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Rationale & objectiveTubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.Study designProspective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).Setting & participantsAdults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without diabetes in the ARIC, REGARDS, and MESA studies.ExposuresBaseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1.OutcomeIncident CKD or end-stage kidney disease.Analytical approachMultivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts.Results872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m2. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31).LimitationsObservational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts.ConclusionsIn 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.

Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression. The average age was 60 ± 10 years; 48% were men; mean eGFR was 96±16 ml/min/1.73 m2; mean LVmvr was 0.93±0.18 g/ml, and mean LVEF was 62±6%. Each twofold greater concentration of plasma soluble urokinase plasminogen activator receptor was associated with a 0.04 g/ml (95% confidence interval [CI] 0.01 to 0.08 g/ml) higher LVmvr and 2.1% (95% CI 0.6 to 3.5%) lower LVEF, independent of risk factors for CVD, eGFR, and albuminuria. Each twofold greater plasma monocyte chemoattractant protein 1 was associated with higher LVmvr with a similar coefficient to that of plasma soluble urokinase plasminogen activator receptor. Each twofold greater concentration of plasma chitinase-3-like protein 1 and urine alpha-1-microglobulin was associated with a 1.1% (95% CI 0.4 to 1.7%) and 1.2% (95% CI 0.2 to 2.2%) lower LVEF, respectively. In conclusion, abnormal kidney tubule health may lead to cardiac dysfunction above and beyond eGFR and albuminuria.

Higher baseline urinary neutrophil gelatinase-associated lipocalin was associated with worse cognitive scores at baseline.Lower concentrations of baseline serum bicarbonate (higher is better) were associated with lower cognitive scores at baseline.We found no associations with urine markers with longitudinal changes in cognition.

Recent studies have suggested that 25-hydroxyvitamin D (25(OH)D) may be a poor biomarker of bone health, in part because measured levels incorporate both protein-bound and free vitamin D. The ratio of its catabolic product (24,25-dihydroxyvitamin D [24,25(OH)2 D]) to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide more information on sufficient vitamin D stores and is not influenced by vitamin D-binding protein concentrations. We evaluated whether the VMR or 25(OH)D are more strongly associated with bone loss and fracture risk in older adults. We performed a retrospective cohort study of 786 community-dwelling adults aged 70 to 79 years who participated in the Health Aging and Body Composition study. Our primary outcomes were annual changes in bone density and incident fracture. The mean age of these participants was 75 ± 3 years, 49% were female, 42% were Black, and 23% had an estimated glomerular filtration rate (eGFR)

ObjectivesFibroblast growth factor (FGF)-23 is a key regulator of mineral metabolism and has been linked with left ventricular hypertrophy in animal models. Most existing epidemiologic studies evaluated a C-terminal FGF23 assay which measures both the intact (active) hormone and inactive fragments. The relationship of intact FGF23 with cause-specific mortality is unknown.DesignProspective analyses of data from Health, Aging, & Body Composition (HABC) study.SettingCommunity-living adults aged 70 to 79 years with longitudinal follow up.

Background25-Hydroxyvitamin D [25(OH)D] may be a poor marker of vitamin D status as it reflects differences in vitamin D binding protein (VDBP) between individuals. The vitamin D metabolite ratio [VMR, ratio of 24,25(OH)2D3 to 25(OH)D3] is a marker of vitamin D status that has been hypothesized to be independent of variability in VDBP. This hypothesis has not been directly evaluated.MethodsWe measured 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and VDBP in 377 community-dwelling older adults that participated in the Health Aging and Body Composition Study. 24,25(OH)2D3 and 25(OH)D3 were used to calculate the VMR. We used linear regression to assess the relationship between VDBP with the VMR, 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3.ResultsParticipants had mean age 75 ± 3 years, 52% were female, 40% were black, and 24% had chronic kidney disease. VDBP concentrations were associated with sex, serum albumin, and VDBP phenotype in multivariable models. In fully adjusted models, each 1% higher VDBP was associated with a 0.92%[95% CI(0.37,1.49%)], 0.76% (0.39, 1.13%), and 0.57% (0.29, 0.85%), higher 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3. The VMR was independent of VDBP concentration, [0.16%(-0.11, 0.44) higher VMR per 1% higher VDBP, P = .25].ConclusionsThe VMR was independent of VDBP concentration, whereas VDBP was strongly directly associated with the individual vitamin D metabolite concentrations. Prior studies evaluating only 25(OH)D3 may have been confounded by absence of data on VDBP status. The VMR may serve as an important biomarker of vitamin D status and clinical outcomes that can be utilized in populations with a large spectrum of VDBP concentrations.

BackgroundUromodulin (UMOD) is released by renal tubular cells into the serum (sUMOD) and urine. Lower urine UMOD has been linked to mortality and cardiovascular disease but much less is known about sUMOD. We evaluated the association of sUMOD with these outcomes in community-dwelling older adults.MethodsWe measured sUMOD in a random subcohort of 933 participants enrolled in the Cardiovascular Health Study. The associations of sUMOD with all-cause mortality, incident heart failure (HF) and incident cardiovascular disease (CVD; myocardial infarction, stroke and mortality due to coronary disease or stroke) were evaluated using multivariable Cox regression, adjusting for study participants' demographics, estimated glomerular filtration rate (eGFR), albuminuria and CVD risk factors. Generalized additive models with splines were used to address the functional form of sUMOD with outcomes. Due to nonlinear associations of sUMOD with all outcomes, 2.5% of the values on either end of the sUMOD distribution were excluded from the analyses, limiting the range of sUMOD to 34.3-267.1 ng/mL.ResultsThe mean age was 78 ± 5 years, 40% were male, sUMOD level was 127 ± 64 ng/mL, eGFR was 63 mL/min/1.73 m2 and 42% had CKD defined as eGFR

Uromodulin is released into serum (sUMOD) and urine (uUMOD) exclusively by renal tubular cells. Both sUMOD and uUMOD are correlated with estimated glomerular filtration rate (eGFR), and associated with mortality and cardiovascular disease (CVD). However, no study to our knowledge has measured both sUMOD and uUMOD in the same population, thus the relationship of sUMOD with uUMOD with one another, and their respective correlates have not been evaluated simultaneously. We evaluated the correlations of sUMOD, uUMOD with eGFR in a random sub-cohort (n = 933) of the Cardiovascular Health Study and their associations with demographic and laboratory parameters and CVD risk factors using multi-variable linear regression analysis. The mean age of the cohort was 78 years, 40% were male and 15% were Black. The mean sUMOD level was 127 ng/mL, uUMOD was 30 500 ng/mL and eGFR was 63 mL/min/1.73 m2 . Correlation between sUMOD and uUMOD, adjusted for eGFR was moderate (r = 0.27 [95% confidence interval = 0.21-0.33]). The correlation of eGFR with sUMOD (r = 0.44 [0.39-0.49]) was stronger than with uUMOD (r = 0.21 [0.15-0.27]). In multi-variable analysis adjusting sUMOD for uUMOD and vice versa, sUMOD was independently associated with eGFR (β = 1.3 [1.1-1.6]), log2 C-reactive protein (β = -4.2 [-6.8 to -1.6]) and male sex (β = -13.6 [-22.7 to -4.5]). In contrast, male sex was associated with higher uUMOD (β = 3700 [400-7000]), while diabetes (β = -6400 [-10 600 to -2100]) and hypertension (-4300 [-7500 to -1100]) were associated with lower uUMOD levels. We conclude that sUMOD is more strongly associated with eGFR compared with uUMOD. Correlates of sUMOD and uUMOD differ substantially, suggesting that apical and basolateral secretion may be differentially regulated.

BackgroundKidney tubular atrophy on biopsy is a strong predictor of chronic kidney disease (CKD) progression, but tubular health is poorly quantified by traditional measures including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of impaired tubule function would be associated with faster eGFR declines in persons with CKD.MethodsWe measured baseline urine concentrations of uromodulin, β2-microglobulin (β2m), and α1-microglobulin (α1m) among 2,428 participants of the Systolic Blood Pressure Intervention Trial with an eGFR

AimsBiomarkers of kidney tubule injury, inflammation and fibrosis have been studied extensively and established as risk markers of adverse kidney and cardiovascular disease (CVD) outcomes. However, associations of markers of kidney tubular function with adverse clinical events have not been well studied, especially in persons with chronic kidney disease (CKD).Methods and resultsUsing a sample of 2377 persons with CKD at the baseline Systolic Blood Pressure Intervention Trial (SPRINT) visit, we evaluated the association of three urine tubular function markers, alpha-1 microglobulin (α1m), beta-2 microglobulin (β2m), and uromodulin, with a composite CVD endpoint (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes) and mortality using Cox proportional hazards regression, adjusted for baseline estimated glomerular filtration rate (eGFR), albuminuria, and CVD risk factors. In unadjusted analysis, over a median follow-up of 3.8 years, α1m and β2m had positive associations with composite CVD events and mortality, whereas uromodulin had an inverse association with risk for both outcomes. In multivariable analysis including eGFR and albuminuria, a two-fold higher baseline concentration of α1m was associated with higher risk of CVD [hazard ratio (HR) 1.25; 95% confidence interval (CI): 1.10-1.45] and mortality (HR 1.25; 95% CI: 1.10-1.46), whereas β2m had no association with either outcome. A two-fold higher uromodulin concentration was associated with lower CVD risk (HR 0.79; 95% CI: 0.68-0.90) but not mortality (HR 0.86; 95% CI: 0.73-1.01) after adjusting for similar confounders.ConclusionAmong non-diabetic persons with CKD, biomarkers of tubular function are associated with CVD events and mortality independent of glomerular function and albuminuria.

Rationale & objectiveUromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy.Study designCase-cohort study and case-control study.Setting & participantsRandom subcohort (n=933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (≥30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS).PredictorsUMOD level.OutcomesESKD (n=14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n=39) during follow-up (10 years, case-cohort study); kidney function decline of≥30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n=56) and additional cases (n=123). 224 participants from the random subcohort served as controls (case-control study).Analytical approachModified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors.ResultsMean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m2. In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14).LimitationsPossibility of survival bias in the kidney function decline analysis.ConclusionsHigher sUMOD levels may identify elderly persons at reduced risk for ESKD.

Background Our objective was to explore the effect of intensive blood pressure (BP) control on kidney and death outcomes among subgroups of patients with chronic kidney disease divided by baseline proteinuria, glomerular filtration rate, age, and body mass index. Methods and Results We included 840 MDRD (Modification of Diet in Renal Disease) trial and 1067 AASK (African American Study of Kidney Disease and Hypertension) participants. We used Cox models to examine whether the association between intensive BP control and risk of end-stage renal disease (ESRD) or death is modified by baseline proteinuria (≥0.44 versus

BackgroundChronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups.MethodsIndividual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models.ResultsA total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function.ConclusionsLow thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

BackgroundWhether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown.ObjectiveTo compare changes in kidney damage biomarkers between incident CKD case participants and matched control participants as well as between case participants in the intensive (

The Chronic Kidney Disease (CKD) Prognosis Consortium is a collaborative author of the above-mentioned article. The CKD Prognosis Consortium investigators/collaborators are as follows: • African American Study of Kidney Disease and Hypertension (AASK): Brad Astor, Lawrence J. Appel; Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT): Adeera Levin, Mila Tang, Ognjenka Djurdjev; Cleveland Clinic CKD Registry Study (CCF): Sankar D. Navaneethan, Stacey E. Jolly, Jesse D. Schold, Joseph V. Nally Jr.; Chronic Renal Impairment in Birmingham (CRIB): David C. Wheeler, Jonathan Emberson, John Townend, Martin Landray; Chronic Renal Insufficiency Cohort Study (CRIC): Harold I. Feldman, Chi-yuan Hsu, James P. Lash, Lawrence J. Appel; Chronic Renal Insufficiency Standards Implementation Study (CRISIS): Philip A. Kalra, James P. Ritchie, Raman Maharajan, Rachel J. Middleton, Donal J. O'Donoghue; German Chronic Kidney Disease Study (GCKD): Kai-Uwe Eckardt, Markus P. Schneider, Anna Köttgen, Florian Kronenberg, Barbara Bärthlein; Geisinger Health System: Alex R. Chang, Jamie A. Green, H. Lester Kirchner, Kevin Ho; Grampian Laboratory Outcomes, Morbidity and Mortality Studies – 2 (GLOMMS2): Angharad Marks, Corri Black, Gordon J. Prescott, Nick Fluck; Gonryo Study: Masaaki Nakayama, Mariko Miyazaki, Tae Yamamoto, Gen Yamada; Hong Kong CKD Studies: Angela Yee-Moon Wang, Sharon Cheung, Sharon Wong, Jessie Chu, Henry Wu; Ontario Institute for Clinical Evaluative Sciences, Provincial Kidney, Dialysis and Transplantation program (ICES KDT): Amit X. Garg, Eric McArthur, Danielle M. Nash; Maccabi Health System: Varda Shalev, Gabriel Chodick; Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner (MASTERPLAN): Peter J. Blankestijn, Jack F.M. Wetzels, Arjan D. van Zuilen, Jan A. van den Brand; Modification of Diet in Renal Disease Study (MDRD): Andrew S. Levey, Lesley A. Inker, Mark J. Sarnak, Hocine Tighiouart; Nanjing CKD Network Cohort Study (Nanjing CKD): Haitao Zhang; NephroTest Study (NephroTest): Benedicte Stengel, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann; National Renal Healthcare Program – Uruguay (NRHP-URU): Pablo G. Rios, Nelson Mazzuchi, Liliana Gadola, Verónica Lamadrid, Laura Sola; New Zealand Diabetes Cohort Study (NZDCS): John F. Collins, C. Raina Elley, Timothy Kenealy; Parcours de Soins des Personnes Agées (PSPA): Olivier Moranne, Cecile Couchoud, Cecile Vigneau; Primary-Secondary Care Partnership to Prevent Adverse Outcomes in Chronic Kidney Disease (PSP CKD): Nigel J. Brunskill, Rupert W. Major, David Shepherd, James F. Medcalf; Racial and Cardiovascular Risk Anomalies in CKD Cohort (RCAV): Csaba P. Kovesdy, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Keiichi Sumida, Praveen K. Potukuchi; Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL): Hiddo J.L. Heerspink, Dick de Zeeuw, Barry Brenner; Stockholm CREAtinine Measurements Cohort (SCREAM): Juan Jesus Carrero, Alessandro Gasparini, Abdul Rashid Qureshi, Carl-Gustaf Elinder; Second Manifestations of ARTerial Disease Study (SMART): Frank L.J. Visseren, Yolanda van der Graaf; Swedish Renal Registry CKD Cohort (SRR CKD): Marie Evans, Maria Stendahl, Staffan Schön, Mårten Segelmark, Karl-Göran Prütz; Sunnybrook Cohort: David M. Naimark, Navdeep Tangri; West of Scotland CKD Study: Patrick B. Mark, Jamie P. Traynor, Colin C. Geddes, Peter C. Thomson.• CKD Prognosis Consortium Steering Committee: Alex R. Chang, Josef Coresh (Chair), Ron T. Gansevoort, Morgan E. Grams, Anna Köttgen, Andrew S. Levey, Kunihiro Matsushita, Mark Woodward, Luxia Zhang.• CKD Prognosis Consortium Data Coordinating Center: Shoshana H. Ballew (Assistant Project Director), Jingsha Chen (Programmer), Josef Coresh (Principal Investigator), Morgan E. Grams (Director of Nephrology Initiatives), Lucia Kwak (Programmer), Kunihiro Matsushita (Director), Yingying Sang (Lead Programmer), Aditya Surapaneni (Programmer), Mark Woodward (Senior Statistician).• Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Prognosis and Optimal Management of Patients with Advanced CKD: Kai-Uwe Eckardt (Conference Co-Chair), Brenda R. Hemmelgarn (Conference Co-Chair), David C. Wheeler (KDIGO Co-Chair), Wolfgang C. Winkelmayer (KDIGO Co-Chair), John Davis (CEO), Danielle Green (Managing Director), Michael Cheung (Chief Scientific Officer), Tanya Green (Communications Director), Melissa McMahan (Programs Director).

[This corrects the article DOI: 10.1016/j.ekir.2018.01.002.].

Background:Animal studies suggest that acidosis protects against arterial calcification, which contributes to arterial stiffness. The goal of this study was to investigate the associations of serum bicarbonate and pH with arterial stiffness in community-living older adults. Methods:We performed cross-sectional analyses among 1698 well-functioning participants 70-79 years of age. Bicarbonate and pH were measured by arterialized venous blood gas at the point of care. Bicarbonate was categorized into low (7.40-7.42 and >7.42. Arterial stiffness was evaluated by pulse wave velocity (PWV) and high ankle-brachial index (ABI; >1.3/incompressible). We used linear and logistic regression to evaluate the association of bicarbonate and AVpH with PWV and high ABI, respectively. Results:The mean age was 76 years and 15% had an estimated glomerular filtration rate (eGFR)

Rationale & objectivesLower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored.Study designCase-cohort study.Setting & participantsWell-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study.PredictorSerum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry.OutcomesMajor kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up.Analytic approachBaseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression.ResultsDuring 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations.LimitationsObservational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race.ConclusionsLower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function.

Rationale & objectiveNovel urinary biomarkers have enabled earlier detection of kidney tubular damage, but their prognostic value for adverse cardiovascular outcomes is uncertain. We hypothesized that tubular damage, measured by urine α1-microglobulin (A1M), amino-terminal propeptide of type III procollagen (PIIINP), and neutrophil gelatinase-associated lipocalin (NGAL), would be associated with higher risks for cardiovascular events and mortality among elders.Study designCase-cohort study.Setting & participantsThis study included a randomly selected subcohort (n=502), cardiovascular disease (CVD) cases (n=245), and heart failure cases (n=220) from the Health, Aging, and Body Composition (Health ABC) Study.PredictorsBaseline urine A1M, PIIINP, and NGAL concentrations.OutcomesIncident CVD, heart failure, and all-cause mortality.Analytical approachCox proportional hazards models were used to evaluate biomarker associations with each outcome.ResultsAt baseline, mean age was 74 years and estimated glomerular filtration rate was 73mL/min/1.73m2. After adjustment for demographics, estimated glomerular filtration rate, albumin-creatinine ratio, and other cardiovascular risk factors, each doubling in biomarker concentration was associated with the following adjusted HRs for CVD: A1M, 1.51 (95% CI, 1.16-1.96); PIIINP, 1.21 (95% CI, 1.00-1.46); and NGAL, 1.12 (95% CI, 1.05-1.20). There were 248 deaths in the subcohort during a median follow-up of 12.4 years. Adjusted associations of each biomarker (HR per doubling) with all-cause mortality were: A1M, 1.29 (95% CI, 1.10-1.51); PIIINP, 1.05 (95%, 0.94-1.18); and NGAL, 1.07 (95% CI, 1.02-1.12). Biomarker concentrations did not have statistically significant associations with heart failure after multivariable adjustment.LimitationsUrine biomarkers were measured at a single time point; no validation cohort available.ConclusionsKidney tubular damage is an independent risk factor for CVD and death among elders. Future studies should investigate mechanisms by which kidney tubular damage may adversely affect cardiovascular risk.

BackgroundPrevious studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders.MethodsWe performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR 60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10.ResultsMean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13).ConclusionsLower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

25-hydroxyvitamin D [25(OH)D] may not optimally indicate vitamin D receptor activity. Higher concentrations of its catabolic product 24,25-dihydroxyvitmin D [24,25(OH)2D] and a higher ratio of 24,25(OH)2D to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide additional information on receptor activity. We compared the strength of associations of these markers with serum PTH concentrations, hip bone mineral density (BMD), and risk of incident hip fracture in community-living older participants in the Cardiovascular Health Study. Among 890 participants, the mean age was 78years, 60% were women, and the mean 25(OH)D was 28±11ng/ml. In cross-sectional analysis, the strength of association of each vitamin D measure with PTH was similar; a 1% higher 25(OH)D, 24,25(OH)2D, and VMR were associated with 0.32%, 0.25%, and 0.26% lower PTH, respectively (p

BackgroundCognitive impairment is common in kidney transplant (KT) recipients and affects quality of life, graft survival, morbidity, and mortality. Failure to identify patients with cognitive impairment can withhold appropriate and timely intervention. This study determines whether measured cognition with standard screening tools offers any advantage over perceived cognition in screening transplant patients for cognitive impairment.MethodsCognition was assessed in 157 KT recipients using the Montreal Cognitive Assessment (MoCA; measured cognition). In addition, transplant physicians and nurse coordinators were asked to rate transplant recipients' level of cognition after routine clinical interactions (perceived cognition). Physicians and nurses were blind to MoCA scores. Perceived cognition scores were compared to MoCA scores.ResultsPerceived cognition scores fairly correlated with MOCA scores (γ = 0.24, p = 0.001 for physicians and γ = 0.33, p < 0.0001 for nurses). Physician scores moderately correlated with nurses scores (κ = 0.44, p < 0.0001). Clinical perception had a low accuracy for identifying patients with cognitive impairment (sensitivity 66% for physicians, 65% for nurses), and those without cognitive impairment (specificity 67% for physicians, 76% for nurses).ConclusionClinical perception is inaccurate at detecting cognitive impairment in KT recipients. Objective tests should be considered to screen KT recipients for cognitive impairment.