Longitudinal urinary neopterin is associated with hearing threshold change over time in independent older adults.

Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management of older people at risk of poorer outcomes. This longitudinal cohort study has determined baseline inflammation using neopterin volatility in monthly urine samples of 45 independent older adults (aged 65-75 years). Measurement of neopterin, an inflammatory metabolite, enabled stratification of individuals into risk categories based on how often in a 12-month period their neopterin level was raised. Hearing was measured (pure-tone audiometry) at baseline, 1 year and 3 years of the study. Results show that those in the highest risk category (neopterin raised greater than 50% of the time) saw greater deterioration, particularly in high-frequency, hearing. A one-way Welch's ANOVA showed a significant difference between the risk categories for change in high-frequency hearing (W (3, 19.6) = 9.164, p = 0.0005). Despite the study size and duration individuals in the highest risk category were more than twice as likely to have an additional age-related morbidity than those in the lowest risk category. We conclude that volatility of neopterin in urine may enable stratification of those at greatest risk of progression of hearing loss.

Urine caffeine metabolites and hearing threshold shifts in US adults: a cross-sectional study.

Previous studies have reported the relationship between effect of caffeine and many diseases. However, studies to evaluate the association between caffeine and hearing loss are contradictory. To examine the relationship of urinary caffeine metabolites with the hearing threshold in US adults, a total of 849 adults aged 20-69 years who participated in the National Health and Nutrition Examination Survey (NHANES, 2011-2012) were enrolled in this study. Urinary caffeine and its 14 metabolites were applied as biomarkers to assess caffeine exposure. Hearing loss was defined as mean pure tone averages > 25 dB HL at 500, 1000, and 2000 Hz in both ears (low frequency); and 3000, 4000, and 6000 Hz in both ears (high frequency). Univariate and multivariate linear regression analyses were conducted to examine the associations of urinary caffeine metabolites with low- and high-frequency hearing thresholds, respectively. Low-frequency hearing loss were 5.08% and 6.10% in male and female participants, respectively; and high-frequency hearing loss were 31.81% and 15.14% in male and female participants, respectively. In the unadjusted model, the P value for trend shows that urinary caffeine metabolites 137X and AAMU were significantly associated with low-frequency PTA, and that 17X, 137X, AAMU were significantly associated with high-frequency PTA, but when the model was adjusted for sex, age, education level, firearm noise exposure, occupational noise exposure, recreational noise exposure, serum cotinine, body mass index, diabetes, hypertension, these were no longer statistically significant. In conclusion, urinary caffeine metabolites were not associated with the hearing threshold shifts in US adults.

Association between hearing organ and renal function in young adult type 1 diabetic patients: A cross-sectional study.

Type 1 diabetes can lead to impaired function of many organs and tissues. The aim of this study was to evaluate associations between hearing and kidney function in young adult type 1 diabetic patients. 31 patients (9 women) with type 1 diabetes, aged <45, with disease duration <10 years were included. Blood and urine samples for laboratory tests and urinary albumin excretion (UAE) assessment were obtained. eGFR was calculated with CKD-EPI formula. In all patients pure-tone audiometry, transient evoked otoacoustic emissions and auditory brainstem responses were evaluated, also eye fundus was examined. Mean patients' age was 29.5 ± 7.0 years and disease duration 4.6 ± 2.6 years. All patients had eGFR > 60.0 ml/min/1.73 m2. In one case microalbuminuria and in 3 patients early retinopathy were revealed. Linear correlation between eGFR and hearing threshold at 4, 6, 8 and 12 kHz was found. Patients with hearing impairment (n = 7) had lower eGFR 108.8 vs. 121.7 ml/min/1.73 m2, p = 0.047 compared to normal-hearing subjects. Also patients with absence of otoacoustic emissions in at least one ear had lower eGFR, 103.1 vs. 123.3 ml/min/1.73 m2, p < 0.001, compared to the remaining group. In auditory brainstem responses we found significant linear correlation between eGFR and wave III and interval I-III latencies, and between UAE and waves III, V and interval I-III latencies. This study suggests existence of relationship between hearing and kidney function in type 1 diabetic patients. Pathways directly linking hearing and renal function are unknown. Larger studies are necessary to further analyze these relationships.

Glomerular Filtration Rate and Urine Albumin to Creatinine Ratio Associated With Hearing Impairment Among Korean Adults With Diabetes: A Nationwide Population-Based Study.

The objective of this study was to examine the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with hearing impairment among diabetic adults in Korea. The study was based on data from Korea National Health and Nutrition Examination Survey 2011 to 2012. Participants were 1206 diabetic adults, aged over 19 years, who completed audiometric testing supervised by nationally certified clinicians. Hearing impairment was defined in three grades: no hearing impairment (pure-tone average 0-25 dB), slight hearing impairment (26-40 dB), and disabling hearing impairment (>40 dB) in the better ear at frequencies 0.5, 1, 2, 3, 4 and 6 kHz. Using logistic regression, risk of hearing impairment was assessed after having controlled for confounding factors. Higher levels of ACR and lower levels of eGFR correlated with an increase in percentage of disabling hearing impairment both unilaterally and bilaterally (P < 0.001). Controlling for possible confounding covariates, odds ratios for hearing impairment showed tendency to increase in higher ACR groups (P for trend = 0.029). Similar pattern was examined between eGFR and hearing impairment (P for trend = 0.006). Odds ratios were 1.981 (1.146, 3.424) for ACR Q4 and 2.773 (1.286, 5.983) for eGFR < 60 mL/min. Fall in eGFR and rise in ACR correlated with severity of hearing impairment. The association existed independently of age, sex, body mass index (BMI), smoking, drinking, exercise, new onset of diabetes, education, income, mental stress, noise exposure, and metabolic syndrome.

Association between low-grade albuminuria and hearing impairment in a non-diabetic Korean population: The Korea National Health and Nutrition Examination Survey (2011-2013).

INTRODUCTION: The objective of the present study was to examine the association between low-grade albuminuria and hearing impairment in the non-diabetic population. MATERIALS AND METHODS: Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study if they were younger than 19 years old, or had urine albumin/creatinine ratio (UACR) ≥ 30 mg/g or diabetes mellitus. There were 10,608 participants included in this study. The participants were divided into three groups according to their UACR tertiles. RESULTS: There were 1560; 1561; and 1552 male and 1982; 1975; and 1978, female participants in the low, middle, and high tertile groups, respectively. The results indicated the association between low-grade albuminuria and the numbers of metabolic syndrome (MetS) components or Framingham risk score, and the presence of MetS or the proportions of participants at high cardiovascular risk. Univariate and multivariate linear regression analyses demonstrated an association between the UACR and average hearing threshold (AHT) that was observed in both sexes. Multivariate analyses showed that mean AHTs in the low, middle, and high tertile groups were, respectively, 16.127 dB, 17.139 dB, and 18.604 dB for men, and 14.842 dB, 15.100 dB, and 16.353 dB, respectively, for women. Low-frequency, mid-frequency, and high-frequency hearing thresholds according to UACR tertiles showed similar trends. In both sexes, multivariate logistic regression analyses revealed that participants in the low and middle tertile groups had a decreased risk for hearing loss compared to participants in the high tertile group. CONCLUSION: Low-grade albuminuria was associated with hearing impairment in the non-diabetic participants of this study.

Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss.

We report on an autosomal-recessive variant of Ehlers-Danlos syndrome (EDS) characterized by severe muscle hypotonia at birth, progressive scoliosis, joint hypermobility, hyperelastic skin, myopathy, sensorineural hearing impairment, and normal pyridinoline excretion in urine. Clinically, the disorder shares many features with the kyphoscoliotic type of EDS (EDS VIA) and Ullrich congenital muscular dystrophy. Linkage analysis in a large Tyrolean kindred identified a homozygous frameshift mutation in FKBP14 in two affected individuals. Based on the cardinal clinical characteristics of the disorder, four additional individuals originating from different European countries were identified who carried either homozygous or compound heterozygous mutations in FKBP14. FKBP14 belongs to the family of FK506-binding peptidyl-prolyl cis-trans isomerases (PPIases). ER-resident FKBPs have been suggested to act as folding catalysts by accelerating cis-trans isomerization of peptidyl-prolyl bonds and to act occasionally also as chaperones. We demonstrate that FKBP14 is localized in the endoplasmic reticulum (ER) and that deficiency of FKBP14 leads to enlarged ER cisterns in dermal fibroblasts in vivo. Furthermore, indirect immunofluorescence of FKBP14-deficient fibroblasts indicated an altered assembly of the extracellular matrix in vitro. These findings suggest that a disturbance of protein folding in the ER affecting one or more components of the extracellular matrix might cause the generalized connective tissue involvement in this disorder. FKBP14 mutation analysis should be considered in all individuals with apparent kyphoscoliotic type of EDS and normal urinary pyridinoline excretion, in particular in conjunction with sensorineural hearing impairment.

Toluene-induced hearing loss in phenobarbital treated rats.

Exposure to aromatic organic solvents may induce hearing loss in rats, the cochlea being the primary target. The aim of this study which was carried out in rat, was to evaluate the impact of the hepatic metabolism of toluene on its ototoxic potency. To this end, the solvent hepatic metabolism was shifted by treating the rats with 50 mg/kg/d of phenobarbital (PhB), a potent inducer of the microsomal cytochromes P450 system, alcohol and aldehyde dehydrogenases, and glutathione-S-transferases. The two main urinary metabolites of the oxidative and conjugate pathways [hippuric (HA) and benzyl mercapturic acids (BMA) respectively] confirmed the efficacy of the PhB treatment. For the PhB-induced rats, the amount of excreted HA increased by 43% and the amount of BMA by 35%. Auditory function impairments were assessed using auditory-evoked potentials. On completion of the auditory tests, the organs of Corti were dissected to evaluate hair cell losses. The permanent auditory threshold shifts were approximately 15 dB greater in the toluene-exposed rats than in the PhB-induced rats. Both the functional and morphological data confirmed that PhB treatment can decrease the ototoxic potency of toluene.