Elevated plasma free sialic acid levels in individuals with reduced glomerular filtration rates.
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ABSTRACT:
SUBMITTER: Fuentes F
PROVIDER: S-EPMC8104432 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The contribution of T cells and graft-reactive antibodies to acute allograft rejection is widely accepted, but the role of graft-infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T-cell-mediated (N = 21), antibody-mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African-American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis. Immunohistochemical analysis revealed CD3(+) T cells as the dominant cell type, followed by CD20(+) B cells and CD138(+) plasma cells in all acute rejection types. Using univariate Cox Proportional Hazard analysis, plasma cell density significantly predicted graft failure while B-cell density trended toward significance. Surprisingly T-cell density did not predict graft failure. The estimated glomerular filtration rate (eGFR) at diagnosis of acute rejection also predicted graft failure, while baseline eGFR ?6 months prior to biopsy did not. Using multivariate analysis, a model including eGFR at biopsy and plasma cell density was most predictive of graft loss. These observations suggest that plasma cells may be a critical mediator and/or an independently sensitive marker of steroid-resistant acute rejection.
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Project description:BACKGROUND AND OBJECTIVES:Metabolomics is instrumental in identifying novel biomarkers of kidney function to aid in the prevention and management of CKD. However, data linking the metabolome to incident eGFR are sparse, particularly in Asian populations with different genetic backgrounds and environmental exposures. Therefore, we aimed to investigate the associations of amino acid and acylcarnitine profiles with change in eGFR in a Chinese cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:This study included 1765 community-living Chinese adults aged 50-70 years with baseline eGFR?60 ml/min per 1.73 m2. At baseline, 22 amino acids and 34 acylcarnitines in plasma were quantified by gas or liquid chromatography coupled with mass spectrometry. Annual rate of change in eGFR was calculated, and incident eGFR decline was defined as eGFR<60 ml/min per 1.73 m2 by the end of 6 years of follow-up. RESULTS:The mean (SD) unadjusted annual change in eGFR was 2.2±2.0 ml/min per 1.73 m2 and the incidence of reduced eGFR was 16%. After Bonferroni correction, 13 of 56 metabolites were significantly associated with annual eGFR change. After multivariable adjustment of baseline covariates, including baseline eGFR, seven of the 13 metabolites, including cysteine, long-chain acylcarnitines (C14:1OH, C18, C18:2, and C20:4), and other acylcarnitines (C3DC and C10), were significantly associated with incident reduced eGFR (relative risks ranged from 1.16 to 1.25 per SD increment of metabolites; P<3.8E-03 after Bonferroni correction of multiple testing of the 13 metabolites). Moreover, principal component analysis identified two factors, consisting of cysteine and long-chain acylcarnitines, respectively, that were associated with incident reduced eGFR. CONCLUSIONS:Elevated plasma levels of cysteine and a panel of acylcarnitines were associated with a higher incidence of reduced eGFR in Chinese adults, independent of baseline eGFR and other conventional risk factors.
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Project description:BackgroundFor the developing kidney, the prenatal period may represent a critical window of vulnerability to environmental insults resulting in permanent nephron loss. Given that the majority of nephron formation is complete in the 3rd trimester, we set out to test whether 1) prenatal lead exposure is associated with decreased preadolescent kidney function and 2) whether preadolescent obesity acts synergistically with early life lead exposure to reduce kidney function.MethodsOur study included 453 mother-child pairs participating in the PROGRESS birth cohort. We assessed prenatal blood lead levels (BLLs) in samples collected in the 2nd and 3rd trimesters and at delivery, as well as tibial and patellar bone lead measures assessed one-month postpartum. Preadolescent estimated glomerular filtration rate (eGFR) was derived from serum levels of creatinine and/or cystatin C measured at age 8-12 years. We applied linear regression to assess the relationship between prenatal bone and BLL with preadolescent eGFR, and adjusted for covariates including age, sex, BMI z-score, indoor tobacco smoke exposure, and socioeconomic status. We also examined sex-specific associations and tested for effect modification by BMI status.ResultsWe observed null associations between prenatal lead exposure and eGFR. However, in interaction analyses we found that among overweight children, there was an inverse association between BLL (assessed at 2nd and 3rd trimester and at delivery) and preadolescent eGFR. For example, among overweight participants, a one ln-unit increase in 2nd trimester BLL was associated with a 10.5 unit decrease in cystatin C-based eGFR (95% CI: -18.1, -2.8; p = 0.008). Regardless of lead exposure, we also observed null relationships between BMI z-score and eGFR overall, as well as among overweight participants. However, among participants with preadolescent obesity, we observed a significant 5.9-unit decrease in eGFR. We observed no evidence of sex-specific effects.ConclusionsOur findings, if confirmed in other studies, suggest a complex interplay between the combined adverse effects of adiposity and perinatal lead exposure as they relate to adolescent kidney function. Future studies will assess kidney function and adiposity trajectories through adolescence to better understand environmental risk factors for kidney function decline.
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Project description:The potential association between altered levels of plasma free amino acids (PFAAs) and uric acid (UA) with estimated glomerular filtration rate (eGFR) remains unknown among patients with hypertension. A total of 2804 healthy controls and 2455 hypertensive patients were included in the current analysis. eGFR was defined as reduced when it was <60 ml/min/1.73 m2. The associations between reduced eGFR and individual PFAAs and UA in the healthy control and hypertension groups were explored by logistic regression analyses adjusted for potential confounding variables. Results show that UA had a significant positive association with reduced eGFR in both healthy control and hypertension groups (P < 0.001). Among the PFAAs, citrulline, glycine and phenylalanine showed significant positive associations with reduced eGFR in both healthy control (P < 0.01 to 0.001) and hypertension (P < 0.001) groups. Moreover, alanine, asparagine and methionine achieved significant positive associations with reduced eGFR only in the hypertension group (P < 0.01 to 0.001). Conversely, serine showed significant inverse associations with reduced eGFR in the hypertension group only (P < 0.001). Our findings provide first evidence for a strong relationship between distinct patterns of PFAAs and elevated UA with reduced eGFR in hypertension. The findings may appear useful in developing effective strategies for the prevention or early detection and treatment of declined kidney function in hypertension.
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Project description:BackgroundWe aimed to investigate the interaction between serum uric acid (SUA) levels with estimated glomerular filtration rate (eGFR) to low muscle strength (LMS) among older people in China.MethodsCohort data were obtained from China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2015. A total of 2,822 community-dwelling adults aged 60 and above were enrolled for the follow-up. Serum uric acid was collected after 8 h of fasting, and handgrip strength was measured with a dynamometer. eGFR was calculated with an equation based on the Chinese population. A generalized additive model was employed for interaction analysis and progressively adjusted confounders.ResultsDuring the follow-up, a total of 659 individuals were excluded due to the lack of grip strength data, leaving 2,163 participants for analysis. Despite the protective effect of high uric acid against low muscle strength, especially in older females, it is not statistically significant (OR = 0.69, 95%CI = 0.45-1.04, P = 0.075). Following the progressive adjustment of covariates, the association between higher eGFR and elevated SUA levels remained statistically significant in females, showing a reduced odds ratio with low muscle strength (OR = 0.82, 95%CI = 0.70-0.97, P = 0.021). However, this trend was not observed in male participants.ConclusionsThis Chinese population-based cohort study suggests that among older females, a higher serum uric acid level combined with a higher estimated glomerular filtration rate is linked to a reduced risk of low muscle strength. This implies that the relationship between high serum uric acid levels and the risk of low grip strength might differ by gender.
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Project description:Circulating metabolites are by-products of endogenous metabolism or exogenous sources and may inform disease states. Our study aimed to identify the source of variability in the association of metabolites with estimated glomerular filtration rate (eGFR) in Hispanics/Latinos with low chronic kidney disease prevalence by testing the association of 640 metabolites in 3,906 participants of the Hispanic Community Health Study/Study of Latinos. Metabolites were quantified in fasting serum through non-targeted mass spectrometry analysis. eGFR was regressed on inverse normally transformed metabolites in models accounting for study design and covariates. To identify the source of variation on eGFR associations, we tested the interaction of metabolites with lifestyle and clinical risk factors, and results were integrated with genotypes to identify metabolite genetic regulation. The mean age was 46 years, 43% were men, 22% were current smokers, 47% had a Caribbean Hispanic background, 19% had diabetes and the mean cohort eGFR was 96.4 ml/min/1.73 m2. We identified 404 eGFR-metabolite associations (False Discovery Rate under 0.05). Of these, 69 were previously reported, and 79 were novel associations with eGFR replicated in one or more published studies. There were significant interactions with lifestyle and clinical risk factors, with larger differences in eGFR-metabolite associations within strata of age, urine albumin to creatinine ratio, diabetes and Hispanic/Latino background. Several newly identified metabolites were genetically regulated, and variants were located at genomic regions previously associated with eGFR. Thus, our results suggest complex mechanisms contribute to the association of eGFR with metabolites and provide new insights into these associations.
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Project description: Not available
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