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  • 1
    Online Resource
    Online Resource
    Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure
    S. Karger AG ; 2018
    In:  American Journal of Nephrology Vol. 47, No. 4 ( 2018), p. 275-282
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 47, No. 4 ( 2018), p. 275-282
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center ­European study involving 91 kidney transplant recipients (KTRs). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, 〈 i 〉 n 〈 /i 〉 = 433), and all individuals who developed kidney allograft failure (cases, 〈 i 〉 n 〈 /i 〉 = 226) during follow-up. Serum uromodulin was determined in this total of 〈 i 〉 n 〈 /i 〉 = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05–5.01] ). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06–3.77). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000489095
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1468523-1
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  • 2
    Online Resource
    Online Resource
    Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease: Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial
    S. Karger AG ; 2017
    In:  American Journal of Nephrology Vol. 46, No. 6 ( 2017), p. 488-497
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 46, No. 6 ( 2017), p. 488-497
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The pathogenesis of chronic kidney disease associated anemia is multifactorial and includes decreased production of erythropoietin (EPO), iron deficiency, inflammation, and EPO resistance. To better understand the trajectory of these parameters, we described temporal trends in hemoglobin (Hb), ferritin, transferrin saturation, C-reactive protein (CRP), and darbepoetin dosing in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed a post hoc analysis of 4,038 participants in TREAT. Mixed effects linear regression models were used to determine the trajectory of parameters of interest prior to end-stage renal disease (ESRD). Likelihood ratio tests were used to determine the overall differences in biomarker values and differences in trajectories between those who did and did not develop ESRD. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Hb declined precipitously in the year prior to the development of ESRD (irrespective of treatment assignment), and was on average 1.15 g/dL (95% CI –1.26 to –1.04) lower in those who developed ESRD versus those who did not, at the time of ESRD/end of follow-up. Simultaneously, the mean darbepoetin dose and CRP concentration increased, while serum ferritin and transferrin saturations were & #x3e;140 μg/L and 20%, respectively. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1–2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000485326
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 1468523-1
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  • 3
    Online Resource
    Online Resource
    Aortic Stiffness and Kidney Disease in an Elderly Population
    S. Karger AG ; 2015
    In:  American Journal of Nephrology Vol. 41, No. 4-5 ( 2015), p. 320-328
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 41, No. 4-5 ( 2015), p. 320-328
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 The causes of chronic kidney disease (CKD) in older people are not well understood. Aortic stiffness increases with age and results in the transmission of increased pulsatility into the kidney microvasculature, potentially contributing to CKD in older populations. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We utilized data from the Age, Gene/Environment, Susceptibility-Reykjavik Study, a community-based prospective cohort study of cardiovascular disease (CVD) in Iceland. The relationship of carotid pulse pressure (CPP) and carotid-femoral pulse wave velocity (CFPWV) with estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C and urine albumin-creatinine ratio (ACR) was assessed using linear regression, adjusting for demographics and CVD risk factors. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 940 participants (mean (SD) age 75.8 (4.7) years, mean (SD) CFPWV 12.9 (4.2) m/s, mean (SD) CPP 69 (21) mm Hg, mean (SD) eGFR 68 (16) ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 , and median (IQR) ACR 3 (2-6) mg/g) were included in this study. At CPP greater than 85 mm Hg, a higher CPP was associated with a lower eGFR in unadjusted analyses but not after adjustment. CPP was significantly associated with a higher ACR in fully adjusted models (β (95% CI) = 0.14 (0.03, 0.24) ln mg/g per SD). Higher CFPWV was associated with lower eGFR and higher ACR in unadjusted analyses but not after adjustment. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Greater aortic stiffness may be associated with modestly higher levels of albuminuria in the elderly. The association between aortic stiffness and lower eGFR may be confounded by age and CVD risk factors.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000431332
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 1468523-1
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