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A healthy renal microcirculation is crucial to ensure adequate tissue perfusion, filtration and removal of toxins from the general circulation. Emerging evidence supports a role of renal microvascular (MV) disease in possibly determining the turning point between reversible and irreversible renal injury. Indeed, previous studies have shown that renal MV rarefaction correlates with the progressive deterioration of renal hemodynamics, filtration, and, tubular function. Furthermore, dysfunctional or damaged microvessels can compromise adequate renal perfusion and nutrition leading to tissue ischemia, which may in turn activate pro-inflammatory and pro-fibrotic factors that could promote renal parenchymal injury. This chapter will discuss the changes in renal MV function and structure and the role of MV disease on the initiation and progression of renal injury. Either as a causative mechanism or a consequence of renal injury, increasing experimental and clinical evidence showed that pathological changes in the renal microvasculature accompany the development and progression of renal injury associated to hypertension, diabetes, obesity, and atherosclerosis. Previous studies have shown that systemic and renal MV disease is associated to cardiovascular risk factors even in the absence of major deterioration of renal function, implying that early changes in renal MV function could later serve as instigator of renal injury. Hence, this chapter will also focus on the development, progression, and mechanisms of renal MV disease in hypertension, diabetes, obesity, and atherosclerosis. [ABSTRACT FROM AUTHOR]

Ultrasound provides the physical capabilities for a fast and save disease diagnosis in various medical scenarios including renal exams and patient trauma assessment. However, the experience of the ultrasound operator is the key element in performing ultrasound diagnosis. Thus, we like to introduce our automatic kidney detection and segmentation algorithm for 3D ultrasound. The approach utilizes basic kidney shape information to detect the kidney position. Following, the Level Set algorithm is applied to segment the detection result. In combination this method may help physicians and inexperienced trainees to achieve kidney detection and segmentation for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Organic cation transporters (OCTs) of the solute carrier family (SLC) 22 and multidrug and toxin extrusion (MATE) transporters of the SLC47 family have been identified as uptake and efflux transporters, respectively, for xenobiotics including several clinically used drugs such as the antidiabetic agent metformin, the antiviral agent lamivudine, and the anticancer drug oxaliplatin. Expression of human OCT1 (SLC22A1) and OCT2 (SLC22A2) is highly restricted to the liver and kidney, respectively. By contrast, OCT3 (SLC22A3) is more widely distributed. MATEs (SLC47A1, SLC47A2) are predominantly expressed in human kidney. Data on in vitro studies reporting a large number of substrates and inhibitors of OCTs and MATEs are systematically summarized. Several genetic variants of human OCTs and in part of MATE1 have been reported, and some of them result in reduced in vitro transport activity corroborating data from studies with knockout mice. A comprehensive overview is given on currently known genotype–phenotype correlations for variants in OCTs and MATE1 related to protein expression, pharmacokinetics/-dynamics of transporter substrates, treatment outcome, and disease susceptibility. [ABSTRACT FROM AUTHOR]

Organic anion transporters 1-10 (OAT1-10) and the urate transporter 1 (URAT1) belong to the SLC22A gene family and accept a huge variety of chemically unrelated endogenous and exogenous organic anions including many frequently described drugs. OAT1 and OAT3 are located in the basolateral membrane of renal proximal tubule cells and are responsible for drug uptake from the blood into the cells. OAT4 in the apical membrane of human proximal tubule cells is related to drug exit into the lumen and to uptake of estrone sulfate and urate from the lumen into the cell. URAT1 is the major urate-absorbing transporter in the apical membrane and is a target for uricosuric drugs. OAT10, also located in the luminal membrane, transports nicotinate with high affinity and interacts with drugs. Major extrarenal locations of OATs include the blood–brain barrier for OAT3, the placenta for OAT4, the nasal epithelium for OAT6, and the liver for OAT2 and OAT7. For all transporters we provide information on cloning, tissue distribution, factors influencing OAT abundance, interaction with endogenous compounds and different drug classes, drug/drug interactions and, if known, single nucleotide polymorphisms. [ABSTRACT FROM AUTHOR]

Historically the gold standard for the management of ureteropelvic junction obstruction (UPJO) has been open pyeloplasty. However, since laparoscopic-assisted pyeloplasty was first described by Schuessler et al. in 1993, the minimally invasive approach has gained wide popularity and acceptance among both academic and community urologists [1, 2]. The goal of correcting a UPJO is not to reverse damage which the kidney has already sustained but to prevent further deterioration of function and to relieve symptoms. Laparoscopic or robotic approaches to correction of UPJO have been well documented in the literature, including reduction in hospital stay, decreased postoperative analgesic requirements, and reduced incision size and amount of esthetically undesirable scarring [3]. [ABSTRACT FROM AUTHOR]

For the past four decades, patients have increasingly chosen the minimally invasive option for their urologic surgical needs to avoid the morbidity of large incisions, and this generally has led to shorter hospital stays, less pain medication requirements, and earlier return to normal activity levels in adult patients. This is especially true for adult patients who have undergone ablative urologic procedures such as nephrectomy or adrenalectomy by conventional laparoscopic techniques. The advantages of minimally invasive surgery also apply to pediatric patients and especially for those who have undergone ablative pediatric urology procedures with similar benefits seen in these patients. Of note, the first reported use of laparoscopy in pediatric urology was for patients with nonpalpable undescended testes in the 1960s [1], and diagnostic laparoscopy in this setting has gained widespread acceptance among pediatric urologists. Over the last two decades, laparoscopic surgical techniques have improved significantly in the adult and pediatric patient populations since the first reported laparoscopic pyeloplasty in the adult population in 1993 [2] and the first pediatric laparoscopic pyeloplasty in 1995 [3], both by the use of conventional laparoscopy. In children, this has led to a reliably safe and effective approach to the kidney for reconstructive urological procedures that require extensive suturing with similar success rates and potential benefits with regard to cosmesis, intraoperative blood loss, postoperative stay, and the length of the overall hospital stay. [ABSTRACT FROM AUTHOR]

Kidney disease is the most common identifiable cause of secondary hypertension in childhood. In this chapter, the prevalence, pathophysiology, and treatment of renal hypertension will be reviewed, with an emphasis on recent clinical trial results demonstrating the benefits of aggressive treatment of hypertension on the rate of progression of chronic kidney disease. [ABSTRACT FROM AUTHOR]

Stem/progenitor cells are in the focus of regenerative medicine for a future therapy of acute and chronic renal failure. However, broad knowledge about parenchymal regeneration in kidney is lacking. For that reason developmental pathways leading from stem/progenitor cells to newly formed tubules have to be investigated. A new technique promotes renal stem/progenitor cells to form numerous tubules between layers of polyester fleeces. This artificial interstitium replaces coating by extracellular matrix proteins, supports spatial extension of renal tubules, and can be used with chemically defined Iscove΄s modified Dulbecco΄s medium (IMDM) during a long-term culture period of 13 days. The development of tubules is stimulated by aldosterone and depends on the applied hormone concentration. The tubulogenic effect cannot be mimicked by precursors of the aldosterone synthesis pathway or by other steroid hormones. Antagonists such as spironolactone or canrenoate prevent the development of tubules, which indicates that the mineralocorticoid receptor (MR) is involved. Administration of geldanamycin, radicicol, quercetin, or KNK 437 in combination with aldosterone blocks development of tubules by disturbing the contact between MR and heat-shock proteins. Transmission electron microscopy (TEM) further demonstrates that generated tubules exhibit a junctional complex between the apical and the lateral plasma membrane. At the basal aspect a continuously developed basal lamina is present. Immuno-label for Troma I (cytokeratin Endo-A) shows isoprismatic cells, while label for laminin ν1, occludin, and Na/K-ATPase α5 confirms typical features of a polarized epithelium. Finally, the introduced system makes it possible to pile and pave renal stem/progenitor cells, so that the spatial development of tubules can be systematically investigated. [ABSTRACT FROM AUTHOR]

Objectives: This chapter focuses on advances in regenerative therapies using stem cells in urology. Different stem cell types will be introduced due to their classification and hierarchic order. Methods: A detailed literature search has been performed using the PubMed database of the National Center of Biotechnology Information (NCBI). Publications of experimental investigations and in vivo trials using stem cells in reconstructive urology have been summarized and critically reviewed. Results: Tissue engineering and autologous cell therapy techniques have been developed in order to generate prostheses for different urologic tissues and organ systems. During the last decade increasing numbers of studies have described stem cells in the context of therapeutic tools. The ability of adult and embryonic stem cells as well as progenitors to improve bladder wall architecture, to improve renal tubule formation or to promote restoration of spermatogenesis or recovery of continence has been investigated in a number of animal models. Another promising stem cell source, the so-called induced pluripotent stem cells, was recently generated, but not further investigated yet. Although results have been encouraging, to date, none of these stem cell-based therapies could reach clinical trials. Conclusions: Review of the current literature has revealed several populations of adult stem cells and progenitor cells as useful cellular sources in the treatment and reconstruction of urologic organs. However, considerable basic research still needs to be performed to ensure the controlled differentiation and long-term fate of stem cells following transplantation. [ABSTRACT FROM AUTHOR]

Radio-frequency (RF) ablation is a minimal invasive thermal therapy, currently considered as an alternative to surgery to eradicate small solid kidney tumors. Our aim is to understand the kinetics of thermal lesion growth in kidney tissue exposed to RF energy by taking into account dynamic time-temperature changes in electrical properties of multiple tissues (i.e. kidney, surrounding fat, muscle). We present a computer model designed to calculate the voltage distribution and the temperature rise in kidney. The model further calculates the RF lesion size based on kinetic processes, which correctly describe coagulative necrosis process. The simulated transient temperatures and lesion size were experimentally validated with good agreement in a porcine kidney model, ex vivo. The expected increase in electrical conductivity of kidney (approximately 3 times) during heating resulted in predicted lesion width and depth that were larger (by as much as 20% and 30% respectively) than those predicted for constant properties. Simulation results also show how the lesion size and shape can be affected by the proximity to the RF electrode of a surrounding layer of fat, which acts as an electro-thermal insulator. The results of this pre-clinical investigation may be useful for treatment planning of RF thermal therapy of kidney tumours. [ABSTRACT FROM AUTHOR]

The kidney is essential for the integrity of the vitamin D endocrine system: Normal kidney function ensures adequate serum levels of 1,25-dihyrdroxyvitamin D ([1,25(OH)2D], the hormonal form of vitamin D) and of its precursor, 25-hydroxyvitamin D [25(OH)D]. In turn, normal serum 1,25(OH)2D and 25(OH)D levels are critical in maintaining normal kidney function and in ameliorating the progression of kidney disease. Research in the last three decades has firmly established that renal conversion of 25(OH)D to 1,25(OH)2D plays a key role in the maintenance of calcium and phosphate homeostasis and skeletal health. 1,25(OH)2D endocrine actions include the coordinated regulation of the synthesis of parathyroid hormone (PTH), the bone phosphatonin FGF23, and its own serum concentrations, and consequently of the hormonal loops and ion fluxes between the parathyroid gland, the intestine, the kidney, and the bone. 1,25(OH)2D tight control of this multi-organ endocrine system is central not only for bone integrity but also in preventing an excess of serum calcium and phosphate predisposing to over-mineralization of bone or ectopic calcification. Importantly, recent epidemiological evidence also suggests that the kidney is essential for the maintenance of normal serum 25(OH)D levels, a requirement for 1,25(OH)2D autocrine actions. Renal uptake of 25(OH)D from the glomerular ultrafiltrate is an active process necessary for both renal and extrarenal 1,25(OH)2D production. Normal renal uptake of 25(OH)D ensures the appropriate delivery of 25(OH)D for its conversion to 1,25(OH)2D by an increasing number of nonrenal cells. Autocrine 1,25(OH)2D actions in 1,25(OH)2D producing cells, which include parathyroid cells, osteoblasts, and cells of the immune and cardiovascular system, appear to mediate the multiple health benefits and the survival advantage conferred to the general population by a normal vitamin D status. This chapter presents the current understanding of the mechanisms mediating renal control of vitamin D metabolism and 1,25(OH)2D endocrine and autocrine actions important in disease prevention, with a special focus on the renoprotective actions of the vitamin D endocrine system that prevent/ameliorate the onset and progression of kidney disease. [ABSTRACT FROM AUTHOR]

In the intestine 1,25-dihydroxyvitamin D3 [1,25(OH)2D] induces various aspects of the transcellular active calcium transport system including calbindin, the basolateral plasma membrane pump, and the epithelial calcium channel, TRPV6. Calcium can enter the enterocyte through the epithelial calcium channel and then bind to calbindin and move through the cytosol. At the basolateral membrane calcium is transported actively by the plasma membrane calcium pump into the extracellular space. There is increasing evidence that, in the intestine, 1,25(OH)2D can also enhance paracellular calcium diffusion. In the distal nephron of the kidney 1,25(OH)2D induces TRPV5 and the calbindins and affects calcium transport, at least in part, by enhancing the action of PTH. A role for the Na+/Ca2+ exchanger in the distal tubule in vitamin D-dependent calcium reabsorption has also been suggested. In the kidney, besides enhancement of calcium transport in the distal nephron, 1,25(OH)2D also modulates the 25(OH)D hydroxylases. Effects on renal phosphate reabsorption have also been suggested. [ABSTRACT FROM AUTHOR]

In the classic view of the renin angiotensin system (RAS), angiotensin II (AngII) is the main effector peptide. Circulating RAS regulates physiological responses, whereas the local RAS is activated during tissue injury and contributes to pathological processes, including cell proliferation/apoptosis, fibrosis, and inflammation. AngII has direct effects on these processes through activation of mitogen-activated protein kinase (MAPKs) and Smad and nuclear factor kappa B (NF-ΚB) transcription factors. In addition, AngII recruits important secondary mediators, such as transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), and chemokines. AngII binds to the angiotensin type 1 and 2 (AT1 and AT2) receptors mediating different cellular responses. Both angiotensin-converting enzyme (ACE) inhibitors and AngII receptor antagonists (ARA II, targeting the AT1 receptor) have demonstrated their therapeutic efficacy in protecting the cardiovascular system and kidneys in humans. Some AngII degradation peptides are also biologically active. Aminopeptidases promote the generation of AngIII and AngIV, two N-terminal degradation products, whereas ACE-2 catalyzes generation of Ang-(1–7). AngIV has been reported to bind to the AngIV-binding-site insulinregulated aminopeptidase (IRAP) and to promote inflammation in vascular cells. Ang-(1–7) activation of the Mas receptor may be beneficial in vascular injury but increases kidney inflammation. [ABSTRACT FROM AUTHOR]

The kidney is one of the most frequently affected organs in several types of systemic amyloidosis. Amyloid nephropathy is diagnosed by Congo red positivity of kidney tissue and by the presence of non-branching, randomly oriented fibrils that are 8–12 nm in diameter and evident by electron microscopy. Amyloid deposits can occur in the mesangium, glomerular capillary loops, tubulo-interstitium, and/or vasculature of the kidney. Amyloid nephropathy is typically characterized by nephrotic syndrome and progression to end-stage renal disease. The rate of decline in kidney function is variable and can be slowed by treatments that reduce the production of amyloidogenic precursor proteins or new amyloid deposits. [ABSTRACT FROM AUTHOR]

Changes in the maternal diet either throughout pregnancy, or at defined stages therein, can have pronounced effects on organogenesis in conjunction with endocrine sensitivity. These processes can be brought about by either maternal consumption of an imbalanced diet and/or a global reduction in macro or micro-nutrient intake. The magnitude of adaptation in the fetus or offspring is dependent on which organ is most rapidly growing and developing at that particular stage of the life cycle. For a majority of organs, the period of developmental plasticity extends beyond the fetal period, continuing through lactation and into the juvenile period. During lactation, enhanced growth of the offspring appears to be a primary determinant of the magnitude of adverse cardiovascular outcome. Consequently, a change in organ development during pregnancy may not necessarily equate with compromised function in later life. In the kidney, for example, adaptations in its endocrine sensitivity to maternal nutrient restriction through fetal development can be protective against the adverse consequences of later obesity. Such adaptations do not simply represent epigenetic modifications but a plethora of responses that, taken together, can prevent, or delay, at least in the kidney, the onset of apoptosis and later glomerulosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: The discovery of secretin initiated the field of endocrinology. Over the past century, multiple gastrointestinal functions of secretin have been extensively studied, and it was discovered that the principal function of this peptide in the gastrointestinal system is to facilitate digestion and to provide protection. In view of the late identification of secretin and the secretin receptor in various tissues, including the central nervous system, the pleiotropic functions of secretin have more recently been an area of intense focus. Secretin is a classical hormone, and recent studies clearly showed secretin''s involvement in neural and neuroendocrine pathways, although the neuroactivity and neural regulation of its release are yet to be elucidated. This chapter reviews our current understanding of the pleiotropic actions of secretin with a special focus on the hormonal and neural interdependent pathways that mediate these actions. [Copyright &y& Elsevier]