scholarly journals Serum Myo-Inositol, Dimethyl Sulfone, and Valine in Combination with Creatinine Allow Accurate Assessment of Renal Insufficiency—A Proof of Concept

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 234
Author(s):  
Jochen Ehrich ◽  
Laurence Dubourg ◽  
Sverker Hansson ◽  
Lars Pape ◽  
Tobias Steinle ◽  
...  

Evaluation of renal dysfunction includes estimation of glomerular filtration rate (eGFR) as the initial step and subsequent laboratory testing. We hypothesized that combined analysis of serum creatinine, myo-inositol, dimethyl sulfone, and valine would allow both assessment of renal dysfunction and precise GFR estimation. Bio-banked sera were analyzed using nuclear magnetic resonance spectroscopy (NMR). The metabolites were combined into a metabolite constellation (GFRNMR) using n = 95 training samples and tested in n = 189 independent samples. Tracer-measured GFR (mGFR) served as a reference. GFRNMR was compared to eGFR based on serum creatinine (eGFRCrea and eGFREKFC), cystatin C (eGFRCys-C), and their combination (eGFRCrea-Cys-C) when available. The renal biomarkers provided insights into individual renal and metabolic dysfunction profiles in selected mGFR-matched patients with otherwise homogenous clinical etiology. GFRNMR correlated better with mGFR (Pearson correlation coefficient r = 0.84 vs. 0.79 and 0.80). Overall percentages of eGFR values within 30% of mGFR for GFRNMR matched or exceeded those for eGFRCrea and eGFREKFC (81% vs. 64% and 74%), eGFRCys-C (81% vs. 72%), and eGFRCrea-Cys-C (81% vs. 81%). GFRNMR was independent of patients’ age and sex. The metabolite-based NMR approach combined metabolic characterization of renal dysfunction with precise GFR estimation in pediatric and adult patients in a single analytical step.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.S Wolter ◽  
J Reifart ◽  
M Renker ◽  
S.D Kriechbaum ◽  
U Fischer-Rasokat ◽  
...  

Abstract Background Acute kidney injury (AKI) is one of the most prevalent (10–30%) complications after transcatheter aortic valve implantation (TAVI). Furthermore, AKI is accompanied by increased mortality, a higher incidence of dialysis and blood transfusion, and a prolonged hospital stay. Although measurement of serum creatinine is the gold standard in diagnosing AKI, changes in serum creatinine may lag behind compromised renal function. Arginine vasopressin (AVP), or antidiuretic hormone, is a nine-amino acid peptide member of the hypothalamo-neurohypophysial axis. Copeptin is the C-terminal moiety of the AVP precursor pre-proAVP that is secreted into the circulation. Recently, copeptin has been suggested to play a role in chronic kidney injury. We evaluated the value of copeptin in the prediction of AKI in patients undergoing TAVI. Methods All patients with severe aortic valve stenosis undergoing TAVI between May 2011 and May 2016 were included in our study. AKI was defined by the VARC-2 definition. Patients with no AKI and stage 1 AKI were compared with patients with stage 2 or 3 AKI. Routine laboratory parameters, including creatinine, were measured immediately after blood draw. Additionally, venous blood samples were collected on admission and after 24, 48, and 72 hours, processed immediately, and stored at −80°C until assay. The copeptin concentration in serum was measured by a sandwich immunoluminometric assay. Results Copeptin levels were available in 642 patients who were treated by TAVI in our centre from 2012–2016. AKI was detected in 113 patients (17.6%), including 61 patients with stage 1 (9.5%), 29 with stage 2 (4.5%), and 23 with stage 3 (3.6%). There were no differences among these patients in baseline measurements, but serum copeptin increased in all patients with AKI 24 h post-procedure according to the AKI stage: no AKI 34.5 (18.0–59.3 pmol/L), AKI stage 1: 68.7 (34.6–130.1 pmol/L); AKI stage 2: 96.0 (48.1–185.1 pmol/L); AKI stage 3: 154.9 (79.5–280.7 pmol/L); ANOVA p<0.001 (Fig. 1). Copeptin showed an earlier and sharper increase than creatinine (Fig. 1), with a negative predictive value of 0.97 to rule out AKI after 24 h. Conclusion AKI subsequent to TAVI is a common and harmful complication that occurred in almost every 5th patient (17.6%) in our cohort. AVP is secreted in response to hypotension, which commonly occurs during TAVI. In our cohort of TAVI patients, those who developed AKI after TAVI showed a rapid increase in copeptin that was earlier than that of creatinine. In light of these observations, copeptin could be a new parameter for detecting early renal dysfunction. Figure 1 Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1392.2-1392
Author(s):  
M. De Oliveira ◽  
P. V. Alabarse ◽  
M. Farinon ◽  
R. Cavalheiro Do Espírito Santo ◽  
R. Xavier

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality and associated with metabolic disorders. Since the metabolomic profile is known to vary in response to different inflammatory conditions, metabolome analysis could substantially improve diagnosis and prognosis of RA.Objectives:To analyze the urine metabolome profile in RA patients and correlate it with disease activity changes over 12 monthsMethods:Seventy-nine RA patients, according to ACR/EULAR 2010 classification criteria, between 40 and 70 years old, were recruited and followed for 12 months. Metabolome analysis was performed by Nuclear Magnetic Resonance spectroscopy (NMR), resulting in the identification of 93 metabolites in urine collected at the baseline and after 12 months. Frequency analysis, Pearson Correlation and Multivariate data analysis with orthogonal projections to latent structures (OPLS) method were performed and a statistical significance was considered as p<0.05.Results:The study population was characterized by the majority of women (86.7%), mean age of 56 years old, around 80% with positive anti-CCP or Rheumatoid Factor. During the one year of follow-up, there was no substantial variation in the DAS28 measurement (baseline: 3.8, after 12 months: 4.0). There was no significant correlation between the metabolome pattern and DAS28 score (p>0.05) over time. However, multivariate analysis (OPLS-DA) demonstrated an adequate differentiation of the population with 0.92 of accuracy (Q2: 0.72 and R2: 0.89).There was a significant increase of L-cysteine, choline, L-Phenylalanin, creatine, L-histidine, oxalacetic acid and xanthine, and a decrease of L-threonine, taurine, butyric and gluconic acid (p<0.05) during the follow-up, metabolites that are involved in the skeletal muscle metabolism.Conclusion:The observed biomarkers indicate,as expected, that the RA metabolic profile is associated with inflammation injury and skeletal muscle amino acid metabolism. Correlations with disease activity changes was compromised by the stable disease status during the 12 months. More studies evaluating correlations with skeletal muscle function and mass are underway.Acknowledgments:Disclosure of interest: Marianne Oliveira: None declared, Rafaela Santo: None declared, Mirian Farinon: None declared, Ricardo Xavier Consultant of: Abbvie, Pfizer, Novartis, Janssen, Lilly, RocheDisclosure of Interests:Marianne de Oliveira: None declared, Paulo Vinicius Alabarse: None declared, Mirian Farinon: None declared, Rafaela Cavalheiro do Espírito Santo: None declared, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche


2021 ◽  
Vol 05 (01) ◽  
pp. 007-011
Author(s):  
Shaheen Afsal ◽  
K. Sujani ◽  
Shashank Viswanathan ◽  
Akshay Bhati ◽  
Harish BR ◽  
...  

AbstractCardiovascular disease (CVD) is a major cause for a significant proportion of all deaths and disability worldwide. Postoperative renal dysfunction following cardiac surgery is not an uncommon complication of cardiac surgery, which has serious implications with regard to morbidity, mortality, financial expenditure, and resource utilization. This study was performed to compare outcomes of patients with preoperative renal dysfunction with those having normal renal function undergoing off-pump coronary artery bypass grafting (OPCABG). Patients were divided into two categories, depending on their preoperative serum creatinine and glomerular filtration rate (GFR). The preoperative renal dysfunction was defined as serum creatinine >1.3 mg/dL and/or estimated GFR (eGFR) of <60 mL/min/1.73 m2. The category A patients had normal renal function defined as serum creatinine ≤1.3 mg/dL and/or eGFR of ≥60 mL/min/1.73 m2 while the category B patients had preoperative renal dysfunction that did not necessitate renal dialysis. Blood samples were collected from both category patients for serum creatinine prior to surgery, following surgery, on postoperative days 1, 2, 3, 4, 5, and on the day of discharge. The occurrence of acute kidney injury (AKI) was defined as an increase in the serum creatinine levels of ≥0.3 mg/dL within 48 hours or an increase of ≥1.5 above baseline known or presumed to have occurred within the previous 7 days based on Kidney Disease Improving Global Outcomes criteria. This study demonstrated that there was worsening of renal function in 7.4% of patients with normal renal function and 10.74% of patients with renal dysfunction that was not statistically different. Based on the results, we conclude that preoperative renal dysfunction may be a contributing predictor of AKI following OPCABG, and we recommend that the patients with more severe renal dysfunction with eGFR of 45–60 mL/min should be studied to demonstrate this hypothesis.


2017 ◽  
Vol 3 (3) ◽  
pp. e160 ◽  
Author(s):  
Sailaja Golla ◽  
Jimin Ren ◽  
Craig R. Malloy ◽  
Juan M. Pascual

Objective:There is a paucity of objective, quantifiable indicators of mitochondrial disease available for clinical and scientific investigation.Methods:To this end, we explore intramyocellular lipid (IMCL) accumulation noninvasively by 7T magnetic resonance spectroscopy (MRS) as a reporter of metabolic dysfunction in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). We reasoned that mitochondrial dysfunction may impair muscle fat metabolism, resulting in lipid deposition (as is sometimes observed in biopsies), and that MRS is well suited to quantify these lipids.Results:In 10 MELAS participants and relatives, IMCL abundance correlates with percent mitochondrial DNA mutation abundance and with disease severity.Conclusions:These results indicate that IMCL accumulation is a novel potential disease hallmark in MELAS.


2016 ◽  
Vol 41 (3) ◽  
pp. 125-130
Author(s):  
Mahbuba Shirin ◽  
Mofazzal Sharif ◽  
Ayeshna Gurung ◽  
Anindita Datta

Diabetes mellitus is one of the systemic diseases affecting the kidneys. Diabetic nephropathy is a serious microvascular complication of diabetes mellitus. It is the most important cause of death in type I diabetic patients, of whom 30%-40% eventually develop end-stage renal failure and 40% of type II diabetics are at risk of developing diabetic nephropathy. So, diagnosis of diabetic nephropathy is paramount for the survivability of the diabetic patients not only because of the consequences of renal progression but also because of the strong association with the risk of developing cardiovascular disease. A total number of 53 subjects were enrolled in this present cross sectional study in the department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU) in collaboration of Nephrology and Medicine of the same institution during two years (2011-13) aim to evaluate the diagnostic usefulness of renal resistive index (RI) by duplex Doppler ultrasonography for detection of renal dysfunction in diabetic patients. Clinically diagnosed diabetic patients having diabetic nephropathy referred to the department of Radiology and Imaging in BSMMU for ultrasonography of Kidneys, Ureters and Bladder (KUB) region or whole abdomen were selected as sample. Biochemical reports (Serum creatinine and Urinary albumin) and the RI value of intrarenal artery were correlated and analyzed. Only those patients biochemically were diagnosed as having diabetic nephropathy was included. Those with incomplete data, hydro nephrosis and renal calculus were excluded. Both the kidneys were visualized by commercially available real time scanner (GE Voluson) equipped with a curvilinear transducer operating at 3.5 MHz First Gray scale ultrasonography was done followed by Color Doppler of intra renal artery and then RI was measured. Majority (45.3%) patients were in 6th decade with the mean age was of 52.66±7.4 years and ranging from 38 to 65 years in patients. Male was found to be 54.7% of diabetic patients with male to female ratio 1.2:1. Resistive index of (? 0.7) was found in 73.6% patients with diabetes with the mean resistive index of 0.71±0.04. Positive correction between resistive index with serum creatinine (r=0.581, p<0.01) and albuminuria (r=0.725, p<0.01) were observed. It can be concluded that Resistive Index measured by duplex Doppler ultrasonography is useful diagnostic modality for detection of renal dysfunction in diabetic nephropathy patients. Resistive Index has value in identifying diabetic patients who are developing nephropathy and can be used as an additional diagnostic tool. Also it is well correlated with Serum Creatinine and Albuminuria which are the biochemical parameters to diagnose diabetic nephropathy.


2018 ◽  
Vol 22 (5) ◽  
pp. 1163-1166 ◽  
Author(s):  
Emil den Bakker ◽  
Berend Koene ◽  
Joanna A. E. van Wijk ◽  
Isabelle Hubeek ◽  
Reinoud Gemke ◽  
...  

2019 ◽  
Vol 6 (1) ◽  
pp. e000286 ◽  
Author(s):  
Hamza Waqar Bhatti ◽  
Umama Tahir ◽  
Noman Ahmed Chaudhary ◽  
Sania Bhatti ◽  
Muhammad Hafeez ◽  
...  

ObjectivesTo assess factors associated with renal dysfunction (RD) in hepatitis C virus (HCV) cirrhosis, correlate renal parameters with Child-Pugh score (CPS) and find a cut-off value of CPS to determine RD.Materials and methodsIt was a cross-sectional study that included 70 cases of liver cirrhosis secondary to HCV from a period of 6 months at Combined Military Hospital, Multan. Diagnosis of HCV was confirmed by serological assay and liver cirrhosis by ultrasonography. CPS was determined and lab reports were taken. Patients were divided into two groups as not having RD (serum creatinine≤1.5 mg/dL) and having RD (serum creatinine≥1.5 mg/dL). Estimated glomerular filtration rate (eGFR) was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Data were analyzed using SPSS V.23.0. χ2, Kruskal-Wallis test and Pearson coefficient of correlation were applied. ROC curve was drawn to evaluate cut-off value of CPS for the presence of RD. Level of significance was set at p<0.05.ResultsPatients with CP grade B or C develop RD as compared to patients with CP grade A (p=0.000). Mean age, urea, creatinine and eGFR varies significantly among patients who develop RD and patients who do not (p=0.02, p=0.000, p=0.000 and p=0.000, respectively). eGFR negatively correlates with CPS (r=−0.359, p=0.002). Creatinine, urea and ALBI score positively correlates with CPS (r=+0.417, p=0.000; r=+0.757, p=0.000; r=+0.362, p=0.002, respectively).ConclusionAscites and encephalopathy are associated with RD in HCV cirrhosis.


2020 ◽  
Vol 9 (4) ◽  
pp. 335-344
Author(s):  
Marcus P.J. van Diemen ◽  
Ellen P. Hart ◽  
Pieter W. Hameeteman ◽  
Emma M. Coppen ◽  
Jessica Y. Winder ◽  
...  

Background: Huntington’s disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. A toxic accumulation of misfolded mutant huntingtin protein (Htt) induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. Improving mitochondrial function has been proposed as an opportunity to treat HD, but it is not known how mitochondrial function in different tissues relates. Objective: We explored associations between central and peripheral mitochondrial function in a group of mild to moderate staged HD patients. Methods: We used phosphorous magnetic resonance spectroscopy (31P-MRS) to measure mitochondrial function in vivo in the calf muscle (peripheral) and the bio-energetic state in the visual cortex (central). Mitochondrial function was also assessed ex vivo in circulating peripheral blood mononuclear cells (PBMCs). Clinical function was determined by the Unified Huntington’s Disease Rating Scale (UHDRS) total motor score. Pearson correlation coefficients were computed to assess the correlation between the different variables. Results: We included 23 manifest HD patients for analysis. There was no significant correlation between central bio-energetics and peripheral mitochondrial function. Central mitochondrial function at rest correlated significantly to the UHDRS total motor score (R = –0.45 and –0.48), which increased in a subgroup with the largest number of CAG repeats. Discussion: We did not observe a correlation between peripheral and central mitochondrial function. Central, but not peripheral, mitochondrial function correlated to clinical function. Muscle mitochondrial function is a promising biomarker to evaluate disease-modifying compounds that improve mitochondrial function, but Huntington researchers should use central mitochondrial function to demonstrate proof-of-pharmacology of disease-modifying compounds.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 930 ◽  
Author(s):  
D. Travis Thomas ◽  
David M. Schnell ◽  
Maja Redzic ◽  
Mingjun Zhao ◽  
Hideat Abraha ◽  
...  

Intramyocellular (IMCL), extramyocellular lipid (EMCL), and vitamin D deficiency are associated with muscle metabolic dysfunction. This study compared the change in [IMCL]:[EMCL] following the combined treatment of vitamin D and aerobic training (DAT) compared with vitamin D (D), aerobic training (AT), and control (CTL). Male and female subjects aged 60–80 years with a BMI ranging from 18.5–34.9 and vitamin D status of ≤32 ng/mL (25(OH)D) were recruited to randomized, prospective clinical trial double-blinded for supplement with a 2 × 2 factorial design. Cholecalciferol (Vitamin D3) (10,000 IU × 5 days/week) or placebo was provided for 13 weeks and treadmill aerobic training during week 13. Gastrocnemius IMCL and EMCL were measured with magnetic resonance spectroscopy (MRS) and MRI. Hybrid near-infrared diffuse correlation spectroscopy measured hemodynamics. Group differences in IMCL were observed when controlling for baseline IMCL (p = 0.049). DAT was the only group to reduce IMCL from baseline, while a mean increase was observed in all other groups combined (p = 0.008). IMCL reduction and the corresponding increase in rVO2 at study end (p = 0.011) were unique to DAT. Vitamin D, when combined with exercise, may potentiate the metabolic benefits of exercise by reducing IMCL and increasing tissue-level VO2 in healthy, older adults.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jong Weon Choi ◽  
Tatsuyoshi Fujii ◽  
Noriyoshi Fujii

The aim of this study was to assess the significance of the neutrophil gelatinase-associated lipocalin/serum creatinine ratio (NGAL/sCr ratio) in patients with renal dysfunction. The percent difference between plasma NGAL level and the NGAL/sCr ratio was 36.7% (95% CI, 18.4–83.7%) in patients with sCr level ≥ 1.2 mg/dL. In a multivariate analysis, high sensitivity C-reactive protein (hsCRP) was significantly associated with the NGAL/sCr ratio and plasma NGAL level (r=0.526andr=0.453, resp.,P<0.001). In a receiver operating characteristics curve, the diagnostic ability of the NGAL/sCr ratio to identify hsCRP > 4.0 mg/dL was superior to that of NGAL [0.783 (95% CI, 0.674–0.892) versus 0.733 (95% CI, 0.615–0.852),P=0.032]. The area under the curve of the NGAL/sCr ratio was larger than that of hsCRP to detect corrected erythrocyte sedimentation rate > 25 mm/h and the neutrophil-to-lymphocyte ratio >4.5 in renal dysfunction. In short, the NGAL/sCr ratio may offer useful information when screening patients with both systemic inflammation and renal dysfunction.


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