Inner medullary lactate production and urine-concentrating mechanism: a flat medullary model

Hervy, Stéphane; Thomas, Sophie

doi:10.1152/ajprenal.00045.2002

Cited by 69 publications

(78 citation statements)

References 46 publications

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“…26 In addition, the adjacency of the lactate-producing thin descending limbs in the outer medulla to lactate-using medullary thick ascending limbs may be critical to the maintenance of the high rates of active sodium chloride transport in the medullary thick ascending limb needed to drive the countercurrent multiplier mechanism. 27 …”

Section: Critical Enzymes In Metabolic Pathwaysmentioning

confidence: 99%

Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment–Specific Transcriptomes

Lee¹,

Chou²,

Knepper³

2015

Journal of the American Society of Nephrology

480

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The function of each renal tubule segment depends on the genes expressed therein. High-throughput methods used for global profiling of gene expression in unique cell types have shown low sensitivity and high false positivity, thereby limiting the usefulness of these methods in transcriptomic research. However, deep sequencing of RNA species (RNA-seq) achieves highly sensitive and quantitative transcriptomic profiling by sequencing RNAs in a massive, parallel manner. Here, we used RNA-seq coupled with classic renal tubule microdissection to comprehensively profile gene expression in each of 14 renal tubule segments from the proximal tubule through the inner medullary collecting duct of rat kidneys. Polyadenylated mRNAs were captured by oligo-dT primers and processed into adapter-ligated cDNA libraries that were sequenced using an Illumina platform. Transcriptomes were identified to a median depth of 8261 genes in microdissected renal tubule samples (105 replicates in total) and glomeruli (5 replicates). Manual microdissection allowed a high degree of sample purity, which was evidenced by the observed distributions of well established cell-specific markers. The main product of this work is an extensive database of gene expression along the nephron provided as a publicly accessible webpage (https://helixweb.nih.gov/ESBL/Database/NephronRNAseq/index.html). The data also provide genomewide maps of alternative exon usage and polyadenylation sites in the kidney. We illustrate the use of the data by profiling transcription factor expression along the renal tubule and mapping metabolic pathways.

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Section: Critical Enzymes In Metabolic Pathwaysmentioning

confidence: 99%

Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment–Specific Transcriptomes

Lee¹,

Chou²,

Knepper³

2015

Journal of the American Society of Nephrology

480

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“…The second term, which represents convective transport, is formulated differently than in other kidney models (17,26), where it is expressed as:…”

Section: Model Equationsmentioning

confidence: 99%

“…To address these questions, we developed a mathematical model of renal Ca 2ϩ transport across all nephron segments below the proximal tubules from the descending limbs of Henle to the inner medullary collecting ducts (IMCD). Our model is based on that of Hervy and Thomas (17), referred to below as the HT model, which describes the transport of water, NaCl, glucose, and lactate in the renal medulla. We modified the HT model to 1) make it dynamic, 2) explicitly represent the distal cortical segments, and 3) incorporate Ca 2ϩ transport.…”

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confidence: 99%

A model of calcium transport along the rat nephron

Tournus

Seguin

Perthame

et al. 2013

American Journal of Physiology-Renal Physiology

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(Ca 2ϩ ) transport along the rat nephron to investigate the factors that promote hypercalciuria. The model is an extension of the flat medullary model of Hervy and Thomas (Am J Physiol Renal Physiol 284: F65-F81, 2003). It explicitly represents all the nephron segments beyond the proximal tubules and distinguishes between superficial and deep nephrons. It solves dynamic conservation equations to determine NaCl, urea, and Ca 2ϩ concentration profiles in tubules, vasa recta, and the interstitium. Calcium is known to be reabsorbed passively in the thick ascending limbs and actively in the distal convoluted (DCT) and connecting (CNT) tubules. Our model predicts that the passive diffusion of Ca 2ϩ from the vasa recta and loops of Henle generates a significant axial Ca 2ϩ concentration gradient in the medullary interstitium. In the base case, the urinary Ca 2ϩ concentration and fractional excretion are predicted as 2.7 mM and 0.32%, respectively. Urinary Ca 2ϩ excretion is found to be strongly modulated by water and NaCl reabsorption along the nephron. Our simulations also suggest that Ca 2ϩ molar flow and concentration profiles differ significantly between superficial and deep nephrons, such that the latter deliver less Ca 2ϩ to the collecting duct. Finally, our results suggest that the DCT and CNT can act to counteract upstream variations in Ca 2ϩ transport but not always sufficiently to prevent hypercalciuria. calcium; finite volume; kidney; mathematical model; transport CALCIUM (CA 2ϩ ) IS THE MOST abundant cation in the body. It plays an essential role in cardiac, skeletal, and smooth muscle function, and extra-and intracellular Ca 2ϩ concentrations ([Ca 2ϩ ]) must therefore be kept within a narrow range. Calcium homeostasis is maintained by the concerted action of the intestine, the parathyroid glands, and the kidneys. Preserving low Ca 2ϩ concentrations in the urinary filtrate is especially important, since hypercalciuria is one of the major risk factors for the formation of kidney stones. Recent studies on Ca 2ϩ handling by the kidney have focused on the molecular transporters and sensors of Ca 2ϩ (2, 9), but our understanding of Ca 2ϩ transport at the organ level remains limited. Whether there is a corticomedullary interstitial [Ca 2ϩ ] gradient has yet to be determined, and the contribution of each nephron segment to perturbations in the renal Ca 2ϩ balance is not fully understood. To address these questions, we developed a mathematical model of renal Ca 2ϩ transport across all nephron segments below the proximal tubules from the descending limbs of Henle to the inner medullary collecting ducts (IMCD). Our model is based on that of Hervy and Thomas (17), referred to below as the HT model, which describes the transport of water, NaCl, glucose, and lactate in the renal medulla. We modified the HT model to 1) make it dynamic, 2) explicitly represent the distal cortical segments, and 3) incorporate Ca 2ϩ transport. For this purpose, we developed a new finite-volume scheme that is robust and fast.About t...

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“…Even if that pathway conducts water movement in vivo, low reflection coefficients to small solutes would imply that it concentrates the macromolecules but not NaCl or urea in DVR plasma. The existence of an additional solute other than NaCl and urea has been postulated to accumulate in the renal medulla to provide a driving force for urinary concentration (34,(128)(129)(130). If such a solute is identified, its ability to drive water flux across the DVR wall of AQP1 null mice should be tested.…”

Section: Summary and Future Directions For Researchmentioning

confidence: 99%

Countercurrent exchange in the renal medulla

Pallone

Turner

Edwards

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

135

102

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Pallone, Thomas L., Malcolm R. Turner, Auré lie Edwards, and Rex L. Jamison. Countercurrent exchange in the renal medulla. Am J Physiol Regul Integr Comp Physiol 284: R1153-R1175, 2003 10.1152/ ajpregu.00657.2002The microcirculation of the renal medulla traps NaCl and urea deposited to the interstitium by the loops of Henle and collecting ducts. Theories have predicted that countercurrent exchanger efficiency is favored by high permeability to solute. In contrast to the conceptualization of vasa recta as simple "U-tube" diffusive exchangers, many findings have revealed surprising complexity. Tubular-vascular relationships in the outer and inner medulla differ markedly. The wall structure and transport properties of descending vasa recta (DVR) and ascending vasa recta (AVR) are very different. The recent discoveries of aquaporin-1 (AQP1) water channels and the facilitated urea carrier UTB in DVR endothelia show that transcellular as well as paracellular pathways are involved in equilibration of DVR plasma with the interstitium. Efflux of water across AQP1 excludes NaCl and urea, leading to the conclusion that both water abstraction and diffusion contribute to transmural equilibration. Recent theory predicts that loss of water from DVR to the interstitium favors optimization of urinary concentration by shunting water to AVR, secondarily lowering blood flow to the inner medulla. Finally, DVR are vasoactive, arteriolar microvessels that are anatomically positioned to regulate total and regional blood flow to the outer and inner medulla. In this review, we provide historical perspective, describe the current state of knowledge, and suggest areas that are in need of further exploration. vasa recta; microperfusion; microcirculation; water channel; urinary concentration; permeability SINCE THE EXPERIMENTAL FINDINGS of Wirz et al. (147) led to the countercurrent theory of the urinary concentrating mechanism, as described by Hargitay and Kuhn (31), most subsequent research has focused on the countercurrent multiplier function of the loops of Henle. According to the theory, a small difference in osmotic pressure (the single effect) is multiplied by countercurrent flow in adjacent channels of the limbs of Henle's loop to produce a large axial difference in osmotic pressure between the renal cortex and the tip of the renal papilla; that is, the multiplier generates a hypertonic renal medulla. Less attention has been paid to countercurrent exchange, which is thought to preserve medullary hypertonicity rather than create it. It is generally accepted that the microcirculation of the renal medulla functions as a countercurrent exchanger that traps NaCl and urea deposited to the interstitium by the loops of Henle and collecting ducts, respectively. Early hypothetical descriptions of this process envisioned a system in which descending vasa recta (DVR) and ascending vasa recta (AVR) are parallel tubes that equilibrate by diffusion. According to that notion, blood flowing from the corticomedullary junction toward the papillary t...

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Inner medullary lactate production and urine-concentrating mechanism: a flat medullary model

Cited by 69 publications

References 46 publications

Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment–Specific Transcriptomes

Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment–Specific Transcriptomes

A model of calcium transport along the rat nephron

Countercurrent exchange in the renal medulla

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