Tag: urinalysis

Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study

Abstract:

Background: Around 10% of people who had COVID-9 infection suffer from persistent symptoms such as fatigue, dyspnoea, chest pain, arthralgia/myalgia, sleep disturbances, cognitive dysfunction and impairment of mental health. Different underlying pathomechanisms appear to be involved, in particular inflammation, alterations in amino acid metabolism, autonomic dysfunction and gut dysbiosis.

Aim: As routine tests are often inconspicuous in patients with Long COVID (LC), similarly to patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), accessible biomarkers indicating dysregulation of specific pathways are urgently needed to identify underlying pathomechanisms and enable personalized medicine treatment. Within this pilot study we aimed to proof traceability of altered metabolism by urine analysis.

Patients and methods: Urine metabolome analyses were performed to investigate the metabolic signature of patients with LC (n = 25; 20 women, 5 men) in comparison to healthy controls (Ctrl, n = 8; 7 women, 1 man) and individuals with ME/CFS (n = 8; 2 women, 6 men). Concentrations of neurotransmitter precursors tryptophan, phenylalanine and their downstream metabolites, as well as their association with symptoms (fatigue, anxiety and depression) in the patients were examined.

Results and conclusion: Phenylalanine levels were significantly lower in both the LC and ME/CFS patient groups when compared to the Ctrl group. In many LC patients, the concentrations of downstream metabolites of tryptophan and tyrosine, such as serotonin, dopamine and catecholamines, deviated from the reference ranges. Several symptoms (sleep disturbance, pain or autonomic dysfunction) were associated with certain metabolites. Patients experiencing fatigue had lower levels of kynurenine, phenylalanine and a reduced kynurenine to tryptophan ratio (Kyn/Trp). Lower concentrations of gamma-aminobutyric acid (GABA) and higher activity of kynurenine 3-monooxygenase (KMO) were observed in patients with anxiety.

Conclusively, our results suggest that amino acid metabolism and neurotransmitter synthesis is disturbed in patients with LC and ME/CFS. The identified metabolites and their associated dysregulations could serve as potential biomarkers for elucidating underlying pathomechanisms thus enabling personalized treatment strategies for these patient populations.

Source: Taenzer M, Löffler-Ragg J, Schroll A, Monfort-Lanzas P, Engl S, Weiss G, Brigo N, Kurz K. Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study. Int J Tryptophan Res. 2023 Dec 22;16:11786469231220781. doi: 10.1177/11786469231220781. PMID: 38144169; PMCID: PMC10748708. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10748708/ (Full text)

Fibrin microthrombi in bladder urothelium after SARS-CoV-2 infection: Case report

Abstract:

A 45-year-old male with diabetes, hypertension and hyperlipidemia was referred to urology due to persistent symptoms of urinary frequency, urgency, nocturia, erectile dysfunction, and constant pain localized to the bladder, pelvis, and perineal area, 3–4 months after SARS-CoV-2 infection. A bladder biopsy showed urothelial mucosa and submucosa with hemorrhage and fibrin microthrombi in blood vessels. Hydrodistention of the bladder and pelvic floor physical therapy resolved symptoms, though bladder and pain symptoms returned upon reinfection with SARS-CoV-2. Urinalysis revealed elevated urinary interleukin-8, which may indicate localized bladder inflammation.

Source: Hoang Roberts L, Zwaans BMM, Jabbar K, Bartolone SN, Padmanabhan P, Peters KM. Fibrin microthrombi in bladder urothelium after SARS-CoV-2 infection: Case report. Urol Case Rep. 2023 Sep 25;51:102575. doi: 10.1016/j.eucr.2023.102575. PMID: 37829494; PMCID: PMC10565678. https://www.sciencedirect.com/science/article/pii/S2214442023002619 (Full text)

Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a known complex, multi-organ system disorder with a sudden or subacute onset. ME/CFS occurs most commonly among women between 30 and 50 years of age. The current diagnostic criteria of ME/CFS, as defined by the Centers for Disease Control and Prevention, includes: profound fatigue and post-exertional malaise (>6 mo) unrelieved by rest, persistent cognitive impairment or orthostatic intolerance, and chronic unrefreshing sleep.

Despite reported associations between ME/CFS onset and exposure to infectious agents (viral, bacterial, or fungal), the pathophysiology of ME/CFS remains unknown. In this prevalence study, we investigated the rates of Aspergillus-derived toxin levels, Aflatoxin (AF), Ochratoxin A (OTA), and Gliotoxin (GT), in the urinalysis of 236 ME/CFS patients with a history of chronic exposure to mold (i.e., from water-damaged buildings).

Among ME/CFS patients reporting chronic exposure to mold, we found evidence of exposure in 92.4 percent of patients, with OTA being the most prevalent mycotoxin. Mold distributions (OTA, AF, and GT) in the urinalysis all demonstrated right skewness, while the distribution of age of ME/CFS patients diagnosed showed no deviation from normality.

This study aims to provide preliminary, epidemiological evidence among ME/CFS patients who were diagnosed in South Florida with a history of exposure to mycotoxins. Based on these findings, we proposed how future control studies should approach investigating the association between chronic mold exposure and the diagnosis of ME/CFS.

Source: Wu TY, Khorramshahi T, Taylor LA, Bansal NS, Rodriguez B, Rey IR. Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients. Int J Environ Res Public Health. 2022 Feb 12;19(4):2052. doi: 10.3390/ijerph19042052. PMID: 35206241. https://www.mdpi.com/1660-4601/19/4/2052 (Full text)

Comparison of differential metabolites in urine of the middle school students with chronic fatigue syndrome before and after exercise

Abstract:

OBJECTIVE: To study the differential metabolites in urine and the characteristics of metabolic pathway of middle school students with chronic fatigue syndrome (CFS) before and after exercise, and then explain the metabolic mechanism of CFS.

METHODS: Eight male middle school students (age:17-19) with CFS were selected as the CFS group according to CFS screening criteria of the U.S. centers.At the same time, 8 male health students of the same age from the same school were selected as the control group. They were administrated to do one-time exercise on the improved Harvard step (up and down steps 30 times/min for 3 minutes). Their urine was collected before and after exercise, and the differential metabolites in urine were detected by liquid chromatography-mass spectrometry (LC-MS). The multidimensional statistical methods were used to analyze the metabolites by principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Finally, MetPA database was used to analyze the metabolites and to construct the correlative metabolic pathways.

RESULTS: Compared with the control group, the creatine, indoleacetaldehyde, phytosphingosine and pyroglutamic acid were selected as differential metabolites and the contents of those were decreased significantly (P<0.05 or P<0.01) in CFS group before the step movement. However, 11 differential metabolites in CFS group were selected out after exercise, which were nonanedioic acid, methyladenosine, acetylcarnitine, capric acid, corticosterone, creatine, levonorgestrel, pantothenic acid, pyroglutamic acid, xanthosine and xanthurenic acid in sequence, the contents of methyladenosine and creatine were significantly increased (P<0.05) and the contents of the other 9 differential metabolites were significantly decreased (P<0.05 or P<0.01)compared with the control group.

The 15 differential metabolites mentioned above were input MetPA database in order to analyze the metabolic pathways weighted score.The results showed that the arginine-proline metabolism pathway disorders were detected in the CFS group before exercise, the marker metabolite was creatine. And 3 metabolic pathways disorder were detected in the CFS group after exercise, which were arginine-proline metabolism, biosynthesis of pantothenic acid and CoA, steroid hormone biosynthesis, and the marker metabolites, in turn, were creatine, pantothenic acid and corticosterone.

CONCLUSIONS: The disorder of arginine-proline metabolic pathway is detected in CFS middle school students before exercise intervention. After exercise, it can be detected that the steroid hormone biosynthetic metabolic pathway, pantothenic acid and CoA metabolic pathways also have metabolic disorders.

Source: Chi AP, Wang ZN, Shi B, Yang XF, Min RX, Song J. Comparison of differential metabolites in urine of the middle school students with chronic fatigue syndrome before and after exercise. [Article in Chinese] Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Apr 8;34(4):340-344 349. doi: 10.12047/j.cjap.5633.2018.078.  https://www.ncbi.nlm.nih.gov/pubmed/30788942

Preliminary determination of a molecular basis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects.

Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion.

Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects.

The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis of chronic fatigue syndrome. Biochem Mol Med. 1996 Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884