Risk of CKD Following Detection of Microscopic Hematuria: A Retrospective Cohort Study

Um, Yoo Jin; Chang, Yoosoo; Kim, Yejin; Kwon, Min‐Jung; Jung, Hyun Suk; Lee, Kyu‐Beck; Joo, Kwan Joong; Cho, In Young; Byrne, Christopher D.; Ryu, Seungho

doi:10.1053/j.ajkd.2022.09.012

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…However, there has been less focus on this trait compared to albuminuria and eGFR. Nonetheless, reports show that hematuria is associated with a higher risk of kidney failure in the Israeli, Korean populations and CRIC cohort 1 – 3 .…”

Section: Introductionmentioning

confidence: 98%

GWAS for the composite traits of hematuria and albuminuria

Gagliano Taliun,

Dinsmore,

Mirshahi

et al. 2023

Sci Rep

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Our GWAS of hematuria in the UK Biobank identified 6 loci, some of which overlap with loci for albuminuria suggesting pleiotropy. Since clinical syndromes are often defined by combinations of traits, generating a combined phenotype can improve power to detect loci influencing multiple characteristics. Thus the composite trait of hematuria and albuminuria was chosen to enrich for glomerular pathologies. Cases had both hematuria defined by ICD codes and albuminuria defined as uACR > 3 mg/mmol. Controls had neither an ICD code for hematuria nor an uACR > 3 mg/mmol. 2429 cases and 343,509 controls from the UK Biobank were included. eGFR was lower in cases compared to controls, with the exception of the comparison in females using CKD-EPI after age adjustment. Variants at 4 loci met genome-wide significance with the following nearest genes: COL4A4, TRIM27, ETV1 and CUBN. TRIM27 is part of the extended MHC locus. All loci with the exception of ETV1 were replicated in the Geisinger MyCode cohort. The previous GWAS of hematuria reported COL4A3-COL4A4 variants and HLA-B*0801 within MHC, which is in linkage disequilibrium with the TRIM27 variant (D′ = 0.59). TRIM27 is highly expressed in the tubules. Additional loci included a coding sequence variant in CUBN (p.Ala2914Val, MAF = 0.014 (A), p = 3.29E−8, OR = 2.09, 95% CI = 1.61–2.72). Overall, GWAS for the composite trait of hematuria and albuminuria identified 4 loci, 2 of which were not previously identified in a GWAS of hematuria.

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Section: Introductionmentioning

confidence: 98%

GWAS for the composite traits of hematuria and albuminuria

Gagliano Taliun,

Dinsmore,

Mirshahi

et al. 2023

Sci Rep

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“…We used the definition of incident CKD that incorporated eGFR ≤60 ml/min per 1.73 m 2 or UACR ≥30 mg/g and that was previously used by others. 7 , 51 – 54 Most of the cases met the incident CKD definition based on UACR, a metric that can experience significant day-to-day variability. 55 However, higher level of albuminuria is an established predictor of declining kidney function, 17 , 56 independently associated with progression to kidney failure and mortality, 57 and even mild albuminuria is established as a predictor of faster eGFR decline.…”

Section: Discussionmentioning

confidence: 99%

Associations of FGF23 with 10-Year Change in eGFR and UACR and with Incident CKD in the CARDIA Cohort

et al. 2023

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Background: The relationship of fibroblast growth factor 23 (FGF23) with incident chronic kidney disease (CKD) has been examined in older but not younger populations. Methods: Linear regression models were used to examine the associations of c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) with 10-year change (1995-96 to 2005-06) in estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Cox proportional hazards models were used to assess the association of cFGF23 with incident CKD, defined as eGFR < 60 ml/min/1.73 m2 or UACR ≥ 30 mg/g. Multivariable models adjusted for age, sex, race, education, field center, physical activity, body mass index, diabetes, smoking, and systolic blood pressure. Results: Among 2511 participants, the mean age was 45 ± 3.6 years, mean eGFR was 96.5 ± 14.0 ml/min/1.73 m2, median UACR was 4.3 (IQR, 3.0 – 6.7) mg/g. Most (62.6%) participants were non-smokers, the prevalence of diabetes was low (6.6%), and median values for 10-year changes in eGFR and UACR were modest (-5.50 ml/min/1.73 m2 and 0.70 mg/g, respectively). No consistent associations between cFGF23 and 10-year change in eGFR and UACR were observed. During a median follow up of 9.98 years, incident CKD developed in 258 participants. There was a non-linear association of cFGF23 with incident CKD, and relative to lowest quartile of cFGF23, significant relationship detected only among participants in the highest quartile (hazard ratio 1.58, 95% confidence interval [1.09, 2.27]). Similar findings were observed for iFGF23. Conclusion: Among middle-aged adults in the CARDIA cohort, median eGFR and UACR changes were modest and cFGF23 and iFGF23 were not consistently associated with 10-year change in eGFR or UACR. A non-linear relationship was observed between cFGF23 and incident CKD, with individuals with highest cFGF23 levels being at risk for developing CKD.

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