Nephron

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The endothelium is the largest organ in the body and recent studies have shown that the endothelial glycocalyx (eGCX) plays a major role in health and disease states. The integrity of eGCX is vital for homoeostasis and disruption of its structure and function plays a major role in several pathologic conditions. An increased understanding of the numerous pathophysiological roles of eGCX may lead to the development of potential surrogate markers for endothelial injury or novel therapeutic targets. This review provides a state-of-the-art update on the structure and function of the eGCX, emphasizing the current understanding of interorgan crosstalk between the eGCX and other organs that might also contribute to the pathogenesis of kidney diseases...

When injury occurs, it implies that attack has overcome defence. Tubulointerstitial injury plays important roles in acute kidney injury (AKI) and chronic kidney disease (CKD) and is the common pathway leading to end-stage renal disease, but how the renal tubulointerstitium defends against attack is poorly understood. Emerging evidence suggests that collecting ducts (CDs), which modify urine from nephrons and drain into ureter, could be key defenders protecting tubulointerstitium from injury; furthermore, the canonical renal vitamin A signalling physiologically confined to CDs could be a key regulator of this protective machinery...

BACKGROUND: Laboratory measures of glomerular function such as the glomerular filtration rate (GFR) contribute toward clinical evaluation of chronic kidney disease (CKD). However, diverse CKD etiologies have distinct pathological mechanisms that may differentially impact the kidney tubules. Little is known regarding how tubular function changes with varying kidney disease types. METHODS: We used targeted mass spectrometry to quantify paired serum and urine concentration of 11 solutes of proximal tubular secretion in 223 patients from an outpatient CKD cohort...

The epithelium of the kidney collecting duct (CD) is composed mainly of two different types of cells with distinct and complementary functions. CD principal cells traditionally have been considered to have a major role in Na+ and water regulation, while intercalated cells (ICs) were thought to largely modulate acid-base homeostasis. In recent years, our understanding of IC function has improved significantly owing to new research findings. Thus, we now have a new model for CD transport that integrates mechanisms of salt and water reabsorption, K+ homeostasis, and acid-base status between principal cells and ICs...

Parietal epithelial cells comprise a heterogeneous cell population lining Bowman's capsule. The study by Kuppe et al. focused on the peritubular region of Bowman's capsule and explored the cell biology of 2 poorly characterized subtypes-the intermediate and the cuboidal parietal epithelial cells. The early and exuberant proliferative response of these subgroups in murine focal segmental glomerulosclerosis (FSGS) and human glomerular tip lesions identified a novel hot spot for glomerular lesion formation.

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Tubuloglomerular feedback and the myogenic mechanism form an ensemble in renal afferent arterioles that regulate single-nephron blood flow and glomerular filtration. Each mechanism generates a self-sustained oscillation, the mechanisms interact, and the oscillations synchronize. The synchronization generates a bimodal electrical signal in the arteriolar wall that propagates retrograde to a vascular node, where it meets similar electrical signals from other nephrons. Each signal carries information about the time-dependent behavior of the regulatory ensemble...

The thick ascending limb (TAL) of Henle's loop is a crucial segment for many tasks of the nephron. Indeed, the TAL is not only a mainstay for reabsorption of sodium (Na+ ), potassium (K+ ), and divalent cations such as calcium (Ca2+ ) and magnesium (Mg2+ ) from the luminal fluid, but also has an important role in urine concentration, overall acid-base homeostasis, and ammonia cycle. Transcellular Na+ transport along the TAL is a prerequisite for Na+ , K+ , Ca2+ , Mg2+ homeostasis, and water reabsorption, the latter through its contribution in the generation of the cortico-medullar osmotic gradient...

Renal fibrosis, especially tubulointerstitial fibrosis, is the inevitable outcome of all progressive chronic kidney diseases (CKDs) and exerts a great health burden worldwide. For a long time, interests in renal fibrosis have been concentrated on fibroblasts and myofibroblasts. However, in recent years, growing numbers of studies have focused on the role of tubular epithelial cells (TECs). TECs, rather than a victim or bystander, are probably a neglected mediator in renal fibrosis, responding to a variety of injuries...

To investigate human glomerular structure under conditions of physiological perfusion, we have analyzed fresh and perfusion-fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, confocal, multiphoton, and electron microscope imaging. Afferent and efferent arterioles (21.5 ± 1.2 µm and 15.9 ± 1.2 µm diameter), recognized from vascular origins, lead into previously undescribed wider regions (43.2 ± 2.8 µm and 38.4 ± 4...

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Tubular injury sensitizes glomeruli to injury. We review potential mechanisms of this tubuloglomerular cross talk. In the same nephron, tubular injury can cause stenosis of the glomerulotubular junction and finally result in atubular glomeruli. Tubular injury also affects glomerular filtration function through tubuloglomerular feedback. Progenitor cells, that is, parietal epithelial cells and renin positive cells, can be involved in repair of injured glomeruli and also may be modulated by tubular injury. Loss of nephrons induces additional workload and stress on remaining nephrons...

The Reynolds number in the renal tubule is extremely low, consistent with laminar flow. Consequently, luminal flow can be described by the Hagen-Poiseuille laminar flow equation. This equation calculates the volumetric flow rate from values of the axial pressure gradient and flow resistance, which is dependent on the length and diameter of each renal tubule segment. Our goal was to calculate the pressure drop along each segment of the renal tubule and determine the points of highest resistance. When the Hagen-Poiseuille equation was used for rat superficial nephrons based on known flow rates, tubule lengths, and diameters for each renal tubule segment, it was found that maximum pressure drop occurred in two segments: the thin descending limbs of Henle and the inner medullary collecting ducts...

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The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane...

The role of salt in the pathogenesis of arterial hypertension is not well understood. According to the current understanding, the central mechanism for blood pressure (BP) regulation relies on classical studies linking BP and Na+ balance, placing the kidney at the very centre of long-term BP regulation. To maintain BP homeostasis, the effective circulating fluid volume and thereby body Na+ content has to be maintained within very narrow limits. From recent work in humans and rats, the notion has emerged that Na+ could be stored somewhere in the body without commensurate water retention to buffer free extracellular Na+ and that previously unidentified extrarenal, tissue-specific regulatory mechanisms are operative regulating the release and storage of Na+ from a kidney-independent reservoir...

Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1+ mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice...

The Centers for Disease Control and Prevention estimates more than 10% of adults in the United States, over 20 million Americans, have chronic kidney disease (CKD). A failure to maintain the glomerular filtration barrier directly contributes to the onset of CKD. The visceral epithelial cells, podocytes, are integral to the maintenance of this renal filtration barrier. Direct podocyte injury contributes to the onset and progression of glomerular diseases such as minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), diabetic nephropathy, and HIV-associated nephropathy (HIVAN)...

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