scholarly journals Increased expression of LCN2 formed a positive feedback loop with activation of the ERK pathway in human kidney cells during kidney stone formation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhang Hui ◽  
Zhu Jiang ◽  
Du Qiao ◽  
Zhao Bo ◽  
Kang Qiyuan ◽  
...  

AbstractKidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation regulation model. In addition, we found that LCN2 plays a role in promoting kidney stones through regulation of the ERK signalling pathway and expression of other kidney stone-related genes. LCN2 expression was upregulated upon oxalate stimulation. P-ERK1/2 inhibition by U0126 in kidney epithelial cells resulted in decreased expression of LCN2. Furthermore, the upregulation of LCN2 not only depended on the activation of the ERK signalling pathway but also regulated the activation of the ERK signalling pathway. Importantly, upregulation of LCN2 not only caused kidney epithelial cell damage but also promoted the expression of other kidney stone-related genes. Our findings improved the understanding of LCN2 and might lead to the development of new therapeutic and prognostic markers for kidney stones.

Minerals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1396
Author(s):  
Yu Tian ◽  
Guilin Han ◽  
Jie Zeng ◽  
Qian Zhang ◽  
Lifang Xu ◽  
...  

The chemical composition of biominerals is essential for understanding biomineral formation and is regarded as an attractive subject in bio-mineralogical research on human kidney stones (urinary calculi). In order to obtain more geochemically interpreted data on biogenic minerals, mineralogical compositions and major and trace element concentrations of sixty-six kidney stone samples derived from kidney stone removal surgeries were measured. Infrared spectroscopy results showed that calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) were the two main mineral components of kidney stones. Geochemical results indicated that major and trace element concentrations were present in the following order: Ca > Mg > Na > K > Zn > Fe > Pb > Ba > Cu > Ti > Mo > Cd > Cr. With the exception of Ca, Mg was the second-most abundant element. Zn exhibited higher concentrations relative to other trace elements, which suggests a potential substitution of calcium by metal ions with a similar charge and radius rather than by metals in kidney stone formation. Pb appeared in significantly higher concentrations than in previous studies, which indicates Pb enrichment in the environment. In order to discern multi-element relationships within kidney stones, principal component analysis was applied. Three principal components (PCs, eigenvalues >1) were extracted to explain 64.4% of the total variance. The first component exhibited positively correlated Na-Zn-Cr-Mo-Cd-Pb, while the second component exhibited more positively weighted Mg-K-Ba-Ti. Fe-Cu demonstrated a positive correlation in the third component. This study suggests that Ca exhibits a preference for uptake by oxalates during human urinary stone crystallization, while other alkali metals and alkaline earth metals precipitate with phosphate.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yutaro Tanaka ◽  
Mihoko Maruyama ◽  
Atsushi Okada ◽  
Yoshihiro Furukawa ◽  
Koichi Momma ◽  
...  

AbstractThe pathogenesis of kidney stone formation includes multi-step processes involving complex interactions between mineral components and protein matrix. Calcium-binding proteins in kidney stones have great influences on the stone formation. The spatial distributions of these proteins in kidney stones are essential for evaluating the in vivo effects of proteins on the stone formation, although the actual distribution of these proteins is still unclear. We reveal micro-scale distributions of three different proteins, namely osteopontin (OPN), renal prothrombin fragment 1 (RPTF-1), and calgranulin A (Cal-A), in human kidney stones retaining original mineral phases and textures: calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD). OPN and RPTF-1 were distributed inside of both COM and COD crystals, whereas Cal-A was distributed outside of crystals. OPN and RPTF-1 showed homogeneous distributions in COM crystals with mosaic texture, and periodically distributions parallel to specific crystal faces in COD crystals. The unique distributions of these proteins enable us to interpret the different in vivo effects of each protein on CaOx crystal growth based on their physico-chemical properties and the complex physical environment changes of each protein. This method will further allow us to elucidate in vivo effects of different proteins on kidney stone formation.


1965 ◽  
Vol 13 (3) ◽  
pp. 155-160 ◽  
Author(s):  
H. J. KEUTEL

Fluorescent labeled antibodies were used for the demonstration of uromucoid. This urine specific mucoprotein is demonstrably present only in the epithelial cells of the proximal segments of the normal human renal tubules and in the matrix of human kidney stones of all the common crystalline compositions.


Author(s):  
Sedat Tastemur ◽  
Samet Senel ◽  
Esin Olcucuoglu ◽  
Emre Uzun

Objective: To examine the relation between perirenal fat volume, which is one of the visceral fat measurements, and kidney stones. Method: 169 patients admitted to our clinic between January 2018 and May 2021 were included in the study. The patients were divided into 2 groups as Control Group and Unilateral Kidney Stone Group (88 patients with unilateral kidney stones). Contrast-enhanced abdominal computed tomography scans were used to measure perirenal fat volume and the results were transferred to workstations. The total perirenal fat volumes in the bilateral kidneys of patients were compared between the two groups. The perirenal fat volume in stone-bearing and non-stone bearing kidneys of patients were also compared. Results: The total perirenal fat volume was higher in the Unilateral Kidney Stone Group than in the other groups and the perirenal fat volume of the patients in this group was higher in the stone bearing kidney (295.6±164.4cm3) than in the non-stone bearing kidney (273.1±179.6cm3). In the ROC analysis, it was concluded that total perirenal fat volume>387cm3 increased the risk of kidney stones. Presence of hypertension, presence of hyperlipidemia and total perirenal fat volume>387cm3 were found to be independent risk factors for the presence of kidney stones. Conclusion: Perirenal fat volume is higher in stone bearing kidneys compared to non-stone bearing kidneys. Therefore, stone formation in a kidney is directly related to the perirenal fat volume of that kidney. Also, total perirenal fat volume>387cm3 increases the risk of kidney stones independently of body mass index, and predicts it better.


2019 ◽  
Vol 20 (19) ◽  
pp. 4889 ◽  
Author(s):  
Gamero-Estevez ◽  
Andonian ◽  
Jean-Claude ◽  
Gupta ◽  
Ryan

: Kidney stones affect 10% of the population. Yet, there is relatively little known about how they form or how to prevent and treat them. The claudin family of tight junction proteins has been linked to the formation of kidney stones. The flavonoid quercetin has been shown to prevent kidney stone formation and to modify claudin expression in different models. Here we investigate the effect of quercetin on claudin expression and localization in MDCK II cells, a cation-selective cell line, derived from the proximal tubule. For this study, we focused our analyses on claudin family members that confer different tight junction properties: barrier-sealing (Cldn1, -3, and -7), cation-selective (Cldn2) or anion-selective (Cldn4). Our data revealed that quercetin’s effects on the expression and localization of different claudins over time corresponded with changes in transepithelial resistance, which was measured continuously throughout the treatment. In addition, these effects appear to be independent of PI3K/AKT signaling, one of the pathways that is known to act downstream of quercetin. In conclusion, our data suggest that quercetin’s effects on claudins result in a tighter epithelial barrier, which may reduce the reabsorption of sodium, calcium and water, thereby preventing the formation of a kidney stone.


2010 ◽  
Vol 38 (3) ◽  
pp. 147-160 ◽  
Author(s):  
Fredric L. Coe ◽  
Andrew P. Evan ◽  
Elaine M. Worcester ◽  
James E. Lingeman

2012 ◽  
Vol 584 ◽  
pp. 504-508 ◽  
Author(s):  
Deeptiman Chatterjee ◽  
Vishaka Verma ◽  
Amiti ◽  
Sheija Rohil ◽  
Narayanasamy Arunai Nambi Raj ◽  
...  

Kidney stones or renal calculi or Nephrolithiasis is a common health problem in both developed and developing nations [1,2]. Analysis of the chemical and physical properties of renal calculi helps in preventing their formation and treatment. In this study, we evaluated the hardness of water used for drinking purposes, in an attempt to correlate water hardness with an increased incidence of stone formation. Identifying risk factors help to develop a preventive strategy to reduce the risk of renal calculi formation. The incidence of kidney stone formation in Vellore district was correlated with the hardness of water samples taken from different areas in Vellore. The study can be employed at a larger demographic level for effective and economic monitoring of the risk of kidney stone formation.


2020 ◽  
Vol 4 (1) ◽  
pp. 1-6
Author(s):  
Akram O. Esmail ◽  
Bahast A. Qadir ◽  
Hawnaz Q. Hamad

This study was conducted in Rania District, Raparin University, during September 2018–March 2019, to test the relation between water hardness and kidney stone formation. The investigation depended on questionnaire form which was distributed on 100 person in Raparin (Rania, Hajiawa, and Chwarqurna) and patients whom vested the Rania clinical during December 1, 2018–January 22, 2019 which were 238 patients and only 20 of them had kidney stones developing which represent 8.4% of the total kidney diseases. The results indicated to significant effect of gender at level of significant 5% on kidney stones formation, 10% of male, and 18% of female having kidney stones. The results of Chi-square test indicated to highly significant effect of age on kidney stone formation at level of significant (0.001). The kidney stone formation increased from 19.23% to 75% with an increase in age class from (14–34) to (54 or more) year. The negative correlation coefficient value of (r = −0.63*) was recorded between water hardness and stone risk index due to the high magnesium content of drinking water in the studied area.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Matteo Bargagli ◽  
Rossella De Leonardis ◽  
Mauro Ragonese ◽  
Angelo Totaro ◽  
Francesco Pinto ◽  
...  

Abstract Background and Aims Nephrolithiasis is a medical condition characterized by high prevalence among the general population both in Europe and in the U.S. and it is responsible for high costs reaching up to $10 billion per year. It is associated with specific comorbidities such as obesity, arterial hypertension, diabetes mellitus, metabolic syndrome and chronic kidney disease. Kidney stones development is believed to start either from Randall’s plaques or from stone plugs. Both these lesions can be seen on renal papillary surfaces, but what promotes the formation of plaques and plugs is not entirely understood. The aim of this study is to investigate the association between the urinary metabolic milieu and a published endoscopic papillary evaluation score (PPLA). We also evaluated the correlation of PPLA score with kidney stone recurrence during follow-up. Method We prospectively enrolled 31 stone forming patients who undergone retrograde intrarenal surgery procedures. Visual inspection of the accessible renal papillae was performed in order to calculate the PPLA score based on the appearance of ductal plugging, surface pitting, loss of papillary contour and Randall’s plaque extension. Demographic information, blood samples, 24h urine collections and kidney stone events during follow-up were collected. Stone composition was analyzed using infrared-spectroscopy. Relative urinary supersaturations (RSS) for calcium oxalate (CaOx), calcium phosphate (CaPi) and uric acid (UA) were calculated using the Equil2 software. PPLA score > 3 was defined as high. Results Median follow-up period was 11 (min/max 5, 34) months. PPLA score was inversely correlated with BMI (rho = −0.39, p = 0.035) and history of recurrent kidney stones (median PPLA 5.0 vs 2.5, p = 0.029), these results were confirmed when PPLA was considered as a categorical variable (median BMI 27 vs 24, recurrent stone disease 12 vs 62%, p= 0.006). Furthermore, high PPLA score was associated with lower odds of new kidney stone events during follow-up (OR 0.154, 95% confidence interval 0.024, 0.998, p = 0.05). No significant correlations were found between PPLA score, stone composition, blood parameters, 24h urine solute excretions and RSS for CaOx, CaPi and UA. Conclusion Different papillary abnormalities seem to be linked to specific mechanisms of stone formation. Although data regarding PPLA score are inconsistent, it may be a valid asset for both medical and surgical management of nephrolithiasis. Larger, long-term prospective clinical studies need to be conducted to assess the validity of PPLA score system in evaluating risk of stone recurrence.


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