Adaptive functional change of the contralateral kidney after partial nephrectomy
Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1: <30 m...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Choi, S. Y., Yoo, S., You, D., Jeong, I. G., Song, C., Hong, B., Hong, J. H., Ahn, H., Kim, C.-S. Tags: RESEARCH ARTICLE Source Type: research
Urinary adenosine excretion in type 1 diabetes
In conclusion, SGLT2i increases urinary adenosine excretion under clamped hyperglycemic conditions in patients with T1D. The potentially protective role of SGLT2i against glomerular hyperfiltration and its mediation by adenosine in diabetes merits further study. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Rajasekeran, H., Lytvyn, Y., Bozovic, A., Lovshin, J. A., Diamandis, E., Cattran, D., Husain, M., Perkins, B. A., Advani, A., Reich, H. N., Kulasingam, V., Cherney, D. Z. I. Tags: RESEARCH ARTICLE Source Type: research
Sex-specific computational models of the spontaneously hypertensive rat kidneys: factors affecting nitric oxide bioavailability
The goals of this study were to 1) develop a computational model of solute transport and oxygenation in the kidney of the female spontaneously hypertensive rat (SHR), and 2) apply that model to investigate sex differences in nitric oxide (NO) levels in SHR and their effects on medullary oxygenation and oxidative stress. To accomplish these goals, we first measured NO synthase (NOS) 1 and NOS3 protein expression levels in total renal microvessels of male and female SHR. We found that the expression of both NOS1 and NOS3 is higher in the renal vasculature of females compared with males. To predict the implications of that fi...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Chen, Y., Sullivan, J. C., Edwards, A., Layton, A. T. Tags: RESEARCH ARTICLE Source Type: research
Intravital imaging of the kidney in a rat model of salt-sensitive hypertension
Hypertension is one of the most prevalent diseases worldwide and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes ...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Endres, B. T., Sandoval, R. M., Rhodes, G. J., Campos-Bilderback, S. B., Kamocka, M. M., McDermott-Roe, C., Staruschenko, A., Molitoris, B. A., Geurts, A. M., Palygin, O. Tags: RESEARCH ARTICLE Source Type: research
Novel contrast mixture improves bladder wall contrast for visualizing bladder injury
Here, we tested whether combined contrast-enhanced magnetic resonance imaging (CCE-MRI), using a mixture of gadolinium- and iron oxide-based contrast agents, can segment the bladder wall from the bladder lumen. CCE-MRI relies on the differences in particle size and contrast mechanisms of two agents for improved image contrast. Under isoflurane anesthesia, T1-weighted imaging of adult female Sprague-Dawley rat bladder was performed using standard turbospin echo sequences at 7 Tesla, before and after transurethral instillation of 0.3 ml of single-contrast MRI or CCE-MRI composed of 0.4–64 mM of gadolinium chelate (Gd-D...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Tyagi, P., Janicki, J. J., Hitchens, T. K., Foley, L. M., Kashyap, M., Yoshimura, N., Kaufman, J. Tags: RESEARCH ARTICLE Source Type: research
Renal cell carcinoma: new insights and challenges for a clinician scientist
There is a growing recognition of the complex interplay between renal cell cancer (RCC), kidney function, mechanical reduction of nephron mass, and systemic agents targeting the cancer. Earlier detection of RCC and rising life expectancy of cancer survivors places a greater emphasis on preservation of renal function after cancer resection and during systemic therapy. Unique adverse effects associated with RCC drugs not only help reveal cancer pathophysiology but also expand our knowledge of normal cell signaling and metabolism. In this review, we outline our current understanding of RCC biology and treatment, their bidirec...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Shingarev, R., Jaimes, E. A. Tags: PERSPECTIVE Source Type: research
Inflammatory cytokines regulate renal sodium transporters: how, where, and why?
Hypertension is growing in epidemic proportions worldwide and is now the leading preventable cause of premature death. For over a century, we have known that the kidney plays a critical role in blood pressure regulation. Specifically, abnormalities in renal sodium transport appear to be a final common pathway that gives rise to elevated blood pressure regardless of the nature of the initial hypertensive stimulus. However, it is only in the past decade that we have come to realize that inflammatory cytokines secreted by innate and adaptive immune cells, as well as renal epithelial cells, can modulate the expression and acti...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Norlander, A. E., Madhur, M. S. Tags: REVIEW Source Type: research
Involvement of ENaC in the development of salt-sensitive hypertension
Salt-sensitive hypertension is associated with renal and vascular dysfunctions, which lead to impaired fluid excretion, increased cardiac output, and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron that plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions. In this mini-review, we summarize recent studies investigating the role of ENaC in ...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Pavlov, T. S., Staruschenko, A. Tags: REVIEW Source Type: research
Slowly cycling Rho kinase-dependent actomyosin cross-bridge "slippage" explains intrinsic high compliance of detrusor smooth muscle
Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displaye...
Source: AJP: Renal Physiology - July 7, 2017 Category: Urology & Nephrology Authors: Neal, C. J., Lin, J. B., Hurley, T., Miner, A. S., Speich, J. E., Klausner, A. P., Ratz, P. H. Tags: RESEARCH ARTICLE Source Type: research
Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction
Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion changes in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary pro...
Source: AJP: Renal Physiology - July 7, 2017 Category: Urology & Nephrology Authors: Lee, H.-W., Osis, G., Handlogten, M. E., Verlander, J. W., Weiner, I. D. Tags: RESEARCH ARTICLE Source Type: research
Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through a TLR4-TRIF-PI3K signaling pathway
Monophosphoryl lipid A (MPLA) is a detoxified derivative of LPS that induces tolerance to LPS and augments host resistance to bacterial infections. Previously, we demonstrated that LPS inhibits HCO3– absorption in the medullary thick ascending limb (MTAL) through a basolateral Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-ERK pathway. Here we examined whether pretreatment with MPLA would attenuate LPS inhibition. MTALs from rats were perfused in vitro with MPLA (1 µg/ml) in bath and lumen or bath alone for 2 h, and then LPS was added to (and MPLA removed from) the bath solution. Pretreat...
Source: AJP: Renal Physiology - July 7, 2017 Category: Urology & Nephrology Authors: Watts, B. A., George, T., Sherwood, E. R., Good, D. W. Tags: RESEARCH ARTICLE Source Type: research
Urothelial proliferation and regeneration after spinal cord injury
The basal, intermediate, and superficial cell layers of the urothelium undergo rapid and complete recovery following acute injury; however, the effects of chronic injury on urothelial regeneration have not been well defined. To address this discrepancy, we employed a mouse model to explore urothelial changes in response to spinal cord injury (SCI), a condition characterized by life-long bladder dysfunction. One day post SCI there was a focal loss of umbrella cells, which are large cells that populate the superficial cell layer and normally express uroplakins (UPKs) and KRT20, but not KRT5, KRT14, or TP63. In response to SC...
Source: AJP: Renal Physiology - July 7, 2017 Category: Urology & Nephrology Authors: Kullmann, F. A., Clayton, D. R., Ruiz, W. G., Wolf-Johnston, A., Gauthier, C., Kanai, A., Birder, L. A., Apodaca, G. Tags: RESEARCH ARTICLE Source Type: research
Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy
Podocytes are highly differentiated epithelial cells wrapping glomerular capillaries to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classic model of glomerular disease. We show that autophagy was induced by adriamycin in cultured podocytes in vitro and ...
Source: AJP: Renal Physiology - July 1, 2017 Category: Urology & Nephrology Authors: Yi, M., Zhang, L., Liu, Y., Livingston, M. J., Chen, J.-K., Nahman, N. S., Liu, F., Dong, Z. Tags: RESEARCH ARTICLE Source Type: research
Responses of distal nephron Na+ transporters to acute volume depletion and hyperkalemia
We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block of Na+ transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (HCTZ; 30 mg/kg) Na+ and K+ excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved -subunit) were detected. In contrast, amiloride (0.6 mg/kg) evoked a similar natriu...
Source: AJP: Renal Physiology - July 1, 2017 Category: Urology & Nephrology Authors: Frindt, G., Yang, L., Uchida, S., Weinstein, A. M., Palmer, L. G. Tags: RESEARCH ARTICLE Source Type: research
Saving the sweetness: renal glucose handling in health and disease
Glucose homeostasis is highly controlled, and the function of the kidney plays an integral role in this process. The exquisite control of blood glucose relies, in part, on renal glucose filtration, renal glucose reabsorption, and renal gluconeogenesis. Particularly critical to maintaining glucose homeostasis is the renal reabsorption of glucose; with ~162 g of glucose filtered by the kidney per day, it is imperative that the kidney have the ability to efficiently reabsorb nearly 100% of this glucose back in the bloodstream. In this review, we focus on this central process, highlighting the renal transporters and regulators...
Source: AJP: Renal Physiology - July 1, 2017 Category: Urology & Nephrology Authors: Shepard, B. D., Pluznick, J. L. Tags: REVIEW Source Type: research
