Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose.

PURPOSE: To compare the effects of osmolality versus viscosity of radio-contrast media on intra-renal oxygenation as determined by blood oxygenation level-dependent (BOLD) MRI in a model of contrast induced nephropathy (CIN). MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided into five groups. Nitric oxide synthase inhibitor L-NAME (10 mg/kg), cyclooxygenase inhibitor indomethacin (10 mg/kg), or saline, and radio-contrast iodixanol (high viscosity, 784 or 1600 mg I/kg) or iothalamate (high osmolality, 1600 mg I/kg) were administered. BOLD MRI images were acquired on Siemens 3 Tesla (T) scanner using a multiple gradient recalled echo sequence at baseline, following L-NAME (or saline), indomethacin (or saline), and radio-contrast agents. R2* (=1/T2*) was used as the BOLD MRI parameter in renal medulla and cortex. Mixed-effects models with first order auto-regressive variance-covariance models were used to analyze the data. RESULTS: The magnitude of change in medullary R2* (MR2*) with same dose of iodine was larger with iodixanol compared with iothalalmate both in pretreated groups (303% versus 225.6%, < 0.01) and the control group (191.6% versus -1.8%, P < 0.01). The MR2* change in high dose iodixanol was approximately twice compared with the low dose (303% versus 133%, P < 0.01). CONCLUSION: The viscosity of radio-contrast seems to play a more significant role than osmolality in terms of renal oxygenation changes as evaluated by BOLD MRI. Additionally, iodixanol induced a dose-dependent increase in renal medullary hypoxia.

[Comprehensive therapeutic protocol of electroacupuncture combined with Chinese herbs and rehabilitation training for treatment of cerebral infarction: a multi-center randomized controlled trial].

OBJECTIVE: To evaluate the therapeutic effect of comprehensive therapeutic protocol of electroacupuncture combined with active-blood-and-dissolve-stasis herbs and rehabilitation training for cerebral infarction. METHODS: A multi-center randomized controlled trial was done, three hundred and twenty cases were divided into four groups: electroacupuncture combined with active-blood and dissolve-stasis herbs and rehabilitation training group (group A), electroacupuncture combined with rehabilitation training group (group B), herbs combined with rehabilitation training group (group C) and rehabilitation training group (group D), 80 cases in each group. The following two groups of acupoints were used alternatively in electroacupuncture treatment: the first group including Vasomotor Area, Jianyu (LI 15), Biguan (ST 31), Hegu (LI 4) and Taichong (LR 3); the second group including Motor Area, Quchi (LI 11), Yanglingquan (GB 34) and Shenshu (BL 23). 20 mL Xiangdan injection and 250 mL 5% glucose injection or 250 mL 0.9% sodium chloride injection were used by intravenous drip in herbs treatment once a day. The rehabilitation training was performed by the professional physical therapist. Each group was treated with corresponding treatment protocol. The therapeutic effect was evaluated by index of the mortality or disability rate 3 months after the onset of disease. The intention to treat analysis (ITT) was used in data. RESULTS: The mortality or handicap rate 3 months after the onset of disease of four groups were 17.5% (14/80) in group A, 22.5% (18/80) in group B, 40. 0% (32/80) in group C, and 31.3% (25/80) in group D, respectively. The group A has a best therapeutic effect (vs group C, group D, both P<0.05), and there was no adverse event. CONCLUSION: The combined application of electroacupuncture, active-blood and dissolve-stasis herbs and rehabilitation training is a better treatment for cerebral infarction in clinic.