The development of the bladder trigone, the center of the anti-reflux mechanism

The urinary tract is an outflow system that conducts urine from the kidneys to the bladder via the ureters that propel urine to the bladder via peristalsis. Once in the bladder, the ureteral valve, a mechanism that is not well understood, prevents backflow of urine to the kidney that can cause severe damage and induce end-stage renal disease. The upper and lower urinary tract compartments form independently, connecting at mid-gestation when the ureters move from their primary insertion site in the Wolffian ducts to the trigone, a muscular structure comprising the bladder floor just above the urethra. Precise connections between the ureters and the trigone are crucial for proper function of the ureteral valve mechanism; however, the developmental events underlying these connections and trigone formation are not well understood. According to established models, the trigone develops independently of the bladder, from the ureters, Wolffian ducts or a combination of both; however, these models have not been tested experimentally. Using the Cre-lox recombination system in lineage studies in mice, we find, unexpectedly, that the trigone is formed mostly from bladder smooth muscle with a more minor contribution from the ureter, and that trigone formation depends at least in part on intercalation of ureteral and bladder muscle. These studies suggest that urinary tract development occurs differently than previously thought, providing new insights into the mechanisms underlying normal and abnormal development.     

Genetic Basis of Ureterocele

Congenital anomalies of the kidney and urinary tract (CAKUT) form a group of heterogeneous disorders that affect the kidneys, ureters and bladder, with frequent asynchronous presentations and multiple CAKUT associations in the same individual. Urinary tract formation is a complex process, dependent of the interaction of multiple genes and their sub-product. The same genic alterations can lead to different molecular expressions and different morphological anomalies. The ureterocele is a cystic dilation of the distal intramural ureter, resulting in obstruction of urine flow, dilation of the ureter and renal pelvis and loss of renal function. Two key steps in the urinary tract ontogenesis may be related to ureterocele development: formation and migration of the ureteric bud and its incorporation in the bladder. This review aims to describe the morphological, cellular and biochemical steps, as well as the genes involved in the occurrence of this anomaly.     

Ectopie rénale iliaque explorée par scintigraphie au 99mTc-DTPA et au 99mTc-DMSA. À propos d’un cas

IntroductionRenal ectopia is a malposition by anomaly of migration during the embryonic development. It can be high, low or crossed. Association with an obstructive malformation is rather frequent. The objective of this work is to highlight the interest of 99mTc-DTPA and 99mTc-DMSA scintigraphy in the exploration of this type of malformation through the observation of a patient presenting an iliac right renal ectopia associated with an ureteral-pelvic junction syndrome.ObservationA 38-year-old patient with an ureteral-pelvic junction syndrome on a right iliac renal ectopia revealed by intravenous urography. The dynamic renal scintigraphy using 99mTc-DTPA with furosemid test evidenced an organic obstruction in the right urinary tract with a right renal function estimated at 40% on the 99mTc-DMSA scintigraphy. A right pyeloplasty was carried out. The evolution was marked by the disappearance of pain and a remarkable improvement of the permeability of the right urinary tract on the follow-up scintigraphy.DiscussionRenal ectopia is not an unfrequent urinary malformation. It is generally low, pelvic or iliac. Association with an ureteral-pelvic junction obstruction is rather frequent. In this purpose, renal scintigraphy intervenes as a means of functional exploration, with low ionizing radiation and non-invasive to assess the permeability of the urinary tracts of the ectopic kidney and to appreciate the relative renal function. This contributes to the orientation of diagnosis and the improvement of therapeutic strategy.     

Obstructed Bifid Uretereric System Causing Unilateral Hydronephrosis

Bifid ureters are a common malformation of the urinary system. In clinical practice, hydronephrosis resulting from obstruction of such a system is rare. The authors present a case involving an 88-year-old man admitted to the hospital with symptoms of renal failure, where bifid ureters were found incidentally in a hydronephrotic kidney during an emergency nephrostomy. This had been missed on a previous CT scan, resulting in a unique therapeutic dilemma.Key words: Bifid ureters, Hydronephrosis, NephrostomyIn 1948, Nordmark described bifid ureters, along with bifid renal pelves, as the most common malformation of the urinary system. Later studies confirmed this, with duplicated ureters being found in 1 in 125 patients (0.8%) in whom postmortem examinations were carried out.^1,2 Often, these remain asymptomatic, and as a result, undiagnosed. In symptomatic patients, bifid ureteric systems are often found to be dilated as a consequence of blind-ending branches. Such cases have frequently been described in medical literature; however, the finding of hydronephrosis resulting from tumor obstructing the bifid ureter is relatively rare.We present a case report of hydronephrosis due to back pressure from obstruction of the ureteric orifice. The obstruction resulted in dilatation of both the moieties of the bifid ureters, causing both a diagnostic and treatment dilemma.     

Structure Organization of Urinary System in the Yellow Spotted Mountain Newts （Salamandridae： Neurergus microspilotus）

This study deals with the histomorphology of the mesonephros in male and female Neurergus microspilotus. The slender and narrow kidneys are positioned in the retro peritoneal position up against the ventral aspect of vertebral column and may extend the length from the esophagus-stomach junction to cloaca. The kidney in both sexes is composed of sexual（anterior） and pelvic（posterior） parts. The duct of sexual kidney is a narrow duct which is lying alongside its lateral edge. In the female, it is connected to the ureters and then the duct of defi nitive kidney. Before entering the cloaca, two ureters are joined together and open to the apex of the cloaca. In the male, after entering the sexual kidney, the sperm leave the testis through efferent ducts, then these ducts join together and eventually form Bidder＇s duct. The Bidder＇s duct joins the Bowman＇s capsule of the nephrons in the sexual kidney and the nephrons make collecting ducts which are fi lled with both sperm and urine. After leaving the kidney, all the collecting ducts are connected to the Wolffi an duct. Wolffi an duct joins the ureters（merge from defi nitive kidney） just before entering the cloaca. Based on serial paraffi n sections, nephrons consist of a fi ltration unit, the Malpighian corpuscle, and a renal tubule, which can be divided into 4 morphologically distinct segments： proximal tubule（first and second segment）, distal tubule, and collecting tubule. Collecting tubules merge and form a branch system that opens into collecting ducts.     

Usefulness of biliary scintigraphy using technetium Tc 99m mebrofenin for detection of disorders of patency of the bile ducts]

The value of the dynamic 99mTc-mebrofenin liver scintigraphy in the diagnosis of extrahepatic bile ducts patency has been assessed. The study included 176 patients in whom an occlusion of bile ducts of any degree was excluded in 111 cases, and bile ducts patency disorders were diagnosed in 65 patients. Time of the appearance of radiolabelled mebrofenin was measured in the selected segments of bile ducts. Time of appearance of radioactivity in the intestines was also noted. Another diagnostic criterion was persistent stasis of radioactivity in the choledochus. Basing on these criteria, patients were classified as "sick" or "healthy". It was possible to exclude the disease in case of negative result with the probability level of 91%. Positive result of scintigraphy points to the impaired patency diagnosis with 96% probability. Technique is simple, free of complications and contraindications. It is also of high predictive value. These features make the procedure particularly useful in the diagnosis of bile ducts patency.     

Development and differentiation of the ureteric bud into the ureter in the absence of a kidney collecting system

Six1-/- mice were found to have apparently normal ureters in the absence of a kidney, suggesting that the growth and development of the unbranched ureter is largely independent of the more proximal portions of the UB which differentiates into the highly branched renal collecting system. Culture of isolated urinary tracts (from normal and mutant mice) on Transwell filters was employed to study the morphogenesis of this portion of the urogenital system. Examination of the ureters revealed the presence of a multi-cell layered tubule with a lumen lined by cells expressing uroplakin (a protein exclusively expressed in the epithelium of the lower urinary tract). Cultured ureters of both the wild-type and Six1 mutant become contractile and undergo peristalsis, an activity preceded by the expression of alpha-smooth muscle actin (alphaSMA). Treatment with a number of inhibitors of signaling molecules revealed that inhibition of PI3 kinase dissociates the developmental expression of alphaSMA from ureter growth and elongation. Epidermal growth factor also perturbed smooth muscle differentiation in culture. Moreover, the peristalsis of the ureter in the absence of the kidney in the Six1-/- mouse indicates that the development of this clinically important function of ureter (peristaltic movement of urine) is not dependent on fluid flow through the ureter. In keeping with this, isolated ureters cultured in the absence of surrounding tissues elongate, differentiate and undergo peristalsis when cultured on a filter and undergo branching morphogenesis when cultured in 3-dimensional extracellular matrix gels in the presence of a conditioned medium derived from a metanephric mesenchyme (MM) cell line. In addition, ureters of Six1-/- urinary tracts (i.e., lacking a kidney) displayed budding structures from their proximal ends when cultured in the presence of GDNF and FGFs reminiscent of UB budding from the wolffian duct. Taken together with the above data, this indicates that, although the distal ureter (at least early in its development) retains some of the characteristics of the more proximal UB, the growth and differentiation (i.e., development of smooth muscle actin, peristalsis and uroplakin expression) of the distal non-branching ureter are inherent properties of this portion of the UB, occurring independently of detectable influences of either the undifferentiated MM (unlike the upper portion of the ureteric bud) or more differentiated metanephric kidney. Thus, the developing distal ureter appears to be a unique anatomical structure which should no longer be considered as simply the non-branching portion of the ureteric bud. In future studies, the ability to independently analyze and study the portion of the UB that becomes the renal collecting system and that which becomes the ureter should facilitate distinguishing the developmental nephrome (renal ontogenome) from the ureterome.     

Excretory function after unilateral renal denervation and administration of propranolol to unanaesthetized dogs

The experiments were carried out on female dogs with exteriorized ureters prior to and following surgical denervation of the left kidney. Propranolol 1.0 mg/kg b.w. was administered intravenously. Sodium, potassium, chloride, calcium, magnesium, zinc, copper, creatinine and urea concentrations in the urine from the denervated and intact kidneys as well as in blood drawn were determined. After renal denervation PAH clearance was determined. As a result of denervation diuresis and calcium and copper excretion were increased while urine osmolality was diminished. No change occurred in kidney blood flow and GFR. After propranolol administration diuresis, calcium and copper excretion in the intact kidney significantly increased. Changes in the excretory function of the left kidney following its denervation were not a result of alterations in renal haemodynamics. Results obtained indicative of that beta-adrenergic receptors contribute to the excretion of calcium and copper ions.     

Intérêt de la scintigraphie rénale dynamique dans le diagnostic de l’hypertension orthostatique (à propos d’un cas)

Orthostatic hypertension (HTO) is a well-known clinical entity and is sometimes associated with excessive renal mobility. During nephroptosis, dynamic renal scintigraphy (SRD) allows the identification of scintigraphic abnormalities suggestive of HTO guiding therapeutic by nephropexy. The authors report a case of HTO combined with a mobile right kidney, treated favourably by nephropexy and whose diagnosis was suggested by DTPA-Tc99m dynamic renal scintigraphy results.     

Prolonged Ethanol Ingestion Increases Renal AQP2 and AQP3 Expression in Adult Ratsand in Their Offspring

This study evaluates the effect of prolonged ethanol ingestion on the renal ability to concentrate urine. Suckling Wistar rats born to mothers given ethanol before and during gestation and suckling periods (ethanol-exposed offspring) were used and the results were compared with those obtained from offspring of dams given diets containing no ethanol. Comparisons were also made between progenitors with or without prolonged ethanol ingestion. Body and kidney weights; arginine-vasopressin (AVP) and aldosterone plasma levels; plasma, urine and renal papillary osmolality; urine outflow; kidney AQP2, AQP3 and AQP4 expression and diencephalon AVP mRNA expression were determined. As compared with control offspring, the ethanol-exposed offspring present i) lower body and kidney weights; ii) lower urine outflow; iii) higher renal AQP2 and AQP3 mRNA; iv) higher renal AQP2 protein content and v) higher urine and renal papillary osmolality. These changes were also observed in the ethanol-treated progenitors, although they were of smaller magnitude. Plasma osmolality, renal AQP4 mRNA, AVP plasma levels and diencephalon AVP mRNA expression were not affected by the ethanol treatment. Plasma levels of aldosterone were only significantly increased in the ethanol-exposed suckling rats. It is concluded that maternal ethanol ingestion before and during gestation and suckling periods affects the renal function of the offspring, up-regulating renal AQP2 expression by an AVP-independent mechanism. Ethanol-treated progenitors manifest similar renal changes, although of lesser magnitude than the offspring.     

Disorders of urine volume in the critically ill child.

This article will provide a pathophysiologic basis for the assessment of critically ill children who have developed disorders of urine volume. The anatomical and pathophysiologic causes of oliguria and polyuria are considered. The physiologic basis for the use of urinary sodium and osmolarity as a guide to the assessment of patients with disorders of urine volume are discussed in detail. In addition, guidelines for the management of children with acute renal failure, with particular emphasis on the consideration for nutritional support of these patients, is discussed as a part of the comprehensive approach to this problem. This article emphasizes an understanding of the pathophysiology of salt and water excretion by the kidney as a foundation to the diagnosis and management of patients with oliguria and polyuria.     

Management of Localized Prostate Cancer and an Incidental Ureteral Duplication With Upper Pole Ectopic Ureter Inserting into the Prostatic Urethra

Ectopic ureters are rare congenital malformations of the renal system that most commonly present in females. It is extremely rare to encounter an ectopic ureter in an older man undergoing radical prostatectomy. We report herein a case of a 66-year-old man with prostate cancer and a complete duplication of the left renal collecting system, with an upper pole ectopic ureter and associated normal functioning renal parenchyma entering into the prostatic urethra. This anomaly was incidentally discovered on preoperative magnetic resonance imaging of the prostate. Open radical retropubic prostatectomy and a left ureteroureterostomy were performed.Key words: Prostate cancer, Ectopic ureter, Prostatic urethra, Prostatectomy, UreteroureterostomyEctopic ureters are rare and occur in about 1 of 1900 live births.¹ Over 85% of ectopic ureters are associated with duplicated systems and most commonly present in females. Ectopic ureters present 2 to 12 times less frequently in males than in females, and in males are most commonly associated with a single collecting system.² Ectopic ureters inserting into the prostatic urethra often present with obstruction and/or urinary tract infections. Few cases of ectopic ureters entering into the prostatic urethra as an incidental finding in men undergoing radical prostatectomy for prostate cancer have been reported in the literature.^3,4 This case report describes a patient with prostate cancer and an asymptomatic upper pole ectopic ureter inserting into the prostatic urethra associated with normal functioning renal parenchyma demonstrated on preoperative mercaptoacetyltriglycine (MAG-3) renogram, magnetic resonance imaging (MRI), and computed tomography (CT). We discuss the treatment plan for this patient and give an overview of ectopic ureters.     

Pharmacology of ureter.

Ureter which performs the important function of transport of urine from kidney to the bladder is not a passive tube, but exhibits characteristic spontaneous (peristaltic) activity. This peristaltic activity is characterized by coordinated muscular contractions, which after originating from a spontaneously active primary pacemaker, situated in the vicinity of the pelvi ureteric junction, propagate downwards along the entire length of the ureter. In addition, the ureter, like the heart, possesses certain cells which become activated when the primary pacemaker is suppressed or there is an interruption of conduction, thereby, acting as latent pacemakers. (1) The peristaltic activity of the ureter is modified by several pharmacologically active substances. Moreover, some of these substances are occasionally able to initiate spontaneous activity even in quiescent ureters. This article briefly reviews the effects of catecholamines (adrenaline, noradrenaline and isoprenaline) and acetylcholine on the ureters of human beings and some domestic and laboratory animals.     

Renal transtubular transport of mercapturic acid in vivo

When $\text{S-}\text{benzyl}\text{-N-}\text{acetyl}\text{-}\text{l}\text{-[}\text{U}\text{-}{}^{14}\text{C}\text{]}\text{cysteine}$, a mercapturic acid, was administered to rats intravenously, the plasma level of radioactivity decreased very rapidly with a concomitant increase in the renal level of radioactivity. The renal radioactivity reached its maximum within 2 min and then decreased rapidly with concomitant appearance of the radioactive mercapturic acid in the urine. Bilateral ligation of the ureters resulted in only a slight decrease in the rate of disappearance of mercapturic acid from the plasma, while bilateral nephrectomy caused a marked retardation of its clearance from the plasma. Intravenous administration of probenecid, a well known inhibitor of a renal transbular transport system for organic acids, caused a significant retardation of mercapturate clearance from the plasma in both of the control and ureter-ligated animals. The renal accumulation of this mercapturic acid as well as its excretion into urine was inhibited by probenecid.All these data suggested that a mercapturic acid in the plasma was preferentially taken up by renal tubule cells from the basolateral side of plasma membranes via the probenecid-sensitive transtubular transport system and then excreted rapidly into the lumenal space. This transtubular transport of a mercapturic acid seems to constitute an important process in the hepato-renal cooperation in the mercapturic acid biosynthesis in vivo.     

Time dependent effects of gentamicin on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in rat kidney tissues

Gentamicin (GM), an antibiotic against life threatening bacterial infection, induces remarkable toxicity in the kidney. Histological studies have indicated that mitochondria, microsomes, lysosomes and plasma membranes of renal proximal convoluted tubules in particular are major GM targets. Despite numerous investigations, the biochemical/cellular basis of GM nephrotoxicity is not well understood. Recently reactive oxygen species (ROS) are considered to be important mediators of GM-induced nephrotoxicity. We hypothesize that GM causes damage to intracellular organelles and affects their structural integrity and alters metabolic and other functional capabilities. To address above hypothesis a long-term, time-dependent effect of GM has been studied on blood/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM) and basolateral (BLM), lysosomes and oxidative stress in renal tissues. A nephrotoxic dose of GM (80 mg/kg body weight) was administered to rats daily for 15 days. The long-term treatment with GM induced a significant increase in serum creatinine, blood urea nitrogen followed by massive proteinuria, glucosuria, enzymuria along with loss of electrolytes in the urine. The activities of the enzymes of carbohydrate metabolism, plasma membranes, lysosomes significantly declined. The activities of antioxidant enzymes e.g. superoxide dismutase, catalase and glutathione peroxidase were severely depressed and lipid peroxidation was significantly increased in the renal cortex and medulla. We conclude that GM administration induced oxidative damage to renal tissues that resulted in impaired carbohydrate metabolism and decreased activities of BBM, BLM and lysosomes associated with increased lipid peroxides.     

Role of polycystins in renal tubulogenesis

Every day, human renal tubules process 140 l of glomerular filtrate into 1 l of urine. They accomplish this by the coordinated function of distinct cell types occupying specific positions along the tubules. This precisely defined structure requires tight regulation of morphogenesis. A group of disorders termed polycystic kidney disease (PKD) is characterized by altered tubular morphology. Mutating genes involved in PKD results in renal tubules that either fail to form properly or 'forget' how to maintain their 'correct' diameter. Study of PKD proteins will elucidate the process of renal tubular morphogenesis and guide the development of therapies. Here, we focus on insights provided by study of the most common form of PKD, autosomal dominant PKD.     

Molecular Pathophysiology of Renal Tubular Acidosis

Renal tubular acidosis (RTA) is characterized by metabolic acidosis due to renal impaired acid excretion. Hyperchloremic acidosis with normal anion gap and normal or minimally affected glomerular filtration rate defines this disorder. RTA can also present with hypokalemia, medullary nephrocalcinosis and nephrolitiasis, as well as growth retardation and rickets in children, or short stature and osteomalacia in adults. In the past decade, remarkable progress has been made in our understanding of the molecular pathogenesis of RTA and the fundamental molecular physiology of renal tubular transport processes. This review summarizes hereditary diseases caused by mutations in genes encoding transporter or channel proteins operating along the renal tubule. Review of the molecular basis of hereditary tubulopathies reveals various loss-of-function or gain-of-function mutations in genes encoding cotransporter, exchanger, or channel proteins, which are located in the luminal, basolateral, or endosomal membranes of the tubular cell or in paracellular tight junctions. These gene mutations result in a variety of functional defects in transporter/channel proteins, including decreased activity, impaired gating, defective trafficking, impaired endocytosis and degradation, or defective assembly of channel subunits. Further molecular studies of inherited tubular transport disorders may shed more light on the molecular pathophysiology of these diseases and may significantly improve our understanding of the mechanisms underlying renal salt homeostasis, urinary mineral excretion, and blood pressure regulation in health and disease. The identification of the molecular defects in inherited tubulopathies may provide a basis for future design of targeted therapeutic interventions and, possibly, strategies for gene therapy of these complex disorders.Key Words: Renal tubular acidosis, acid-base homeostasis, molecular physiology, tubular transport, gene mutations.     

Glomerular and postglomerular transcapillary exchange in dog kidney

The multiple-indicator dilution technique (MIDT) was used to study glomerular and postglomerular permselectivity to neutral dextran molecular weight markers in anesthetized dogs undergoing mannitol diuresis. Renal vein and urine outflow curves were obtained after an intraarterial pulse injection of 125I-labeled albumin (plasma reference), creatinine (extracellular reference), [14C]inulin, and chromatographically homogeneous 3H-labeled neutral dextrans. The urine recovery data reflect solute losses across the glomerulus. The renal vein outflow curves contain information about both glomerular and postglomerular extraction. For dextrans less than 13,500 daltons the urine transit pattern was superimposed on the glomerular markers creatinine and inulin. Relative to 125I-labeled albumin, the renal vein recoveries for creatinine, inulin, and dextrans (less than 13,500 daltons) were all equal. The renal vein mean transit time (tdextran) was greater than talbumin and less than tcreatinine. With increasing dextran size, tdextran progressively decreased. Eventually for dextrans greater than 15,500 daltons, tdextran became equal to talbumin in the renal vein, whereas urine recovery relative to inulin decreased with increasing size. Urine recovery of 3H-labeled dextran (ED) relative to inulin (Ei) provided a measure of unidirectional fractional glomerular extraction (ED/Ei). Constant infusion fractional clearance measurement of the same dextrans [U/P)D/(U/P)i) was found to equal ED/Ei obtained from the MIDT. Within the autoregulatory range of glomerular filtration, ED/Ei was invariant with reduction in renal plasma flow. Therefore, under the experimental conditions employed in the present study, diffusion across the glomerulus was negligible relative to convection. This permitted estimation of the reflection coefficients for the series of neutral dextrans. Postglomerular extraction was markedly flow dependent, which implies a major diffusion limitation. Application of a barrier-limited distributed model permitted quantitation of postglomerular capillary permeability coefficients for neutral markers of less than 5000 daltons.     

Unraveling trafficking of the kidney anion exchanger 1 in polarized MDCK epithelial cells.

Kidney anion exchanger 1 (kAE1) is a membrane glycoprotein expressed at the basolateral membrane of type A intercalated cells in the kidney collecting tubule. Mutations occurring in the gene encoding this protein can give rise to distal renal tubular acidosis (dRTA), a disease characterized by an impaired urine acidification, nephrocalcinosis, and renal failure. Here we review how the study of dRTA mutants in polarized epithelial cells has shed light on the cellular mechanisms resulting in this renal disease.