Renal function is associated with blood neurofilament light chain level in older adults

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Abstract

Neurofilament light chain (NfL) is a novel biomarker of neurodegenerative diseases. It is detectable in the peripheral blood, allowing low-invasive assessment of early signs of neurodegeneration. The level of NfL gradually increases with age; however, what other factors affect it remains unclear. The present study examined the association between blood NfL level and renal function among healthy participants undergoing a health check (n = 43, serum NfL) and patients with diabetes mellitus (n = 188, plasma NfL). All participants were 60 years of age or older; none were diagnosed with dementia. In each group, levels of blood NfL and serum creatinine significantly correlated (coefficient r = 0.50, 0.56). These associations remained statistically significant even after adjustment for age, sex, and body mass index. These findings indicate that blood NfL level might be partially affected by renal function. We recommend measuring renal function for a more precise evaluation of neuroaxonal damage, in particular, among older adults.

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Most cited references 32

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Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses.

Franz Faul, Edgar Erdfelder, Axel Buchner … (2009)

G*Power is a free power analysis program for a variety of statistical tests. We present extensions and improvements of the version introduced by Faul, Erdfelder, Lang, and Buchner (2007) in the domain of correlation and regression analyses. In the new version, we have added procedures to analyze the power of tests based on (1) single-sample tetrachoric correlations, (2) comparisons of dependent correlations, (3) bivariate linear regression, (4) multiple linear regression based on the random predictor model, (5) logistic regression, and (6) Poisson regression. We describe these new features and provide a brief introduction to their scope and handling.

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Revised equations for estimated GFR from serum creatinine in Japan.

Seiichi Matsuo, Enyu Imai, Masaru Horio … (2009)

Estimation of glomerular filtration rate (GFR) is limited by differences in creatinine generation among ethnicities. Our previously reported GFR-estimating equations for Japanese had limitations because all participants had a GFR less than 90 mL/min/1.73 m2 and serum creatinine was assayed in different laboratories. Diagnostic test study using a prospective cross-sectional design. New equations were developed in 413 participants and validated in 350 participants. All samples were assayed in a central laboratory. Hospitalized Japanese patients in 80 medical centers. Patients had not participated in the previous study. Measured GFR (mGFR) computed from inulin clearance. Estimated GFR (eGFR) by using the modified isotope dilution mass spectrometry (IDMS)-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation using the previous Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSN-CKDI) coefficient of 0.741 (equation 1), the previous JSN-CKDI equation (equation 2), and new equations derived in the development data set: modified MDRD Study using a new Japanese coefficient (equation 3), and a 3-variable Japanese equation (equation 4). Performance of equations was assessed by means of bias (eGFR - mGFR), accuracy (percentage of estimates within 15% or 30% of mGFR), root mean squared error, and correlation coefficient. In the development data set, the new Japanese coefficient was 0.808 (95% confidence interval, 0.728 to 0.829) for the IDMS-MDRD Study equation (equation 3), and the 3-variable Japanese equation (equation 4) was eGFR (mL/min/1.73 m2) = 194 x Serum creatinine(-1.094) x Age(-0.287) x 0.739 (if female). In the validation data set, bias was -1.3 +/- 19.4 versus -5.9 +/- 19.0 mL/min/1.73 m2 (P = 0.002), and accuracy within 30% of mGFR was 73% versus 72% (P = 0.6) for equation 3 versus equation 1 and -2.1 +/- 19.0 versus -7.9 +/- 18.7 mL/min/1.73 m(2) (P < 0.001) and 75% versus 73% (P = 0.06) for equation 4 versus equation 2 (P = 0.06), respectively. Most study participants had chronic kidney disease, and some may have had changing GFRs. The new Japanese coefficient for the modified IDMS-MDRD Study equation and the new Japanese equation are more accurate for the Japanese population than the previously reported equations.

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Chronic Kidney Disease.

Angela Webster, Evi V Nagler, Rachael Morton … (2017)

The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m(2), or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries.

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Author and article information

Contributors

Takashi Kudo: kudo@psy.med.osaka-u.ac.jp

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 23 November 2020

Publication date PMC-release: 23 November 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 20350

Affiliations

[1 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Mental Health Promotion, , Osaka University Graduate School of Medicine, ; Suita, Osaka Japan

[2 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Health and Counseling Center, , Osaka University, ; Toyonaka, Osaka Japan

[3 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Psychological Health Promotion, , Osaka University Graduate School of Medicine, ; Suita, Osaka Japan

[4 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Psychiatry, , Osaka University Graduate School of Medicine, ; Suita, Osaka Japan

[5 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Metabolic Medicine, , Osaka University Graduate School of Medicine, ; Suita, Osaka Japan

[6 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Diabetes Care Medicine, , Osaka University Graduate School of Medicine, ; Suita, Osaka Japan

[7 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Metabolism and Atherosclerosis, , Osaka University Graduate School of Medicine, ; Suita, Osaka Japan

[8 ]GRID grid.417245.1, ISNI 0000 0004 1774 8664, Department of Internal Medicine, , Toyonaka Municipal Hospital, ; Osaka, Japan

Article

Publisher ID: 76990

DOI: 10.1038/s41598-020-76990-7

PMC ID: 7683708

PubMed ID: 33230211

SO-VID: f0756825-edbe-4adb-9782-50df5b6d997f

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 6 April 2020

Date accepted : 4 November 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;

Award ID: 19K23943

Award ID: JP17H05091

Award Recipient : Shoshin Akamine

Funded by: FundRef http://dx.doi.org/10.13039/100009619, Japan Agency for Medical Research and Development;

Award ID: JP18ek0109316

Award ID: JP19dk0207039

Award ID: JP19dk0207042

Award Recipient : Manabu Ikeda Takashi Kudo

Funded by: FundRef http://dx.doi.org/10.13039/501100008667, SENSHIN Medical Research Foundation;

Funded by: FundRef http://dx.doi.org/10.13039/100007449">Takeda Science Foundation, Takeda Science Foundation;

Funded by: FundRef http://dx.doi.org/10.13039/501100005865, Mochida Memorial Foundation for Medical and Pharmaceutical Research;

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ScienceOpen disciplines: Uncategorized

Keywords: neurodegenerative diseases,kidney diseases,type 2 diabetes,biomarkers,neurology

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ScienceOpen disciplines: Uncategorized

Keywords: neurodegenerative diseases, kidney diseases, type 2 diabetes, biomarkers, neurology

Renal function is associated with blood neurofilament light chain level in older adults

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Abstract

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Karger: Nephrology

Most cited references 32

Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses.

Revised equations for estimated GFR from serum creatinine in Japan.

Chronic Kidney Disease.

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