Interorgan handling of fibroblast growth factor-23 in humans
Fibroblast growth factor-23 (FGF-23) accumulates in blood of patients with chronic kidney disease (CKD) and is associated both with cardiovascular complications and disease progression. However, our knowledge of the sites and mechanisms that regulate plasma FGF-23 is still incomplete. We measured plasma intact FGF-23 across the kidney, splanchnic organs, and lung in 11 patients [estimated glomerular filtration rate (eGFR) 60 ± 6 ml/min] during elective diagnostic cardiac catheterizations. In these patients FGF-23 was removed by the kidney, with a fractional extraction (FE) of ~22%. The FE of FGF-23 across the kidney...
Source: AJP: Renal Physiology - January 31, 2017 Category: Urology & Nephrology Authors: Verzola, D., Ansaldo, F., Milanesi, S., Parodi, E. L., Rosa, G. M., Sofia, A., Bonanni, A., Viazzi, F., Balbi, M., Garibotto, G. Tags: RAPID REPORT Source Type: research
Collecting duct (pro)renin receptor targets ENaC to mediate angiotensin II-induced hypertension
The (pro)renin receptor (PRR) is abundantly expressed in the collecting duct (CD) and the expression is further induced by angiotensin II (ANG II). The present study was conducted to investigate the role of CD PRR during ANG II-induced hypertension and to further explore the underlying mechanism. Radiotelemetry demonstrated that a 1-wk ANG II infusion gradually and significantly induced hypertensive response in floxed mice and this response was significantly attenuated in mice lacking PRR in the CD (termed CD PRR KO). ANG II infusion in floxed mice increased urinary renin activity and selectively induced renal medullary &a...
Source: AJP: Renal Physiology - January 31, 2017 Category: Urology & Nephrology Authors: Peng, K., Lu, X., Wang, F., Nau, A., Chen, R., Zhou, S.-F., Yang, T. Tags: RESEARCH ARTICLE Source Type: research
Endoplasmic reticulum stress inhibition limits the progression of chronic kidney disease in the Dahl salt-sensitive rat
Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment. We assessed blood pressure and markers of CKD, including proteinuria, albuminuria, and renal p...
Source: AJP: Renal Physiology - January 8, 2017 Category: Urology & Nephrology Authors: Yum, V., Carlisle, R. E., Lu, C., Brimble, E., Chahal, J., Upagupta, C., Ask, K., Dickhout, J. G. Tags: ARTICLES Source Type: research
Nephron morphometry in mice and rats using tomographic microscopy
The aim was to quantify the glomerular capillary surface area, the segmental tubular radius, length, and area of single nephrons in mouse and rat kidneys. Multiple 2.5-µm-thick serial Epon sections were obtained from three mouse and three rat kidneys for three-dimensional reconstruction of the nephron tubules. Micrographs were aligned for each kidney, and 359 nephrons were traced and their segments localized. Thirty mouse and thirty rat nephrons were selected for further investigation. The luminal radius of each segment was determined by two methods. The luminal surface area was estimated from the radius and length o...
Source: AJP: Renal Physiology - January 8, 2017 Category: Urology & Nephrology Authors: Letts, R. F. R., Zhai, X.-Y., Bhikha, C., Grann, B. L., Blom, N. B., Thomsen, J. S., Rubin, D. M., Christensen, E. I., Andreasen, A. Tags: ARTICLES Source Type: research
Bimodal dynamics of granular organelles in primary renin-expressing cells revealed using TIRF microscopy
Renin is the initiator and rate-limiting factor in the renin-angiotensin blood pressure regulation system. Although renin is not exclusively produced in the kidney, in nonmurine species the synthesis and secretion of the active circulatory enzyme is confined almost exclusively to the dense core granules of juxtaglomerular (JG) cells, where prorenin is processed and stored for release via a regulated pathway. Despite its importance, the structural organization and regulation of granules within these cells is not well understood, in part due to the difficulty in culturing primary JG cells in vitro and the lack of appropriate...
Source: AJP: Renal Physiology - January 8, 2017 Category: Urology & Nephrology Authors: Buckley, C., Dun, A. R., Peter, A., Bellamy, C., Gross, K. W., Duncan, R. R., Mullins, J. J. Tags: ARTICLES Source Type: research
Antioxidant treatment attenuates lactate production in diabetic nephropathy
In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - January 8, 2017 Category: Urology & Nephrology Authors: Laustsen, C., Nielsen, P. M., Norlinger, T. S., Qi, H., Pedersen, U. K., Bertelsen, L. B., Ostergaard, J. A., Flyvbjerg, A., Ardenkjaer-Larsen, J. H., Palm, F., Stodkilde-Jorgensen, H. Tags: ARTICLES Source Type: research
An experimentum crucis in salt sensitivity
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - January 8, 2017 Category: Urology & Nephrology Authors: Pao, A. C., Chang, T. I. Tags: EDITORIAL FOCUS Source Type: research
Ion transport in the zebrafish kidney from a human disease angle: possibilities, considerations, and future perspectives
Unique experimental advantages, such as its embryonic/larval transparency, high-throughput nature, and ease of genetic modification, underpin the rapid emergence of the zebrafish (Danio rerio) as a preeminent model in biomedical research. Particularly in the field of nephrology, the zebrafish provides a promising model for studying the physiological implications of human solute transport processes along consecutive nephron segments. However, although the zebrafish might be considered a valuable model for numerous renal ion transport diseases and functional studies of many channels and transporters, not all human renal elec...
Source: AJP: Renal Physiology - January 8, 2017 Category: Urology & Nephrology Authors: Kersten, S., Arjona, F. J. Tags: REVIEW Source Type: research
A small molecule screening to detect potential therapeutic targets in human podocytes
Widmeier E, Tan W, Airik M, Hildebrandt F. A small molecule screening to detect potential therapeutic targets in human podocytes. Am J Physiol Renal Physiol 312: F157–F171, 2017. First published October 19, 2016; doi:10.1152/ajprenal.00386.2016. Steroid-resistant nephrotic syndrome (SRNS) inevitably progresses to end-stage kidney disease, requiring dialysis or transplantation for survival. However, treatment modalities and drug discovery remain limited. Mutations in over 30 genes have been discovered as monogenic causes of SRNS. Most of these genes are predominantly expressed in the glomerular epithelial cell, the po...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Widmeier, E., Tan, W., Airik, M., Hildebrandt, F. Tags: INNOVATIVE METHODOLOGY Source Type: research
The mechanosensitive BK{alpha}/{beta}1 channel localizes to cilia of principal cells in rabbit cortical collecting duct (CCD)
Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca2+- and/or stretch-dependent flow-induced K+ secretion (FIKS) and contributes to K+ adaptation in response to dietary K+ loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K+ secretory processes. In support of a role for ICs in FIKS is the higher density of immunoreactive apical BKα (pore-forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα expression in response to a high-K+ diet. PCs possess a...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Carrisoza-Gaytan, R., Wang, L., Schreck, C., Kleyman, T. R., Wang, W.-H., Satlin, L. M. Tags: RESEARCH ARTICLE Source Type: research
A new mouse model of hemorrhagic shock-induced acute kidney injury
Current animal models of hemorrhagic shock-induced acute kidney injury (HS-induced AKI) require extensive surgical procedures and constant monitoring of hemodynamic parameters. Application of these HS-induced AKI models in mice to produce consistent kidney injury is challenging. In the present study, we developed a simple and highly reproducible mouse model of HS-induced AKI by combining moderate bleeding and renal pedicle clamping, which was abbreviated as HS-AKI. HS was induced by retroorbital bleeding of 0.4 ml blood in C57BL/6 mice. Mice were left in HS stage for 30 min, followed by renal pedicle clamping for 18 min at...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Wang, L., Song, J., Buggs, J., Wei, J., Wang, S., Zhang, J., Zhang, G., Lu, Y., Yip, K.-P., Liu, R. Tags: RESEARCH ARTICLE Source Type: research
Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction
In conclusion, these findings suggested that mPGES-1 exerts a potentially protective effect against renal fibrosis and inflammation induced by UUO in mice. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Luo, R., Kakizoe, Y., Wang, F., Fan, X., Hu, S., Yang, T., Wang, W., Li, C. Tags: RESEARCH ARTICLE Source Type: research
Deletion of protein kinase C-{varepsilon} attenuates mitochondrial dysfunction and ameliorates ischemic renal injury
This study tested whether deletion of PKC- decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC- levels in mitochondria of ischemic kidneys increased 24 h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44 and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC--deficient (KO) mice after ischemia. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic ki...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Nowak, G., Takacsova-Bakajsova, D., Megyesi, J. Tags: RESEARCH ARTICLE Source Type: research
The native TRPP2-dependent channel of murine renal primary cilia
Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening monogenic renal disease. ADPKD results from mutations in either of two proteins: polycystin-1 (also known as PC1 or PKD1) or transient receptor potential cation channel, subfamily P, member 2 (TRPP2, also known as polycystin-2, PC2, or PKD2). Each of these proteins is expressed in the primary cilium that extends from many renal epithelial cells. Existing evidence suggests that the cilium can promote renal cystogenesis, while PC1 and TRPP2 counter this cystogenic effect. To better understand the function of TRPP2, we investigated its el...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: Kleene, S. J., Kleene, N. K. Tags: RESEARCH ARTICLE Source Type: research
Serine/threonine phosphatases and aquaporin-2 regulation in renal collecting duct
Phosphorylation of the aquaporin-2 (AQP2) water channel at four COOH-terminal serines plays a central role in the regulation of water permeability of the renal collecting duct. The level of phosphorylation at these sites is determined by a balance between phosphorylation by protein kinases and dephosphorylation by phosphatases. The phosphatases that dephosphorylate AQP2 have not been identified. Here, we use large-scale data integration techniques to identify serine-threonine phosphatases likely to interact with AQP2 in renal collecting duct principal cells. As a first step, we have created a comprehensive list of 38 S/T p...
Source: AJP: Renal Physiology - December 31, 2016 Category: Urology & Nephrology Authors: LeMaire, S. M., Raghuram, V., Grady, C. R., Pickering, C. M., Chou, C.-L., Umejiego, E. N., Knepper, M. A. Tags: RESEARCH ARTICLE Source Type: research
