Midlife Blood Pressure and Late-Life GFR and Albuminuria: An Elderly General Population Cohort

Inker, Lesley A.; Okparavero, Aghogho; Tighiouart, Hocine; Aspelund, Thor; Andrésdóttir, Margrét B.; Eiríksdóttir, Guðný; Harris, Tamara B.; Launer, Lenore J.; Nikulasdottir, Hjalmfridur; Sverrisdottir, Jóhanna Eyrún; Guðmundsdóttir, Hrefna; Noubary, Farzad; Mitchell, Gary F.; Pálsson, Runólfur; Indridason, Ólafur S.; Gudnason, Vilmundur; Levey, Andrew S.

doi:10.1053/j.ajkd.2015.03.030

Cited by 28 publications

(19 citation statements)

References 48 publications

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“…Between 2007 and 2011, 3411 participants returned for a second AGES-Reykjavik Study visit; in 2010–2011, participants were recruited and enrolled into AGES-Kidney, of whom 805 completed determination of measured GFR (mGFR). 4 For the present analysis the AGES-Kidney study sample included 683 participants after excluding participants with missing serum filtration marker measurements or missing data on factors hypothesized to be associated with non-GFR determinants. AGES-Kidney was approved by Icelandic Bioethics Committee; approval number VSN-00-063 and the Institutional Review Boards for the National Institute on Aging and Tufts Medical Center and participants provided written informed consent.…”

Section: Methodsmentioning

confidence: 99%

“…4,7 Serum levels of creatinine, cystatin C, B2M and BTP were measured at the University of Minnesota using stored samples collected during the AGES-Kidney and MESA-Kidney study visits.…”

Section: Methodsmentioning

confidence: 99%

“…Other clinical factors were ascertained during the most recent prior AGES or MESA visit using standard protocols as previous described. 4, 7 CRP was measured using the Immunoturbidimetric Roche methods on the COBAS 6000 chemistry analyzer (Roche Diagnostics) (CV 6.7% at 3.12 mg/L and 5.1% at 1.05 mg/L). Albumin was measured using the Bromcresol Purple method on the COBAS 6000 chemistry analyzer (Roche Diagnostics) (CV 2.6% at 3.90 g/dL and 2.2% at 2.68 g/dL).…”

Section: Methodsmentioning

confidence: 99%

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Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney

Foster

Levey

Inker

et al. 2017

American Journal of Kidney Diseases

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Background Studies in chronic kidney disease populations suggest that the non-GFR determinants of serum levels of the low molecular weight (LMW) protein filtration markers cystatin C, beta-2 microglobulin (B2M) and beta trace protein (BTP) are less affected by age, sex and ethnicity than those of creatinine. Study Design Cross-sectional study. Setting & Participants Predominantly elderly participants selected from the Age, Gene/Environment Susceptibility Kidney Study [AGES-Kidney, N=683, mean (SD) age 79 (4), GFR 62 (17) ml/min/1.73 m2] and from the Multi-Ethnic Study of Atherosclerosis Kidney Study [MESA-Kidney, N=273, mean (SD) age 70.5 (9), GFR 73 (19) ml/min/1.73 m2]. Predictors Demographic and clinical factors hypothesized to be associated with conditions affecting non-GFR determinants of the filtration markers. Outcomes mGFR and eGFRs based on creatinine, cystatin C, B2M and BTP (eGFRcr, eGFRcys, eGFRB2M and eGFRBTP, respectively). Residual associations of factors with eGFR after accounting for mGFR as the parameter of interest. Results eGFRcys, eGFRB2M and eGFRBTP had significantly less strong residual associations with age and sex than eGFRcr in both AGES-Kidney and MESA-Kidney, and were not associated with ethnicity (black vs. white) in MESA-Kidney. After adjusting for age, sex and ethnicity, residual associations with most clinical factors were smaller than observed with age and sex. eGFRcys, eGFRB2M, but not eGFRBTP had significant residual associations with CRP in both studies. Limitations Small sample size may limit power to detect associations. Participants may be healthier than the general population. Conclusions Similar to previous studies in chronic kidney disease, in community-dwelling elders, cystatin C, B2M and BTP are less affected than creatinine by age and sex and are not affected by ethnicity. Both cystatin C and B2M may be affected by inflammation. These findings are important for the development and use of GFR estimating equations based on LMW serum proteins throughout the range in GFR.

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Section: Methodsmentioning

confidence: 99%

“…4,7 Serum levels of creatinine, cystatin C, B2M and BTP were measured at the University of Minnesota using stored samples collected during the AGES-Kidney and MESA-Kidney study visits.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney

Foster

Levey

Inker

et al. 2017

American Journal of Kidney Diseases

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“…This study includes cohorts from the Age, Gene/Environment Susceptibility-Kidney Study (AGES-Kidney), Berlin Initiative Study (BIS), and Renal Iohexol Clearance Survey Follow-up Study (RENIS-FU), which have all been described previously. [7][8][9] Briefly, the 3 cohorts were recruited from Reykjavik (Iceland), Berlin (Germany), and Tromsø (Norway) and were all population based. RENIS-FU (n = 1,324) included persons aged between 56 and 70 years; AGES-Kidney (n = 805), between 74 and 93 years; and BIS (n = 570), between 70 and 97 years.…”

Section: Study Cohorts and Designmentioning

confidence: 99%

Comparability of Plasma Iohexol Clearance Across Population-Based Cohorts

Eriksen

Schaeffner

Melsom

et al. 2020

American Journal of Kidney Diseases

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Rationale & Objective: Glomerular filtration rate (GFR) estimation based on creatinine or cystatin C level is currently the standard method for assessing GFR in epidemiologic research and clinical trials despite several important and well-known limitations. Plasma iohexol clearance has been proposed as an inexpensive method for measuring GFR that could replace estimated GFR in many research projects. However, lack of standardization for iohexol assays and the use of different protocols such as single-and multiplesample methods could potentially hamper comparisons across studies. We compared iohexol assays and GFR measurement protocols in 3 population-based European cohorts.Study Design: Cross-sectional investigation.Setting & Participants: Participants in the Age, Gene/Environment Susceptibility-Kidney Study (AGES-Kidney; n = 805), the Berlin Initiative Study (BIS, n = 570), and the Renal Iohexol Clearance Survey Follow-up Study (RENIS-FU; n = 1,324).Tests Compared: High-performance liquid chromatography analyses of iohexol. Plasma iohexol clearance calculated using single-versus multiple-sample protocols.Outcomes: Measures of agreement between methods.Results: Frozen samples from the 3 studies were obtained and iohexol concentrations were remeasured in the laboratory at the University Hospital of North Norway. Lin's concordance correlation coefficient ρ was >0.96 and C b (accuracy) was >0.99 for remeasured versus original serum iohexol concentrations in all 3 cohorts, and Passing-Bablok regression did not find differences between measurements, except for a slope of 1.025 (95% CI, 1.006-1.046) for the log-transformed AGES-Kidney measurements. The multiple-sample iohexol clearance measurements in AGES-Kidney and BIS were compared with single-sample GFRs derived from the same iohexol measurements. Mean bias for multiple-sample relative to single-sample GFRs in AGES-Kidney and BIS were −0.25 and −0.15 mL/min, and 99% and 97% of absolute differences were within 10% of the multiple-sample result, respectively.Limitations: Lack of comparison with an independent gold-standard method.Conclusions: Agreement between the iohexol assays and clearance protocols in the 3 investigated cohorts was substantial. Our findings indicate that plasma iohexol clearance measurements can be compared across these studies. P lasma iohexol clearance is considered a precise and accurate method for measuring glomerular filtration rate (GFR). 1,2 Estimation of GFR from endogenous filtration markers-such as creatinine and cystatin C-may be affected by non-GFR determinants and lacks precision in the high GFR range. [3][4][5][6] It has been argued that plasma iohexol clearance should be used in research projects in which unbiased and precise GFR results are necessary. Low cost and easy implementation make plasma iohexol clearance a reasonable option for both clinical trials and epidemiologic studies. However, standardization of iohexol assays is lacking, and different sampling protocols may lead to difficulties comparing results across studies.We ...

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“…SBP and DBP are among the strongest independent predictors of decline in renal function as well as albuminuria in the elderly (60). A general perception is that, in patients with type 2 diabetes and/or CKD, a lower target BP should be achieved, even though it has not been established whether lower targets will result in reduced morbidity or mortality or delay decline in renal function; in this view, there is no specific BP target for elderly hypertensive patients with diabetes and with CKD.…”

Section: Target Bp In Elderly Patients With Ckdmentioning

confidence: 99%

What Should Be the Target Blood Pressure in Elderly Patients With Diabetes?

Solini

Grossman

2016

Diabetes Care

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Hypertension is very common in elderly subjects with type 2 diabetes. The coexistence of hypertension and diabetes can be devastating to the cardiovascular system, and in these patients, tight blood pressure (BP) control is particularly beneficial. Little information is available regarding the target BP levels in elderly hypertensive patients with type 2 diabetes, and therefore extrapolation from data in the general population should be done. However, it is difficult to extrapolate from the general population to these frail individuals, who usually have isolated systolic hypertension, comorbidities, organ damage, cardiovascular disease, and renal failure and have a high rate of orthostatic and postprandial hypotension. On the basis of the available evidence, we provide arguments supporting the individualized approach in these patients. Target BP should be based on concomitant diseases, orthostatic BP changes, and the general condition of the patients. It is recommended to lower BP in the elderly patient with diabetes to <140-150/90 mmHg, providing the patient is in good condition. In patients with isolated systolic hypertension, the same target is reasonable providing the diastolic BP is >60 mmHg. In patients with coronary artery disease and in patients with orthostatic hypotension, excessive BP lowering should be avoided. In elderly hypertensive patients with diabetes, BP levels should be monitored closely in the sitting and the standing position, and the treatment should be tailored to prevent excessive fall in BP.High blood pressure (BP) is a major risk factor for cardiovascular (CV) events. Linear relationships between CV morbidity and mortality risk and both systolic BP (SBP) and diastolic BP (DBP) levels starting from 115 and 75 mmHg, respectively, have been reported in the general population, independently of age, sex, ethnicity, and presence of comorbidities (1,2). A similar association either for micro-or for macrovascular complications has also been noted for patients with type 2 diabetes (3). The incidence of hypertension in patients with type 2 diabetes is approximately twofold higher than in age-matched subjects without the disease (4), and data from the Framingham study show that the excess CV risk in type 2 diabetes is attributable to coexistent hypertension (5). Therefore, the definition of hypertension is more stringent in diabetes, and BP levels .130/80 mmHg are already defined as hypertension (6).Life expectancy has increased over the years, and the world population is getting older. Hypertension is very common in elderly people (.60 years of age), reaching a prevalence of 60-80% in individuals in the U.S. (7). The rate of events in the elderly is high, and despite the fact that the association between BP levels and CV events is less steep in the elderly than in the young, the impact of elevated BP, in particular SBP, on CV morbidity and mortality in the elderly is significant (1,8). Therefore, BP control is also expected to provide benefits in aging individuals. A recent cost-effective analysis

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Midlife Blood Pressure and Late-Life GFR and Albuminuria: An Elderly General Population Cohort

Cited by 28 publications

References 48 publications

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney

Comparability of Plasma Iohexol Clearance Across Population-Based Cohorts

What Should Be the Target Blood Pressure in Elderly Patients With Diabetes?

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