bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANGIOTENSIN II-INDUCED EPITHELIAL-MESENCHYMAL TRANSITION IN PODOCYTES IS AGGRAVATED BY HOMOCYSTEINE VIA PI3K/AKT SIGNALING PATHWAY
Authors: Xu Rui , Zhao Xuan 
Published: April 2021

Objective:
To evaluate the effects of Ang II on epithelial-mesenchymal transition (EMT) in podocytes and to explore whether homocysteine (Hcy) could aggravate it and the possible mechanisms.

Design and method:
A recently generated conditionally immortalized mouse podocyte cell line was cultivated as described before. Podocytes were divided into three groups, control group (CG), Ang II group (AG) and Hcy + Ang II group (H + A G). Podocytes of AG and H + A G were exposed to Ang II (10–6 mol/l) for 24 h, and meanwhile podocytes of H + A G were exposed to Hcy (8∗10–4 mol/l) for 24 h. All cells were FBS-deprived for 12 h before each experiment. EMT is characterized by loss of nephrin and observation of mesenchymal marker such as desmin. The expression of nephrin and desmin were assessed by quantitative real-time PCR (qRT-PCR) and Western blotting. The expression of AKT and p-AKT were assessed by Western blotting.

Results:
(1) Compared with CG, nephrin mRNA and protein were obviously decreased and desmin mRNA and protein were increased significantly (P < 0.05) in AG. (2) The decrease in nephrin and the increase in desmin were much more significant in H + A G than those in AG (P < 0.05). (3) An increased expression of P-AKT/AKT was observed in podocytes in H + A G, when compared with that in AG (P < 0.05).

Conclusions:
Ang II is a contributing factor to EMT in podocytes and Hcy could aggravate Ang II induced EMT via PI3K / AKT signaling pathway.
ASSOCIATION OF URIC ACID IN SERUM AND URINE WITH SUBCLINICAL RENAL DAMAGE: HANZHONG ADOLESCENT HYPERTENSION STUDY
Authors: Wang Yang , Chen Chen , Yan Yu , Yuan Yue , Wang Ke-Ke , Chu Chao , Hu Jia-Wen , Ma Qiong , Liao Yue-Yuan , Fu Bo-Wen , Gao Ke , Zhu Wen-Jing , Yang Lei , Sun Yue , Mu Jian-Jun 
Published: April 2021

Objective:
Uric acid (UA) has been proposed as an important risk factor for cardiovascular and renal morbidity. The aim of the study was to examine the associations of UA in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort.

Design and method:
In 1987, we established the Hanzhong Adolescent Hypertension Study cohort based on a baseline survey of 4623 adolescents aged 6–15 years in Hanzhong, Shaanxi, China.
1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD.
2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline.

Results:
In cross-sectional analysis, uACR levels were positively correlated with serum UA (β = 0.093, P < 0.001), and urinary uric acid/creatinine ratio (uUA/Cre) (β = 0.042, P = 0.041). eGFR was negatively associated with serum UA (β = −0.300, P < 0.001) but positively associated with uUA/Cre levels (β = 0.086, P < 0.001) in all subjects. Furthermore, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255–5.664) for uUA/Cre. We further assessed the effect of UA excretion on the risk of SRD when uUA/Cre was modelled in quartiles. After adjusting for multiple confounders, the ORs (95% CIs) of SRD across increasing quintiles of uUA/Cre were 1.00, 1.122 (0.756–1.664), 1.362 (0.928–1.998) and 2.480 (1.719–3.578) (P for trend < 0.001). In longitudinal analysis, 4-year changes in uUA/Cre (β = −0.114, P = 0.040) and serum UA (β = 0.187, P = 0.001) were significantly associated with eGFR decline.

Conclusions:
This study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.
RENAL PROTECTIVE EFFECTS OF URIC ACID-LOWERING THERAPY IN HYPERTENSIVE PATIENTS BY TOPIROXOSTAT AND FEBXOSTAT, NEWLY AVAILABLE XANTHINE OXIDASE INHIBITORS
Authors: Satoh Fumitoshi , Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Yamanami Hiroaki , Morimoto Ryo , Ito Sadayoshi 
Published: April 2021

Objective:
Elevated serum uric acid were related not only with cardiovascular disease but also with higher incident of chronic kidney disease in many cohort studies. Lower eGFR and higher urine albumin to creatine ratio (UACR) are associated with all-cause and cardiovascular mortality as well as future renal end-stage. Febxostat (FBX) and topiroxostat (TPX), new xanthine oxidase inhibitors with much less side effects as comparison to allopurinol, are available now. To demonstrate the effects of FBX and TPX on renal functions (eGFR and UACR) in well-controlled hypertensive patients.

Design and method:
We retrospectively collected 252 well-controlled hypertensive patients with hyperuricemia (HU) who newly received a prescription of FBX or TPX and continued 24 weeks without the addition of any other drugs. Those who had other uric acid-lowering drugs, diabetes mellitus or severe proteinuria were excluded. Total 252 Participants were selected and divided into FBX (128 patients) group and TPX (124 patients) group, both of who were matched for % mean dose/dairy conventional dose, age, sex, uric acid (UA), blood pressure (BP), UACR and eGFR. The changes of UA, BP, eGFR and UACR were evaluated between at the baseline and at the 24-week treatment by FBX and TPX.

Results:
The baseline characteristics were not significantly different between both treatment groups, which were analyzed by Mann-Whitney U test. Administration of FBX and TPX lowered UA significantly (p < 0.0001). Decrements of UA in both group were not significantly different. Diastolic BP of FBX group was only significantly reduced (BP129.3 ± 17.8/78.7 ± 12.4 mmHg to BP126.1 ± 16.3/76.2 ± 11.1 mmHg, p = 0.049). The eGFR in both FBX group and TPX group were significantly increased from 55.2 ± 15.0 to 56.8 ± 15.7 mL/min/1.73m2 (p = 0.0082) and from 57.3 ± 16.3 to 61.5 ± 16.3 mL/min/1.73m2 (p = 0.0002), respectively. In TPX and FBX groups, there were no significant differences in change of eGFR between patients using high and low amount of TPX and FBX, respectively. UACR was significantly decreased only in TPX group(90.0 ± 336 mg/gCr to 48.9 ± 171 mg/gCr, p = 0.027), while UACR in FBX group was not reduced (113 ± 376 mg/gCr to 120 ± 488 mg/gCr).

Conclusions:
FBX could improve eGFR and diastolic BP, and TPX could renoprotectively reduce UACR as well as increase eGFR.
HEALTH RELATED QUALITY OF LIFE AMONG HAEMODIALYSIS AND KIDNEY TRANSPLANT RECIPIENTS FROM NEPAL: A CROSS SECTIONAL STUDY USING WHOQOL-BREF
Authors: Ranabhat Kamal , Mishra Shiva Raj , Khanal Pratik , Adhikari Bhoj Raj , Sigdel Mahesh Raj , Pradhan Bandana 
Published: April 2021

Objective:
Very less is known about health-related quality of life (HRQOL) among patients with kidney diseases in Nepal. This study examined HRQOL among haemodialysis and kidney transplant recipients in Nepal.

Design and method:
The Nepali version of World Health Organization Quality of Life Instruments -(WHOQOL-BREF) questionnaire was administered using face to face interviews among end stage renal disease (ESRD) patients, from two large national referral centers in Nepal. The differences in socio-demographic characteristics among ESRD patients were examined using the Chi-square test. The group differences in quality of life (QOL) were examined using the Mann-Whitney U test and Kruskal-Wallis tests.

Results:
Of the 161 participants, 92 (57.1%) were renal transplant recipients and 62 (42.9%) patients were on maintenance haemodialysis. Hypertension (70.9%) was the most common co-morbidity among ESRD patients. Haemodialysis patients scored significantly lower than the transplant recipients in all four domains as well as in overall perception of quality of life and general health. Ethnicity (p = 0.020), socio-economic status (p < 0.001), educational status (p < 0.001) and employment status (p = 0.009) were significantly associated with the overall QOL in ESRD patients. Across patient groups, educational status (p = 0.012) was positively associated with QOL in dialysis patients, while urban residence (p = 0.023), higher socio-economic status (p < 0.001), higher educational status (p = 0.004) and diabetes status (p = 0.010) were significantly associated with better QOL in transplant recipients.

Conclusions:
The overall QOL of the renal transplant recipients was higher than that of the patients on maintenance haemodialysis; this was true in all four domains of the WHOQOL-BREF. ESRD patients with low HRQOL could benefit from targeted risk modification intervention.
ORAL ETHINYLESTRADIOL-LEVONORGESTREL COUNTERACTS FRUCTOSE IMPACTS ON RENAL METABOLIC FUNCTION IN FEMALE WISTAR RATS
Authors: Olaniyi Kehinde , Olatunji Lawrence 
Published: April 2021

Objective:
Renal function is critical in the regulation of cardiovascular parameters such as blood pressure and endothelial factors. However, evidence suggests that the excessive intake of fructose (FRU) induces insulin resistance (IR)-associated renal impairment, which perhaps contribute to global increase in cardiovascular disease (CVD). Similarly, the use of estrogen-progestin formulation of oral contraceptive (EEL) has been associated with metabolic disruption with consequent attendant CVD risk factors, and its non-contraceptive benefits especially in metabolic pathologies remain inconclusive. Therefore, the present study was designed to investigate the effects of EEL on renal metabolic function in female rats exposed to high fructose drink.

Design and method:
Female Wistar rats weighing 140–170 g were randomly allotted into control, EEL, FRU and EEL+FRU groups (6 rats per group). The groups received vehicle (p.o.), EEL containing 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel (p.o.), fructose (10%; w/v) and EEL plus FRU respectively, daily for 8 weeks. Insulin resistance, pancreatic beta-cell function and insulin sensitivity were estimated by homeostatic model of assessment (HOMA-IR), HOMA-beta and quantitative insulin sensitivity check index (QUICKI) respectively. Plasma and tissue biochemical parameters were determined using enzyme-linked immunosorbent assay kits or fluorescence assay as appropriate.

Results:
Data revealed that FRU or EEL caused IR, impaired glucose tolerance and hyperinsulinemia with corresponding increase in plasma or renal triglyceride, total cholesterol, atherogenic lipid, xanthine oxidase, uric acid, lactate synthesis, renal glycogen synthesis, decreased plasma or renal adenosine, glucose-6-dehydrogenase (G6PD) and glutathione (GSH). High fructose but not EEL increased plasma glucose, urea and creatinine, plasma or renal gamma-glutamyl transferase, malondialdehyde and decreased plasma or renal NO and pancreatic beta-cell function. Interestingly, these alterations were attenuated when EEL was concomitantly administered with FRU exposure.

Conclusions:
The results of the study demonstrate that high fructose intake causes renal impairment, attributable to lipid and glycogen deposition, and collectively accompanied by excessive lipid peroxidation, impaired NO/adenosine-dependent endothelial function and defective G6PD/GSH-dependent antioxidant defense. The findings also suggest that EEL blots the renal effects of high fructose by possibly improving insulin sensitivity, endothelial function and antioxidant defense.
THE INFLUNECE OF PULSE WAVE VELOCITY ON RENAL FUNCTION IN CHINESE EARLY KIDNEY DYSFUNCTION POPULATION: RESULTS FROM A LARGE-SCALE CROSS-SECTIONAL AND A 5-YEAR LOGITUDINAL STUDY
Authors: Len Yiming , Lu Yao , Yuan Hong 
Published: April 2021

Objective:
Extensive researches show that arterial stiffness has been associated with chronic kidney disease, but the association with deterioration of renal function and its progression still remains unclear. We sought to investigate the relevance between arterial stiffness and the dynamic changes of renal function in Chinese populations,with or without chronic kidney disease.

Design and method:
This large-scale observational study comprised one cross-sectional and one longitudinal population samples totalling 655289 individuals, aged 21 to 74 years (mean age = 42.8 ± 12.7 years) from the Health Management Center in the Third Xiangya Hospital of Central South University with brachial-ankle pulse wave velocity (baPWV) measurements available. Associations with potential risk conditions were analysed using linear regression and linear mixed-effects models.

Results:
After adjusted for age,sex, BMI and MAP,baPWV showed a negative correlation with individuals with renal dysfunction (−0.01,−0.015∼-0.004,p < 0.001).Notably,it did not show significant correlation with individuals whose renal function was normal. The change of PWV was negatively associated with eGFR. The 5-year increase in PWV was associated with decrease in eGFR (−0.02,−0.035∼−0.012,p < 0.001) in mixed effect models adjusted for age, sex, ethnicity, age, BMI, and MAP.

Conclusions:
The increase of PWV showed extraordinary relevance among patients with the progression of kidney dysfunction rather than patients with normal kidney function,suggesting PWV measurement may help prompt the deterioration of kidney function. The current study may unravel a new understanding of the role arterial stiffening played in kidney dysfunction and set ground for the further clinical use as an early warning indicator.
LOCALIZATION OF NATRIURETIC PEPTIDE RECEPTORS IN HUMAN KIDNEY TISSUE
Authors: Jensen Mia , Frees Andreas , Assersen Kasper Bostlund , Madsen Kirsten , Lund Lars , Zamani Reza , Toft Anja , Hansen Pernille B. Lærkegaard , Schweda Frank , Jensen Boye Lagerbon 
Published: April 2021

Objective:
Subsequent to partial and total nephrectomy, the remaining kidney tissue compensates by functional adaption. The glomerular filtration rate (GFR) and the renal blood flow increases. The post-nephrectomy GFR increases rapidly (as early as 8 h) from 50% up to 65–80% compared to pre-nephrectomy. The molecular mechanism is still unexplained. We hypothesized that the cardiac hormones atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) could mediate this response and thus, that their receptors would be expressed in the human kidney preglomerular vasculature, both in smooth muscle and in endothelial cells.
This study was conducted to localize the Natriuretic Peptide Receptor A (NPRA) and C (NPRC) at mRNA and protein level in human kidney tissue.

Design and method:
The localization of the receptors was investigated by; 1) determining vascular reactivity ex vivo in human intrarenal arteries in response to ANP and BNP; 2) microdissection of vessels and glomeruli from nephrectomy specimens followed by polymerase chain reaction (PCR); 3) immunohistochemistry and fluorescence analyses of fixed-paraffin embedded kidney sections and 4) RNAscope detection of mRNA in tissue sections.

Results:
ANP and BNP caused relaxation of K+-precontracted human arteries. NPRC mRNA was uniformly present in all arteries whereas NPRB was not detected and NPRA was seemingly less abundant in microvessels NPRC. Both NPRA and -C were observed in isolated glomeruli by PCR. NPRA was associated with glomeruli, glomerular podocytes and parietal layer of Bowman's capsule but not mesangial cells. Arteries, arterioles and vasa recta displayed uniform immunolabeling associated with endothelium across sex and age of the patients whereas vascular smooth muscle cells were more faintly and non-uniformly labeled. NPRA was detected in both the descending and ascending vasa recta. No labeling of tubular compartment for NPRA was seen. NPRB was not detected in human kidney tissue. By RNAscope on kidney sections, NPRC was observed in glomeruli but also in proximal tubules and collecting ducts.

Conclusions:
We conclude that functional NPRA and NPRC are located in human renal tissue, both NPRA and -C are found in the vasculature and could be involved in the acute increase of the GFR following nephrectomy.
EFFECTS OF NUCLEAR FACTOR OF ACTIVATED T-CELLS 5 (NFAT5) KNOCKOUT IN RENAL TUBULAR CELLS ON RENAL FIBROGENESISNFAT5 (NUCLEAR FACTOR OF ACTIVATED T-CELLS 5) IS A TRANSCRIPTION FACTOR
Authors: Izumi Yuichiro , Ono Makoto , Eguchi Koji , Matsuo Naomi , Hiramatsu Akiko , Nakayama Yushi , Inou Hideki , Kakizoe Yutaka , Kuwabara Takashige , Mukoyama Masashi 
Published: April 2021

Objective:
NFAT5 (nuclear factor of activated T-cells 5) is a transcription factor that stimulates the expression of osmoprotective genes in response to extracellular hypertonicity, contributing to cell survival even in extreme hypertonic conditions as seen in renal medulla. Recent studies have suggested that activation of NFAT5 in macrophages in the skin induces lymphangiogenesis in response to high-salt diet, alleviating salt-sensitive hypertension. Pathophysiological roles of NFAT5 in the kidney, however, are still obscure. Not only hypertonicity but also hypoxia, oxidative stress, and toll-like receptor signaling, which promote fibrogenesis in the kidney, have been suggested to increase the NFAT5 activity. In the present study, the role of NFAT5 in renal fibrogenesis was examined using renal tubular cell-specific NFAT5 conditional knockout mice.

Design and method:
We generated renal tubular cell-specific NFAT5 conditional knockout (cKO) mice by crossing NFAT5 floxed mice with Pax8-rtTA/LC-1 mice, in which Cre recombinase was specifically expressed in renal tubular cells by the treatment with doxycycline. Wild-type (WT) mice and NFAT5 cKO mice were subjected to unilateral ureteral obstruction (UUO) or sham-operation. After 7 days, mice were sacrificed and kidneys were removed. The mRNA expression levels of NFAT5 and markers for fibrogenesis (TGF-beta, alfa-SMA, CCL2, Col1, Col3, KIM-1, and NGAL) in the kidney were examined by real-time PCR. Renal fibrosis was evaluated by Azan staining.

Results:
In WT mice, the expression of NFAT5 mRNA was two times greater in the kidney from UUO mice than that from sham-operated mice. Expressions of fibrogenesis-related genes were significantly increased in the kidney from UUO mice compared with those from sham-operated mice. In the UUO groups, the expressions of fibrogenesis-related mRNAs were significantly higher in the kidney from NFAT5 cKO mice compared with those from WT mice. Azan staining showed that UUO-induced renal fibrosis tended to get worse in NFAT5 cKO mice compared to WT mice.

Conclusions:
NFAT5 in renal tubular cells may exert protective actions against the development of renal fibrosis caused by UUO.
EPIDEMIOLOGY OF HYPERTENSION AMONG PATIENTS ON HEMODIALYSIS AND THE SIGNIFICANCE OF VOLUME OVERLOAD
Authors: Tsikliras N. , Georgianos P. , Karpetas A. , Minasidis E. , Syrganis C.H. , Anagnostara A. , Chatzidimitriou C. , Pikilidou M. , Liakopoulos V. , Zebekakis P. , Balaskas E. 
Published: April 2021

Objective:
Earlier cross-sectional studies provided variable estimates of the prevalence and control of hypertension among patients on hemodialysis due to their heterogeneity in definitions and because they were based mainly on routine blood pressure (BP) recordings obtained within the dialysis-unit. The aim of the present study was to explore the epidemiology of hypertension in hemodialysis using home BP monitoring (HBPM).

Design and method:
A total of 120 prevalent hemodialysis patients underwent HBPM over 1 week with the validated automatic device HEM-705 CP (Omron, Healthcare). BP was recorded 3 times daily — on awaking up, between noon and at bedtime. The volume status of participants was assessed via bioelectrical-impendence-analysis (BIA) after the completion of the mid-week dialysis session using the BCM monitor (Fresenius Medical Care, Germany).

Results:
Hypertension (defined as 1-week averaged home BP higher than 135/85 mmHg or current use of antihypertensive medications) was detected in 88.8% of participants. Although 92.2% of hypertensives were being treated with an average of 2.0 BP-lowering medications, adequate control of home BP was achieved in only 32.6%. In multivariate logistic regression analysis, compared with those participants not receiving antihypertensive treatment (reference category), the odds ratio (OR) for uncontrolled hypertension was 3.15 for those receiving 1 antihypertensive, 3.85 for those receiving 2 antihypertensives and 18.1 for those receiving above 3 antihypertensives (P = 0.028 for the interaction). Each 1 L higher postdialysis overhydration was associated with 1.72 higher OR for uncontrolled home BP (P = 0.002).

Conclusions:
Hypertension in hemodialysis diagnosed by HBPM is highly prevalent and remains poorly controlled. Excessive antihypertensive drug use and extracellular volume expansion appear to be the strongest determinants of inadequate BP control in this population.
THE ROLE OF CALCIUM IN UROMODULIN EXPRESSION AND SECRETION FROM RENAL MEDULLARY EPITHELIAL CELLS OF HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Boder Philipp , Mary Sheon , Graham Lesley , Delles Christian 
Published: April 2021

Objective:
Uromodulin (UMOD) is the most abundantly secreted protein found within the urine, primarily produced by medullary thick ascending limb (mTAL) epithelial cells of the kidneys. There is accruing genetic evidence implicating UMOD in blood pressure regulation and consequently hypertension. The aim of this study was to investigate the potential role of extracellular calcium and the calcium-sensing receptor (CaSR) on UMOD production and secretion in TAL cells with the hope of defining novel clinical targets for the treatment of hypertension.

Design and method:
mTAL tubules from Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) female rats were incubated with calcium, nifedipine (calcium channel blocker), CaSR agonist (spermine) and antagonist (NPS2143). UMOD protein levels were detected by Western blot. Gene expression of Umod was determined by qRT-PCR.

Results:
Calcium increased mTAL UMOD secretion in WKY and SHRSP. Nifedipine slightly decreased UMOD secretion in WKY without calcium. In both strains, NPS2143 increased calcium-induced UMOD secretion, with an enhanced effect in SHRSP. Stimulation of CaSR with spermine decreased UMOD secretion in WKY. Analysis of intracellular UMOD levels in these conditions demonstrated increased accumulation when extracellular secretion was low, and vice versa. Incubation of primary mTAL cells with calcium confirmed increased localisation of UMOD at the membrane compared to cytosol. The Umod mRNA level changes were not statistically significant among conditions.

Conclusions:
Trafficking of UMOD is influenced by the CaSR ligand and the biased nature of G-protein coupled CaSR signalling. Unravelling the signalling events post-calcium will be necessary for identification of key regulators of UMOD secretion.