المؤلفون: Eriksson, Mikael¹ mikael.e.eriksson@uu.se, Lipcsey, Miklós^1,2, Ilboudo, Yann³, Satoshi Yoshiji^3,4,5, Richards, Brent^3,6,7,8, Hultström, Michael^1,3,6,9

المصدر: Physiological Genomics. May2024, Vol. 56 Issue 5, p409-416. 8p.

مصطلحات موضوعية: *SEPSIS, *UROMODULIN, *ACUTE kidney failure, *SINGLE nucleotide polymorphisms, *PNEUMONIA, *INTENSIVE care units

مستخلص: The outcome for patients with sepsis-associated acute kidney injury in the intensive care unit (ICU) remains poor. Low serum uromodulin (sUMOD) protein levels have been proposed as a causal mediator of this effect. We investigated the effect of different levels of sUMOD on the risk of sepsis and severe pneumonia and outcomes in these conditions. A two-sample Mendelian randomization (MR) study was performed. Single-nucleotide polymorphisms (SNPs) associated with increased levels of sUMOD were identified and used as instrumental variables for association with outcomes. Data from different cohorts were combined based on disease severity and meta-analyzed. Five SNPs associated with increased sUMOD levels were identified and tested in six datasets from two biobanks. There was no protective effect of increased levels of sUMOD on the risk of sepsis [two cohorts, odds ratio (OR) 0.99 (95% confidence interval 0.95-1.03), P = 0.698, and OR 0.95 (0.91-1.00), P = 0.060, respectively], risk of sepsis requiring ICU admission [OR 1.04 (0.93-1.16), P = 0.467], ICU mortality in sepsis [OR 1.00 (0.74-1.37), P = 0.987], risk of pneumonia requiring ICU admission [OR 1.05 (0.98-1.14), P = 0.181], or ICU mortality in pneumonia [OR 1.17 (0.98-1.39), P = 0.079]. Meta-analysis of hospital-admitted and ICU-admitted patients separately yielded similar results [OR 0.98 (0.95-1.01), P = 0.23, and OR 1.05 (0.99-1.12), P = 0.86, respectively]. Among patients with sepsis and severe pneumonia, there was no protective effect of different levels of sUMOD. Results were consistent regardless of geographic origins and not modified by disease severity. [ABSTRACT FROM AUTHOR]

المؤلفون: Schleicher, Eva Maria^1,2 (AUTHOR), Gairing, Simon Johannes^1,2 (AUTHOR), Castven, Darko³ (AUTHOR), Hock, Charlotte Sophie^1,2 (AUTHOR), Dobbermann, Henrike³ (AUTHOR), Heinrich, Sophia¹ (AUTHOR), Meineck, Myriam¹ (AUTHOR), Kaps, Leonard^1,2 (AUTHOR), Galle, Peter Robert^1,2 (AUTHOR), Weinmann-Menke, Julia¹ (AUTHOR), Nguyen-Tat, Marc¹ (AUTHOR), Marquardt, Jens U.^1,2,3 (AUTHOR), Labenz, Christian^1,2 (AUTHOR) Christian.labenz@unimedizin-mainz.de

المصدر: American Journal of Physiology: Gastrointestinal & Liver Physiology. May2024, Vol. 326 Issue 5, pG583-G590. 8p.

مصطلحات موضوعية: *HEPATORENAL syndrome, *UROMODULIN, *ACUTE kidney failure, *CIRRHOSIS of the liver, *PROGNOSIS

مستخلص: Hepatorenal syndrome (HRS) is associated with a dismal prognosis in patients with cirrhosis, and therapeutic options are limited. Biomarkers to identify patients with poor response to therapy are urgently needed. This study aimed to evaluate the predictive value of serum levels of uromodulin (sUMOD) in patients with cirrhosis and HRS treated with terlipressin and albumin (T/A). In total, 156 patients [81 patients with HRS treated with T/A, 42 patients with cirrhosis without kidney injury, and 33 patients with cirrhosis with prerenal acute kidney injury (AKI)] were included. sUMOD levels were analyzed by ELISA. Patients with HRS were prospectively followed for the composite endpoint of hemodialysis-/liver transplantation-free survival (HD/LTx-free survival). Of the 81 patients with HRS, 40 had HRS type 1 and 41 type 2. In the cohort of patients with HRS treated with T/A, median sUMOD level was 100 ng/mL (IQR 64; 144). sUMOD differed significantly between patients with HRS compared with patients without AKI (P = 0.001) but not between patients with HRS and prerenal AKI (P = 0.9). In multivariable analyses, sUMOD levels in the lowest quartile were independently associated with a lower rate of complete response to T/A (OR 0.042, P = 0.008) and a higher risk for reaching the composite endpoint of HD/LTX-free survival (HR 2.706, P = 0.013) in patients with HRS type 2 treated with T/A. In contrast, sUMOD was not significantly associated with these outcomes in patients with HRS type 1. sUMOD may be a valuable biomarker for identifying patients with HRS type 2 treated with T/A to predict response and prognosis. NEW & NOTEWORTHY: Biomarkers identifying patients with hepatorenal syndrome (HRS) and poor response to therapy are urgently needed. In this study, lower serum uromodulin (sUMOD) levels were associated with poorer response to therapy with terlipressin and albumin and consequently with poorer prognosis in patients with HRS type 2. In patients with HRS type 1, there was no association between sUMOD and poorer prognosis. [ABSTRACT FROM AUTHOR]

المؤلفون: Ananth, Soma¹, Sharma, M. Sreedhar², Reddy, P. L. Venkata Pakki² drreddyvenkat@gmail.com, Umare, Manoj³

المصدر: International Journal of Medicine & Public Health. Apr-Jun2024, Vol. 14 Issue 2, p191-195. 5p.

مصطلحات موضوعية: *UROMODULIN, *CHRONIC kidney failure, *KIDNEY physiology, *KIDNEY diseases, *BIOMARKERS, *CHRONICALLY ill, *DYSLIPIDEMIA

مستخلص: Background: Uromodulin (Tamm-Horsfall protein), the most common protein in normal urine present in a bundant quantity, is increasingly considered as a potential biomarker relevant to kidney function and tubular reserve, chronic kidney disease and hypertension. A reduced number of tubular cells, is paralleled by reduced urinary and serum concentrations of uromodulin. Therefore, uromodulin might represent a promising biomarker for CKD. Aim: To evaluate the use of serum uromodulin as a biomarker in chronic kidney disease patients. Material and Methods: In an observational study, on 100 subjects with 50 normal healthy and 50 with CKD 1 - 5 stages patients attending Nephrology department in a tertiary care hospital for two years were enrolled. Lipid profile, Serum calcium, proteins, creatinine and serum Uromodulin along with e GFR was investigated. Data was analyzed using SPSS 16 and by using t test, ANOVA and correlation coefficients. Results: Mean age of the study participants was 47.47 ± 10.66 years. And 71% were male. On comparison between cases and controls, Serum Uromodulin, calcium, HDL was lower and other lab findings were significantly more in Cases than in controls. Serum Uromodulin was significantly decreased with severity of CKD. Conclusion: A comparative analysis of serum uromodulin with e GFR shows that eGFR is positively correlated with uromodulin. Lower serum uromodulin reflects a decline in kidney function. Thus serum uromodulin is a helpful marker in diagnosis of CKD at a nearly stage. The estimation of serum uromodulin level may aid in early diagnosis of kidney dysfunction and also in predicting the progression of disease. [ABSTRACT FROM AUTHOR]

المؤلفون: Yoshimura, Kaori¹ (AUTHOR), Ito, Yukinobu² (AUTHOR) yukinobuito@med.kanazawa-u.ac.jp, Suzuki, Mina² (AUTHOR), Horie, Masafumi² (AUTHOR), Nishiuchi, Takumi³ (AUTHOR), Shintani‐Domoto, Yukako⁴ (AUTHOR), Shigehara, Kazuyoshi⁵ (AUTHOR), Oshima, Hiroko⁶ (AUTHOR), Oshima, Masanobu⁶ (AUTHOR), Goto, Akiteru⁷ (AUTHOR), Nojima, Takayuki¹ (AUTHOR), Tsuzuki, Toyonori⁸ (AUTHOR), Mizokami, Atsushi⁵ (AUTHOR), Ikeda, Hiroko¹ (AUTHOR), Maeda, Daichi² (AUTHOR)

المصدر: Pathology International. Apr2024, Vol. 74 Issue 4, p187-196. 10p.

مصطلحات موضوعية: *UROMODULIN, *MASS spectrometry, *ADENOMA, *RENAL tubular transport disorders, *URINARY organs, *RADIATION injuries

مستخلص: Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82‐year‐old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid‐Schiff staining‐positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm−Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion. [ABSTRACT FROM AUTHOR]

المؤلفون: Vora, Kunj¹ (AUTHOR) kunj.vora@ims.fraunhofer.de, Kordas, Norbert¹ (AUTHOR) karsten.seidl@ims.fraunhofer.de, Seidl, Karsten^1,2 (AUTHOR)

المصدر: Sensors (14248220). Dec2023, Vol. 23 Issue 24, p9696. 9p.

مصطلحات موضوعية: *UROMODULIN, *ATOMIC layer deposition, *BIOSENSORS, *KIDNEY diseases, *PASSIVATION, *TANTALUM oxide, *BIOMARKERS

مستخلص: We demonstrate the development of a label-free, impedance-based biosensor by using a passivation layer of 50-nm tantalum pentoxide (Ta2O5) on interdigitated electrodes (IDE). This layer was fabricated by atomic layer deposition (ALD) and has a high dielectric constant (high- κ), which improves the capacitive property of the IDE. We validate the biosensor's performance by measuring uromodulin, a urine biomarker for kidney tubular damage, from artificial urine samples. The passivation layer is functionalized with uromodulin antibodies for selective binding. The passivated IDE enables the non-faradaic impedance measurement of uromodulin concentrations with a measurement range from 0.5 ng/mL to 8 ng/mL and with a relative change in impedance of 15 % per ng/mL at a frequency of 150 Hz (log scale). This work presents a concept for point-of-care biosensing applications for disease biomarkers. [ABSTRACT FROM AUTHOR]

المؤلفون: Varra, Manasa¹ dr.manasa88@gmail.com, Sundaresan, N. R.², Kumar, V. Girish³, Chandranaik, B. M.⁴, Sejian, Veerasamy⁵, Sudha, G.⁶, Suchitra, B. R.⁷

المصدر: Agricultural Science Digest. Dec2023, Vol. 43 Issue 6, p858-863. 6p.

مصطلحات موضوعية: *UROMODULIN, *ESTRUS, *PROTEIN expression, *GENITALIA, *LITERATURE reviews, *URINE

مستخلص: Background: Identifying buffaloes in estrus is crucial for enhancing the efficiency of reproduction as silent heat is a major concern in this species. Review of literature indicated the role of Tamm-Horsfall protein (THP) is associated with the physiological events around the estrus stage. Hence, the present study was aimed to quantify the expression level of THP in urine of buffaloes to ascertain its suitability as a marker for identifying buffaloes in estrus. Methods: The grouping of animals as mid-diestrus (Group-I/G-I/Control group), regular estrus (Group-II/G-II) and silent estrus (Group-III/G-III) buffaloes was done using a combinatorial approach. The expression of THP in the urine of three groups of animals was quantified by western blot. Result: The results of the present study revealed higher levels of urinary THP in G-II animals when compared to G-III and G-I animals, although it was statistically non-significant (p>0.05). The present study revealing for increased urinary expression of THP in G-II and G-III animals when compared to G-I animals probably construes the antimicrobial role of THP in the female reproductive tract and its role during estrus to prevent microbiota population beyond the physiological levels. For THP to be considered as biomarker for detecting buffaloes in silent heat there is need for further studies involving large number of animals. Nonetheless, an easy method has been developed that facilitated THP detection and quantification in urine of buffaloes by western blot. [ABSTRACT FROM AUTHOR]

المؤلفون: Lin, Tianhai^1,2 (AUTHOR), Chen, Zhuo³ (AUTHOR), Luo, Mengqi¹ (AUTHOR), Zhao, Yang⁴ (AUTHOR), Zeng, Wenjuan¹ (AUTHOR), Zheng, Shanshan¹ (AUTHOR), Su, Tao¹ (AUTHOR), Zhong, Yi¹ (AUTHOR), Wang, Shisheng¹ (AUTHOR), Jin, Youmei¹ (AUTHOR), Hu, Liqiang¹ (AUTHOR), Zhao, Wanjun⁵ (AUTHOR), Li, Jiaxu⁶ (AUTHOR), Wang, Xuanyi⁷ (AUTHOR), Wu, Changwei⁸ (AUTHOR), Li, Dapeng⁹ (AUTHOR), Liu, Fang¹ (AUTHOR) liufangfh@163.com, Li, Guisen⁸ (AUTHOR) guisenli@163.com, Yang, Hao^1,3 (AUTHOR) yanghao@scu.edu.cn, Zhang, Yong^1,3 (AUTHOR) nankai1989@foxmail.com

المصدر: Analyst. 10/21/2023, Vol. 148 Issue 20, p5041-5049. 9p.

مصطلحات موضوعية: *UROMODULIN, *DIATOMACEOUS earth, *IGA glomerulonephritis, *GLYCOPROTEINS, *URINE, *TRYPSIN, REPRODUCTIVE isolation

مستخلص: Uromodulin (Umod, Tamm–Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function. [ABSTRACT FROM AUTHOR]

المؤلفون: Mo, Boris¹ (AUTHOR), Scharf, Birte¹ (AUTHOR), Gutheil, Christian² (AUTHOR), Letzel, Matthias C.² (AUTHOR), Hensel, Andreas¹ (AUTHOR) ahensel@uni-muenster.de

المصدر: Scientific Reports. 10/19/2023, Vol. 13 Issue 1, p1-11. 11p.

مصطلحات موضوعية: *UROMODULIN, *EXCRETION, *URINARY tract infections, *OLIGOSACCHARIDE analysis, *GLYCANS

مستخلص: Tamm–Horsfall protein (THP) is a highly N-glycosylated protein from epithelial cells of the ascending limb of Henle loop. It is secreted into the urine as part of the innate immune response against uropathogenic pathogens. As women are more likely to suffer from urinary tract infections, biomedical studies were conducted to investigate sex-differences in THP excretion, as well as differences in the THP N-glycosylation pattern. A total of 238 volunteers (92 men, 146 women, 69 with hormonal contraceptives) participated in this study, providing urine samples. Women showed a clear tendency to have higher THP concentration and excretion rates than men (p < 0.16). Regular intake of hormonal contraceptives had no significant influence on urinary THP concentration compared to no regular intake. The individual N-glycosylation pattern of THP in urine samples from randomly selected individuals (10 female, 10 male) was investigated after enzymatic release and MS analysis of the oligosaccharides. Female subjects tended to have an increased proportion of oligomannose type N-glycans and non-fucosylated glycans, whereas men had an increased proportion of fucosylated complex-type glycans. The higher level of oligomannose-type glycans in THP from women might be explained by a self-defence mechanism to overcome the higher infections pressure by the female anatomical properties. [ABSTRACT FROM AUTHOR]

المؤلفون: Thielemans, Raïsa¹ (AUTHOR) raisa.thielemans@ugent.be, Speeckaert, Reinhart² (AUTHOR) reinhart.speeckaert@uzgent.be, Delrue, Charlotte¹ (AUTHOR) charlotte.delrue@ugent.be, De Bruyne, Sander³ (AUTHOR) sander.debruyne@uzgent.be, Oyaert, Matthijs³ (AUTHOR) matthijs.oyaert@uzgent.be, Speeckaert, Marijn M.^1,4 (AUTHOR) marijn.speeckaert@ugent.be

المصدر: Diagnostics (2075-4418). Oct2023, Vol. 13 Issue 19, p3077. 42p.

مصطلحات موضوعية: *UROMODULIN, *KIDNEY disease diagnosis, *KIDNEY stones, *ACUTE kidney failure, *CHRONIC kidney failure, *CARDIOVASCULAR diseases, *KIDNEY diseases

مستخلص: Uromodulin, also known as Tamm-Horsfall protein, represents the predominant urinary protein in healthy individuals. Over the years, studies have revealed compelling associations between urinary and serum concentrations of uromodulin and various parameters, encompassing kidney function, graft survival, cardiovascular disease, glucose metabolism, and overall mortality. Consequently, there has been a growing interest in uromodulin as a novel and effective biomarker with potential applications in diverse clinical settings. Reduced urinary uromodulin levels have been linked to an elevated risk of acute kidney injury (AKI) following cardiac surgery. In the context of chronic kidney disease (CKD) of different etiologies, urinary uromodulin levels tend to decrease significantly and are strongly correlated with variations in estimated glomerular filtration rate. The presence of uromodulin in the serum, attributable to basolateral epithelial cell leakage in the thick ascending limb, has been observed. This serum uromodulin level is closely associated with kidney function and histological severity, suggesting its potential as a biomarker capable of reflecting disease severity across a spectrum of kidney disorders. The UMOD gene has emerged as a prominent locus linked to kidney function parameters and CKD risk within the general population. Extensive research in multiple disciplines has underscored the biological significance of the top UMOD gene variants, which have also been associated with hypertension and kidney stones, thus highlighting the diverse and significant impact of uromodulin on kidney-related conditions. UMOD gene mutations are implicated in uromodulin-associated kidney disease, while polymorphisms in the UMOD gene show a significant association with CKD. In conclusion, uromodulin holds great promise as an informative biomarker, providing valuable insights into kidney function and disease progression in various clinical scenarios. The identification of UMOD gene variants further strengthens its relevance as a potential target for better understanding kidney-related pathologies and devising novel therapeutic strategies. Future investigations into the roles of uromodulin and regulatory mechanisms are likely to yield even more profound implications for kidney disease diagnosis, risk assessment, and management. [ABSTRACT FROM AUTHOR]

المؤلفون: Kira, Shunnosuke, Namba, Takashi, Hiraishi, Masaya, Nakamura, Teppei, Otani, Yuki, Kon, Yasuhiro, Ichii, Osamu

المصدر: PLoS ONE; 7/3/2024, Vol. 19 Issue 7, p1-18, 18p

مصطلحات موضوعية: KIDNEY tubules, PROXIMAL kidney tubules, UROMODULIN, DOGS, KIDNEY cortex, AQUAPORINS

مستخلص: The histomorphological features of normal kidneys in cats and dogs have been revealed despite the high susceptibility of cats to tubulointerstitial damage. Herein, the histological characteristics of the two species were compared. Cytoplasmic lipid droplets (LDs) were abundant in the proximal convoluted tubules (PCTs) of cats aged 23–27 months but scarce in dogs aged 24–27 months. LDs were rarely observed in the distal tubules (DTs) and collecting ducts (CDs) of either species, as visualized by the expression of Tamm–Horsfall protein 1, calbindin-D28K, and aquaporin 2. The occupational area ratio of proximal tubules (PTs) in the renal cortex was higher, but that of DTs or CDs was significantly lower in adult cats than in dogs. Single PT epithelial cells were larger, but PCT, DT, and CD lumens were significantly narrower in adult cats than in dogs. Unlike adults, young cats at 6 months exhibited significantly abundant cytoplasmic LDs in proximal straight tubules, indicating lipid metabolism-related development. Histochemistry of the 21 lectins also revealed variations in glycosylation across different renal tubules and CDs in both species. Sodium-glucose cotransporter 2 was expressed only in PTs, excluding the proximal straight tubules with few LDs in adult cats or the PCTs of young cats and adult dogs. These findings are crucial for understanding species-specific characteristics of renal histomorphology and pathogenesis. [ABSTRACT FROM AUTHOR]

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