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Bulletin of Mathematical Biology Jun 2016The mammalian kidney consumes a large amount of energy to support the reabsorptive work it needs to excrete metabolic wastes and to maintain homeostasis. Part of that...
The mammalian kidney consumes a large amount of energy to support the reabsorptive work it needs to excrete metabolic wastes and to maintain homeostasis. Part of that energy is supplied via the metabolism of glucose. To gain insights into the transport and metabolic processes in the kidney, we have developed a detailed model of the renal medulla of the rat kidney. The model represents water and solute flows, transmural fluxes, and biochemical reactions in the luminal fluid of the nephrons and vessels. In particular, the model simulates the metabolism of oxygen and glucose. Using that model, we have identified parameters concerning glucose transport and basal metabolism that yield predicted blood glucose concentrations that are consistent with experimental measurements. The model predicts substantial axial gradients in blood glucose levels along various medullary structures. Furthermore, the model predicts that in the inner medulla, owing to the relatively limited blood flow and low tissue oxygen tension, anaerobic metabolism of glucose dominates.
Topics: Anaerobiosis; Animals; Glucose; Kidney Medulla; Mathematical Concepts; Models, Biological; Oxygen Consumption; Rats
PubMed: 27371260
DOI: 10.1007/s11538-016-0188-7 -
Biological Trace Element Research Oct 2019In the body, disorders in the composition and concentration of trace elements, including copper, can lead to the development of various alterations that may result in...
In the body, disorders in the composition and concentration of trace elements, including copper, can lead to the development of various alterations that may result in incorrect functioning of the kidneys. Data on the concentrations of copper in human kidneys are discussed; however, little is known about the concentration of trace elements within rejected renal grafts and kidneys with tumor lesions. The aim of our study was to compare the copper concentration between cancerous kidneys and rejected renal grafts with the division on renal cortex and renal medulla. Material consisted of kidneys from patients hospitalized at the Department of Urology and General Surgery and Transplantation of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, north-western Poland. The study material consisted of kidneys with tumor lesions (n = 33), and renal grafts (n = 10), obtained from patients belongs to the north-western areas of Poland. The examination was performed using ICP-AES method. Regarding the pathological kidneys, excluding grafts, the concentration of Cu in the renal cortex was 52% higher than in medullary region and the difference between the compared concentrations was statistically confirmed (p < 0.05). Taking into account renal grafts, the concentration of Cu in the medulla was slightly lower than in the cortex (less than 3%). In summary, copper in rejected and cancerous kidneys tends to accumulate in higher amount in the renal cortex than medulla, what can be explained by the fact that renal corpuscles, where the first phase of filtration is performed, are located only in the cortical region of the kidney. Furthermore, renal grafts accumulate significantly less copper than kidneys with neoplastic changes, what could have been caused by immunosuppressive medicines used by the graft recipients. The lower copper concentration in renal grafts could be a consequence of the altered immune system, including inflammatory process or/and non-immune mechanisms. Additionally, cancerous and non-cancerous kidneys exhibit different perfusion rate in renal glomeruli, what can finally lead to disparity in chemical elements concentration, including copper.
Topics: Adult; Aged; Copper; Female; Humans; Kidney; Kidney Medulla; Kidney Neoplasms; Kidney Transplantation; Male; Middle Aged
PubMed: 30645698
DOI: 10.1007/s12011-018-1621-6 -
Kidney International Oct 1992Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte...
Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral Na-K-ATPase activity. In addition, the organic osmolytes glycerophosphorylcholine (GPC), betaine, inositol and sorbitol in cortex, outer medulla and inner medulla were measured using HPLC. Both loop diuretics significantly reduced sodium and chloride concentrations and rubidium uptake in thick ascending limb cells, but did not affect sodium concentration or rubidium uptake in the proximal straight tubule (PST) cells or in the light or dark cells of the outer medullary collecting duct (OMCD). Chloride concentrations in these cells (that is, PST cells, OMCD light and dark cells) were lowered by loop diuretics, albeit less than in thick ascending limb cells. Administration of both loop diuretics for only 20 minutes was sufficient to significantly depress tissue concentrations of GPC, betaine, and myo-inositol in the outer medulla and of GPC, betaine and sorbitol at the papillary tip. These results indicate that loop diuretics, presumably by blocking apical sodium entry, decrease thick ascending limb cellular sodium concentration and, as a consequence, reduce Na-K-ATPase activity as assessed by cell rubidium uptake. Although this has been shown previously in in vitro preparations, the present study confirms this for the first time in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Diuretics; Electrolytes; Furosemide; Kidney Medulla; Male; Osmolar Concentration; Rats; Rats, Wistar; Sulfonamides; Torsemide
PubMed: 1453580
DOI: 10.1038/ki.1992.359 -
American Journal of Physiology. Renal... Feb 2011A new, region-based mathematical model of the urine concentrating mechanism of the rat renal medulla was used to investigate the significance of transport and structural...
A new, region-based mathematical model of the urine concentrating mechanism of the rat renal medulla was used to investigate the significance of transport and structural properties revealed in anatomic studies. The model simulates preferential interactions among tubules and vessels by representing concentric regions that are centered on a vascular bundle in the outer medulla (OM) and on a collecting duct cluster in the inner medulla (IM). Particularly noteworthy features of this model include highly urea-permeable and water-impermeable segments of the long descending limbs and highly urea-permeable ascending thin limbs. Indeed, this is the first detailed mathematical model of the rat urine concentrating mechanism that represents high long-loop urea permeabilities and that produces a substantial axial osmolality gradient in the IM. That axial osmolality gradient is attributable to the increasing urea concentration gradient. The model equations, which are based on conservation of solutes and water and on standard expressions for transmural transport, were solved to steady state. Model simulations predict that the interstitial NaCl and urea concentrations in adjoining regions differ substantially in the OM but not in the IM. In the OM, active NaCl transport from thick ascending limbs, at rates inferred from the physiological literature, resulted in a concentrating effect such that the intratubular fluid osmolality of the collecting duct increases ~2.5 times along the OM. As a result of the separation of urea from NaCl and the subsequent mixing of that urea and NaCl in the interstitium and vasculature of the IM, collecting duct fluid osmolality further increases by a factor of ~1.55 along the IM.
Topics: Animals; Biological Transport, Active; Computer Simulation; Kidney Concentrating Ability; Kidney Medulla; Kidney Tubules; Loop of Henle; Models, Biological; Osmolar Concentration; Rats; Sodium Chloride; Urea; Water
PubMed: 21068086
DOI: 10.1152/ajprenal.00203.2010 -
Connective Tissue Research Dec 2018Purpose/Aim: The most common kidney stone composed of calcium oxalate forms on interstitial calcium phosphate mineral known as a Randall's plaque (RP). Due to limited...
UNLABELLED
Purpose/Aim: The most common kidney stone composed of calcium oxalate forms on interstitial calcium phosphate mineral known as a Randall's plaque (RP). Due to limited information about events leading to the initial deposition of nanometer size interstitial calcium phosphate pre-clusters, there continues to be a debate on the initial site of calcium phosphate deposition and factors leading to stone formation.
MATERIALS AND METHODS
High-resolution X-ray micro-computed tomography (CT), and light and electron microscopy techniques were used to characterize human renal pyramids and five representative kidney stones with identifiable stems. Mineral densities of mineralized aggregates within these specimens were correlated with micro- and ultra-structures as seen using light and electron microscopy techniques.
RESULTS
The earliest detectable biominerals in the human renal papilla were proximal intratubular plate-like calcium phosphate deposits. Unoccluded tubules in stems connected to calcium phosphate stones were observed by electron microscope and X-ray micro-CT. These tubules were similar in diameter (30-100 μm) and shape to those observed in the distal regions of the renal papilla.
CONCLUSIONS
Observations were patterned through a novel and unified theory of stepwise-architecture guided biomineralization (a combination of smaller structures leading to a larger but similar structural framework). A plausible stepwise progression in renal biomineralization is proposed; proximal intratubular calcium phosphate deposits can lead to interstitial yet calcium phosphate rich RP and mature into a stem on which a calcium oxalate stone grows within the collecting system of a kidney.
Topics: Calcium Oxalate; Calcium Phosphates; Humans; Kidney Calculi; Kidney Medulla; X-Ray Microtomography
PubMed: 29745818
DOI: 10.1080/03008207.2017.1409219 -
American Journal of Hypertension Oct 2021We have previously shown that high salt stimulates the expression of miR-429 in the renal medulla, which induces mRNA decay of HIF prolyl-hydroxylase 2 (PHD2), an enzyme...
BACKGROUND
We have previously shown that high salt stimulates the expression of miR-429 in the renal medulla, which induces mRNA decay of HIF prolyl-hydroxylase 2 (PHD2), an enzyme to promote the degradation of hypoxia-inducible factor (HIF)-1α, and increases the HIF-1α-mediated activation of antihypertensive genes in the renal medulla, consequently promoting extra sodium excretion. Our preliminary results showed that high salt-induced increase of miR-429 was not observed in Dahl S rats. This present study determined whether correction of this impairment in miR-429 would reduce PHD2 levels, increase antihypertensive gene expression in the renal medulla and attenuate salt-sensitive hypertension in Dahl S rats.
METHODS
Lentiviruses encoding rat miR-429 were transfected into the renal medulla in uninephrectomized Dahl S rats. Sodium excretion and blood pressure were then measured.
RESULTS
Transduction of lentiviruses expressing miR-429 into the renal medulla increased miR-429 levels, decreased PHD2 levels, and upregulated HIF-1α target gene NOS-2, which restored the adaptive mechanism to increase the antihypertensive gene after high-salt intake in Dahl S rats. Functionally, overexpression of miR-429 transgene in the renal medulla significantly improved pressure natriuretic response, enhanced urinary sodium excretion, and reduced sodium retention upon extra sodium loading, and consequently, attenuated the salt-sensitive hypertension in Dahl S rats.
CONCLUSIONS
Our results suggest that the impaired miR-429-mediated PHD2 inhibition in response to high salt in the renal medulla may represent a novel mechanism for salt-sensitive hypertension in Dahl S rats and that correction of this impairment in miR-429 pathway could be a therapeutic approach for salt-sensitive hypertension.
Topics: Animals; Gene Expression; Hypertension; Kidney Medulla; MicroRNAs; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Transgenes
PubMed: 34089591
DOI: 10.1093/ajh/hpab089 -
American Journal of Physiology.... Dec 2005Dahl salt-sensitive (SS) and consomic, salt-resistant SS-13(BN) rats possess substantial differences in blood pressure salt-sensitivity even with highly similar genetic... (Comparative Study)
Comparative Study
Dahl salt-sensitive (SS) and consomic, salt-resistant SS-13(BN) rats possess substantial differences in blood pressure salt-sensitivity even with highly similar genetic backgrounds. The present study examined whether increased oxidative stress, particularly H2O2, in the renal medulla of SS rats contributes to these differences. Blood pressure was measured using femoral arterial catheters in three groups of rats: 1) 12-wk-old SS and consomic SS-13(BN) rats fed a 0.4% NaCl diet, 2) SS rats fed a 4% NaCl diet and chronically infused with saline or catalase (6.9 microg x kg(-1) x min(-1)) directly into the renal medulla, and 3) SS-13(BN) fed high salt (4%) and infused with saline or H2O2 (347 nmol x kg(-1) x min(-1)) into the renal medullary interstitium. After chronic blood pressure measurements, renal medullary interstitial H2O2 concentration ([H2O2]) was collected by microdialysis and analyzed with Amplex red. Blood pressure and [H2O2] were both significantly higher in SS (126 +/- 3 mmHg and 145 +/- 17 nM, respectively) vs. SS-13(BN) rats (116 +/- 2 mmHg and 56 +/- 14 nM) fed a 0.4% diet. Renal interstitial catalase infusion significantly decreased [H2O2] (96 +/- 41 vs. 297 +/- 52 nM) and attenuated the hypertension (146 +/- 2 mmHg catalase vs. 163 +/- 4 mmHg saline) in SS rats after 5 days of high salt (4%). H2O2 infused into the renal medulla of consomic SS-13(BN) fed high salt (4%) for 7 days accentuated the salt sensitivity (145 +/- 2 mmHg H2O2 vs. 134 +/- 1 mmHg saline). [H2O2] was also increased in the treated group (83 +/- 1 nM H2O2 vs. 44 +/- 9 nM saline). These data show that medullary production of H2O2 may contribute to salt-induced hypertension in SS rats and that chromosome 13 of the Brown Norway contains gene(s) that protect against renal medullary oxidant stress.
Topics: Animals; Dose-Response Relationship, Drug; Hydrogen Peroxide; Hypertension, Renal; Kidney Medulla; Male; Rats; Rats, Inbred BN; Rats, Inbred Dahl; Sodium Chloride; Species Specificity
PubMed: 16109803
DOI: 10.1152/ajpregu.00525.2005 -
The British Journal of Radiology Nov 2020To investigate the diffusion properties in the kidneys affected by renal artery stenosis (RAS) using diffusion tensor imaging (DTI).
OBJECTIVE
To investigate the diffusion properties in the kidneys affected by renal artery stenosis (RAS) using diffusion tensor imaging (DTI).
METHODS
In this prospective study, 35 patients with RAS and 15 patients without renal abnormalities were enrolled and examined using DTI. Cortical and medullary regions of interest (ROIs) were located to obtain the corresponding values of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The cortical and medullary ADC and FA were compared in the kidney affected by variable degrees of stenosis (RAS 50-75% and >75%) controls, using the one-way ANOVA and Student's -test. The Spearman correlation test was used to correlate the mean ADC and FA values in the cortex and medulla with the estimate glomerular filtration rate (eGFR).
RESULTS
For the controls, the ADC value was significantly ( = 0.03) higher in the cortex than in the medulla; the FA value was significantly ( = 0.001) higher in the medulla than in the cortex. Compared with the controls, a significant reduction in the cortical ADC was present with a RAS of 50-75% and >75% ( = 0.001 and 0.041, respectively); a significant reduction in the medullary FA was verified only for RAS >75% ( = 0.023). The Spearman correlation test did not show a statistically significant correlation between the cortical and medullary ADC and FA, and the eGFR.
CONCLUSION
The alterations of the diffusional parameters caused by RAS can be detected by DTI and could be useful in the diagnostic evaluation of these patients.
ADVANCES IN KNOWLEDGE
1. Magnetic resonance DTI could provide useful information about renal involvement in RAS.2. Magnetic resonance DTI allows non-invasive repeatable evaluation of the renal parenchyma, without contrast media.
Topics: Adult; Aged; Analysis of Variance; Anisotropy; Case-Control Studies; Diffusion Tensor Imaging; Female; Glomerular Filtration Rate; Humans; Kidney Cortex; Kidney Medulla; Male; Middle Aged; Prospective Studies; Renal Artery Obstruction; Statistics, Nonparametric
PubMed: 32903036
DOI: 10.1259/bjr.20200101 -
Magnetic Resonance in Medicine Jun 1999High-resolution magic angle spinning 1H NMR (MAS-NMR) spectroscopy was used to investigate the biochemical composition of normal renal cortex and renal papilla samples...
High-resolution magic angle spinning 1H NMR (MAS-NMR) spectroscopy was used to investigate the biochemical composition of normal renal cortex and renal papilla samples from rats, and results were compared with those from conventional 1H NMR analysis of protein-free tissue extracts. 1H MAS NMR spectra of samples obtained from inner and outer cortex were found to be broadly similar in terms of metabolite profile, and intra- and inter-animal variability was small. However, the MAS NMR spectra from renal papilla samples were qualitatively and quantitatively different from those obtained from cortex. High levels of free amino acids and several organic acids were detected in the cortex, together with choline, glucose, and trimethylamine-N-oxide. The dominant metabolite resonances observed in papillary tissue were from glycerophosphocholine (GPC), betaine, myo-inositol, and sorbitol. On increasing the magic angle spinning rate from 4,200 to 12,000 Hz, the lipid MAS 1H NMR signal profile remained largely unchanged in papillary tissue, whereas "new" resonances from triglycerides appeared in the spectra of cortical tissue, this effect being reversible on returning the spinning rate to 4,200 Hz. Further investigation into the behavior of the lipid components under different spinning rates suggested that the lipids in the cortex were present in more motionally constrained environments than those in the papilla. 1H MAS NMR spectra of tissues are of value both in interrogation of the biochemical composition of whole tissue, and in obtaining information on the mobility and compartmentalization of certain metabolites.
Topics: Animals; Kidney Cortex; Kidney Medulla; Magnetic Resonance Spectroscopy; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tissue Extracts
PubMed: 10371442
DOI: 10.1002/(sici)1522-2594(199906)41:6<1108::aid-mrm6>3.0.co;2-m -
PloS One 2013Protein carbamylation is a post-translational modification that can occur in the presence of urea. In solution, urea is in equilibrium with ammonium cyanate, and...
Protein carbamylation is a post-translational modification that can occur in the presence of urea. In solution, urea is in equilibrium with ammonium cyanate, and carbamylation occurs when cyanate ions react with the amino groups of lysines, arginines, protein N-termini, as well as sulfhydryl groups of cysteines. The concentration of urea is elevated in the renal inner medulla compared with other tissues. Due to the high urea concentration, we hypothesized that carbamylation can occur endogenously within the rat inner medulla. Using immunoblotting of rat kidney cortical and medullary homogenates with a carbamyl-lysine specific antibody, we showed that carbamylation is present in a large number of inner medullary proteins. Using protein mass spectrometry (LC-MS/MS) of rat renal inner medulla, we identified 456 unique carbamylated sites in 403 proteins, including many that play important physiological roles in the renal medulla [Data can be accessed at https://helixweb.nih.gov/ESBL/Database/Carbamylation/Carbamylation_peptide_sorted.html]. We conclude that protein carbamylation occurs endogenously in the kidney, modifying many physiologically important proteins.
Topics: Animals; Chromatography, Liquid; Kidney; Kidney Medulla; Male; Protein Processing, Post-Translational; Proteins; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Water
PubMed: 24386107
DOI: 10.1371/journal.pone.0082655