Architecture of the rat nephron-arterial network: analysis with micro-computed tomography
Among solid organs, the kidney’s vascular network stands out, because each nephron has two distinct capillary structures in series and because tubuloglomerular feedback, one of the mechanisms responsible for blood flow autoregulation, is specific to renal tubules. Tubuloglomerular feedback and the myogenic mechanism, acting jointly, autoregulate single-nephron blood flow. Each generates a self-sustained periodic oscillation and an oscillating electrical signal that propagates upstream along arterioles. Similar electrical signals from other nephrons interact, allowing nephron synchronization. Experimental measurements...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Marsh, D. J., Postnov, D. D., Rowland, D. J., Wexler, A. S., Sosnovtseva, O. V., Holstein-Rathlou, N.-H. Tags: RESEARCH ARTICLE Source Type: research
Magnesium improves cisplatin-mediated tumor killing while protecting against cisplatin-induced nephrotoxicity
Approximately 30% of all cancer patients treated with cisplatin, a widely used broad-spectrum chemotherapeutic agent, experience acute kidney injury (AKI). Almost all patients receiving cisplatin have magnesium (Mg) losses, which are proposed to aggravate AKI. Currently, there are no methods to successfully treat or prevent cisplatin-AKI. Whereas Mg supplementation has been shown to reduce AKI in experimental models and several small clinical trials, the effects of Mg status on tumor outcomes in immunocompetent tumor-bearing mice and humans have not been investigated. The purpose of this study was to further examine the ef...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Kumar, G., Solanki, M. H., Xue, X., Mintz, R., Madankumar, S., Chatterjee, P. K., Metz, C. N. Tags: RESEARCH ARTICLE Source Type: research
Cross-sex transplantation alters gene expression and enhances inflammatory response in the transplanted kidneys
In conclusion, cross-sex-KTX alters gene expression levels and induces inflammatory responses, which might play an important role in long-term graft function. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Wang, L., Song, J., Wang, S., Buggs, J., Chen, R., Zhang, J., Wang, L., Rong, S., Li, W., Wei, J., Liu, R. Tags: RESEARCH ARTICLE Source Type: research
Sodium storage in human tissues is mediated by glycosaminoglycan expression
The current paradigm regarding sodium handling in animals and humans postulates that total body sodium is regulated predominately via regulation of extracellular volume. Active sodium storage independent of volume retention is thought to be negligible. However, studies in animals, hypertensive patients, and healthy humans suggest water-free storage of sodium in skin. We hypothesized that tissue sodium concentrations ([Na]T) found in humans vary and reflect regulation due to variable glycosaminoglycan content due to variable expression of XYLT-1. Twenty seven patients on dialysis and 21 living kidney transplant donors free ...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Fischereder, M., Michalke, B., Schmöckel, E., Habicht, A., Kunisch, R., Pavelic, I., Szabados, B., Schönermarck, U., Nelson, P. J., Stangl, M. Tags: RESEARCH ARTICLE Source Type: research
IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through the JAK2/STAT3 signaling pathway
This study was designed to investigate the role of IL-6 in EMT and peritoneal membrane dysfunction in long-term PD patients by assessing the level of IL-6 in dialysate and exploring the relationship between IL-6, the related signaling pathway JAK2/STAT3, and EMT, using in vitro cellular and molecular techniques. Plasma and dialysate levels of IL-6 were significantly higher in PD ultrafiltration failure patients compared with patients without ultrafiltration failure and were negatively correlated with measures of PD adequacy. In vitro IL-6 treatment changed human peritoneal mesothelial cell phenotype from a typical cobblest...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Xiao, J., Gong, Y., Chen, Y., Yu, D., Wang, X., Zhang, X., Dou, Y., Liu, D., Cheng, G., Lu, S., Yuan, W., Li, Y., Zhao, Z. Tags: RESEARCH ARTICLE Source Type: research
Coping with nephron loss: transport at a price
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Weinstein, A. M. Tags: EDITORIAL FOCUS Source Type: research
PDGF receptor-{beta} uses Akt/mTORC1 signaling node to promote high glucose-induced renal proximal tubular cell collagen I ({alpha}2) expression
Increased expression of PDGF receptor-β (PDGFRβ) has been shown in renal proximal tubules in mice with diabetes. The core molecular network used by high glucose to induce proximal tubular epithelial cell collagen I (α2) expression is poorly understood. We hypothesized that activation of PDGFRβ by high glucose increases collagen I (α2) production via the Akt/mTORC1 signaling pathway in proximal tubular epithelial cells. Using biochemical and molecular biological techniques, we investigated this hypothesis. We show that high glucose increases activating phosphorylation of the PDGFRβ, resulting...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Das, F., Ghosh-Choudhury, N., Venkatesan, B., Kasinath, B. S., Ghosh Choudhury, G. Tags: RESEARCH ARTICLE Source Type: research
Hypoxia-inducible factor-1{alpha} activation improves renal oxygenation and mitochondrial function in early chronic kidney disease
In conclusion, we report significant impairment of renal oxygenation and mitochondrial function at the early stages of CKD and demonstrate the beneficial role of HIF-1α activation on renal function and metabolism. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Thomas, J. L., Pham, H., Li, Y., Hall, E., Perkins, G. A., Ali, S. S., Patel, H. H., Singh, P. Tags: RESEARCH ARTICLE Source Type: research
Urinary DcR2 is a novel biomarker for tubulointerstitial injury in patients with diabetic nephropathy
This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients who were diagnosed by renal biopsy. uDcR2 levels were measured by ELISA, and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2 and renal functional parameters were evaluated. Receiver operating characteristics (ROC) curve analyzed area under the curve (AUC) of uDcR2 for assessing TII. Double staining was undertaken for renal DcR2 with proximal and distal tubular markers; senescent ma...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Chen, J., Zhang, W.-W., Chen, K.-H., Lin, L.-R., Dai, H.-Z., Li, K.-L., Zhang, J.-G., Zheng, L.-Q., Fu, B.-Q., He, Y.-N. Tags: RESEARCH ARTICLE Source Type: research
Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury
Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription a...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: MacManes, M. D. Tags: RESEARCH ARTICLE Source Type: research
PGF2{alpha} regulates the basolateral K channels in the distal convoluted tubule
Our aim is to examine the role of PGF2α receptor (FP), a highly expressed prostaglandin receptor in the distal convoluted tubule (DCT) in regulating the basolateral 40-pS K channel. The single-channel studies demonstrated that PGF2α had a biphasic effect on the 40-pS K channel in the DCT–PGF2α stimulated at low concentrations (less than 500 nM), while at high concentrations (above 1 µM), it inhibited the 40-pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF2α (a metabolite of PGF2α) nor PGE2 was able to mimic the effect of PGF2α on the 40-pS K channel in the DCT. The ...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Wang, L., Zhang, C., Su, X.-T., Lin, D.-H., Wu, P., Schwartzman, M. L., Wang, W.-H. Tags: RESEARCH ARTICLE Source Type: research
A pseudo-three-dimensional model for quantification of oxygen diffusion from preglomerular arteries to renal tissue and renal venous blood
To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the 11 branching levels (known as "Strahler" orders) of the preglomerular renal vasculature in the rat, with an analysis of an extensive data set obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Furthermore, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, per...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Lee, C.-J., Ngo, J. P., Kar, S., Gardiner, B. S., Evans, R. G., Smith, D. W. Tags: RESEARCH ARTICLE Source Type: research
Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia
We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension (PtO2) or microvascular oxygen tension (µPo2) were within ±1 SE of the mean value observed experimentally. The predicted Pt...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Lee, C.-J., Gardiner, B. S., Ngo, J. P., Kar, S., Evans, R. G., Smith, D. W. Tags: RESEARCH ARTICLE Source Type: research
MicroRNA-148b regulates megalin expression and is associated with receptor downregulation in mice with unilateral ureteral obstruction
Megalin is a multiligand, endocytic receptor that is important for the normal, proximal tubule reabsorption of filtered proteins, hormones, enzymes, essential nutrients, and nephrotoxins. Megalin dysfunction has been associated with acute, as well as chronic kidney diseases. Tubular proteinuria has been observed following unilateral ureteral obstruction (UUO), suggesting megalin dysfunction; however, the pathophysiological mechanism has not been determined. To identify potential regulators of megalin expression, we examined renal microRNAs (miRNAs) expression and observed an upregulation of microRNA-148b (miR-148b) in obst...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Wen, L., Andersen, P. K., Husum, D. M. U., Norregaard, R., Zhao, Z., Liu, Z., Birn, H. Tags: RESEARCH ARTICLE Source Type: research
Adaptive changes in GFR, tubular morphology, and transport in subtotal nephrectomized kidneys: modeling and analysis
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevations in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat. Model simulations indicate that nephrectomy-induced SNGFR increa...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Layton, A. T., Edwards, A., Vallon, V. Tags: RESEARCH ARTICLE Source Type: research
