Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in Obstructive Nephropathy

Renal damage due to urinary tract obstruction accounts for up to 30% of acute kidney injury in paediatrics and adults. Bilateral ureteral obstruction (BUO) is associated with polyuria and reduced urinary concentrating capacity. We investigated the renal handling of water and electrolytes together with the renal expression and the urinary excretion of the Na-K-Cl cotransporter (NKCC2) after 1 (BUO-1), 2 (BUO-2), and 7 (BUO-7) days of release of BUO. Immunoblotting and immunohistochemical studies showed that NKCC2 expression was upregulated in apical membranes both from BUO-2 and from BUO-7 rats. The apical membrane expression, where NKCC2 is functional, may be sufficient to normalize water, potassium, sodium, and osmolytes tubular handling. NKCC2 abundance in homogenates and mRNA levels of NKCC2 was significantly decreased in almost all groups suggesting a decrease in the synthesis of the transporter. Urinary excretion of NKCC2 was increased in BUO-7 groups. These data suggest that the upregulation in the expression of NKCC2 in apical membranes during the postobstructive phase of BUO could contribute to improving the excretion of sodium and consequently also the excretion of potassium, osmolytes, and water. Moreover, the increase in urinary excretion of NKCC2 in BUO-7 group could be a potential additional biomarker of renal function recovery.

Download Full-text

Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction

International Journal of Molecular Sciences ◽

10.3390/ijms21155490 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5490 ◽

Cited By ~ 1

Author(s):

Satoshi Washino ◽

Keiko Hosohata ◽

Tomoaki Miyagawa

Keyword(s):

Renal Function ◽

Urinary Tract ◽

Interstitial Fibrosis ◽

Urinary Tract Obstruction ◽

Kidney Injury ◽

Upper Urinary Tract ◽

Obstructive Nephropathy ◽

Ureteral Stricture ◽

Kidney Injury Molecule 1 ◽

Upper Urinary Tract Obstruction

Partial or complete obstruction of the urinary tract is a common and challenging urological condition caused by a variety of conditions, including ureteral calculi, ureteral pelvic junction obstruction, ureteral stricture, and malignant ureteral obstruction. The condition, which may develop in patients of any age, induces tubular and interstitial injury followed by inflammatory cell infiltration and interstitial fibrosis, eventually impairing renal function. The serum creatinine level is commonly used to evaluate global renal function but is not sensitive to early changes in the glomerular filtration rate and unilateral renal damage. Biomarkers of acute kidney injury are useful for the early detection and monitoring of kidney injury induced by upper urinary tract obstruction. These markers include levels of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1, kidney injury molecule 1, N-acetyl-b-D-glucosaminidase, and vanin-1 in the urine and serum NGAL and cystatin C concentrations. This review summarizes the pathophysiology of kidney injury caused by upper urinary tract obstruction, the roles played by emerging biomarkers of obstructive nephropathy, the mechanisms involved, and the clinical utility and limitations of the biomarkers.

Download Full-text

Renal expression and urinary excretion of aquaporin-2 in postobstructive uropathy in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0481 ◽

2021 ◽

pp. 1-8

Author(s):

Anabel Brandoni ◽

Adriana M. Torres

Keyword(s):

Time Course ◽

Renal Cortex ◽

Renal Medulla ◽

Obstructive Nephropathy ◽

Kidney Cortex ◽

Mrna Levels ◽

Whole Cell Lysate ◽

Aquaporin 2 ◽

Immunohistochemical Techniques ◽

Apical Membranes

This work assessed the time course of water renal management together with aquaporin-2 (AQP2) kidney expression and urinary AQP2 levels (AQP2u) in obstructive nephropathy. Adult male Wistar rats were monitored after 1, 2, and 7 days of bilateral ureteral release (bilateral ureteral obstruction (BUO); BUO-1, BUO-2 and BUO-7). Renal water handling was evaluated using conventional clearance techniques. AQP2 levels were assessed by immunoblotting and immunohistochemical techniques. AQP2 expression in apical membranes was downregulated in BUO-1 rats and upregulated both in BUO-2 and BUO-7 animals. AQP2 protein expression in whole cell lysate fraction from kidney cortex and medulla were significantly decreased in all the experimental groups. Concomitantly, mRNA levels of AQP2 decreased in renal medulla of all groups and in renal cortex from BUO-1; however, in renal cortex from BUO-2 and BUO-7 a recovery and an increase in the level of AQP2 mRNA were, respectively, observed. BUO-7 group showed a significant increase in AQP2u. The alterations observed in apical membranes AQP2 expression could explain, at least in part, the evolution time of water kidney management in the postobstructive phase of BUO. Additionally, the AQP2u increase after 7 days of ureteral release may be postulated as a biomarker of improvement in the kidney function.

Download Full-text

Neonatal obstructive nephropathy induces necroptosis and necroinflammation

Scientific Reports ◽

10.1038/s41598-019-55079-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Bastian Popper ◽

Marian Theodor Rammer ◽

Mojca Gasparitsch ◽

Teresa Singer ◽

Ursula Keller ◽

...

Keyword(s):

Ureteral Obstruction ◽

Kidney Development ◽

Urinary Tract Obstruction ◽

Kidney Injury ◽

Kinase Domain ◽

Obstructive Nephropathy ◽

Tubular Necrosis ◽

Basement Membrane Thickening ◽

Tnf Α ◽

Kidney Injury Molecule 1

AbstractUrinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed necrosis mediated by the receptor-interacting serine/threonine-protein kinase-3 (RIPK3) and the pseudokinase mixed lineage kinase domain-like (MLKL). Necrosis induces inflammation and stimulates cell death in an autoamplification loop named necroinflammation. Here, we studied necroptosis and necroinflammation in obstructive nephropathy induced by unilateral ureteral obstruction (UUO) in neonatal C57Bl/6J mice. Ureteral obstruction induced tubular dilatation, tubular basement membrane thickening, cast formation, and increased expression of kidney injury molecule-1 (KIM-1). Morphological investigations showed either apoptotic or necrotic cells in the tubular compartment. Biochemical analysis revealed increased caspase-8 activity and upregulation of RIPK3 as well as phosphorylated-MLKL in UUO-kidneys. Pro-inflammatory cytokines (IL-1α, INF-γ, TNF-α) were upregulated following UUO. Taken together we show that necroptosis and necroinflammation are accompanied phenomena in neonatal kidneys with obstruction. These findings may help to develop novel strategies to treat congenital obstructive nephropathy.

Download Full-text

Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis

Liver International ◽

10.1111/liv.12047 ◽

2013 ◽

Vol 33 (3) ◽

pp. 398-409 ◽

Cited By ~ 58

Author(s):

Naina Shah ◽

Fatma E. Mohamed ◽

Maria Jover-Cobos ◽

Jane Macnaughtan ◽

Nathan Davies ◽

...

Keyword(s):

Acute Kidney Injury ◽

Urinary Excretion ◽

Kidney Injury ◽

Renal Expression

Download Full-text

Renal expression and urinary excretion of Na+/dicarboxylate cotransporter 1 (NaDC1) in obstructive nephropathy: a candidate biomarker for this pathology

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-018-2200-6 ◽

2018 ◽

Vol 470 (12) ◽

pp. 1777-1786 ◽

Cited By ~ 6

Author(s):

Romina V. Campagno ◽

María J. Severin ◽

Evangelina C. Nosetto ◽

Anabel Brandoni ◽

Adriana Mónica Torres

Keyword(s):

Urinary Excretion ◽

Obstructive Nephropathy ◽

Renal Expression

Download Full-text

Abstract P144: DHA is a Superior Treatment Over 12/15-lipoxygenase Inhibition in LPS-induced Acute Kidney Injury via Increased Resolvin D2 and IL-10 Levels

Hypertension ◽

10.1161/hyp.68.suppl_1.p144 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Mohamed Katary ◽

Nehal M Elsherbini ◽

Ahmed S Ibrahim ◽

Mohamed Al-Shabrawey ◽

Ahmed A Elmarakby

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Urinary Excretion ◽

Renal Injury ◽

Kidney Injury ◽

Intercellular Adhesion Molecule ◽

Protective Mechanism ◽

Thiobarbituric Acid Reactive Substance ◽

Omega 3 ◽

Renal Expression

Acute kidney injury (AKI) is characterized by loss of kidney function and is often associated with high mortality rate. The polyunsaturated, omega-3 fatty acid, docosahexaenoic acid (DHA), has a promising role in preventing AKI; however; DHA reno-protective mechanism remains unclear. Our aim is to investigate whether and how DHA attenuates lipopolysaccharide (LPS)-induced AKI. Four groups of wild type C57BL/6 (WT) mice were used; control, LPS injected (4 mg/kg i.p), LPS treated with the 12/15-lipoxygenase (12/15-LO) inhibitor baicalein (20 mg/kg i.p for 6 days) and LPS treated with DHA (50 mg/kg i.p for 6 days). LPS-injected mice showed significant elevation in markers of renal injury as urinary excretion levels of protein, podocalyxin and albumin were elevated compared to WT untreated mice (albuminuria was 112±4 vs. 8±1 μg/day and podocalyxin was 3.5±0.6 vs. 0.6±0.1 μg/day in LPS injected mice vs. control WT, P< 0.05). The elevation in renal injury markers were also associated with increases in urinary excretion of thiobarbituric acid reactive substance (TBARs), as a marker of oxidative stress and monocyte chemoattractant protein-1 (MCP-1), as a marker of inflammation, in LPS injected mice. Treatment of LPS injected mice with either DHA or baicalein significantly reduced markers of renal injury, inflammation and oxidative stress. DHA or baicalein treatment also significantly reduced the elevation in renal mRNA expression levels of intercellular adhesion molecule 1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in LPS injected mice. DHA was superior over baicalein in reducing renal expression of Interleukin-6 (IL-6) and IL-1β and in increasing the renal expression of the anti-inflammatory cytokine IL-10 in LPS injected mice. DHA reduced renal tubular necrosis and vaculated cells and lowered renal expression of CD45, a marker of leucocyte adhesion, in LPS injected mice. DHA also restored the decrease in plasma resolvin D2 (RvD2) in LPS injected mice. In conclusion, our data suggest that 12/15-LO activation is involved in LPS-induced acute kidney injury and DHA is a superior treatment over 12/15-LO inhibitor in preventing LPS-induced kidney injury, at least in part, via 12/15-LO-induced resolvin D2.

Download Full-text

Mineral Element Deposition and Gene Expression across Different Tissues of Cherry Valley Ducks

Animals ◽

10.3390/ani11010238 ◽

2021 ◽

Vol 11 (1) ◽

pp. 238

Author(s):

Qianqian Song ◽

Yi Zhang ◽

Hao Bai ◽

Li Zhong ◽

Xiaofan Li ◽

...

Keyword(s):

Significant Negative Correlation ◽

Mineral Elements ◽

Breast Muscle ◽

Thigh Muscle ◽

Mrna Levels ◽

High Quality ◽

Atomic Fluorescence ◽

Breeding Efficiency ◽

Almost All ◽

Different Tissues

This study was conducted to investigate the deposition of several mineral elements and the mRNA levels of mineral-related genes across different tissues of cherry valley ducks. The contents of magnesium (Mg), potassium (K), zinc (Zn), and selenium (Se) in ducks’ breast muscle, thigh muscle, liver, skin, and tibia at the age of 0, 21, 35, 49, and 63 days, respectively, were measured using an atomic fluorescence spectrophotometer, while the mRNA levels of mineral-related genes were detected by qRT-PCR. The results revealed that the dynamics of Mg and K were generally similar in each tissue, with a significant positive correlation (p < 0.05). In the breast muscle, thigh muscle, and liver, the contents of almost all mineral elements reached their peak values (p < 0.05) at the age of 49 to 63 days. Interestingly, the expression of most mineral-related genes was the highest at birth (p < 0.05). In addition, there was a significant negative correlation between the expression of ATP1A1 and the deposition of K (r = −0.957, p < 0.05), and a similar result was found for the expression of ATP8 and the deposition of Zn (r = −0.905, p < 0.05). Taken together, Mg and K could be used as joint indicators for the precise breeding of the high-quality strain of cherry valley ducks, while the age of 49 to 63 days could be used as the reference for the best marketing age. In addition, ATP1A1 and ATP8 could be used as the key genes to detect K and Zn, respectively. Hence, the findings of this study can be used to improve the production and breeding efficiency of high-quality meat ducks.

Download Full-text

Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

Scientific Reports ◽

10.1038/s41598-020-80940-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maki Murakoshi ◽

Tomohito Gohda ◽

Eri Adachi ◽

Saki Ichikawa ◽

Shinji Hagiwara ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Kidney Injury ◽

Proximal Tubules ◽

Tubular Damage ◽

Standard Diet ◽

Mrna Levels ◽

High Fat ◽

Organ Specific

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.

Download Full-text

Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats

AJP Renal Physiology ◽

10.1152/ajprenal.00184.2017 ◽

2018 ◽

Vol 314 (4) ◽

pp. F584-F601 ◽

Cited By ~ 21

Author(s):

Siree Asvapromtada ◽

Hiroko Sonoda ◽

Minami Kinouchi ◽

Sayaka Oshikawa ◽

Saki Takahashi ◽

...

Keyword(s):

Renal Fibrosis ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Interacting Protein ◽

Aquaporin 1 ◽

Water Handling ◽

Marker Proteins ◽

Apical Trafficking ◽

Renal Expression

Acute kidney injury (AKI) is an important risk factor for the development of chronic kidney disease (CKD), and an alteration in renal water handling has been observed during the transition of AKI to CKD. Urinary exosomal release of aquaporin-1 (AQP1) and AQP2, important proteins for renal water handling, has recently been reported to predict their levels of renal expression. Therefore, we examined the patterns of urinary exosomal release of AQP1 and AQP2, and the exosomal marker proteins tumor susceptibility 101 protein (TSG101) and ALG-2 interacting protein X (Alix), in the acute and chronic phases following induction of AKI by renal bilateral ischemia/reperfusion (I/R) in rats. Blood tests and histological examinations indicated that AKI occurred before at 7 days after renal I/R ( day 7) and that renal fibrosis developed progressively thereafter. Immunoblotting demonstrated significant decreases in the urinary exosomal release of AQP1 and AQP2 during severe AKI. Urinary exosomal release of Alix and TSG101 was significantly increased on day 7. These data were also confirmed in rats with unilateral renal I/R causing more serious AKI. Urinary exosomal release of either the Ser-256- or Ser-269-phosphorylated form of AQP2, both of which are involved in apical trafficking of AQP2, was positively correlated with that of total AQP2. These results suggest that urinary exosomal release of AQP1 and AQP2 is reduced in I/R-induced AKI, whereas that of Alix and TSG101 is increased in the initial phase of renal fibrosis. Furthermore, apical trafficking of AQP2 appears to be related to urinary exosomal release of AQP2.

Download Full-text