?.Kidney Int. 2009; 76: 825-830Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar). Within the first year after transplantation, resumption of corticosteroids occurs in a minority of patients (17Woodle ES Peddi VR Tomlanovich S Mulgaonkar S Kuo PC A prospective, randomized, multicenter study evaluating early corticosteroid withdrawal with thymoglobulin in living-donor kidney transplantation.Clin Transplant. 2010; 24: 73-83Crossref PubMed Scopus (51) Google Scholar,18Dube GK EZ Thompson AM Hardy MA Ratner LE Cohen DJ Early withdrawal of steroids in high risk transplant recipients.J Am Soc Nephrol. 2007; 18: 232AGoogle Scholar) and 5-year graft survival and function rates for patients remaining on ECSW are equivalent to those discharged with corticosteroids (14Luan FL Steffick DE Gadegbeku C Norman SP Wolfe R Ojo AO Graft and patient survival in kidney transplant recipients selected for de novo steroid-free maintenance immunosuppression.Am J Transplant. 2009; 9: 160-168Crossref PubMed Scopus (53) Google Scholar,16Woodle ES First MR Pirsch J Shihab F Gaber AO Van Veldhuisen P A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy.Ann Surg. 2008; 248: 564-577Crossref PubMed Scopus (376) Google Scholar). Several small studies have demonstrated that in comparison to corticosteroid-based immunosuppression (CSBI), corticosteroid withdrawal was associated with preserved bone mass after transplantation (19Aroldi A Tarantino A Montagnino G Cesana B Cocucci C Ponticelli C Effects of three immunosuppressive regimens on vertebral bone density in renal transplant recipients: A prospective study.Transplantation. 1997; 63: 380-386Crossref PubMed Scopus (144) Google Scholar, 20Farmer CK Hampson G Abbs IC et al.Late low-dose steroid withdrawal in renal transplant recipients increases bone formation and bone mineral density.Am J Transplant. 2006; 6: 2929-2936Crossref PubMed Scopus (25) Google Scholar, 21van den Ham EC Kooman JP Christiaans ML van Hooff JP The influence of early steroid withdrawal on body composition and bone mineral density in renal transplantation patients.Transpl Int. 2003; 16: 82-87Crossref PubMed Scopus (58) Google Scholar, 22Ing SW Sinnott LT Donepudi S Davies EA Pelletier RP Lane NE Change in bone mineral density at one year following glucocorticoid withdrawal in kidney transplant recipients.Clin Transplant. 2010; 25: E113-E123Crossref PubMed Scopus (21) Google Scholar). However, these studies lacked statistical power to determine whether ECSW was associated with lower fracture risk than CSBI. In light of data suggesting that ECSW preserves bone early after transplant, we hypothesized that fracture rates in kidney transplant recipients discharged without corticosteroids are lower than in those who are discharged with corticosteroids. We evaluated our hypothesis using the United States Renal Data Systems (USRDS) in patients undergoing first kidney transplantation between 2000 and 2006. The USRDS is the largest kidney transplantation registry and combines the United Networks for Organ Sharing (UNOS) transplantation registry data with payment data from the Centers for Medicare and Medicaid Services (CMMS) (23Greer JW End stage renal disease and Medicare.Health Care Financ Rev. 2003; 24: 1-5PubMed Google Scholar,24System USRDUSRDS 2009 annual data report: Atlas of chronic kidney disease and end-stage renal disease in the United States.. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD2009Google Scholar). We estimated incident fractures leading to hospitalization among patients with a first kidney transplant between January 1, 2000 and December 31, 2006 (n = 77 430; CSBI = 66 266; ECSW = 11 164) who were discharged from the hospital either with or without corticosteroids. Patients were excluded for transplantation before 2000, a history of multiple kidney or other organ transplantations or graft failure within 180 days of transplantation. Follow-up continued until death, graft failure, fracture or December 31, 2007. Our reported rates of graft survival included death as cause of graft failure. Fractures leading to hospitalizations were chosen because they are less subject to interpretation than outpatient cases of fractures, especially because the USRDS database has no information on radiographic studies; also these fracture rates can be compared directly to the National Center for Health Statistics (1Abbott KC Oglesby RJ Hypolite IO et al.Hospitalizations for fractures after renal transplantation in the United States.Ann Epidemiol. 2001; 11: 450-457Crossref PubMed Scopus (112) Google Scholar). Corticosteroid administration at time of discharge was determined from UNOS Immunosuppression Treatment Forms (25Available from: http://www.usrds.org/2008/rg/forms/10_UNOS_Transplant_Forms.pdf. Accessed May 18, 2011.Google Scholar) contained within USRDS, which are submitted at the time of transplantation. UNOS forms contain information regarding induction regimen and duration, type of immunosuppression maintenance at hospital discharge and the treatment of rejection episodes; however, medication doses are not included. First-time fractures resulting in hospitalization were determined from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for fracture (ICD-9-CM codes 805·0–829·9) contained within USRDS and obtained from claims data submitted to CMMS. Both phalangeal (ICD-9-CM 816.0–816.9; 826.0–826.9) and skull (ICD9-CM 850–854) fractures were excluded. In the event of multiple fractures in the same patient, we considered first listing of a fracture specific ICD-9-CM code as the fracture event. Both traumatic and fragility fractures were included because the level of trauma associated with fracture was not completely recorded in USRDS; similar to low-trauma fractures, high-trauma fractures are associated with low bone mineral density (BMD) and increased risk of future fracture (26Mackey DC Lui LY Cawthon PM et al.High-trauma fractures and low bone mineral density in older women and men.Jama. [Research Support, N.I.H., Extramural]. 2007; 298: 2381-2388Google Scholar). Fracture covariates obtained from USRDS were selected on the basis of epidemiologic studies that demonstrated their ability to predict fracture in chronic kidney disease (CKD) and kidney transplant populations (3Ball AM Gillen DL Sherrard D et al.Risk of hip fracture among dialysis and renal transplant recipients.JAMA: J Am Med Assoc. 2002; 288: 3014-3018Crossref PubMed Scopus (355) Google Scholar,27Alem AM Sherrard DJ Gillen DL et al.Increased risk of hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 396-399Abstract Full Text Full Text PDF PubMed Scopus (666) Google Scholar, 28Stehman-Breen CO Sherrard DJ Alem AM et al.Risk factors for hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 2200-2205Abstract Full Text Full Text PDF PubMed Google Scholar, 29Nickolas TL McMahon DJ Shane E Relationship between moderate to severe kidney disease and hip fracture in the United States.J Am Soc Nephrol. 2006; 17: 3223-3232Crossref PubMed Scopus (284) Google Scholar, 30Coco M Rush H Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.Am J Kidney Dis. 2000; 36: 1115-1121Abstract Full Text Full Text PDF PubMed Scopus (499) Google Scholar, 31Mussolino ME Looker AC Madans JH Langlois JA Orwoll ES Risk factors for hip fracture in white men: The NHANES I epidemiologic follow-up study.J Bone Miner Res. 1998; 13: 918-924Crossref PubMed Scopus (153) Google Scholar, 32Ensrud KE Lipschutz RC Cauley JA et al.Body size and hip fracture risk in older women: A Prospective study. Study of Osteoporotic Fractures Research Group.Am J Med. 1997; 103: 274-280Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar). These included age at transplantation (years), gender, race (White, Black, Asian and Other), body mass index (BMI), HLA-matching (0; 1–2; 3–4 and 5–6), donor type (deceased or living), induction at transplant, parathyroidectomy (before or after transplantation) and a history of pretransplantation dialysis, pretransplantation fracture and pre-transplantation diabetes. BMI was evaluated both as continuous and categorical parameters: underweight (BMI <18.5), normal (BMI 18.5–24.9), overweight (BMI 25–29.9) and obese (BMI of >30). BMI >50 (n = 155) was considered a measurement error and was classified along with those missing BMI measurements (n = 12 370) as a separate covariate in analyses. Pretransplantation fracture was determined by the presence of an ICD-9-CM fracture code with a date of service before transplantation. We did not separately adjust for pretransplant peritoneal- or hemodialysis; both in univariate and multivariate models, peritoneal- and hemodialysis were associated with increased fracture risk, which was not materially different from that of a combined dialysis variable alone. We also adjusted the multivariate model for other factors associated with kidney transplantation that may affect posttransplantation fracture risk due to necessary corticosteroid administration, including: (1) a history of rejection (yes, no), as these episodes are usually treated with corticosteroid and may result in long-term corticosteroid administration; and (2) etiologies of ESRD, such as nephrosis and nephritis, that may be treated with corticosteroids both before and after transplantation due to their underlying causes (i.e., USA systemic lupus erythematosis). Finally, our main multivariate model did not adjust for dialysis duration because a date of first dialysis was not listed for 3465 patients with a history of pretransplantation dialysis. However, we reported relationships between duration of pretransplantation dialysis and fracture based on a separate analysis that excluded patients without a dialysis start date. Analyses were performed using STATA (version 8.2; StataCorp LP, College Station, TX, USA) and SAS (v9.2, Cary, NC, USA). Analyses were designed to: (1) compare characteristics of patients with a first transplant discharged with or without corticosteroids; (2) evaluate time to first fracture; (3) quantify fracture risk by immunosuppression regimen at discharge while controlling for fracture covariates and (4) evaluate modulation of fracture risk according to corticosteroid use at discharge, considering both modifiable and nonmodifiable fracture risk factors. Categorical and continuous parameters were compared using chi-square and Student t-tests, respectively. Time to first fracture and patient and graft survival were modeled using the Kaplan–Meier method, with the log-rank test. Proportional hazard regression was used to quantify fracture risk with ECSW in comparison to CSBI, while adjusting for covariates of fracture determined from univariate analyses. Preliminary diagnostics revealed nonproportional hazards for fracture (i.e. fracture risk varied with time). To model this association the main hazard model was stratified by follow-up time at 3 years. To evaluate modulation of fracture risk by corticosteroid use at discharge, the hazard model was scored by logistic regression. Fracture risk for a transplant recipient with both modifiable (pretransplant dialysis) and nonmodifiable (age, gender, race and pretransplant diabetes) risk factors for fracture was then stratified by corticosteroid at discharge and presented as the population median (interquartile range [IQR]) risk. Finally, in a randomized clinical trial risk factors for fracture would have been evenly distributed between ECSW and CSBI groups. However, in this observational study, multiple fracture covariates were unequally distributed between immunosuppression groups. Therefore, in order to validate our findings, we conducted a separate analysis (data not presented) using propensity scores for corticosteroid administration at discharge (33D’Agostino Jr., RB Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group.Stat Med. 1998; 17: 2265-2281Crossref PubMed Scopus (4410) Google Scholar). Inclusion of propensity score as a covariate in the model of interest (outcome = fracture) did not substantially alter results. Using the USRDS, 77 430 adults who had a first kidney transplant between January 1, 2000 and December 31, 2006 were identified. Immunosuppression regimen at hospital discharge was determined. Follow-up data regarding both immunosuppression and acute rejection were incomplete; UNOS reported rates of rejection were significantly lower in patients discharged without than with corticosteroid (8.6% vs. 13.1%, p-value < 0.001). Graft survival in patients managed with ECSW was equivalent to those managed with CSBI at 1 year (96.1% vs. 95.7%; p-value = 0.07), slightly greater than in those managed with CSBI at 3 years (88.8% vs. 87.5%; p-value = 0.009) and equivalent at 5 years (80.4% vs. 78.7%; p-value = 0.1). For ECSW, patient survival was equivalent at 1 year (96.9% vs. 96.7% with CSBI; p = 0.3) but was slightly greater at 3 years (92.6% vs. 91.6% with CSBI; p-value = 0.01) and 5 years (87.2% vs. 85.1% with CSBI; p-value = 0.03). There were small but significant differences between patients discharged with and without corticosteroids (Table 1). Patients discharged without corticosteroids were slightly older and had a slightly higher BMI; they were more likely to be male or white, to have diabetic nephropathy, to have received induction, to have a zero HLA mismatch or received a living donor transplant and to have had a slightly shorter time on dialysis; they were less likely to have been on pretransplant dialysis, or have undergone parathyroidectomy. Prevalence of pretransplantation fracture did not differ between groups. Consistent with previous reported rates of ECSW protocols, rates of discharge without corticosteroid increased between the years 2000 and 2006; more than 30% of recipients were discharged without corticosteroids in 2006 (14Luan FL Steffick DE Gadegbeku C Norman SP Wolfe R Ojo AO Graft and patient survival in kidney transplant recipients selected for de novo steroid-free maintenance immunosuppression.Am J Transplant. 2009; 9: 160-168Crossref PubMed Scopus (53) Google Scholar,15Luan FL Steffick DE Ojo AO Steroid-free maintenance immunosuppression in kidney transplantation: Is it time to consider it as a standard therapy?.Kidney Int. 2009; 76: 825-830Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar).Table 1:Cohort characteristics for first-time kidney transplantation recipients, 2000–2006, stratified by corticosteroid use at hospital dischargeVariable(n = 11 164)(n = 66 266)p-ValueFracturePrekidney transplant (%)1.41.3NSPostkidney transplant (%)1.73.3<0.001Age at transplantation in years (SD)49.9 (13.4)48.9 (13.4)<0.001Female gender38%40%<0.001RaceWhite68.8%65.3%<0.001Black19.8%25.1%<0.001Asian3.7%4.7%<0.001Other7.7%4.9%<0.001BMI in kg/m2 (SD)27.5 (5.7)27.1 (5.5)<0.001BMI < 18 .52.6%2.5%NSBMI 18.5–2529.5%30.0%NSBMI 25–3029.8%28.6%.0170BMI >3027.5%23.3%<0.001Missing10.6%15.5%<0.001Mean HLA-A, HLA-B and HLA-DR mismatches (SD)2.2 (1.7)2.3 (1.7)0.020 mismatches (%)15.9%14.9%0.0071–2 mismatches (%)41.8%41.4%NS3–4 mismatches (%)29.9%30.9%0.035–6 mismatches (%)11.4%11.1%NSDonor type (%)<0.001Living donor49%41%Deceased donor51%59%Induction99.3%83.0%<0.001Rejection (any vs. none)8.6%13.1%<0.001Pretransplant diabetes (recipient %)33%30%<0.001End-stage renal disease (%)Nephritis17.6%19.2%<0.001Nephrosis7.2%6.8%0.06Diabetes mellitus26.0%24.1%<0.001Hypertension20.6%21.8%0.003Tubulo-interstitial16.0%15.1%0.01Other12.6%13.1%NSPretransplantation dialysis (%)78.5%82.0%<0.001Parathyroidectomy (%)Pretransplant1.8%2.5%<0.001Posttransplant1.0%2.0%<0.001Year of transplant<0.00120002.4%97.6%20014.2%95.8%20025.8%94.2%200311.5%88.5%200420.0%80.0%200523.9%76.1%200632.2%67.8% Open table in a new tab Median (IQR) follow-up was 924 (600–1370) and 1501 (880–2142) days for patients discharged with and without corticosteroid, respectively. The incidence of fractures leading to hospitalizations during follow-up from January 1, 2000 to December 31, 2007 was significantly lower for patients discharged without than with corticosteroids (1.7% vs. 3.3%, respectively, p-value < 0.001); the absolute risk reduction was 1.6%. After transplantation, 2395 fractures resulting in hospitalizations were identified during 306 923 patient-years of follow-up; 5.8 and 8.0 fractures per 1000 patient-years were observed for recipients discharged without and with corticosteroid, respectively. The most common fracture sites were femur (29%), ankle (15%) and spine (11%). The distribution of fracture sites did not differ between immunosuppression groups. Although Kaplan–Meier analysis of time to fracture demonstrated a small decrease in the incidence of fractures 12 months after transplantation in patients discharged without corticosteroids, the incidence was significantly lower at 24 months after transplantation, (p-value < 0·0001, Figure 1). In multivariate proportional hazard regression analysis, adjusting for other fracture risk factors, there was an associated 31% (p-value < 0.001) reduction in fracture risk for patients managed with ECSW compared to CSBI (Table 2). In addition, age, female gender, low BMI, the presence of diabetes and a history of dialysis and fracture before transplantation were all significantly associated with increased risk of posttransplant fracture. Higher BMI and both Asian and Black race were protective against sustaining a fracture. Although rates of induction, rejection and parathyroidectomy differed between groups, these covariates did not affect fracture risk in multivariate analysis. In a subset analysis excluding patients without a date of first dialysis, each year of dialysis before transplantation was associated with a 4% increased fracture risk after transplantation (HR 1.04; 95% CI 1.03–1.06); duration of pretransplantation dialysis did not affect the reduction in fracture risk associated with ECSW.Table 2:Multivariate Cox regression model of risk of fracture after kidney transplantationVariableHazard ratio (HR)95% Confidence intervalsp-ValueCorticosteroid at hospital dischargeSteroid-based(Reference)Steroid-withdrawal0.690.590.81<0.001Age at transplantation18–50(Reference)50–651.761.591.94<0.001>653.272.913.67<0.001GenderMale(Reference)Female1.421.311.55<0.001RaceWhite(Reference)Black0.630.560.70<0.001Asian0.340.260.47<0.001Other0.890.731.09NSBMI (kg/m2)BMI < 181.391.081.780.01BMI 18–25(Reference)BMI 25–300.870.780.960.008BMI > 300.830.750.930.002HLA-A, HLA-B and HLA-DR mismatches0 mismatches(Reference)1–2 mismatches1.010.891.14NS3–4 mismatches1.030.901.17NS5–6 mismatches1.070.931.25NSDonor typeLiving donor(Reference)Deceased donor1.361.241.49<0.001Rejection (any vs. none)1.100.981.23NSPretransplant fracture1Between time of ESRD listing and transplant.2.822.333.43<0.001Pretransplant diabetes (recipient)2.051.762.39<0.001Cause of end stage renal diseaseNephritis0.850.731.000.05Nephrosis0.730.570.930.01Diabetes mellitus1.391.181.64<0.001Hypertension(Reference)Tubulo-interstitial0.890.761.05NSOther0.940.801.11NSPretransplant dialysis1.561.361.77<0.001Year of transplant2000(Reference)20011.110.971.26NS20021.100.961.26NS20031.080.931.25NS20041.090.931.28NS20051.150.971.37NS20061.100.891.35NS1 Between time of ESRD listing and transplant. Open table in a new tab To account for variable fracture rates with time, hazard models were stratified at 3 years follow-up. Fracture risk was 26% (HR 95%CI 1.06–1.50) and 70% (HR 95%CI 1.18–2.46) higher in patients managed with CSBI, in comparison to ECSW, with less than and more than 3 years of follow-up, respectively. Modifiable risk factors for fracture, including discharge with corticosteroids and pretransplantation dialysis resulted in a 45% and 56% increased risk of facture, respectively (Figure 2). However, nonmodifiable risk factors for fracture, including older age and a history either of pretransplantation fracture or diabetes had greater influence on fracture risk after transplantation than corticosteroid use. In order to estimate the influence of corticosteroids on fracture risk in the presence of other important risk factors for fracture, we created a risk model based on patients within USRDS who had modifiable and nonmodifiable risk factors for fracture including: pretransplantation dialysis, both older and younger age, male or female gender and the presence or absence of pretransplantation diabetes (Figure 3). In general, fracture r" @default.
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• W1543301013 date "2012-03-01" @default.
• W1543301013 modified "2023-10-03" @default.
• W1543301013 title "Reduced Fracture Risk With Early Corticosteroid Withdrawal After Kidney Transplant" @default.
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