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• W1995320421 abstract "Mortality has decreased in children with end-stage kidney disease. Decreases in mortality during dialysis and improved graft survival contributed to this improvement. However, it is unknown whether rates of death with graft function have also improved. We measured this in first transplant recipients under 21 years of age registered in the US Renal Data System. Cox models were used with a time-dependent renal replacement therapy modality variable to estimate the hazard ratios (HRs) for death with graft function associated with a 1-year increment in the calendar year of transplant. There were 157,201 person-years of observation among 17,468 recipients, with 82.2% of study time during graft function and 17.8% during dialysis after graft failure. There were 2003 deaths (12.7 deaths per 1000 person-years) overall, of which 985 occurred with graft function (7.6 deaths per 1000 person-years) and 1018 occurred during dialysis after graft failure (36.1 deaths per 1000 person-years). Each 1-year increment in calendar year of first transplant was associated with a significantly lower risk of death, both overall observation (HR 0.97 (0.96, 0.98)) and focusing on time with graft function (HR 0.98 (0.97, 0.99)). Living donation was significantly associated with better survival, whereas dialysis after graft failure was associated with a much higher mortality risk (HR 4.85 (4.40, 5.35)) compared with graft function. Thus, the risk of death with graft function has decreased in children receiving a first kidney transplant. Increasing living donation and minimizing dialysis may further improve outcomes. Mortality has decreased in children with end-stage kidney disease. Decreases in mortality during dialysis and improved graft survival contributed to this improvement. However, it is unknown whether rates of death with graft function have also improved. We measured this in first transplant recipients under 21 years of age registered in the US Renal Data System. Cox models were used with a time-dependent renal replacement therapy modality variable to estimate the hazard ratios (HRs) for death with graft function associated with a 1-year increment in the calendar year of transplant. There were 157,201 person-years of observation among 17,468 recipients, with 82.2% of study time during graft function and 17.8% during dialysis after graft failure. There were 2003 deaths (12.7 deaths per 1000 person-years) overall, of which 985 occurred with graft function (7.6 deaths per 1000 person-years) and 1018 occurred during dialysis after graft failure (36.1 deaths per 1000 person-years). Each 1-year increment in calendar year of first transplant was associated with a significantly lower risk of death, both overall observation (HR 0.97 (0.96, 0.98)) and focusing on time with graft function (HR 0.98 (0.97, 0.99)). Living donation was significantly associated with better survival, whereas dialysis after graft failure was associated with a much higher mortality risk (HR 4.85 (4.40, 5.35)) compared with graft function. Thus, the risk of death with graft function has decreased in children receiving a first kidney transplant. Increasing living donation and minimizing dialysis may further improve outcomes. Kidney transplantation is the treatment of choice for children and adolescents with end-stage kidney disease (ESKD).1.Horslen S. Barr M.L. Christensen L.L. et al.Pediatric transplantation in the United States, 1996-2005.Am J Transplant. 2007; 7: 1339-1358Crossref PubMed Scopus (100) Google Scholar Dialysis therapy, either before transplant or after graft failure, is associated with worse survival and quality of life and greater costs compared with transplant.2.McDonald S.P. Craig J.C. Long-term survival of children with end-stage renal disease.N Engl J Med. 2004; 350: 2654-2662Crossref PubMed Scopus (605) Google Scholar, 3.Foster B.J. Dahhou M. Zhang X. et al.Change in mortality risk over time in young kidney transplant recipients.Am J Transplant. 2011; 11: 2432-2442Crossref PubMed Scopus (70) Google Scholar, 4.Goldstein S.L. Rosburg N.M. Warady B.A. et al.Pediatric end stage renal disease health-related quality of life differs by modality: a PedsQL ESRD analysis.Pediatr Nephrol. 2009; 24: 1553-1560Crossref PubMed Scopus (67) Google Scholar, 5.Gillen D.L. Stehman-Breen C.O. Smith J.M. et al.Survival advantage of pediatric recipients of a first kidney transplant among children awaiting kidney transplantation.Am J Transplant. 2008; 8: 2600-2606Crossref PubMed Scopus (83) Google Scholar, 6.US Renal Data System, USRDS 2013 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, MD, USA2013Google Scholar Unlike adults, almost all children with ESKD are eligible for transplant in the United States.7.Mitsnefes M.M. Laskin B.L. Dahhou M. et al.Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990-2010.JAMA. 2013; 309: 1921-1929Crossref PubMed Scopus (141) Google Scholar Nevertheless, children receiving a kidney transplant have a life expectancy 20 years shorter than the general population.8.Mitsnefes M.M. Cardiovascular disease in children with chronic kidney disease.J Am Soc Nephrol. 2012; 23: 578-585Crossref PubMed Scopus (246) Google Scholar The first kidney transplant was performed in a child 50 years ago, and there have since been significant improvements specific to the care of transplant recipients,9.Shapiro R. Sarwal M.M. Pediatric kidney transplantation.Pediatr Clin North Am. 2010; 57: 393-400Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar including improvements in immunosuppression protocols, and in infectious disease monitoring, prophylaxis, and treatment. In addition, advances in surgical techniques have allowed successful transplantation in smaller and younger children. These changes may have affected outcomes.10.North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Annual Transplant Report.https://web.emmes.com/study/ped/index.htmDate: 2010Google Scholar, 11.Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR) OPTN/SRTR 2011 Annual Data Report. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD, USA2012Google Scholar, 12.Kasiske B.L. Zeier M.G. Craig J.C. et al.KDIGO clinical practice guideline for the care of kidney transplant recipients.Am J Transplant. 2009; 9: S1-S157Crossref PubMed Google Scholar Patient survival has improved over time for pediatric transplant recipients.3.Foster B.J. Dahhou M. Zhang X. et al.Change in mortality risk over time in young kidney transplant recipients.Am J Transplant. 2011; 11: 2432-2442Crossref PubMed Scopus (70) Google Scholar,13.Van Arendonk K.J. Boyarsky B.J. Orandi B.J. et al.National trends over 25 years in pediatric kidney transplant outcomes.Pediatrics. 2014; 133: 594-601Crossref PubMed Scopus (131) Google Scholar Although there are many possible reasons, there are three major paths to the better survival of transplant recipients: improvements in graft survival, decreases in mortality risk after graft failure, and decreases in the risk of death with graft function. Graft survival has improved over time for pediatric recipients.13.Van Arendonk K.J. Boyarsky B.J. Orandi B.J. et al.National trends over 25 years in pediatric kidney transplant outcomes.Pediatrics. 2014; 133: 594-601Crossref PubMed Scopus (131) Google Scholar Because mortality rates are lower for patients with graft function than for those being treated with dialysis,2.McDonald S.P. Craig J.C. Long-term survival of children with end-stage renal disease.N Engl J Med. 2004; 350: 2654-2662Crossref PubMed Scopus (605) Google Scholar,3.Foster B.J. Dahhou M. Zhang X. et al.Change in mortality risk over time in young kidney transplant recipients.Am J Transplant. 2011; 11: 2432-2442Crossref PubMed Scopus (70) Google Scholar improvements in graft survival will result in improved patient survival. We recently showed that patient survival has also improved over time among children receiving dialysis.7.Mitsnefes M.M. Laskin B.L. Dahhou M. et al.Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990-2010.JAMA. 2013; 309: 1921-1929Crossref PubMed Scopus (141) Google Scholar Therefore, decreased mortality risk following return to dialysis after graft failure may also have contributed to decreases in overall mortality. It remains unknown whether the risk of death with graft function has changed over time. Half of the deaths after pediatric kidney transplant occur in patients with graft function.3.Foster B.J. Dahhou M. Zhang X. et al.Change in mortality risk over time in young kidney transplant recipients.Am J Transplant. 2011; 11: 2432-2442Crossref PubMed Scopus (70) Google Scholar We aimed to determine whether the risk of death with graft function has changed over calendar time among children and adolescents who received their first kidney transplant from 1990 to 2010 in the United States. On the basis of prior work,2.McDonald S.P. Craig J.C. Long-term survival of children with end-stage renal disease.N Engl J Med. 2004; 350: 2654-2662Crossref PubMed Scopus (605) Google Scholar,3.Foster B.J. Dahhou M. Zhang X. et al.Change in mortality risk over time in young kidney transplant recipients.Am J Transplant. 2011; 11: 2432-2442Crossref PubMed Scopus (70) Google Scholar,7.Mitsnefes M.M. Laskin B.L. Dahhou M. et al.Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990-2010.JAMA. 2013; 309: 1921-1929Crossref PubMed Scopus (141) Google Scholar,13.Van Arendonk K.J. Boyarsky B.J. Orandi B.J. et al.National trends over 25 years in pediatric kidney transplant outcomes.Pediatrics. 2014; 133: 594-601Crossref PubMed Scopus (131) Google Scholar,14.Groothoff J.W. Gruppen M.P. Offringa M. et al.Mortality and causes of death of end-stage renal disease in children: a Dutch cohort study.Kidney Int. 2002; 61: 621-629Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar,15.Samuel S.M. Tonelli M.A. Foster B.J. et al.Survival in pediatric dialysis and transplant patients.Clin J Am Soc Nephrol. 2011; 6: 1094-1099Crossref PubMed Scopus (61) Google Scholar we hypothesized that mortality rates improved over time. We identified 17,468 children and adolescents who received their first kidney transplant at <21 years of age from January 1990 until December 2010. The cohort was followed up for a median of 8.4 years (interquartile range 4.2–13.6 years), with 157,201 person-years of observation, of which 129,146 person-years (82.2%) were during graft function, with the remainder during dialysis after graft failure. Table 1 summarizes the characteristics of patients receiving their first kidney transplant during the observation period. The age at first transplant remained stable, but the proportion of all first transplants in recipients aged 18–21 years decreased from 30.2% in 1990–1994 to 22.1% in 2005–2010. Consistent with data from the general US population,16US Census Bureau. http://www.census.gov/. Accessed on 8 May 2014.Google Scholar the proportion of recipients classified as ‘Other’ race (not white or black) increased over the observation period. Primary kidney disease, socioeconomic status (SES), duration of dialysis before first transplant, proportion of preemptive transplants, and primary insurance coverage appeared stable from 1990 to 2010. The proportion of living donor first transplants was lower in the most recent, compared with earlier, periods. The greatest amounts of missing data were in the earliest time period and involved the insurance coverage and comorbidity variables. Few patients had ≥1 recorded comorbidity; however, the proportion of subjects with at least one recorded comorbidity was higher in 2005–2010 than earlier.Table 1Patient characteristicsYear of first kidney transplant1990–19941995–19992000–20042005–2010Number of first transplants3740404143005387Age at first transplant (years)15.4 (9.4–18.6)14.8 (9.3–18.0)14.8 (9.3–18.0)15.0 (9.3–17.7)Recipient 18–21 years old at first transplant1130 (30.2)1017 (25.2)1055 (24.5)1190 (22.1)Male2186 (58.5)2369 (58.6)2496 (58.1)3136 (58.2)Race White2780 (74.3)2976 (73.7)3107 (72.3)3544 (65.8) Black756 (20.2)840 (20.8)852 (19.8)924 (17.2) Other204 (5.5)225 (5.6)341 (7.9)919 (17.1)Primary kidney disease Congenital anomalies of the kidney and urinary tract690 (18.5)1057 (26.2)1256 (29.2)1662 (30.9) Glomerulonephritis996 (26.6)1024 (25.3)885 (20.6)904 (16.8) Focal segmental glomerulosclerosis355 (9.5)478 (11.8)522 (12.1)719 (13.4) Other835 (22.3)915 (22.6)1006 (23.4)1205 (22.4) Unknown315 (8.4)306 (7.6)392 (9.1)602 (11.2) Missing549 (14.7)261 (6.5)239 (5.6)295 (5.5)Socioeconomic quartile Lowest716 (19.1)745 (18.4)795 (18.5)962 (17.9) Mid-low694 (18.6)686 (17.0)751 (17.5)956 (17.8) Mid-high948 (25.4)942 (23.3)1032 (24.0)1236 (22.9) Highest1187 (31.7)1314 (32.5)1500 (34.9)1797 (33.4) Missing195 (5.2)354 (8.8)222 (5.2)436 (8.1)Years on dialysis before first transplant0.6 (0.0–1.4)0.7 (0.0–1.5)0.8 (0.0–1.8)0.8 (0.0–1.7)Living donor first transplant1944 (52.0)2301 (56.9)2533 (58.9)2321 (43.1)Pre-emptive first transplant845 (22.7)979 (24.2)1066 (24.8)1393 (25.9)Primary insurance coverage Medicare/Medicaid939 (25.1)1008 (24.9)1267 (29.5)1910 (35.5) Employer/Other857 (22.9)2010 (49.7)2501 (58.2)2943 (54.6) No coverage123 (3.3)256 (6.3)247 (5.7)234 (4.3) Missing1821 (48.7)767 (19.0)285 (6.6)300 (5.6)Comorbidities None1580 (42.3)3106 (76.9)3754 (87.3)4425 (82.1) ≥1 Comorbidity361 (9.7)352 (8.7)278 (6.5)665 (12.3) Missing1799 (48.1)583 (14.4)268 (6.2)297 (5.5)Data presented as median (interquartile range) or n (%). Open table in a new tab Data presented as median (interquartile range) or n (%). Table 2 summarizes the crude all-cause mortality rates and recorded causes of death for the cohort. There were 2003 deaths during observation (12.7 deaths per 1000 person-years); five deaths occurred during the transplant surgery. Of all deaths, 985 (49.2%) deaths occurred during graft function (7.6 deaths per 1000 person-years) and the remaining 1018 (50.8%) deaths were during dialysis after graft failure (36.1 deaths per 1000 person-years).Table 2Crude all-cause mortality rates and cause of deathYear of first kidney transplant1990–19941995–19992000–20042005–2010Entire intervalPerson-years of observation57,86949,39733,94215,993157,201Total number of deaths9116063521342003Crude all-cause mortality rate (per 1000 person-years)15.712.310.48.412.7Deaths during graft function (% of all deaths)387 (42.5)305 (50.3)196 (55.7)97 (72.4)985 (49.2)Deaths during dialysis after graft failure (% of all deaths)aIncludes five deaths during the transplant surgery.524 (57.5)301 (49.7)156 (44.3)37 (27.6)1018 (50.8)Recorded cause of deathbInfectious causes included the following: septicemia, peritoneal access, peritonitis, hepatitis, viral infection, tuberculosis, AIDS, or central nervous system, heart, lung, abdomen, or genitourinary infections. Cardiovascular causes included the following: acute myocardial infarction, pericarditis, cardiac tamponade, atherosclerotic heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest (cause unknown), valvular heart disease, congestive heart failure, pulmonary embolus, or cerebrovascular accident including intracranial hemorrhage. by posttransplant renal replacement therapy (% of deaths by modality) Missing N (% of deaths with graft function)141 (36.4)94 (30.8)56 (28.6)35 (36.1)326 (33.1) N (% of deaths after graft failure)74 (14.2)43 (14.4)34 (21.8)9 (25.0)160 (15.8) Unknown N (% of deaths with graft function)71 (18.3)55 (18.0)41 (20.9)17 (17.5)184 (18.7) N (% of deaths after graft failure)55 (10.5)30 (10.0)10 (6.4)1 (2.8)96 (9.5) Infection N (% of deaths with graft function)62 (16.0)42 (13.8)34 (17.3)20 (20.6)158 (16.0) N (% of deaths after graft failure)70 (13.4)39 (13.0)16 (10.3)4 (11.1)129 (12.7) Cardiovascular N (% of deaths with graft function)40 (10.3)51 (16.7)32 (16.3)18 (18.6)141 (14.3) N (% of deaths after graft failure)236 (45.2)119 (39.8)65 (41.7)15 (41.7)435 (42.9) Malignancy N (% of deaths with graft function)29 (7.5)29 (9.5)10 (5.1)3 (3.1)71 (7.2) N (% of deaths after graft failure)6 (1.1)5 (1.7)1 (0.6)0 (0.0)12 (1.2) Other N (% of deaths with graft function)22 (5.7)15 (4.9)12 (6.1)1 (1.0)50 (5.1) N (% of deaths after graft failure)46 (8.8)36 (12.0)11 (7.0)7 (19.4)100 (9.9) Hemorrhage N (% of deaths with graft function)8 (2.1)9 (2.9)4 (2.0)2 (2.1)23 (2.3) N (% of deaths after graft failure)15 (2.9)12 (4.0)6 (3.8)0 (0.0)33 (3.3) Trauma N (% of deaths with graft function)12 (3.1)8 (2.6)3 (1.5)1 (1.0)24 (2.4) N (% of deaths after graft failure)7 (1.3)7 (2.3)6 (3.8)0 (0.0)20 (2.0) Metabolic N (% of deaths with graft function)2 (0.5)2 (0.7)4 (2.0)0 (0.0)8 (0.8) N (% of deaths after graft failure)13 (2.5)8 (2.7)7 (4.5)0 (0.0)28 (2.8)a Includes five deaths during the transplant surgery.b Infectious causes included the following: septicemia, peritoneal access, peritonitis, hepatitis, viral infection, tuberculosis, AIDS, or central nervous system, heart, lung, abdomen, or genitourinary infections. Cardiovascular causes included the following: acute myocardial infarction, pericarditis, cardiac tamponade, atherosclerotic heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest (cause unknown), valvular heart disease, congestive heart failure, pulmonary embolus, or cerebrovascular accident including intracranial hemorrhage. Open table in a new tab Among those who died, the median time from first transplant to death was 6.6 years (interquartile range 2.5–10.9 years) at any time after first transplant, 3.9 years (interquartile range 0.6–8.6 years) for those who died with graft function, and 8.8 years (interquartile range 5.3–11.9 years) for those who died after graft failure. The length of follow-up was not equal for all subjects. The 5-year patient survival was 93.2% for those receiving a first transplant from 1990 to 1994, 95.3% for those receiving a first transplant from 1995 to 1999, and 95.1% for those receiving a first transplant from 2000 to 2004. Kaplan–Meier survival curves for the cohort are shown in Figure 1. The most commonly recorded causes of death with a functioning allograft that were not missing (33.1%) or unknown (18.7%) were infection (16.0%), cardiovascular (14.3%), or malignancy (7.2%). The proportion of deaths during graft function attributed to cardiovascular disease or infection did not appear to change over time (Table 2). Cause of death during dialysis after a failed transplant was missing in 15.8%, and the most commonly recorded causes were cardiovascular (42.9%) or infection (12.7%). Table 3 shows the hazard ratios (HRs) for all-cause mortality per 1-year increment in calendar year of first transplant from 1990 to 2010. In the adjusted model, each 1-year increment in calendar year of first transplant was associated with a HR of 0.97 (95% confidence interval (CI) 0.96, 0.98) for death at any time after the first transplant. Focusing on time with graft function, each 1-year increment in calendar year of first transplant was associated with a lower mortality risk (adjusted HR of 0.98, 95% CI 0.97, 0.99). Removing insurance coverage and comorbidity status from the models did not change the point estimates or CIs for the HRs for death.Table 3All-cause hazard ratios for mortality after first kidney transplant (1990–2010)All observation after first transplantObservation with graft functionUnadjusted (calendar year of first transplant)0.97 (0.96, 0.98)aIndicates statistically significant hazard ratio.0.98 (0.97, 0.99)aIndicates statistically significant hazard ratio.Adjusted modelbAdjusted for recipient age, recipient age squared, donor (living vs. deceased), gender, primary renal disease, socioeconomic status quartile, duration of dialysis before first transplant, race, insurance coverage, and number of comorbidities. Models focusing on observation with graft function (last column) were also adjusted for renal replacement therapy modality (graft function vs. dialysis after graft failure—a time-dependent variable).0.97 (0.96, 0.98)aIndicates statistically significant hazard ratio.0.98 (0.97, 0.99)aIndicates statistically significant hazard ratio.Data are shown as hazard ratio (95% confidence intervals) for mortality per 1-year increment in calendar year of first transplant.a Indicates statistically significant hazard ratio.b Adjusted for recipient age, recipient age squared, donor (living vs. deceased), gender, primary renal disease, socioeconomic status quartile, duration of dialysis before first transplant, race, insurance coverage, and number of comorbidities. Models focusing on observation with graft function (last column) were also adjusted for renal replacement therapy modality (graft function vs. dialysis after graft failure—a time-dependent variable). Open table in a new tab Data are shown as hazard ratio (95% confidence intervals) for mortality per 1-year increment in calendar year of first transplant. Insurance coverage and comorbidity status were more frequently missing in the 1990–1994 time period. To examine the impact of missing covariate data, we conducted a sensitivity analysis, restricting the cohort to subjects who received their first transplant from 1995 to 2010. The all-cause mortality HRs for patients transplanted from 1995 to 2010 were similar in magnitude compared with the full cohort, with an adjusted HR of 0.98 (95% CI 0.96, 0.99) during all observation time after transplant and an adjusted HR of 0.99 (95% CI 0.97, 1.00) during periods of graft function. There was a significant interaction between recipient age and year of transplant in univariate models examining survival at any time after first transplant (P=0.006); this interaction did not reach significance in univariate models focused on time with graft function (P=0.06). We also show results of analyses stratified by age in Table 4. There was a greater improvement in survival over calendar time for children <5 years of age at transplant than for those ≥5 years of age during all observation time after first transplant and when focusing on observation with graft function.Table 4Age-stratified mortality after first kidney transplant (1990–2010)All observation after first transplantObservation with graft functionAge <5 yearsAge ≥5 yearsAge <5 yearsAge ≥5 yearsNumber of first transplants235915,104235915,104Person-years of observation20,378136,82418,896110,250Total number of deaths2231775178807Crude all-cause mortality rate (per 1000 person-years)10.913.09.47.3Hazard ratios for all-cause mortality per 1-year increment in calendar year of first kidney transplant Unadjusted (calendar year of first transplant)0.94 (0.92, 0.97)aIndicates statistically significant hazard ratio.0.97 (0.96, 0.98)aIndicates statistically significant hazard ratio.0.95 (0.93, 0.98)aIndicates statistically significant hazard ratio.0.98 (0.97, 0.99)aIndicates statistically significant hazard ratio. Adjusted modelbAdjusted for recipient age, donor (living vs. deceased), gender, primary renal disease, socioeconomic status quartile, duration of dialysis before first transplant, race, insurance coverage, and number of comorbidities. Models focusing on observation with graft function (last two columns) were also adjusted for renal replacement therapy modality (graft function vs. dialysis after graft failure—a time-dependent variable).0.95 (0.92, 0.98)aIndicates statistically significant hazard ratio.0.98 (0.97, 0.99)aIndicates statistically significant hazard ratio.0.96 (0.93, 0.98)aIndicates statistically significant hazard ratio.0.98 (0.97, 0.99)aIndicates statistically significant hazard ratio.Data are shown as hazard ratio (95% confidence intervals) for mortality, unless otherwise indicated.a Indicates statistically significant hazard ratio.b Adjusted for recipient age, donor (living vs. deceased), gender, primary renal disease, socioeconomic status quartile, duration of dialysis before first transplant, race, insurance coverage, and number of comorbidities. Models focusing on observation with graft function (last two columns) were also adjusted for renal replacement therapy modality (graft function vs. dialysis after graft failure—a time-dependent variable). Open table in a new tab Data are shown as hazard ratio (95% confidence intervals) for mortality, unless otherwise indicated. The associations between other variables included in the multivariable models and mortality are shown in Figure 2. Higher mortality risk was independently associated with the presence of ≥1 recorded comorbidity, public insurance (vs. no coverage), lower estimated SES, ‘Other’ primary disease, and female gender. Receiving a living donor transplant was associated with a substantially lower risk of death, even in models adjusted for renal replacement therapy modality (graft function vs. dialysis after graft failure). Younger recipient age was associated with a higher risk of death during graft function. Black race was associated with a higher risk of death than white race at any time after the first transplant, but not when comparisons were limited to time with graft function. There were no significant associations between mortality and the degree of human leukocyte antigen (HLA) mismatch or donor age (data not shown). Treatment with dialysis after graft failure was associated with a 4.85-time higher risk of death (95% CI 4.40, 5.35) compared with periods of graft function. Each additional year of dialysis before first transplant was associated with a small but significantly higher risk of death with graft function (0.3% increased risk of death, P=0.01) and of death at any time after transplant (0.4% increased risk of death, P=0.001). We examined changes in survival during graft function among over 17,000 US children and adolescents who received their first kidney transplant from 1990 to 2010. Although we found significant improvements in mortality risk over calendar time, these improvements amounted to a decrease in mortality of about 3% per year during all observation time after first transplant and about 2% per year during periods of graft function. Similar to what we previously observed in children with ESKD who were initially treated with dialysis,7.Mitsnefes M.M. Laskin B.L. Dahhou M. et al.Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990-2010.JAMA. 2013; 309: 1921-1929Crossref PubMed Scopus (141) Google Scholar survival improved for both the youngest and older children after transplantation, but it appeared to be greater for children <5 years of age. Others have examined changes in patient survival over calendar time in children undergoing kidney transplantation.2.McDonald S.P. Craig J.C. Long-term survival of children with end-stage renal disease.N Engl J Med. 2004; 350: 2654-2662Crossref PubMed Scopus (605) Google Scholar,3.Foster B.J. Dahhou M. Zhang X. et al.Change in mortality risk over time in young kidney transplant recipients.Am J Transplant. 2011; 11: 2432-2442Crossref PubMed Scopus (70) Google Scholar,10.North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Annual Transplant Report.https://web.emmes.com/study/ped/index.htmDate: 2010Google Scholar,15.Samuel S.M. Tonelli M.A. Foster B.J. et al.Survival in pediatric dialysis and transplant patients.Clin J Am Soc Nephrol. 2011; 6: 1094-1099Crossref PubMed Scopus (61) Google Scholar,17.Herthelius M. Celsi G. Edstrom Halling S. et al.Renal transplantation in infants and small children.Pediatr Nephrol. 2012; 27: 145-150Crossref PubMed Scopus (38) Google Scholar An analysis of the Scientific Registry of Transplant Recipients included children <18 years of age receiving a kidney transplant in the US and reported that mortality decreased by about 5% per calendar year13.Van Arendonk K.J. Boyarsky B.J. Orandi B.J. et al.National trends over 25 years in pediatric kidney transplant outcomes.Pediatrics. 2014; 133: 594-601Crossref PubMed Scopus (131) Google Scholar–a substantially larger improvement than what we observed. In contrast to our findings that younger children (<5 years of age) may have seen greater improvements than older children, that study found no difference in improvements in mortality risk by recipient age. The differences in the magnitude of improvement over time and in the observed associations with age between studies may be owing to several factors. For example, the analysis of Scientific Registry of Transplant Recipients data included repeat transplants, did not adjust for renal replacement therapy modality, and used the missing indicator method to deal with missing covariate data, potentially leading to bias.18.Greenland S.R. Rothman K.J. Fundamentals of epidemiologic data analysis.in: Rothman K.J. Greenland S. Modern Epidemiology. 2nd edn. Lippincott, Williams, and Wilkins, Philadelphia, PA, USA1998: 207-208Google Scholar We adjusted for renal replacement therapy modality in order to examine changes in the rates of death with graft function to consider the relative contribution of improvements specific to transplant or dialysis care. Several factors may have contributed to the observed decreases in mortality in our study. Changes in immunosuppression protocols have occurred over the observation period, with fewer children receiving prednisone at transplant or at 1 year of follow-up.11.Organ Procurement and Transplantati" @default.
• W1995320421 created "2016-06-24" @default.
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• W1995320421 title "The mortality risk with graft function has decreased among children receiving a first kidney transplant in the United States" @default.
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