- Research article
- Open Access
Racial differences in inflammation and outcomes of aging among kidney transplant candidates
BMC Nephrology volume 20, Article number: 176 (2019)
Inflammation is more common among African Americans (AAs), and it is associated with frailty, poor physical performance, and mortality in community-dwelling older adults. Given the elevated inflammation levels among end-stage renal disease (ESRD) patients, inflammation may be associated with adverse health outcomes such as frailty, physical impairment, and poor health-related quality of life (HRQOL), and these associations may differ between AA and non-AA ESRD patients.
One thousand three ESRD participants were recruited at kidney transplant evaluation (4/2014–5/2017), and inflammatory markers (interleukin-6 [IL-6], tumor necrosis factor-a receptor-1 [TNFR1], C-reactive protein [CRP]) were measured. We quantified the association with frailty (Fried phenotype), physical impairment (Short Physical Performance Battery [SPPB]), and fair/poor HRQOL at evaluation using adjusted modified Poisson regression and tested whether these associations differed by race (AA vs. non-AA).
Non-AAs had lower levels of TNFR1 (9.7 ng/ml vs 14.0 ng/ml, p < 0.001) and inflammatory index (6.7 vs 6.8, p < 0.001) compared to AAs, but similar levels of IL-6 (4.5 pg/ml vs 4.3 pg/ml, p > 0.9) and CRP (4.7 μg/ml vs 4.9 μg/ml, p = 0.4). Non-AAs had an increased risk of frailty with elevated IL-6 (RR = 1.58, 95% CI:1.27–1.96, p < 0.001), TNFR1 (RR = 1.60, 95% CI:1.25–2.05, p < 0.001), CRP (RR = 1.41, 95% CI:1.10–1.82, p < 0.01), and inflammatory index (RR = 1.82, 95% CI:1.44–2.31, p < 0.001). The associations between elevated inflammatory markers and frailty were not present among AAs. Similar results were seen with SPPB impairment and poor/fair HRQOL.
Non-AAs with elevated inflammatory markers may need closer follow-up and may benefit from prehabilitation to improve physical function, reduce frailty burden, and improve quality of life prior to transplant.
ESRD patients experience accelerated aging resulting in adverse health outcomes of aging such as frailty, lower extremity impairment, and poor health-related quality of life (HRQOL) [1,2,3,4,5]. More specifically, frailty, a syndrome of decreased physiologic reserve , is present in 41.8% of hemodialysis patients [2, 3, 7] and is associated with falls , hospitalizations [1, 7, 8], poor cognitive function , decreased HRQOL , and mortality [1, 7]. Lower extremity impairment, measured using the Short Physical Performance Battery (SPPB) , is an important predictor of mortality in ESRD patients undergoing KT and is associated with longer length of stay after KT . Additionally, poor HRQOL is associated with frailty [4, 10] and predicts cardiovascular health and physical performance in ESRD patients .
In community dwelling older adults, elevated inflammatory markers including interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α receptor-1 (TNFR1) are associated with higher risk of multiple adverse health outcomes of aging including frailty , disability , and decreased grip strength ; furthermore, these adverse health outcomes of aging are important risk factors for mortality [15, 16]. Additionally, chronic dialysis is associated increased inflammation , and inflammation is a risk factor for mortality in ESRD patients [18, 19]. Among patients undergoing hemodialysis, there is a differential impact of inflammatory markers on mortality by race [20, 21]. Therefore, it is likely that the association between inflammatory marker levels and adverse health outcomes of aging also differ by race.
Quantifying the association between inflammatory markers and adverse health outcomes of aging such as frailty, lower extremity impairment, and poor HRQOL may provide insight into the role of aging biology to explain racial disparities related to poor outcomes for ESRD patients. Thus, the goals of this study were to: 1) quantify the association between inflammation and adverse health outcomes of aging (frailty, lower extremity function, and poor HRQOL) and 2) test whether there are differential associations between elevated inflammatory markers and adverse health outcomes of aging by race (African American [AA] vs. non-AA) among KT candidates.
This was a cross-sectional cohort study of 1003 English-speaking ESRD consecutive participants 18 years or older who were evaluated for KT at the Johns Hopkins Hospital, Baltimore, Maryland, from April 2014 to May 2017 (N = 891) and the University of Michigan, Ann Arbor, Michigan, from July 2015 to March 2016 (N = 112). Participants were eligible for enrollment if they were English speaking and aged 18 or older; the refusal rate during the enrollment period was 18%. At the time of KT evaluation, we measured Fried frailty, SPPB, HRQOL, and obtained a blood sample as described below. Additional participant characteristics were also assessed at KT evaluation or abstracted from the transplant evaluation medical record (age, sex, race, time on dialysis, type of dialysis, Charlson comorbidity index [CCI]). Race was measured using self-reported data from the electronic health record, EPIC. Participants selected among Black/African American (AA), White/Caucasian, Asian, Native Hawaiian, or Other. Participants who were not on dialysis at time of KT evaluation were classified as pre-emptive transplant. Comorbidities were classified as present if the participant currently suffered from the disease or had a previous history the disease. The Johns Hopkins Institutional Review Board and the University of Michigan Institutional Review Board approved the study and participants provided written informed consent.
We studied the physical frailty phenotype defined and validated by in community-dwelling older adults [6, 10, 22,23,24,25,26,27,28,29,30] and by our research group in ESRD and KT populations [2,3,4,5, 7, 8, 31,32,33,34,35,36,37,38]. Frailty was defined as a score of three or more of the Fried frailty components: shrinking (self-report of unintentional weight loss of more than 10 pounds in the past year based on dry weight); weakness (grip-strength below an established cutoff based on gender and BMI); exhaustion (self-report); low activity (Kcals/week below an established cutoff); and slowed walking speed (walking time of 15 ft below an established cutoff by gender and height) . Each of the 5 components was scored as 0 (absence) or 1 (presence). The aggregate frailty score was calculated as the sum of the component scores (range 0–5). Nonfrail was defined as a score of 0 and frail was defined as a score of ≥3.
Short physical performance battery (SPPB)
The SPPB is an objective test of lower extremity function (balance, walking speed, repeated chair stands) . Each component has a score ranging from 0 to 4, for a summed composite score ranging from 0 to 12. SPPB impairment was defined as having a SPPB score < 10 on a scale 0 to 12 [5, 9]. The test is administered by trained research assistants and takes approximately 5 min to complete. For the balance portion, recipients are asked to stand and remain in several progressively more difficult positions (side-by-side, semi-tandem, and full-tandem stances) for 10 s each. For the walking speed test, recipients’ walking speed is measured as they are asked to walk 15-ft at a normal pace. Finally, for the chair stand portion, recipients are asked to fold their arms across their chest and rise from a chair five times as quickly as possible. A full description of administration and scoring has been detailed elsewhere .
Health related quality of life (HRQOL)
HRQOL was measured using a single question instrument for global subjective health from the kidney disease quality of life assessment: “In general, would you say your health is …”. Participants reported HRQOL as being “Excellent”, “Very Good”, “Good”, “Fair” or “Poor” during KT evaluation. These classifications have been used in previous populations of ESRD patients and KT recipients [4, 37].
Measures of inflammation
Serum inflammatory markers, IL-6, TNFR1, and CRP, were collected at KT evaluation, as these markers are frequently elevated in frailty and end-stage renal disease . The blood samples were collected after evaluation in kidney transplant clinic at the same time as routine kidney transplant lab testing for all participants. There were no differences in sample volume (10 mL) between hemodialysis and non-hemodialysis participants. A full description of inflammation measurements performed by our research group has been detailed elsewhere . We calculated the inflammatory index score using IL-6 and TNFR1 as has been previously published: [1/3 x log(IL-6)] + [2/3 x log(TNFR1)] . Elevated inflammation markers were defined as >1SD higher level of IL-6, TNFR1, CRP or inflammation index on the log scale .
Adverse health outcomes of aging and inflammation
Modified Poisson regression was used to estimate the association between inflammatory markers (IL-6, TNFR1, CRP, and inflammatory index) and adverse health outcomes of aging (frailty, SPPB impairment, and poor HRQOL). Elevated inflammation markers were defined as >1SD higher level of IL-6, TNFR1, CRP or inflammation index on the log scale. For each change in 1SD, there was an association between inflammation an adverse health outcome of aging. These models were stratified by race (AA and non-AA) and adjusted for age, sex, CCI, type of dialysis (hemodialysis, peritoneal dialysis, and no dialysis), and time on dialysis. We also used modified Poisson regression with a Wald test to estimate the interaction between non-AA and AA for each inflammatory marker with adjustment for the same confounders above.
Continuous variables were compared using t-tests and categorical variables were compared using χ2 tests. For all analyses, a P value < 0.05 was considered significant. All analyses were performed using Stata 14.0 (College Station, Texas).
Among 1003 KT evaluation participants, the mean age was 55 (SD = 13), 40.0% were female, 41.3% were AA, 53.0% were on hemodialysis, and 34.4% were evaluated for pre-emptive KT (Table 1). The mean CCI score was 2.0 (SD = 2.4) (Table 1). AA KT candidates were more likely to be younger (mean age at evaluation: 53 years vs. 56 years, p < 0.001), have diabetes (49.2% vs. 40.7%, p = 0.008), and be HIV+ (8.7% vs. 0.9%, p < 0.001) (Table 1). The mean CCI score (2.1 vs. 2.0, p = 0.50) was similar between AAs and non-AAs. AAs were more likely to be on hemodialysis (61.9% vs. 45.1%, p < 0.001) and more likely to be on dialysis for more than 2 years (32.4% vs. 19.4%, p < 0.001), but less likely to evaluated for pre-emptive transplant (26.2% vs. 43.2%, p < 0.001).
Race and inflammatory markers
AAs had higher TNFR1 levels (median [IQR]: 14.0 [7.8–20.5] ng/ml vs. 9.7 [5.8–17.7] ng/ml, p < 0.001) and inflammatory index scores (6.8 [6.5–7.2] vs. 6.7 [6.2–7.1], p < 0.001) compared to non-AAs (Table 1) (Fig. 1a, d). However, AAs had similar IL-6 (4.3 [2.8–8.1] pg/ml vs. 4.5 [2.8–8.4] pg/ml, p = 0.95) and CRP (4.9 [2.2–11.0] ug/ml vs. 4.7 [1.9–10.2] ug/ml, p = 0.36) levels compared to non-AAs (Table 1, Fig. 1b, c).
Race and adverse health outcomes of aging
At the time of evaluation, 19.1% of KT candidates were frail, 40.0% had SPPB impairment, and 49.2% reported poor HRQOL. Additionally, AAs were more likely to be frail (23.4% vs. 16.1%, p = 0.01) and have SPPB impairment (46.0% vs. 36.3%, p = 0.003) compared to non-AAs, but the prevalence of poor HRQOL was similar between AAs and non-AAs (50.9% vs. 48.0%, p = 0.37) (Table 1).
Frailty, inflammation, and race
The risk of frailty associated with elevated IL-6 varied by participant race (interaction p = 0.04): Elevated IL-6 was associated with a 1.58-fold (95% CI: 1.27–1.96, p < 0.001) increased risk of frailty among non-AAs but did not increase the risk of frailty among AAs (aRR: 1.18, 95% CI: 0.99–1.42, p = 0.06) (Table 2). The risk of frailty associated with elevated TNFR1 also varied by participant race (interaction p = 0.02): Elevated TNFR1 was associated with a 1.60-fold (95% CI: 1.25–2.05, p < 0.001) increased risk of frailty among non-AAs, but it was not associated with an increased risk of frailty among AAs (aRR: 1.18, 95% CI: 0.92–1.51, p = 0.2). The risk of frailty by elevated CRP did not vary by participant race (interaction p = 0.1): Elevated CRP was associated with a 1.41-fold (95% CI: 1.10–1.82, p < 0.01) increased risk of frailty among non-AAs but not among AAs (aRR: 1.11, 95% CI: 0.92–1.33, p = 0.3). The risk of frailty associated with elevated inflammatory index varied by participant race (interaction p < 0.001): Elevated inflammatory index was associated with a 1.82-fold (95% CI: 1.44–2.31, p < 0.001) increased risk of frailty among non-AAs and a 1.26-fold (95% CI: 1.02–1.56, p = 0.03) increased risk of frailty among AAs (Table 2).
SPPB impairment, inflammation, and race
The risk of SPPB impairment associated with elevated IL-6 varied by participant race (interaction p < 0.01): Elevated IL-6 was associated with a 1.49-fold (95%CI: 1.33–1.67, p < 0.001) increased risk of SPPB impairment among non-AAs and a 1.20-fold (95%CI: 1.08–1.32, p = 0.001) increased risk of SPPB impairment among AAs (Table 2). The risk of SPPB impairment associated with elevated TNFR1 also varied by participant race (interaction p < 0.01): Elevated TNFR1 was associated with a 1.47-fold (95% CI: 1.27–1.71, p < 0.001) increased risk of SPPB impairment among non-AAs and a 1.17-fold (95% CI: 1.01–1.36, p = 0.04) increased risk of SPPB impairment among AAs. The risk of SPPB impairment associated with elevated CRP did not vary by participant race (interaction p = 0.09): Elevated CRP was associated with an increased risk of SPPB impairment in non-AAs (aRR: 1.32, 95% CI: 1.16–1.49, p < 0.001) and AAs (aRR: 1.14, 95% CI: 1.02–1.27, p = 0.02). The risk of SPPB impairment associated with elevated inflammatory index varied by participant race (interaction p < 0.001): Elevated inflammatory index was associated with a 1.67-fold (95%CI: 1.48–1.90, p < 0.001) increased risk of SPPB impairment among non-AAs and a 1.28-fold (95%CI: 1.13–1.46, p < 0.001) increased risk of SPPB impairment among AAs (interaction p < 0.001) (Table 2).
Fair/poor HRQOL, inflammation, and race
The risk of fair/poor HRQOL and elevated IL-6 varied by participant race (interaction p < 0.001): Elevated IL-6 was associated with a 1.19-fold (95% CI: 1.09–1.29, p < 0.001) increased risk of fair/poor HRQOL among non-AAs, but it was not associated an increased risk of fair/poor HRQOL among AAs (aRR: 0.96, 95% CI: 0.87–1.06, p = 0.4) (Table 2). The risk of having fair/poor HRQOL and elevated TNFR1 varied by participant race (interaction p < 0.01): Elevated TNFR1 was not associated with an increased risk of fair/poor HRQOL among non-AAs (aRR: 1.06, 95% CI: 0.95–1.19, p = 0.3) and AAs (aRR: 0.88, 95% CI: 0.78–1.00, p = 0.05). The risk of Fair/Poor HRQOL and elevated CRP varied by participant race (interaction p < 0.01): Elevated CRP was associated with a 1.18-fold (95% CI: 1.08–1.30, p < 0.001) increased risk of fair/poor HRQOL among non-AAs but was not associated with an increased risk of fair/poor HRQOL among AAs (aRR: 0.99, 95% CI: 0.91–1.09, p = 0.9). The risk of fair/poor HRQOL and elevated inflammatory index varied by participant race (interaction p < 0.001): Elevated inflammatory index was associated with a 1.16-fold (95% CI: 1.05–1.29, p < 0.01) increased risk of having fair/poor HRQOL among non-AAs, but it was not associated with an increased risk of fair/poor HRQOL among AAs (aRR: 0.92, 95% CI: 0.82–1.03, p = 0.1) (Table 2).
Using a two-center prospective cohort of 1003 ESRD participants evaluated for KT, we found that AAs had higher levels of TNFR1 (p < 0.001) and inflammatory index (p < 0.001) compared to non-AAs, and we found that AAs and non-AAs had similar levels of IL-6 (p > 0.9) and CRP (p = 0.4). Despite higher levels of some inflammatory markers in AAs, non-AAs had a higher risk of adverse health outcomes of aging, including frailty, SPPB impairment, and fair/poor HRQOL compared to AAs. In non-AAs elevation of all inflammatory markers (IL-6, TNFR1, CRP, and inflammatory index) were independently associated with an increased risk of frailty and SPPB impairment after accounting for potential confounders. Elevated inflammatory markers (IL-6, CRP, and inflammatory index) were associated with an increased risk of fair/poor HRQOL in non-AA KT candidates. Among AA KT candidates, elevated inflammatory markers (IL-6, TNFR1, CRP, and inflammatory index) were associated with an increased risk of SPPB impairment, and an elevated inflammatory index was associated with an increased risk of frailty. However, elevated inflammatory markers were not associated with an increased risk of having fair/poor HRQOL in AA candidates.
Our findings of higher levels of inflammatory markers among AAs compared to non-AAs are consistent with studies in community-dwelling adult populations [39, 40]. In the multi-ethnic population of the Dallas Heart Study, black subjects had higher CRP levels than white subjects , and as part of the Adventist Health Study-2, blacks had higher levels of CRP and IL6 compared to whites, yet no difference in TNFR1 levels.  Notably, we extend these community-dwelling studies of older adults (mean age 64–71) to ESRD patients across all ages and show that AAs have higher levels of TNFR1 and inflammatory index. The chronologic age of ESRD patients is likely not reflective of the true physiologic reserve you would see in community-dwelling patients of the same age. Thus, findings seen in older community-dwelling older adults are often seen in younger end-stage renal disease patients. We feel that ESRD does play a significant role in the accelerated aging process and puts these patients at increased risk of adverse health outcomes of aging.
Previous studies have shown greater survival of AAs on dialysis at higher levels of CRP  and IL-6  which is consistent with our findings on the association between lower risk of adverse health outcomes and elevated inflammation in AAs compared to non-AAs. While inflammation, marked by elevated CRP and IL-6 levels, has been previously associated with frailty  and poorer physical function in older adults  our study extended these findings into a population of KT candidates, encompassing all ages. Our research builds on these previous findings and shows that elevated inflammation is an important measure to identify the risk of specific adverse health outcomes of aging such as frailty, SPPB impairment, and fair/poor HRQOL, all of which have been previously associated with poor outcomes including death and disability. Furthermore, we have shown that the impact of inflammation on adverse health outcomes of aging in KT candidates may be somewhat mitigated in AAs, and comorbidities in AAs may confound the association of inflammation and adverse health outcomes of aging. These findings are important to consider in the clinical practice and evaluation of end-stage renal disease patients showing that elevated inflammatory levels may lead to adverse outcomes in non-AAs and comorbidities in AAs may lead to more adverse outcomes rather than elevated inflammatory levels alone. Clinicians should consider measurement of inflammatory markers in addition traditional comorbidity assessment to identify who may benefit from prehabilitation or exercise training to prevent subsequent adverse health outcomes of aging .
This study has several important strengths, including a large sample size from two different hospitals, the measurement of the novel gerontology factor of frailty, lower extremity impairment, and fair/poor HRQOL (rather than the use of proxies), and the analysis of 3 inflammatory markers collected at the time of KT evaluation. Additionally, to preserve stored samples, we only analyzed the most recent serum samples (from 4/2014); those with and without analyzed blood samples only differed on smoking status. The blood draw included in this study was a cross-sectional representation on one day, so variability in inflammatory markers may be missed due to dialysis, infections, medications, or hospitalizations. This study has several limitations worth noting. This study is a cross-sectional analysis of inflammatory markers and adverse health outcomes of aging, so it is difficult to conclude a causal relationship between the exposure and outcome; unmeasured confounding is inherent in any observational study and may lead to inappropriate inferences. Additionally, we do not have information on the type of hemodialysis access (arteriovenous fistula, graft, or catheter) or the timing of lab draws relative to dialysis.
We have shown that elevated inflammatory markers are associated with an increased risk of frailty, lower extremity impairment, and poor HRQOL among non-AAs with ESRD. While AAs experience an increased risk of frailty and lower extremity impairment with elevated inflammatory markers, non-AAs with elevated inflammatory markers had a higher risk of these adverse health outcomes of aging than non-AAs. This quantification provides early epidemiological evidence that the inflammatory pathway may be a novel and important target for reducing frailty burden and improving physical performance among KT candidates of all ages, especially among non-AAs. These findings highlight easy to measure markers of increased frailty, lower extremity impairment, and poor HRQOL risk and suggest that inflammatory markers should be measured during the evaluation process in order to identify individuals who may benefit from exercise training intervention or prehabilitation to improve their physical performance and lower their frailty burden while waiting for KT.
Charlson comorbidity index
End-stage renal disease
Health-related quality of life
Short physical performance battery
Tumor necrosis factor-α receptor-1
Bao Y, Dalrymple L, Chertow GM, Kaysen GA, Johansen KL. Frailty, dialysis initiation, and mortality in end-stage renal disease. Arch Intern Med. 2012;172(14):1071–7.
McAdams-DeMarco MA, Suresh S, Law A, Salter ML, Gimenez LF, Jaar BG, Walston JD, Segev DL. Frailty and falls among adult patients undergoing chronic hemodialysis: a prospective cohort study. BMC Nephrol. 2013;14:224.
McAdams-DeMarco MA, Tan J, Salter ML, Gross A, Meoni LA, Jaar BG, Kao WH, Parekh RS, Segev DL, Sozio SM. Frailty and cognitive function in incident hemodialysis patients. Clin J Am Soc Nephrol. 2015;10(12):2181–9.
McAdams-DeMarco MA, Ying H, Olorundare I, King EA, Desai N, Dagher N, Lonze B, Montgomery R, Walston J, Segev DL. Frailty and health-related quality of life in end stage renal disease patients of all ages. J Frailty Aging. 2016;5(3):174–9.
Nastasi AJ, McAdams-DeMarco MA, Schrack J, Ying H, Olorundare I, Warsame F, Mountford A, Haugen CE, Gonzalez Fernandez M, Norman SP, et al. Pre-kidney transplant lower extremity impairment and post-kidney transplant mortality. Am J Transplant. 2018;18(1):189–96.
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.
McAdams-DeMarco MA, Law A, Salter ML, Boyarsky B, Gimenez L, Jaar BG, Walston JD, Segev DL. Frailty as a novel predictor of mortality and hospitalization in individuals of all ages undergoing hemodialysis. J Am Geriatr Soc. 2013;61(6):896–901.
Johansen KL, Dalrymple LS, Delgado C, Chertow GM, Segal MR, Chiang J, Grimes B, Kaysen GA. Factors associated with frailty and its trajectory among patients on hemodialysis. Clin J Am Soc Nephrol. 2017;12(7):1100–8.
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–94.
McAdams-DeMarco MA, Ying H, Olorundare I, King EA, Haugen C, Buta B, Gross AL, Kalyani R, Desai NM, Dagher NN, Lonze BE, Montgomery RA, Bandeen-Roche K, Walston JD, Segev DL. Individual Frailty Components and Mortality in Kidney Transplant Recipients. Transplantation. 2017;101(9):2126–32.
Rogan A, McCarthy K, McGregor G, Hamborg T, Evans G, Hewins S, Aldridge N, Fletcher S, Krishnan N, Higgins R, et al. Quality of life measures predict cardiovascular health and physical performance in chronic renal failure patients. PLoS One. 2017;12(9):e0183926.
Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med. 2011;27(1):79–87.
Wu IC, Lin CC, Hsiung CA. Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine. Biomedicine (Taipei). 2015;5(1):1.
Norman K, Stobaus N, Kulka K, Schulzke J. Effect of inflammation on handgrip strength in the non-critically ill is independent from age, gender and body composition. Eur J Clin Nutr. 2014;68(2):155–8.
Brinkley TE, Leng X, Miller ME, Kitzman DW, Pahor M, Berry MJ, Marsh AP, Kritchevsky SB, Nicklas BJ. Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci. 2009;64(4):455–61.
Varadhan R, Yao W, Matteini A, Beamer BA, Xue QL, Yang H, Manwani B, Reiner A, Jenny N, Parekh N, et al. Simple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults. J Gerontol A Biol Sci Med Sci. 2014;69(2):165–73.
Kooman JP, Dekker MJ, Usvyat LA, Kotanko P, van der Sande FM, Schalkwijk CG, Shiels PG, Stenvinkel P. Inflammation and premature aging in advanced chronic kidney disease. Am J Physiol Renal Physiol. 2017;313(4):F938–50.
Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis. 2000;35(3):469–76.
Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 1999;55(2):648–58.
Crews DC, Sozio SM, Liu Y, Coresh J, Powe NR. Inflammation and the paradox of racial differences in dialysis survival. J Am Soc Nephrol. 2011;22(12):2279–86.
Noori N, Kovesdy CP, Dukkipati R, Feroze U, Molnar MZ, Bross R, Nissenson AR, Kopple JD, Norris KC, Kalantar-Zadeh K. Racial and ethnic differences in mortality of hemodialysis patients: role of dietary and nutritional status and inflammation. Am J Nephrol. 2011;33(2):157–67.
Newman AB, Gottdiener JS, McBurnie MA, Hirsch CH, Kop WJ, Tracy R, Walston JD, Fried LP. Cardiovascular health study research G: associations of subclinical cardiovascular disease with frailty. J Gerontol A Biol Sci Med Sci. 2001;56(3):M158–66.
Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, Gottdiener J, Fried LP. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the cardiovascular health study. Arch Intern Med. 2002;162(20):2333–41.
Xue QL, Bandeen-Roche K, Varadhan R, Zhou J, Fried LP. Initial manifestations of frailty criteria and the development of frailty phenotype in the Women's health and aging study II. J Gerontol A Biol Sci Med Sci. 2008;63(9):984–90.
Newman AB, Sachs MC, Arnold AM, Fried LP, Kronmal R, Cushman M, Psaty BM, Harris TB, Robbins JA, Burke GL, et al. Total and cause-specific mortality in the cardiovascular health study. J Gerontol A Biol Sci Med Sci. 2009;64(12):1251–61.
Leng SX, Xue QL, Tian J, Walston JD, Fried LP. Inflammation and frailty in older women. J Am Geriatr Soc. 2007;55(6):864–71.
Fried LP, Xue QL, Cappola AR, Ferrucci L, Chaves P, Varadhan R, Guralnik JM, Leng SX, Semba RD, Walston JD, et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci. 2009;64(10):1049–57.
Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev. 2011;10(3):319–29.
Roubenoff R, Parise H, Payette HA, Abad LW, D'Agostino R, Jacques PF, Wilson PW, Dinarello CA, Harris TB. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham heart study. Am J Med. 2003;115(6):429–35.
Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, Zeger SL, Fried LP. Phenotype of frailty: characterization in the women’s health and aging studies. J Gerontol A Biol Sci Med Sci. 2006;61(3):262–6.
Haugen CE, Mountford A, Warsame F, Berkowitz R, Bae S, Thomas AG, CHt B, Brennan DC, Neufeld KJ, Carlson MC, et al. Incidence, risk factors, and sequelae of post-kidney transplant delirium. J Am Soc Nephrol. 2018;29(6):1752–9.
McAdams-DeMarco MA, Law A, King E, Orandi B, Salter M, Gupta N, Chow E, Alachkar N, Desai N, Varadhan R, et al. Frailty and mortality in kidney transplant recipients. Am J Transplant. 2015;15(1):149–54.
McAdams-DeMarco MA, Law A, Tan J, Delp C, King EA, Orandi B, Salter M, Alachkar N, Desai N, Grams M, et al. Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients. Transplantation. 2015;99(4):805–10.
Thomas AG, Ruck JM, Shaffer AA, Haugen CE, ScM HY, Warsame F, Chu N, Carlson MC, Gross AL, Norman SP, Segev DL, McAdams-DeMarco M. Kidney Transplant Outcomes in Recipients with Cognitive Impairment: A National Registry and Prospective Cohort Study. Transplantation. 2018.
Warsame F, Haugen CE, Ying H, Garonzik-Wang JM, Desai NM, Hall RK, Kambhampati R, Crews DC, Purnell TS, Segev DL, McAdams-DeMarco MA. Limited health literacy and adverse outcomes among kidney transplant candidates. Am J Transplant. 2019;19(2):457–65.
Konel JM, Warsame F, Ying H, Haugen CE, Mountford A, Chu NM, Crews DC, Desai NM, Garonzik-Wang JM, Walston JD, et al. Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients. Clin Transpl. 2018:e13391.
McAdams-DeMarco MA, Olorundare IO, Ying H, Warsame F, Haugen CE, Hall R, Garonzik-Wang JM, Desai NM, Walston JD, Norman SP, et al. Frailty and Postkidney transplant health-related quality of life. Transplantation. 2018;102(2):291–9.
McAdams-DeMarco MA, Ying H, Thomas AG, Warsame F, Shaffer AA, Haugen CE, Garonzik-Wang JM, Desai NM, Varadhan R, Walston J, et al. Frailty, inflammatory markers, and waitlist mortality among patients with end-stage renal disease in a prospective cohort study. Transplantation. 2018;102(10):1740–6.
Khera A, McGuire DK, Murphy SA, Stanek HG, Das SR, Vongpatanasin W, Wians FH Jr, Grundy SM, de Lemos JA. Race and gender differences in C-reactive protein levels. J Am Coll Cardiol. 2005;46(3):464–9.
Paalani M, Lee JW, Haddad E, Tonstad S. Determinants of inflammatory markers in a bi-ethnic population. Ethn Dis. 2011;21(2):142–9.
McAdams-DeMarco MA, Ying H, Van Pilsum Rasmussen S, Schrack J, Haugen CE, Chu NM, Gonzalez Fernandez M, Desai N, Walston JD, Segev DL. Prehabilitation prior to kidney transplantation: results from a pilot study. Clin Transpl. 2019;33(1):e13450.
Patients at the Johns Hopkins Hospital and University of Michigan.
Study conception and design- PS, CEH, NC, AS, JGW, SN, JW, DLS, MMD. Acquisition of data- PS, CEH, AS, SN. Analysis and interpretation of data- PS, CEH, SN, JW, DLS, MMD. Drafting of manuscript- PS, CEH, NC, AS, JGW, SN, JW, DLS, MMD. Critical revisions- PS, CEH, NC, AS, JGW, SN, JW, DLS, MMD.
Approval of final manuscript version- PS, CEH, NC, AS, JGW, SN, JW, DLS, MMD.
This study was supported by the NIH: grants F32AG053025 (PI: Christine Haugen), K24DK101828 (PI: Dorry Segev), R01AG055781 (PI: McAdams-DeMarco), K01AG043501 (PI: McAdams-DeMarco), and R01DK114074 (PI: McAdams-DeMarco).
Availability of data and materials
The datasets used and/or analyzed are available from the corresponding author upon request.
Ethics approval and consent to participate
This study was approved by the Johns Hopkins Institutional Review Board (NA_00015758). All patients provided written consent to participate.
Consent for publication
Authors have no competing interest to report as described by BMC Nephrology.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Shrestha, P., Haugen, C.E., Chu, N.M. et al. Racial differences in inflammation and outcomes of aging among kidney transplant candidates. BMC Nephrol 20, 176 (2019). https://doi.org/10.1186/s12882-019-1360-8
- End-stage renal disease