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Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgements
  8. REFERENCES

Objective

To identify predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality among children with lupus nephritis–associated end-stage renal disease (ESRD).

Methods

Children ages 5–18 years with new-onset lupus nephritis–associated ESRD were identified in the US Renal Data System (1995–2006). Demographic and clinical characteristics, causes of death, and predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality during the first 5 years of ESRD were investigated. Cox proportional hazards models were used.

Results

A total of 583 children had incident lupus nephritis–associated ESRD. The mean ± SD age of the patients at the time of ESRD onset was 16.2 ± 2.4 years; 49% were African American, and 24% were Hispanic. During the 5-year period after the onset of ESRD, 292 (49%) were wait-listed, 193 (33%) received a kidney transplant, and 131 (22%) died. The main causes of death were cardiopulmonary (31%) and infectious (16%). Children living in the northeast and west were more than twice as likely as children in the south to be wait-listed and were >50% more likely than children in the south to undergo transplantation. There were fewer kidney transplants among older versus younger patients (odds ratio [OR] 0.59, P = 0.009), African American versus white patients (OR 0.48, P < 0.001), Hispanic versus non-Hispanic patients (OR 0.63, P = 0.03), and those with Medicaid versus those with private insurance (OR 0.70, P = 0.03). Mortality among African American children was almost double that among white children (OR 1.83, P < 0.001).

Conclusion

Among US children with lupus nephritis–associated ESRD, age, race, ethnicity, type of medical insurance, and geographic region were associated with significant variation in 5-year wait-listing for kidney transplantation, kidney transplantation, and mortality.

Systemic lupus erythematosus (SLE) in childhood accounts for 15–20% of all cases of SLE, and nephritis affects 20–75% of pediatric patients with SLE (1–5). Lupus nephritis in childhood usually presents after age 10 years, and presentation before age 5 years is rare (2, 6). Prior studies suggest that childhood lupus is more abrupt in onset compared with adult lupus, and that children with SLE are more likely to have renal and central nervous system involvement (1–4, 7–9). For both adult and pediatric patients with SLE, lupus nephritis is more common and more severe among African American and Hispanic than among white adult and pediatric SLE patients in the US (6, 10–14). Similarly, racial and ethnic disparities or inequities in access to and receipt of kidney transplantation according to sociodemographic factors, resulting in adverse health outcomes, have been documented among adults and children with end-stage renal disease (ESRD) in the US, with lower rates of wait-listing and kidney transplantation among African Americans and Hispanics (15–19).

Compared with adults with lupus, children with lupus receive more intensive drug therapy and accrue more organ damage, which often is related to steroid toxicity (4, 8, 20, 21). Among children with lupus nephritis, recent 5-year renal survival rates have ranged from 77% to 93%, and overall 5-year patient survival is 78–97% (6, 22–24). Information on the outcomes of pediatric patients with ESRD due to lupus nephritis remains sparse and is based on only a few studies involving small patient samples (6). In many of the early studies of pediatric lupus nephritis–associated ESRD, high rates of morbidity and mortality were observed (4, 8, 24). For example, McCurdy et al reported that among 10 children with ESRD due to lupus nephritis who did not receive kidney transplants, 5 died after a mean of 3.4 years on dialysis (24).

For adult patients with lupus nephritis–associated ESRD, kidney transplantation has proven benefits, including improved survival and quality of life (25–28). Early evaluation for kidney transplantation and placement on the waiting list for a kidney allograft are beneficial, although rates of graft failure and mortality increase with prolonged wait times (29, 30). It is assumed that kidney transplantation is also beneficial for pediatric patients with lupus nephritis–associated ESRD, although previous studies on the outcome of transplantation in this population have involved small numbers of patients (11, 26). Much of the knowledge regarding predictors and outcomes among pediatric patients with lupus nephritis–associated ESRD has been extrapolated from adult data and transplant studies, and little information is available on the sociodemographic predictors of waiting list access, kidney transplantation, and mortality in children with lupus nephritis–associated ESRD.

In this study, we examined the baseline demographic and clinical characteristics of children with lupus nephritis–associated ESRD and investigated potential sociodemographic and clinical predictors of wait-listing for and receipt of a kidney transplant and overall mortality from 1995 to 2006.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgements
  8. REFERENCES

Study population.

The United States Renal Data System (USRDS) is the national registry of patients with ESRD. Because Medicare is mandated to pay for the health care of these patients regardless of age, the Medicare claims of these patients form the backbone of the registry. The claims information is supplemented by data that must be reported to the Centers for Medicare and Medicaid Services (CMS) by providers on special forms, including the Medical Evidence Report (CMS-2728) and the ESRD Death Notification (CMS-2746). The USRDS database includes ∼94% of the patients in the US who receive renal replacement therapy such as dialysis or kidney transplantation and in 2006 included information on 1.6 million patients with ESRD reported since 1988 (31).

For each new patient at the time of enrollment, the attending nephrologist is required to complete the Medical Evidence Report. It serves to establish Medicare eligibility for those who were not previously eligible for Medicare, to reclassify previously eligible Medicare beneficiaries as ESRD patients, and to provide demographic and diagnostic information, including the etiology of ESRD, for all new patients with ESRD according to International Classification of Diseases, Ninth Revision (ICD-9) codes. The date of first service is derived from the earliest starting date of dialysis in patients with kidney failure (as reported on the medical evidence form); the date of kidney transplantation (as reported on a CMS or Organ Procurement Transplant Network transplant form, the Medical Evidence Report, or a hospital inpatient claim); or the date of the first Medicare dialysis claim. Patients who received transient dialysis for acute renal failure or who died before being enrolled in the database or refused renal replacement therapy are not included.

From the USRDS, we identified all individuals ages 5–18 years for whom SLE (ICD-9 code 710.0) was identified as the cause of ESRD on the Medical Evidence Report at the time of USRDS enrollment, from January 1, 1995 to December 31, 2006. We were interested in lupus nephritis–associated ESRD, which tends to occur later than SLE diagnosis. To capture all pediatric cases of lupus nephritis–associated ESRD, we included children who were entered into the USRDS at 18 years of age or younger.

Patient characteristics.

Based on the Medical Evidence Report, the USRDS contains information concerning patient demographics, including age at the time of initiation of renal replacement therapy, sex, race (white, African American, Asian, or American Indian), and Hispanic ethnicity. The region of residence at the time of initiation of ESRD treatment is categorized into northeast, midwest, south, or west. The USRDS Medical Evidence Report also includes the individual's body mass index (BMI; kg/m2), diagnoses of hypertension or diabetes mellitus at the time of enrollment, and certain laboratory measurements. The type of medical insurance prior to the onset of ESRD is also recorded (private, Medicaid, Medicare, other, or none), as is receipt of an erythropoiesis-stimulating agent prior to the onset of ESRD and the type of initial renal therapy received (hemodialysis, peritoneal dialysis, or preemptive kidney transplantation).

Study outcomes.

The outcomes of interest were time from ESRD to 1) being added to the waiting list for kidney transplantation, 2) receiving a kidney transplant, and 3) mortality from any cause, all of which are standard definitions in the USRDS. In addition, we distinguished between kidney transplantation from a living donor versus a deceased donor and a related living donor versus an unrelated living donor. Cause of death information was also available from the USRDS, as reported in the Death Notification form.

Statistical analysis.

Baseline characteristics were tabulated by race category and Hispanic ethnicity. The outcome variables wait-listing for kidney transplantation, receipt of a kidney transplant, and overall mortality were approached using time-to-event analyses. Followup was censored at the earlier of 5 years after initiation of renal replacement therapy or end of database (December 31, 2006). Predictors of the study outcomes were identified using age- and sex-adjusted Cox proportional hazards models and multivariable-adjusted models, additionally adjusting for race, ethnicity, US region of residence, and type of medical insurance. Tests for the proportional hazards assumption were completed using interaction terms between each of the covariates and time. The relationships between age and the outcomes of interest were explored with quartiles of age. Age was included in the final models both as a binary predictor (median split ≥16 years and <16 years) and as a continuous covariate in multivariable-adjusted models investigating other predictors. In additional multivariable Cox models, we investigated the effects of additional adjustment for clinical characteristics including type of initial ESRD therapy, albumin and hemoglobin levels, presence of hypertension and diabetes, treatment with erythropoiesis-stimulating agents prior to ESRD, and BMI.

Data were obtained through a data-use agreement with the USRDS, and our results are presented according to their policies. (Table cell counts of fewer than 11 individuals have been suppressed.) The Partners' Healthcare Institutional Review Board deemed this protocol as being exempt from human studies research approval.

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgements
  8. REFERENCES

We identified 583 children (ages 5–18 years) in whom renal replacement therapy was initiated between 1995 and 2006 and whose underlying renal disease was reported as lupus nephritis. The mean ± SD age of the patients at the time of ESRD onset was 16.2 ± 2.4 years. Table 1 presents the sociodemographic and clinical characteristics of the total population and stratified by race and ethnicity. African American children comprised almost half of the cohort, 24% of the children were Hispanic, and American Indian children comprised a small percentage (2.4%). No patients were missing data on date of birth or date of first service for ESRD, and no patients were missing data on ethnicity.

Table 1. Sociodemographic and clinical characteristics of US children with lupus-associated ESRD*
CharacteristicRaceEthnicity
Total (n = 583)White (n = 219)African American (n = 287)Asian (n = 46)Hispanic (n = 142)Non-Hispanic (n = 441)
  • *

    Except where indicated otherwise, values are the number (%). Race and ethnicity were reported separately. Race data were missing for 17 patients, medical insurance data were missing for 8 patients, region of residence data were missing for 5 patients, data on use of an erythropoiesis-stimulating drug were missing for 14 patients, and data for initial therapy were missing for 25 patients. ESRD = end-stage renal disease; NS = not shown; BMI = body mass index.

  • Includes employer group health insurance and insurance provided by the Veterans Administration.

  • Based on US Census Bureau state codes.

  • §

    Preemptive kidney transplantation was performed in <11 patients.

Age at onset of ESRD, mean ± SD years16.2 ± 2.416.1 ± 2.316.1 ± 2.516.0 ± 2.316 ± 2.416.1 ± 2.4
Female sex442 (76)167 (76)218 (76)39 (85)107 (73)335 (76)
Medical insurance prior to ESRD      
 Private224 (39)99 (46)87 (34)27 (60)52 (37)172 (40)
 Medicaid285 (50)90 (41)163 (58)14 (31)68 (48)217 (50)
 No insurance52 (9)22 (10)26 (9)NS20 (14)32 (7)
 Medicare14 (2)NSNSNSNS12 (3)
US region of residence      
 Northeast82 (14)28 (13)43 (15)NS18 (13)64 (15)
 South247 (43)64 (29)161 (56)13 (32)41 (30)206 (47)
 Midwest97 (17)30 (14)53 (19)NSNS91 (21)
 West146 (25)96 (44)30 (10)16 (39)71 (52)75 (17)
BMI, mean ± SD kg/m223.2 ± 6.223.0 ± 6.023.4 ± 6.122.5 ± 6.422.7 ± 5.823.4 ± 6.3
Presence of diabetes12 (2)NSNSNSNSNS
Presence of hypertension347 (60)125 (57)174 (61)26 (57)84 (59)263 (60)
Use of an erythropoiesis-stimulating agent prior to ESRD      
 Yes185 (33)68 (33)90 (32)17 (40)42 (31)143 (33)
 No359 (64)130 (63)183 (64)26 (60)88 (65)271 (63)
 Unknown21 (4)NS11 (4)NSNS15 (4)
Initial therapy§      
 Hemodialysis438 (75)150 (68)230 (80)34 (74)101 (71)337 (76)
 Peritoneal dialysis116 (20)55 (25)44 (15)11 (24)32 (23)84 (19)

The mean age of the children at the onset of ESRD was similar across racial groups. Female patients comprised the majority of cases in all races and ethnicities. More Asian and white patients had private medical insurance at the time of ESRD onset than did patients in other racial groups. Correspondingly, higher proportions of African Americans, Hispanics, and American Indians (data not shown due to small numbers) were enrolled in Medicaid or did not have medical insurance. The geographic distribution of the children by race and ethnicity was also uneven: the largest proportion of African American children resided in the south, and the largest proportion of white children resided in the west. Hispanic children with ESRD due to lupus nephritis resided mainly in the west and the south.

The mean ± SD BMI was 23.2 ± 6.2 kg/m2 for the total cohort, with the highest BMI observed among American Indian children (25 ± 7.5 kg/m2) and the lowest BMI observed among Asian children (22.5 ± 6.4 kg/m2). Within 5 years of the onset of ESRD, 292 children (49%) were placed on the waiting list for kidney transplantation, 193 (33%) received a kidney transplant, and 131 (22%) died. The mean ± SD age at the time of kidney transplantation was 18.2 ± 3.4 years, and the mean ± SD age at the time of death was 19.5 ± 3.5 years. The causes of death in this cohort were predominantly cardiopulmonary (31%) (Table 2).

Table 2. Causes of 5-year mortality among 131 US children with lupus-associated end-stage renal disease*
  • *

    Values are the number (%). Cardiopulmonary causes include pericarditis/cardiac tamponade, cardiomyopathy, cardiac arrhythmia, cardiac arrest, valvular heart disease, pulmonary edema, and embolus. Infectious causes include septicemia due to vascular access, peritonitis, pulmonary infections, and other infections. Neurologic causes include cerebrovascular accident, ischemic brain damage, and seizures. Hemorrhagic causes include hemorrhage from vascular access, surgery, other hemorrhage, and gastrointestinal hemorrhage. Other causes include mesenteric infarction/ischemic bowel, liver failure, pancreatitis, bone marrow depression, accident unrelated to treatment, renal conditions (including hyperkalemia and withdrawal from dialysis/uremia), and other identified cause of death.

Cardiopulmonary40 (31)
Infectious21 (16)
Neurologic13 (10)
Hemorrhagic13 (10)
Other25 (19)
Unknown19 (15)
Total131 (100)

Using multivariable Cox proportional hazards models adjusting for sociodemographic factors, we observed that the region of residence was the only important predictor of an increased rate of wait-listing for kidney transplantation (Table 3). Children living in the midwest, northeast, and west were up to twice as likely to be wait-listed as children living in the south. Residence in the west and northeast, compared with the south, was also associated with increased rates of kidney transplantation (Table 4).

Table 3. Sociodemographic determinants of wait-listing for kidney transplantation among 579 US children with lupus-associated end-stage renal disease*
Sociodemographic factorAge- and sex-adjusted OR (95% CI)Multivariable-adjusted OR (95% CI)
  • *

    Patients who received transplants preemptively were excluded. Multivariable models were adjusted for race, ethnicity, US region of residence, and medical insurance. Race data were missing for 17 children, region data were missing for 5 children, and medical insurance data were missing for 8 children. OR = odds ratio; 95% CI = 95% confidence interval (determined by Wald's test).

  • Age was used as a predictor, defined by the median split ≤16 years and >16 years. Age as a covariate for adjustment in the multivariable-adjusted models was included as continuous age in years.

Age
 ≤16 years (n = 317)1.0 (referent)1.0 (referent)
 >16 years (n = 262)0.89 (0.69–1.13)0.96 (0.74–1.23)
Sex
 Female (n = 439)1.0 (referent)1.0 (referent)
 Male (n = 140)1.09 (0.82–1.45)1.13 (0.85–1.51)
Race
 White (n = 216)1.0 (referent)1.0 (referent)
 African American (n = 286)0.87 (0.67–1.13)1.24 (0.88–1.75)
 Asian (n = 46)0.86 (0.54–1.37)1.21 (0.71–2.03)
 American Indian (n = 14)0.44 (0.16–1.21)0.45 (0.16–1.23)
Ethnicity
 Non-Hispanic (n = 438)1.0 (referent)1.0 (referent)
 Hispanic (n = 141)1.22 (0.93–1.60)1.37 (0.94–2.00)
US region of residence
 South (n = 247)1.0 (referent)1.0 (referent)
 West (n = 145)2.11 (1.56–2.85)2.11 (1.52–2.54)
 Midwest (n = 96)1.40 (0.97–2.02)1.54 (1.06–2.25)
 Northeast (n = 80)2.06 (1.45–2.94)2.07 (1.44–2.98)
Medical insurance
 Private (n = 221)1.0 (referent)1.0 (referent)
 Medicaid (n = 284)1.0 (0.77–1.29)1.02 (0.78–1.33)
 Medicare (n = 14)0.74 (0.33–1.69)0.92 (0.57–1.50)
 No insurance (n = 52)0.89 (0.56–1.43)0.61 (0.27–1.39)
Table 4. Sociodemographic determinants of kidney transplantation among 579 US children with lupus-associated end-stage renal disease*
Sociodemographic factorAge- and sex-adjusted OR (95% CI)Multivariable-adjusted OR (95% CI)
  • *

    Patients who received transplants preemptively were excluded. Multivariable models were adjusted for race, ethnicity, US region of residence, and medical insurance. Race data were missing for 17 children, region data were missing for 5 children, and medical insurance data were missing for 8 children. OR = odds ratio; 95% CI = 95% confidence interval (determined by Wald's test).

  • Age was used as a predictor, defined by the median split ≤16 years and >16 years. Age as a covariate for adjustment in the multivariable-adjusted models was included as continuous age in years.

Age
 ≤16 years (n = 317)1.0 (referent)1.0 (referent)
 >16 years (n = 262)0.56 (0.41–0.76)0.59 (0.43–0.81)
Sex  
 Female (n = 439)1.0 (referent)1.0 (referent)
 Male (n = 140)0.86 (0.59–1.24)0.90 (0.62–1.32)
Race  
 White (n = 216)1.0 (referent)1.0 (referent)
 African American (n = 286)0.53 (0.38–0.73)0.48 (0.32–0.71)
 Asian (n = 46)0.97 (0.59–1.60)0.80 (0.47–1.38)
 Native American (n = 14)0.67 (0.21–2.14)0.73 (0.22–2.35)
Ethnicity  
 Non-Hispanic (n = 438)1.0 (referent)1.0 (referent)
 Hispanic (n = 141)0.95 (0.67–1.33)0.63 (0.41–0.96)
US region of residence  
 South (n = 247)1.0 (referent)1.0 (referent)
 West (n = 145)1.98 (1.36–2.89)1.54 (1.03–2.31)
 Midwest (n = 96)1.39 (0.88–2.17)1.13 (0.71–1.81)
 Northeast (n = 80)2.17 (1.43–3.28)1.94 (1.28–2.95)
Medical insurance  
 Private (n = 221)1.0 (referent)1.0 (referent)
 Medicaid (n = 284)0.65 (0.47–0.89)0.70 (0.51–0.97)
 Medicare (n = 14)1.29 (0.59–2.79)0.55 (0.28–1.07)
 No insurance (n = 52)0.47 (0.25–0.92)1.20 (0.55–2.61)

We determined that the rate of kidney transplantation among children older than age 16 years was almost half the rate among children ages 16 years or younger (Table 4). Race and ethnicity were also important predictors of kidney transplantation. The 5-year rate of kidney transplantation among African American children was approximately half that among white children, even after adjustment for US region of residence and type of medical insurance. Hispanic compared with non-Hispanic children also had 37% lower rates of kidney transplantation in multivariable models. We also observed 30% lower rates of transplantation among children with Medicaid insurance compared with those with private insurance (Table 4).

In our analyses of mortality, we observed that race was the most important factor. African American children had almost double the risk of death compared with white children, even after multivariable adjustment (Table 5). Mortality did not differ between Hispanic and non-Hispanic children. Additional multivariable analyses including clinical factors (type of initial ESRD therapy, albumin and hemoglobin levels, presence of hypertension and diabetes, treatment with erythropoiesis-stimulating agents prior to ESRD, and BMI) did not significantly change our estimates for any of these 3 outcomes, and hence clinical factors did not appear to be independent predictors of outcomes in these children.

Table 5. Sociodemographic determinants of overall mortality among 583 US children with lupus-associated end-stage renal disease*
Sociodemographic factorAge- and sex-adjusted OR (95% CI)Multivariable-adjusted OR (95% CI)
  • *

    Multivariable models were adjusted for race, ethnicity, US region of residence, and medical insurance. Race data were missing for 17 children, medical insurance data were missing for 8 children, and region data were missing for 5 children. OR = odds ratio; 95% CI = 95% confidence interval (determined by Wald's test).

  • Age was used as a predictor, defined by the median split ≤16 years and >16 years. Age as a covariate for adjustment in the multivariable-adjusted models was included as continuous age in years.

Age  
 ≤16 years (n = 319)1.0 (referent)1.0 (referent)
 >16 years (n = 264)1.40 (0.96–2.03)1.36 (0.93–2.00)
Sex  
 Female (n = 442)1.0 (referent)1.0 (referent)
 Male (n = 141)1.40 (0.93–2.10)1.35 (0.89–2.04)
Race  
 White (n = 219)1.0 (referent)1.0 (referent)
 African American (n = 287)2.05 (1.31–3.21)1.83 (1.03–3.24)
 Asian (n = 46)1.51 (0.68–3.32)1.44 (0.61–3.43)
 Native American (n = 14)2.27 (0.79–6.52)2.22 (0.75–6.61)
Ethnicity  
 Non-Hispanic (n = 441)1.0 (referent)1.0 (referent)
 Hispanic (n = 142)0.66 (0.40–1.06)0.76 (0.39–1.49)
US region of residence  
 South (n = 247)1.0 (referent)1.0 (referent)
 West (n = 146)0.75 (0.47–1.19)0.62 (0.33–1.16)
 Midwest (n = 97)0.67 (0.39–1.17)0.69 (0.39–1.23)
 Northeast (n = 82)0.56 (0.30–1.05)0.62 (0.33–1.16)
Medical insurance  
 Private (n = 224)1.0 (referent)1.0 (referent)
 Medicaid (n = 285)1.38 (0.91–2.08)1.27 (0.83–1.94)
 Medicare (n = 14)1.19 (0.37–3.88)1.22 (0.37–4.01)
 No insurance (n= 52)1.52 (0.79–2.93)1.42 (0.73–2.78)
 Unknown (n = 25)0.66 (0.09–4.83)0.73 (0.10–5.41)

Among the children who underwent transplantation, 61% received a kidney from a deceased donor, and 39% received a kidney from a living donor (90% from a related donor and 10% from an unrelated donor). The proportion of transplanted kidneys received from a deceased donor was higher among children ages 16 years and younger (71%) compared with children older than 16 years of age (45%) and among African American (71%) and Asian (70%) children compared with white children (51%). Fifty-eight percent of Hispanic children received a kidney from a deceased donor. We also observed an increasing proportion of transplants involving kidneys from deceased donors over time by calendar year era, from 55% in 1995–1997, to 71% in 2004–2006. The proportion of kidneys received from deceased donors did not differ by region of residence.

DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgements
  8. REFERENCES

ESRD is a devastating potential consequence of lupus nephritis, and disparities in ESRD outcomes and lupus nephritis according to race and ethnicity are well documented in the literature. However, there is a scarcity of recent data on children with lupus nephritis–associated ESRD. We examined baseline demographic and clinical characteristics of children with ESRD due to lupus nephritis and investigated potential sociodemographic and clinical predictors of wait-listing for and receipt of a kidney transplant and overall mortality. We observed significant variations in wait-listing for kidney transplantation, receipt of a kidney transplant, and overall mortality by age, race, ethnicity, US region of residence, and type of medical insurance.

Clinical factors including type of initial ESRD therapy, albumin and hemoglobin levels, presence of hypertension and diabetes, treatment with erythropoiesis-stimulating agents prior to ESRD, and BMI did not appear to be significant in our multivariable models. We observed that children residing in the south were less likely to be wait-listed for kidney transplantation than were children residing in other regions of the US. Children with lupus nephritis–associated ESRD were also more likely to receive a kidney transplant if they resided in the west and northeast compared with the south. We also observed striking differences in rates of transplantation among different racial and ethnic groups, with African American and Hispanic children having lower rates of transplantation compared with white and non-Hispanic children. Overall survival among African American children was much lower when compared with that among white children.

The mean ages of the patients in this cohort at the time of ESRD onset and kidney transplantation are consistent with past data from pediatric lupus nephritis transplant cohorts, showing an older age at the time of transplantation among patients with SLE compared with children whose kidneys failed for other causes and who then received a kidney transplant (32, 33). The female-to-male ratio of 3.8:1 in this cohort is lower than ratios reported in pediatric lupus nephritis cohorts ranging from 4.5:1 to 7.8:1 (2, 24, 34). This difference highlights the need to investigate sex differences in the risk of ESRD developing among pediatric patients with lupus nephritis. Causes of death among the 131 patients who died included cardiopulmonary causes in 31% and infectious causes in 16%. This is consistent with cardiovascular complications being the most common cause of death among children with all-cause ESRD (31).

Our finding of decreased wait-listing rates in the southern region of the US is in agreement with a previous study that included pediatric patients with ESRD regardless of their underlying kidney disease, in which an increased likelihood of activation on kidney transplant waiting lists was observed in the northeast and midwest regions of the US compared with the south (17). For SLE patients in the US, decreased rates of wait-listing for kidney transplant are likely related to decreased kidney transplantation rates in the south, although differences in disease severity among patients may also be involved. Similar regional variation in treatment practices has been observed for adult patients with ESRD, and the observed heterogeneity was not explained by differences in the clinical characteristics of the patients (35, 36).

We also observed decreased 5-year rates of kidney transplantation among African American and Hispanic children compared with white children; this difference remained statistically significant after adjustment for US region of residence and type of medical insurance. Kidney transplantation rates in the US are known to be significantly lower among disadvantaged groups, in particular among African Americans, women, individuals of low socioeconomic status, those with inadequate insurance, and those residing in rural areas (15–19, 37). A lower rate of wait-listing for kidney transplantation and receipt of a transplant among African Americans with all causes of ESRD has also been documented in adults and children in the US (16, 17).

Possible explanations for the sociodemographic variation in kidney transplantation rates suggested by the results of previous studies include an HLA-based allocation strategy that limits access for minority racial and ethnic patients with ESRD (15, 16), barriers in the completion of the complicated renal transplantation evaluation process for socioeconomically disadvantaged patients, delayed referral to a nephrologist, and restricted access to a high-volume transplant center. All of these factors are demonstrated predictors of time to transplantation wait-listing and receipt of a transplant (18, 19, 38–41). Furthermore, physicians' perceptions that minority patients may prefer not to undergo kidney transplantation or that medical nonadherence (more common in socioeconomically disadvantaged populations) deems these patients less appropriate transplant candidates may contribute to differences in transplantation rates (42, 43).

Our finding of decreased overall survival among African American children compared with white children with lupus nephritis–associated ESRD is in remarkable contrast to survival in the all-cause adult ESRD population, in which African American patients have a marked survival advantage over white patients with otherwise similar characteristics (44). Racial differences in the severity of underlying SLE could explain some of the disparities in survival (16). Furthermore, our findings are consistent with those of studies demonstrating decreased survival among non-white SLE populations (14, 45), a phenomenon that does not hold true for other non-lupus–associated causes of ESRD. In our analyses, adjustment for regional variation and medical insurance attenuated the increase in mortality only slightly (from an increase of >2-fold to an 83% increase in African American patients compared with white patients), and adjustment for the clinical characteristics available at the time of ESRD onset, including laboratory parameters, comorbidities, BMI, and initial ESRD therapy, did not further affect this increased risk.

Prior smaller studies have compared outcomes among pediatric patients with lupus-associated ESRD with outcomes among patients with other causes of ESRD. A study of 94 patients with SLE in the North American Pediatric Renal Trials and Cooperative Studies demonstrated no difference in patient survival at 3 years (89% versus 95% in patients with SLE versus controls) (33). The United Network for Organ Sharing (UNOS) study that included 254 patients with pediatric lupus–associated ESRD who had received kidney transplants showed that over a median followup period of 4.2 years, mortality was 1.8-fold higher in those with SLE than in those with other causes of ESRD (32). African American race, transplantation of an organ from a deceased donor, and transplantation before 1993 were all related to an increased risk of mortality. The UNOS study also showed that children with lupus-associated ESRD had a longer duration of dialysis therapy before transplantation, similar to findings in adults (11, 26).

In the current study, we observed that initial ESRD therapy varied according to race, with a higher proportion of African American children receiving hemodialysis and fewer being placed initially on peritoneal dialysis compared with white children. This phenomenon has been reported for adults and children with all causes of ESRD in the US in recent years; the rate of hemodialysis initiation among African American patients rather than peritoneal dialysis is nearly 4-fold that reported for white patients (31). A study of children enrolled in the USRDS in 2000 revealed that African American race was strongly associated with the use of hemodialysis, which suggests that family, patient, or provider preferences could account for the racial difference observed in choice of therapy (46).

Transplantation of a kidney obtained from a related living donor confers superior outcomes for pediatric patients compared with transplantation of a kidney from a deceased donor (47). The small number of kidneys received from living donors precluded a detailed analysis of survival comparing transplantations involving related living donors and unrelated living donors. Among all of the patients in our study who received transplants, we observed an increase in the proportion of transplants involving deceased donors with increasing calendar year. This is consistent with trends observed in pediatric kidney transplantation since the implementation in 2005 of the revised allocation policy (Share 35) that conferred preferential allocation of allografts from young deceased donors (younger than age 35 years) to pediatric patients younger than age 18 years (48). This policy change resulted in an overall increase in the number of pediatric kidney transplantations per quarter and a reduced waiting time to receive a kidney from a deceased donor, as well as a marginally significant increase in overall HLA mismatching of recipients younger than age 18 years (47, 49). Because the type of kidney transplant (living versus deceased donor) has implications for survival of the transplanted kidney, the impact of this change in allocation upon future retransplantation rates is still unclear.

Our study has several strengths. This is the largest study of pediatric lupus nephritis–associated ESRD reported to date. The USRDS contains data from patients across the US and includes almost all incident cases involving receipt of Medicare-reimbursed renal replacement therapy. We analyzed and reported on data collected over 10 years on a pediatric subset of this population, for whom there were few published studies to date. We used well-documented and validated outcomes: wait-listing, kidney transplantation, and mortality (50).

The limitations of our study are that USRDS data on acute renal failure or rates of recovered renal function for 1995–2006 are not available. Date and age of SLE onset, kidney biopsy results, measures of lupus disease activity, and damage in other organ systems are also not available. Because all of these factors are important predictors of disease outcomes and mortality and are also related to race, ethnicity, and socioeconomic status, their inclusion would improve the interpretability of our findings. Our study is also limited by small numbers of Asian and American Indian patients with SLE, which impacts the ability to detect significant associations in these populations.

Our study sheds new light on several well-described differences in outcomes among pediatric patients with lupus-associated ESRD. Our results suggest that important disparities in access to care and in outcomes exist according to region of residence, age, race, ethnicity, and type of medical insurance. Additional research is needed to identify and refine factors affecting long-term outcomes in children with ESRD due to lupus nephritis.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgements
  8. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Hiraki had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Hiraki, Lu, Solomon, Winkelmayer, Costenbader.

Acquisition of data. Hiraki, Lu, Shaykevich, Winkelmayer, Costenbader.

Analysis and interpretation of data. Hiraki, Lu, Alexander, Shaykevich, Alarcón, Solomon, Winkelmayer, Costenbader.

Acknowledgements

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgements
  8. REFERENCES

We thank M. Alan Brookhart, PhD, for his input and assistance in using the USRDS data.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgements
  8. REFERENCES
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