Analysis of a Urinary Biomarker Panel for Incident Kidney Disease and Clinical Outcomes

O’Seaghdha, Conall M.; Hwang, Shih‐Jen; Larson, Martin G.; Meigs, James B.; Vasan, Ramachandran S.; Fox, Caroline S.

doi:10.1681/asn.2013010019

Cited by 66 publications

(45 citation statements)

References 50 publications

(46 reference statements)

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“…Moreover, we recently reported that higher urinary KIM-1 is associated with an increased risk for incident heart failure hospitalizations in the community-based ULSAM cohort (19). Our findings of an association between urinary KIM-1 and total mortality is in accordance with two recent community-based studies (27,28); however, in one of these, no association between KIM-1 and cardiovascular mortality was found (28). Perhaps differences in the protocol for urine collection (spot sample versus 24-hour collection), or differences in age and gender distribution of the study samples may explain the discrepancy between the previous study and the present study.…”

Section: Comparison With the Literaturesupporting

confidence: 91%

Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men

Carlsson

Larsson

Helmersson‐Karlqvist

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality. Results During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, $175 ng/mmol), low eGFR (#60 ml/min per 1.73 m 2 ), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio$3 g/mol) had a .8-fold increased risk compared with participants with low KIM-1/creatinine (,175 ng/mmol), normal eGFR (.60 ml/min per 1.73 m 2 ), and normoalbuminuria (albumin/creatinine ratio,3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P,0.001).Conclusions These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

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Section: Comparison With the Literaturesupporting

confidence: 91%

Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men

Carlsson

Larsson

Helmersson‐Karlqvist

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…The relationship between urinary uromodulin excretion and glomerular filtration has long been debated, with some studies showing positive associations (11,12) and others not (33). Our data demonstrate a linear, positive association between uromodulin and eGFR, but only when eGFR is ,90 ml/min per 1.73 m 2 .…”

Section: Discussionsupporting

confidence: 41%

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population

Pruijm¹,

Ponte²,

Ackermann³

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study.Design, setting, participants, & measurements Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age6SD, 45617 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53611 years) with fresh spot morning urine samples. We calculated eGFRs using the CKDEpidemiology Collaboration formula and by 24-hour creatinine clearance.Results In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR,90 ml/min per 1.73 m 2 .Conclusion Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

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“…Wu et al (32) additionally showed that individuals with drug-induced interstitial nephritis had higher levels of urine a1m compared with age-and sex-matched controls and that urine a1m levels correlated with the degree of inflammatory infiltration, interstitial edema, and tubular atrophy on kidney biopsy. Finally, O'Seaghdha et al (33) investigated the associations of multiple urinary biomarkers, including a1m, with incident kidney disease and related outcomes in 2948 Framingham Heart Study participants. Although urine a1m was not associated with incident CKD or albuminuria, each 1 SD of log-transformed a1m was associated with a 30% higher risk for all-cause mortality (33).…”

Section: Discussionmentioning

confidence: 99%

Association of Urine α1-Microglobulin with Kidney Function Decline and Mortality in HIV-Infected Women

Jotwani

Scherzer

Abraham

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Despite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of a1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women.Design, setting, participants, & measurements In the Women's Interagency HIV Study, urine a1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was ,1%. Participants were categorized into three categories by level of a1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated.Results Urine a1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P,0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest a1-microglobulin category, HIV-infected women in the highest a1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest a1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest a1-microglobulin category.Conclusions Proximal tubular dysfunction, indicated by urine a1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women.

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Analysis of a Urinary Biomarker Panel for Incident Kidney Disease and Clinical Outcomes

Cited by 66 publications

References 50 publications

Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men

Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population

Association of Urine α1-Microglobulin with Kidney Function Decline and Mortality in HIV-Infected Women

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